Urofollitropin: A protein extract of human menopausal urine in which LUTEINIZING HORMONE has been partially or completely removed. Urofollitropin represents FOLLICLE STIMULATING HORMONE from the urine. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
| ID Source | ID |
|---|---|
| PubMed CID | 62819 |
| SCHEMBL ID | 19712185 |
| MeSH ID | M0008869 |
| Synonym |
|---|
| follicle-stimulating hormone |
| 146479-72-3 |
| 97048-13-0 |
| urofollitropin |
| 1-[19-amino-7-(2-amino-2-oxoethyl)-13-butan-2-yl-10-(1-hydroxyethyl)-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-n-[1-[(2-amino-2-oxoethyl)amino]-4-methyl-1-oxopentan-2-yl]pyrrolidine-2-carbox |
| SCHEMBL19712185 |
| Q4006490 |
| AT36867 |
| 1-{19-amino-7-(2-amino-2-oxoethyl)-13-(butan-2-yl)-10-(1-hydroxyethyl)-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentaazacycloicosane-4-carbonyl}prolylleucylglycinamide |
| DTXSID10869286 |
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 11 (45.83) | 29.6817 |
| 2010's | 12 (50.00) | 24.3611 |
| 2020's | 1 (4.17) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.
| This Compound (111.52) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 9 (36.00%) | 5.53% |
| Reviews | 1 (4.00%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 1 (4.00%) | 0.25% |
| Other | 14 (56.00%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
| Trial | Phase | Enrollment | Study Type | Start Date | Status | ||
|---|---|---|---|---|---|---|---|
| Age-related Variability of the Efficacy and Tolerability of Alternative Pituitary Suppression Regimens in Follicular Stimulation for Assisted Reproduction Purposes. A Randomised, Prospective, Multi-centre Clinical Trial [NCT01107470] | 2,000 participants (Anticipated) | Observational | 2010-04-30 | Recruiting | |||
| A Prospective, Observational Study on the Use of Cetrotide (GnRH Antagonist) With GONAL-f in Assisted Reproductive Technologies (ART) [NCT01109654] | 2,175 participants (Actual) | Observational | 2008-09-30 | Completed | |||
| A Prospective, Single Center, Observational Study on the Predictive Factors of Ovarian Response in Ovulation Induction (OI) With Intrauterine Insemination (IUI) of a Gonal-f Low-dose Step-up Regimen [NCT01100346] | 30 participants (Actual) | Observational | 2010-01-31 | Terminated | |||
| Follow-up Protocol to Collect the Outcome and Safety of Frozen-thawed Embryo Transfer (FTET) Cycles After Cryopreservation of Embryos in Clinical Study P06029 (Phase 3; Protocol No. P06031) [NCT01146418] | Phase 3 | 307 participants (Actual) | Interventional | 2010-06-02 | Completed | ||
| Use of r-hLH (Luveris) Late Follicular Phase for Controlled Ovarian Stimulation (COS) in Donor Patients Previously Treated With r-hFSH (Gonal F)in a Long Luteal Downregulated Cycle With GnRH Agonist. A Cross-over Study [NCT01223079] | 20 participants (Actual) | Interventional | 2005-12-31 | Completed | |||
| A Phase III, Randomized, Double-Blind, Active-Controlled, Non-Inferiority Clinical Trial to Investigate the Efficacy and Safety of a Single Injection of Org 36286 (Corifollitropin Alfa) to Induce Multifollicular Development for Controlled Ovarian Stimulat [NCT00696800] | Phase 3 | 1,509 participants (Actual) | Interventional | 2006-06-27 | Completed | ||
| A Phase 2, Open Label, Randomized Trial to Investigate the Dose-Response Relationship of a Single Injection of Org 36286 (Corifollitropin Alfa) to Initiate Multiple Follicular Growth in a Controlled Ovarian Hyperstimulation Protocol for IVF or ICSI. [NCT00598208] | Phase 2 | 325 participants (Actual) | Interventional | 2003-05-19 | Completed | ||
| [NCT02454556] | Phase 3 | 106 participants (Actual) | Interventional | 2015-04-30 | Completed | ||
| Cumulative Pregnancy Rate With Lower and Higher Dose of Gonadotropin During Controlled Ovarian Hyperstimulation During IVF Among Expected Poor Responders: a Prospective, Randomized Controlled Trial [NCT05103228] | 700 participants (Anticipated) | Interventional | 2021-12-02 | Recruiting | |||
| Pregnancy and Neonatal Follow-up of Ongoing Pregnancies Established After Controlled Ovarian Stimulation in Clinical Trial 38833 for Org 36286 (Corifollitropin Alfa) [NCT00702520] | 15 participants (Actual) | Observational | 2006-04-01 | Completed | |||
| Open Randomized Study Comparing Clinical Efficacy of Corifollitropin Alfa (Elonva) in Combination With Menotropin (Merional) With Follitropin and Lutropin Alfa (Pergoveris) for Ovarian Stimulation in Expected Suboptimal Responders [NCT03177538] | Phase 4 | 32 participants (Actual) | Interventional | 2017-09-04 | Completed | ||
| Endometrial Gene Expression Profiles During Ovarian Stimulation With Recombinant FSH With or Without the Addition of Recombinant LH in Genuine Poor Responders [NCT05405686] | Phase 4 | 30 participants (Anticipated) | Interventional | 2023-05-01 | Not yet recruiting | ||
| A Phase 3, Randomized, Double-blind, Active-controlled, Non-inferiority Trial to Investigate the Efficacy and Safety of a Single Injection of SCH 900962 (Corifollitropin Alfa) to Induce Multifollicular Development for Controlled Ovarian Stimulation (COS) [NCT01144416] | Phase 3 | 1,424 participants (Actual) | Interventional | 2010-06-30 | Completed | ||
| Protocol for Drug Use Investigation of Follistim Injection [NCT00920634] | 384 participants (Actual) | Observational | 2007-07-31 | Completed | |||
| A Randomised, Controlled, Assessor-blind, Parallel Groups, Multicentre, Multinational Trial Comparing the Ovarian Response of a Starting Dose of 15 μg Follitropin Delta (REKOVELLE) to a Starting Dose of 225 IU Follitropin Alfa (GONAL-F) in Conventional Re [NCT05263388] | Phase 3 | 300 participants (Anticipated) | Interventional | 2022-07-10 | Recruiting | ||
| A Randomised, Controlled, Assessor-blind, Parallel Groups, Multicentre Trial in India Comparing the Efficacy and Safety of FE 999049 (Follitropin Delta) With Follitropin Alfa (GONAL-F) in Controlled Ovarian Stimulation in Women Undergoing an Assisted Repr [NCT04773353] | Phase 3 | 220 participants (Actual) | Interventional | 2021-12-03 | Active, not recruiting | ||
| A Randomized Controlled Trial to Compare the Efficacy Between Pergoveris and Follitropin Alfa in Ovarian Stimulation in Patients Aged ≥ 35 Years [NCT02244866] | 240 participants (Actual) | Interventional | 2012-10-31 | Completed | |||
| Impact on Ovarian Reserve of Second Laparoscopic Surgery for Recurrent Unilateral Endometriomas: a Case-control Study. [NCT02047838] | 36 participants (Actual) | Observational | 2007-01-31 | Completed | |||
| [NCT01319695] | Phase 1/Phase 2 | 140 participants (Actual) | Interventional | 2011-01-31 | Completed | ||
| Prediction Of Reproductive Outcome in Assisted Conception Cycles in Women With Unexplained Infertility [NCT03846388] | 292 participants (Actual) | Interventional | 2019-02-01 | Completed | |||
| A Phase I, Open-label, Randomized, Three-period, Crossover, Single-center Trial to Assess the Bioequivalence of the Co-administration of 900 IU of Follitropin Alfa (Gonal-f) and 450 IU of Lutropin Alfa (Luveris) Versus the Fixed Combination of 900 IU Foll [NCT04899193] | Phase 1 | 72 participants (Actual) | Interventional | 2021-05-08 | Completed | ||
| Designated Drug Use Investigation 1 of Follistim Injection [NCT00920361] | 1,664 participants (Actual) | Observational | 2005-11-30 | Completed | |||
| A Prospective, Open Label, Randomised, Parallel Group, Comparative Pilot Study to Study the Efficacy and Safety of Highly Purified Menotrophin Versus Recombinant FSH (Follitropin Alfa) Administered Subcutaneously to Subfertile Female Patients Undergoing I [NCT00257556] | Phase 4 | 80 participants (Actual) | Interventional | 2005-10-31 | Completed | ||
| Assessment of Sexual Maturation in β-Thalassemia Major Patients Receiving Iron Chelation Therapy in Assiut University Hospital [NCT03847558] | 100 participants (Anticipated) | Observational | 2019-04-15 | Not yet recruiting | |||
| A Prospective, Multi-center, Observational Study of Gonal-F Filled by Mass Pens in Multifollicular Stimulation Prior to IVF/ICSI [NCT01075854] | 1,539 participants (Actual) | Observational | 2009-04-30 | Completed | |||
| A Prospective, Observational and Multicentric Study to Compare the Dose of GONAL-fTM FbM Prescribed by the Doctor With the Recommendation of the Dose Calculator Consort and to Evaluate the Ease of Use of Pre-filled Pen of GONAL-fTM FbM Pen [NCT01080729] | 25 participants (Actual) | Observational | 2009-02-28 | Terminated | |||
| In Vitro Maturation of Human Eggs [NCT02516462] | 100 participants (Anticipated) | Interventional | 2015-07-31 | Recruiting | |||
| Pregnancy and Neonatal Follow-up of Ongoing Pregnancies Established After Ovulation Induction in Clinical Trial 107010 for the Development of Org 36286 (Corifollitropin Alfa) [NCT00702338] | 1 participants (Actual) | Observational | 2008-05-15 | Completed | |||
| A Phase III, Randomized, Double-blind, Active-controlled, Equivalence Clinical Trial to Investigate the Efficacy and Safety of a Single Injection of 100 µg Org 36286 (Corifollitropin Alfa) to Induce Multifollicular Development for Controlled Ovarian Stimu [NCT00702845] | Phase 3 | 397 participants (Actual) | Interventional | 2006-12-28 | Completed | ||
| Pregnancy and Neonatal Follow-up of Ongoing Pregnancies Established During Phase II Clinical Trials for the Development of Org 36286 (Corifollitropin Alfa). [NCT00702195] | 29 participants (Actual) | Observational | 2002-01-01 | Completed | |||
| How do Different Ovarian Stimulation Protocols Affect Endometrial Receptivity During a Fresh In-vitro Fertilization Attempt [NCT03755973] | Phase 4 | 24 participants (Actual) | Interventional | 2020-01-29 | Completed | ||
| A Multicenter, Double-blind, Non-inferiority, Phase 3 RCT Comparing GenSci094 and Recombinant FSH During the First Seven Days of Ovarian Stimulation in Chinese ART Patients [NCT06091436] | Phase 3 | 176 participants (Anticipated) | Interventional | 2023-03-24 | Recruiting | ||
| Retrospective Study of High Dose Follitropin Delta in a Mixed Protocol With Human Chorionic Gonadotropin [NCT05873725] | 150 participants (Anticipated) | Observational | 2023-05-20 | Active, not recruiting | |||
| Study on the Efficacy and Safety of Pulsatile Gonadotropin Releasing Hormone Pump Treatment in Patients With Idiopathic Hypogonadotropic Hypogonadism [NCT02310074] | Phase 4 | 76 participants (Actual) | Interventional | 2010-01-31 | Active, not recruiting | ||
| A Phase II, Randomized, Controlled, Open-label, Feasibility Trial to Evaluate if a Single or Repeated Dose of Org 36286 (Corifollitropin Alfa) Followed by a Low Daily Dose of Either hCG or Recombinant FSH Can Induce Monofollicular Growth in Women With WHO [NCT00697255] | Phase 2 | 8 participants (Actual) | Interventional | 2007-05-15 | Terminated | ||
| An Interventional Study to Assess the Efficacy and Safety of Gonapure® in Multifollicular Stimulation in Egyptian Women Undergoing IVF/ICSI [NCT03057574] | Phase 4 | 200 participants (Anticipated) | Interventional | 2017-02-09 | Recruiting | ||
| A Randomized, Double-blind, Placebo-controlled, Parallel Groups, Multicenter Trial Investigating the Efficacy and Safety of FE 999049 in Controlled Ovarian Stimulation in Women Aged 35-42 Years Undergoing Assisted Reproductive Technology [NCT03738618] | Phase 3 | 521 participants (Actual) | Interventional | 2018-10-29 | Completed | ||
| Comparison of Assisted Reproductive Technology (ART) Outcomes Between Two Protocols of Induction of Ovulation by Using Recombinant Luteinizing Hormone (rLH) and Recombinant Follicle Stimulating Hormone (rFSH) in Patients With Hypogonadotropic Hypogonadism [NCT02140515] | Phase 4 | 90 participants (Anticipated) | Interventional | 2012-11-30 | Recruiting | ||
| Prospective Multi-centre Observational Study to Determine the Mono-bifollicular Development in Infertile Women Subjected to Ovulation Induction With Follitropin α [NCT01111084] | 410 participants (Actual) | Observational | 2004-03-31 | Completed | |||
| [NCT01037699] | Phase 3 | 720 participants (Actual) | Interventional | 2005-01-31 | Completed | ||
| Phase IV Study to Evaluate the Ease of Use, Local Tolerance Safety and Effectiveness of Gonal-f® (Filled-by-Mass in a Prefilled Pen) [NCT01115725] | 76 participants (Actual) | Observational | 2005-11-30 | Completed | |||
| The Performance of an Individual Dosing Regimen of Follitropin Delta for Controlled Ovarian Stimulation for IVF in a Real-word Setting: a Non-interventional Observational Study [NCT05173597] | 850 participants (Anticipated) | Observational | 2021-12-08 | Recruiting | |||
| A Phase I, Monocenter, Randomized, Placebo and Comparator Controlled, Single Blind, Rising Dose, Clinical Study to Determine Single Dose Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Four Doses of FSH-GEX™ According to Adaptive Design (25 [NCT01354886] | Phase 1 | 19 participants (Actual) | Interventional | 2011-04-30 | Completed | ||
| A Randomized Study to Analysis the Effectiveness of Estradiol Valerate Pretreatment in Antagonist Protocol for Poor Ovarian Response Patient [NCT03300518] | 552 participants (Actual) | Interventional | 2017-11-15 | Completed | |||
| A Randomised, Controlled, Assessor-blind, Parallel Groups, Multicentre, Multinational Trial Comparing the Efficacy and Safety of FE 999049 With Follitropin Alfa (GONAL-F) in Controlled Ovarian Stimulation in Women Undergoing an Assisted Reproductive Techn [NCT01956110] | Phase 3 | 1,329 participants (Actual) | Interventional | 2013-10-31 | Completed | ||
| Pregnancy and Neonatal Follow-up of Ongoing Pregnancies Established During Clinical Trial 38826 for the Development of Org 36286 (Corifollitropin Alfa). [NCT00702988] | 44 participants (Actual) | Observational | 2003-10-01 | Completed | |||
| Observational Study GONAL-f® Consort [NCT01100333] | 2,552 participants (Actual) | Observational | 2008-04-30 | Completed | |||
| Aneuploidy Rate Impact in Oocyte From Egg Donation Cycle With Different Stimulation Protocol: Recombinant FSH vs Human FSH [NCT01164943] | 80 participants (Actual) | Interventional | 2010-07-31 | Terminated | |||
| "An Observational Study FOLLITROPIN Comparing the Efficacy of Follitropin Alpha Biosimilar: the Real-world Data" [NCT04854707] | 5,484 participants (Actual) | Observational | 2020-01-12 | Completed | |||
| Prospective, Randomized Open Trial to Evaluate the Efficacy of Highly Purified Urinary FSH Versus Recombinant FSH in Oocyte Donors Undergoing Controlled Ovarian Stimulation Based on Receptor N680S FSH Gene Polymorphism. Genodon Trial [NCT02625519] | Phase 4 | 180 participants (Anticipated) | Interventional | 2015-12-31 | Recruiting | ||
| The Impact of Frozen - Thawed Blastocyst Morphological Development and Blastocoele Re-expansion on Clinical Pregnancy Outcome After One Controlled Ovarian Stimulation Cycle Using REKOVELLE® [NCT03697031] | 362 participants (Actual) | Observational | 2018-09-01 | Terminated(stopped due to Permanently terminated due to halt of recruitment due to COVID-19 pandemic) | |||
| A Multi-Center, Randomized, Open-Label Evaluation of MENOPUR® Versus FOLLISTIM® in Polycystic Ovarian Syndrome (PCOS) Patients [NCT00805935] | Phase 4 | 110 participants (Actual) | Interventional | 2009-01-31 | Completed | ||
| A Randomized, Open-label, Two-Period, Two-Crossover Study to Compare the Safety and Pharmacokinetics of Recombinant Human Follicle Stimulating Hormone Injection (LM001) and Gonal-F® in Healthy Female Volunteers [NCT03535103] | Phase 1 | 32 participants (Anticipated) | Interventional | 2018-06-01 | Not yet recruiting | ||
| Follow-up Protocol to Collect the Outcome of Frozen-thawed Embryo Transfer Cycles After Cryopreservation of Embryos in Clinical Trial 38819 [NCT00702273] | 344 participants (Actual) | Observational | 2006-04-19 | Completed | |||
| A Randomised, Controlled, Assessor-blind, Parallel Groups, Multicentre, Pan-Asian Trial Comparing the Efficacy and Safety of FE 999049 With Follitropin Alfa (GONAL-F) in Controlled Ovarian Stimulation in Women Undergoing Assisted Reproductive Technology P [NCT03296527] | Phase 3 | 1,011 participants (Actual) | Interventional | 2017-12-01 | Completed | ||
| A Randomised, Controlled, Assessor-blind, Parallel Groups, Multicentre Trial Assessing the Efficacy and Safety of FE 999049 in Controlled Ovarian Stimulation in Japanese Women Undergoing an Assisted Reproductive Technology Programme [NCT03228680] | Phase 3 | 373 participants (Actual) | Interventional | 2017-07-29 | Completed | ||
| An Open-Label Randomized Controlled Trial (RCT) of 6 Weeks of Human Growth Hormone (HGH) Prior to Ovulation Induction for In Vitro Fertilization (IVF) [NCT02179255] | Phase 1/Phase 2 | 30 participants (Anticipated) | Interventional | 2014-08-01 | Enrolling by invitation | ||
| A Phase I Clinical Trial of an Infusion of Autologous T Cells Genetically Engineered With a Chimeric Receptor to Target the Follicle-Stimulating Hormone Receptor in Patients With Recurrent Ovarian Cancer [NCT05316129] | Phase 1 | 48 participants (Anticipated) | Interventional | 2022-04-28 | Recruiting | ||
| Phase III Study on the Convenience, Safety and Efficacy of Follitropin Alfa Liquid Formulation Applied by a Pen Versus Follitropin Beta Liquid Formulation Applied by Pen [NCT01081639] | Phase 3 | 34 participants (Actual) | Interventional | 2003-11-30 | Completed | ||
| Role of FSH in Human Gonadal Development [NCT00064987] | Phase 2 | 19 participants (Actual) | Interventional | 2001-04-30 | Terminated(stopped due to Recruitment was at a standstill. We are currently preparing our results for publication.) | ||
| Highly Purified Human Menopausal Gonadotropin Versus Recombinant Follicle Stimulating Hormone in Ovarian Hyperstimulation With Gonadotropin Releasing Hormone Antagonists. A Randomized Study. [NCT00669786] | Phase 3 | 0 participants | Interventional | Completed | |||
| A Phase II, Multicenter, Randomized, Assessor-blinded, Active-comparator, Dose-finding Study to Evaluate AS900672 Enriched Versus Follitropin Alfa (Gonal-f®) in Stimulating Multiple Follicular Development in Infertile Women Undergoing Assisted Reproductiv [NCT00505752] | Phase 2 | 520 participants (Actual) | Interventional | 2007-01-31 | Completed | ||
| A RCT Study to Evaluate the Safety and Efficacy of the Fixed Day-5 Antagonist Protocol Versus the Flexible Antagonist Protocol for the Controlled Ovarian Stimulation in Chinese Women With Predicted High Ovarian Response [NCT02635607] | 200 participants (Anticipated) | Interventional | 2016-01-31 | Not yet recruiting | |||
| An Exploratory Study to Explore the Correlation Between the Symptoms and Signs of Polycystic Ovarian Syndrome (PCOS) and Risk of Over-response Using New Gonal-f® Pen in Assisted Reproductive Technology (ART) Treatment in China [NCT02607293] | 1,064 participants (Actual) | Observational | 2015-12-31 | Completed | |||
| A Phase IV Prospective, Multicenter, Randomized, Open-label Trial to Assess the Efficacy and Safety of GONAL f® at a Dose Based on Subject Baseline Characteristics Determined According to the CONSORT Calculator Compared With a Standard Dose of GONAL f® 15 [NCT00829244] | Phase 4 | 200 participants (Actual) | Interventional | 2008-08-31 | Completed | ||
| Prospective, Randomized Open Trial to Evaluate the Efficacy of an Ovarian Stimulation Protocol Based on FSH Receptor Genotype [NCT00749853] | Phase 3 | 165 participants (Anticipated) | Interventional | 2015-05-31 | Suspended(stopped due to PI left the institution) | ||
| Parallel-Group Comparative Study of SJ-0021 and Purified Pituitary Gonadotropin in Subjects With Amenorrhea I or Anovulatory Cycles - Phase III Single-Blind Study [NCT01185782] | Phase 3 | 300 participants (Actual) | Interventional | 2007-02-28 | Completed | ||
| A Phase IIIb Randomized Open-label Study to Compare the Estradiol Level on the Releasing Day in Two Regimen of Cetrotide® 0.25 mg Used From Day 1 or From Day 7 of the Menstrual Cycle (Day 0 or Day 6 of Stimulation) in Polycystic Ovarian (PCO) Women in ART [NCT01185704] | Phase 3 | 136 participants (Actual) | Interventional | 2008-11-30 | Completed | ||
| Lutropin Alpha in the Middle of the Controlled Ovarian Stimulation Follicular Phase in Women With Reduced Ovarian Reserve: Comparative Study, in Phase II, With Parallel Control [NCT01110707] | Phase 2 | 131 participants (Actual) | Interventional | 2005-01-10 | Completed | ||
| A Randomized Comparison of One Controlled Ovarian Stimulation With Corifollitropin Alfa Versus up to Three Modified Natural Cycles in Expected and Established Poor Responders [NCT04487925] | Phase 4 | 208 participants (Anticipated) | Interventional | 2022-01-25 | Recruiting | ||
| A Phase III, Multicentric, Randomized, Open, Comparative Study to Evaluate if the Addition of Recombinant Human Luteinising Hormone [r-hLH (Luveris®)] to Follicle Stimulating Hormone (FSH) From Day 8 of Ovarian Stimulation is Able to Decrease Total FSH Do [NCT01071200] | Phase 3 | 133 participants (Actual) | Interventional | 2005-03-31 | Terminated | ||
| A Comparison Between Corifollitropin Alfa and Recombinant FSH for Follicular Recruitment in Women With Polycystic Ovaries Who Undergo IVM Treatment [NCT03197077] | Phase 3 | 145 participants (Actual) | Interventional | 2017-11-01 | Completed | ||
| Prospective Randomised Clinical Study on Pharmacogenetics of Gonadotropin Receptors in Relation to Pregnancy and Life Birth Rate as Well as Unwanted Side Effects Such as Ovarian Hyper Stimulation Syndrome During Assisted Reproduction. [NCT03737253] | Phase 4 | 796 participants (Actual) | Interventional | 2016-09-01 | Completed | ||
| A Multi-Center, Randomized, Open-Label Evaluation of MENOPUR® Versus FOLLISTIM® in GnRH Antagonist Cycles [NCT00802360] | Phase 4 | 173 participants (Actual) | Interventional | 2008-12-31 | Completed | ||
| A Randomised, Controlled, Assessor-blind, Parallel Groups, Multicentre Trial Comparing the Ovarian Response of a Starting Dose of Either 10 μg or 15 μg Follitropin Delta (FE 999049) to a Starting Dose of Either 150 IU or 225 IU Follitropin Alfa (GONAL-F) [NCT06173869] | Phase 3 | 300 participants (Anticipated) | Interventional | 2024-04-01 | Not yet recruiting | ||
| Profile of Mother-caregivers of Children With Duchenne Muscular Dystrophy [NCT01921374] | 60 participants (Actual) | Interventional | 2013-08-31 | Completed | |||
| A Randomized, Parallel-group, Multi-Center, Assessor-blind Phase 3 Study to Compare the Efficacy, Safety and Ease of Use of Two Follicle Stimulating Hormone -Human Recombinant (r-hFSH) 900 IU (66.0 μg) / 1.5mL Solution for Injection in Prefilled Pen (Foli [NCT05266924] | Phase 3 | 250 participants (Anticipated) | Interventional | 2022-07-23 | Active, not recruiting | ||
| The Impact of Ovarian Stimulation Intensity on Embryo Euploidy in Advanced Age Women [NCT06154083] | Phase 4 | 110 participants (Anticipated) | Interventional | 2023-12-12 | Recruiting | ||
| A Phase IV, Multicenter, Randomized, Double-blinded, Clinical Trial to Confirm the Efficacy of the 75 IU Dose of Luveris® vs. Placebo When Administered With Follitropin Alfa for Induction of Follicular Development and Pregnancy in Hypogonadotropic Hypogon [NCT00328926] | Phase 4 | 11 participants (Actual) | Interventional | 2006-03-31 | Terminated(stopped due to "Please see Purpose statement") | ||
| A Multicentre, Open-label, Non-comparative Phase IIIb Study to Evaluate the Acceptability of GONAL-f® Prefilled Liquid Formulation Administered by Pen in an Outpatient Setting for Ovarian Stimulation [NCT01183143] | Phase 3 | 215 participants (Actual) | Interventional | 2004-05-11 | Completed | ||
| Impact of FSH Dosage During Ovarian Stimulation for IVF/ICSI on the Expression of FSH- and LH-receptors in Granulosa Cells [NCT05330130] | Phase 1 | 10 participants (Anticipated) | Interventional | 2023-07-05 | Recruiting | ||
| A Phase IV, Open-label, Post Marketing, Prospective, Randomized, Controlled, Multicentre, Multinational Study to Investigate Tailoring of Recombinant FSH Use in Ovulation Stimulation Treatment in Chronic Anovulatory Subjects (WHO Group II) [NCT01081626] | Phase 4 | 310 participants (Actual) | Interventional | 2009-03-31 | Completed | ||
| Randomized Phase II Trial of Niraparib With Standard Combination Radiotherapy and Androgen Deprivation Therapy (ADT) in High Risk Prostate Cancer (With Initial Phase I) [NCT04037254] | Phase 2 | 180 participants (Anticipated) | Interventional | 2019-06-03 | Suspended(stopped due to Protocol specified toxicity analysis) | ||
| Concomitant Administration of FSH With HCG Improves Oocyte Maturation and Quality Double -Blinded Randomized Trial [NCT00854373] | Phase 4 | 232 participants (Actual) | Interventional | 2006-06-30 | Completed | ||
| The Role of Inactive Follicle Stimulating Hormone in Ovarian Dysfunction in Galactosemia [NCT00619333] | 25 participants (Anticipated) | Interventional | 2007-03-31 | Active, not recruiting | |||
| A Phase III Assessor-blinded Randomized Parallel Group Multi-centre Study to Compare Efficacy and Safety of Two r-hFSH Formulations (AFOLIA Versus Gonal-f) in Women for Assisted Reproductive Treatment [NCT01121666] | Phase 3 | 460 participants (Actual) | Interventional | 2010-06-30 | Completed | ||
| Lutropin Alfa (Luveris®) in Mid Follicular Phase for Controlled Ovarian Stimulation (COS) in Advanced Reproductive Age: Phase II Clinical Trial [NCT01079949] | Phase 2 | 93 participants (Actual) | Interventional | 2007-11-30 | Terminated(stopped due to Trial was terminated due to low recruitment rate) | ||
| A Randomized, Double-blind, Placebo-controlled, Parallel Groups, Multicenter Trial Investigating the Efficacy and Safety of FE 999049 in Controlled Ovarian Stimulation in Women Aged 18-34 Years Undergoing Assisted Reproductive Technology [NCT03740737] | Phase 3 | 579 participants (Actual) | Interventional | 2018-10-26 | Completed | ||
| Exploratory Study to Determine the Effect of Lutropin Alfa on Embryo Quality and Their Implantation in Women of Advanced Reproductive Age [NCT01075815] | Phase 2 | 76 participants (Actual) | Interventional | 2008-11-30 | Terminated | ||
| A Randomised, Controlled, Assessor-blind, Parallel Groups, Multicentre Trial Assessing the Dose-response Relationship of FE 999049 in Controlled Ovarian Stimulation in Japanese Women Undergoing an Assisted Reproductive Technology Programme [NCT02309671] | Phase 2 | 159 participants (Actual) | Interventional | 2014-12-31 | Completed | ||
| Initiation of Ovarian Stimulation With Recombinant-human FSH (Bemfola®) in the Late Follicular Phase, a Randomised Controlled Pilot Study. [NCT03767218] | Phase 3 | 71 participants (Actual) | Interventional | 2018-11-01 | Completed | ||
| Comparison of Recombinant Follicle Stimulating Hormone and the Combination of Recombinant Follicle Stimulating Hormone With Clomiphene Citrate in Stimulated Intrauterine Insemination Cycles: A Prospective Randomized Controlled Multicentric Study [NCT05670795] | 254 participants (Anticipated) | Interventional | 2023-01-01 | Recruiting | |||
| A Phase I, Mono-center, Placebo and Comparator Controlled, Single-blind, Randomized, Parallel Group, Clinical Study to Determine Multiple Dose Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of FSH-GEX(TM) Administered Subcutaneously in Healt [NCT01477073] | Phase 1 | 57 participants (Actual) | Interventional | 2011-10-31 | Completed | ||
| Reduction of Progesterone Elevation at Trigger in Poor Responder Bologna' Criteria Patients After Controlled Ovarian Stimulation With Long Acting Standard Stimulation Protocol Compared With Conventional Daily Protocol: a Single Center Prospective Randomiz [NCT04695483] | Phase 4 | 110 participants (Anticipated) | Interventional | 2021-03-07 | Not yet recruiting | ||
| A Controlled, Assessor-blind, Parallel Groups, Multicentre, Multinational Trial Evaluating the Immunogenicity of FE 999049 in Repeated Cycles of Controlled Ovarian Stimulation in Women Undergoing an Assisted Reproductive Technology Programme [NCT01956123] | Phase 3 | 513 participants (Actual) | Interventional | 2014-03-26 | Completed | ||
| Recombinant LH Supplementation to Recombinant FSH During the Final Days of Controlled Ovarian Stimulation for IVF: a Multicentre, Prospective, Randomized, Controlled Trial [NCT00553293] | Phase 4 | 526 participants (Actual) | Interventional | 2003-08-31 | Completed | ||
| Embryo Kinetcis From Embryos Deriving From Egg Donation Cycle With Different Stimulation Protocol: Recombinant FSH vs Human FSH [NCT01678651] | 80 participants (Actual) | Interventional | 2012-08-31 | Terminated | |||
| Effect of Personalized Dosages of Rekovelle on the Number of Mature Follicles Reached in Intra-uterine Insemination [NCT03830723] | Phase 2 | 110 participants (Actual) | Interventional | 2020-01-09 | Completed | ||
| A Phase IIIB/IV, Open Label Study to Assess the Efficacy and Safety of a Pre-defined, Fixed Dose of Gonal-f® (Filled-by-Mass in a Prefilled Pen) Based on Subject Baseline Characteristics, for Ovarian Stimulation in Subjects Undergoing in Vitro Fertilizati [NCT00249834] | Phase 4 | 166 participants (Actual) | Interventional | 2004-09-22 | Completed | ||
| A Phase IIIb, Prospective, Multicenter Trial to Evaluate Subject Satisfaction With Follitropin Alfa Injection Applied by Pen Device Compared With Other Injectable Gonadotropins in Oligoanovulatory Infertile Women Undergoing Ovulation Induction [NCT00230815] | Phase 3 | 62 participants (Actual) | Interventional | 2004-07-31 | Completed | ||
| Study of Optimal Posology of Gonadotrophins in Patients With Insufficient Ovarian Response Due to Age [NCT00575302] | Phase 4 | 400 participants (Anticipated) | Interventional | 2007-12-31 | Withdrawn(stopped due to 36 cases were included and the 4 centers and they are unable to increase their recruitment to obtain the 400 cases necessary to reach statistical significance.) | ||
| A Phase IIIB, Multicentre, Multinational, Randomized, Open-label Trial to Compare the Efficacy and Safety of Ovarian Stimulation With GONAL-f® Day 1 to Day 5 Followed by Pergoveris® Starting Day 6 to Pergoveris® Starting Day 1 in Women Between 36 and 40 Y [NCT01297465] | Phase 3 | 202 participants (Actual) | Interventional | 2011-05-31 | Completed | ||
| Luteal Phase Recombinant FSH vs. Follicular Phase Recombinant FSH for IVF Stimulation in the Poor Responder [NCT00225433] | Phase 4 | 20 participants (Actual) | Interventional | 2005-09-30 | Completed | ||
| Multicentric Prospective, Randomised, Controlled Clinical Study on Clinical Efficacy and Tolerability of Urinary FSH (Fostimon® , IBSA) Versus r-FSH (Gonal-F®, Serono) in ICSI. [NCT00335725] | Phase 3 | 151 participants (Actual) | Interventional | 2003-03-31 | Completed | ||
| Soft Versus Conventional Protocol in Ovarian Stimulation in Intracytoplasmic Sperm Injection Cycles for Poor Responders [NCT04193930] | 0 participants (Actual) | Interventional | 2021-01-01 | Withdrawn(stopped due to no women were recruited) | |||
| The Effectiveness and Safety of the Early Follicular Phase Prolonged Down-regulation Protocol for Controlled Ovarian Hyperstimulation: a Randomized, Paralleled, Controlled, Multicenter Trial [NCT03809221] | Phase 4 | 1,892 participants (Anticipated) | Interventional | 2019-02-01 | Not yet recruiting | ||
| A Multicenter, Randomized, Open-label, Parallel-group Study Comparing the Combination of Menopur® and Bravelle® With Menopur® Alone in Subjects Undergoing Assisted Reproductive Technology (ART) [NCT01417195] | Phase 4 | 122 participants (Actual) | Interventional | 2011-07-31 | Completed | ||
| Serum Prolidase Activity in Primary Ovarian Insufficiency [NCT05443282] | 133 participants (Actual) | Observational | 2021-08-10 | Completed | |||
| A Randomised, Double-blind, Placebo-controlled, Parallel-group, Dose-range Trial to Investigate the Efficacy and Safety of FE 999302 as add-on Treatment to Follitropin Delta (REKOVELLE) in Women Undergoing Controlled Ovarian Stimulation in a Long GnRH Ago [NCT03564509] | Phase 2 | 620 participants (Actual) | Interventional | 2018-05-14 | Completed | ||
| Prospective Multicentre Non-Interventional Study to Assess the Patterns of Use of REKOVELLE® in Women Undergoing In Vitro Fertilisation or Intracytoplasmic Sperm Injection Procedures in Routine Clinical Practice [NCT03393780] | 1,018 participants (Actual) | Observational | 2018-03-16 | Completed | |||
| A Phase IV, Multicenter, Open-label, Randomized Study to Compare the Safety and Efficacy of Cetrotide® 3 mg Versus Antagon™ in the Inhibition of a Premature LH Surge in a r-hFSH/hMG Stimulation Cycle With OCP Programming in Women Undergoing Ovarian Stimul [NCT00298025] | Phase 4 | 185 participants (Actual) | Interventional | 2003-09-30 | Completed | ||
| A Randomised, Double-blind, Placebo-controlled Trial to Assess the Efficacy and Safety of FE 999049 for Treatment of Men With Idiopathic Infertility [NCT05403476] | Phase 2 | 400 participants (Anticipated) | Interventional | 2022-08-16 | Recruiting | ||
| Predicting Ovarian Response in Artificial Insemination With Low Stimulation [NCT01662180] | 510 participants (Anticipated) | Observational | 2012-12-31 | Recruiting | |||
| Open-label, Single-arm, Multicenter Phase III Trial to Evaluate the Efficacy and Safety of COL-1620 8% Vaginal Progesterone Gel for Luteal Phase Support in In-vitro Fertilization and Embryo Transfer (IVF/ET) Cycles in Japanese Women [NCT01863680] | Phase 3 | 178 participants (Actual) | Interventional | 2013-07-31 | Completed | ||
| Assessment of Implantation Potential of Embryos Cultured by Time-lapse Technology (Embryoscope) Before Transfer in In-vitro Fertilization (IVF) / Intracytoplasmic Sperm Injection (ICSI) Cycles: A Randomized Control Study. [NCT01760278] | Phase 4 | 200 participants (Anticipated) | Interventional | 2012-12-31 | Active, not recruiting | ||
| A Phase II, Multicentre, Multinational, Randomised, Assessor-Blind Trial to Investigate the Efficacy and Safety of Various Dosages of FSH-GEX™ in Comparison With 150 IU Gonal-f® in Women Undergoing ICSI Treatment [NCT01794208] | Phase 2 | 267 participants (Actual) | Interventional | 2013-01-08 | Completed | ||
| Prospective, Open-label, Uncontrolled Clinical Trial Evaluating Multiple Controlled Ovarian Hyperstimulation Cycles in Oocyte Donor, to Assess the Immunogenicity of FSH-IBSA [NCT01785095] | Phase 3 | 41 participants (Actual) | Interventional | 2013-03-31 | Completed | ||
| Estradiol and Progesterone Levels in Early Pregnancy After Natural, Estradiol + Progesterone or Gonadotrophin Stimulated Frozen Embryo Transfer Cycle [NCT04997525] | Phase 4 | 300 participants (Anticipated) | Interventional | 2021-04-20 | Recruiting | ||
| A Phase II, Multicentre, Randomised, Assessor-blinded, Active-comparator, Parallel-group Dose Finding Trial to Evaluate AS900672-enriched Versus Follitropin Alfa (GONAL-f®) in Oligo-anovulatory Infertile Women Undergoing Ovulation Induction (OI) [NCT00553514] | Phase 2 | 71 participants (Actual) | Interventional | 2007-12-31 | Terminated(stopped due to The study was terminated after Merck Serono had taken the decision not to pursue the development of AS900672-enriched in ovulation induction) | ||
| A Randomized, Assessor-blinded, Parallel Group, Multi-center, Non-inferiority Study Investigating the Efficacy and Safety of Highly Purified Urofollitropin for Injection Compared to Recombinant Human Follitropin Alfa for Injection for Ovulation Induction [NCT01923194] | Phase 3 | 215 participants (Actual) | Interventional | 2013-10-31 | Completed | ||
| Study of Safety, Tolerance and Pharmacokinetics of Primapur and Gonal-f Upon Single-dose Subcutaneous Administration in Healthy Volunteers [NCT03857230] | Phase 1 | 28 participants (Actual) | Interventional | 2015-10-29 | Completed | ||
| Clinical Trial on Application of Injectable Recombinant Human Luteinizing Hormone (Luveris®) in the Treatment of Chinese Female Patients With Hypogonadotropic Hypogonadism: A Multi-center, Open, Prospective Drug Clinical Trial for Registration [NCT01084265] | Phase 3 | 31 participants (Actual) | Interventional | 2004-02-29 | Completed | ||
| Multicentre Study to Compare Efficacy and Safety of Primapur and Gonal-f in Women for Assisted Reproductive Treatment [NCT03088137] | Phase 3 | 118 participants (Actual) | Interventional | 2017-02-08 | Completed | ||
| Pilot Trial to Investigate a Higher Dose of Rekovelle in Oocyte Donors [NCT04778358] | Phase 2 | 40 participants (Actual) | Interventional | 2021-09-28 | Completed | ||
| Pregnancy and Neonatal Follow-up of Ongoing Pregnancies Established After Controlled Ovarian Stimulation in Clinical Trial 107012 for the Development of Org 36286 (Corifollitropin Alfa) [NCT00702624] | 113 participants (Actual) | Observational | 2007-04-30 | Completed | |||
| A Randomized Controlled Study on the Short-term Intervention of Traditional Chinese Medicine Herbs in the Freeze-all IVF Cycle to Improve Pregnancy Rate [NCT04935073] | Phase 3 | 90 participants (Anticipated) | Interventional | 2021-06-15 | Not yet recruiting | ||
| Prospective Randomized Study Comparing Ovarian Stimulation With Pergoveris Supported by a GnRH Agonist in a Long Protocol Versus Multidose GnRH Antagonist Regimen in Young Infertile Women Treated With ICS [NCT01565265] | 5 participants (Actual) | Interventional | 2012-04-30 | Completed | |||
| An Open-label, Randomized, Two-period, Two-sequence Crossover Trial to Assess the Bioequivalence of the Liquid Formulation Versus the Freeze-dried Formulation of 900 IU r-hFSH and 450 IU r-hLH in Pergoveris®, Administered Subcutaneously in Pituitary Suppr [NCT02317809] | Phase 1 | 34 participants (Actual) | Interventional | 2015-01-31 | Completed | ||
| Open-Label, Parallel-Group, Randomized, Multicenter Phase III Trial to Compare the Efficacy and Safety of a 250 mcg SC Dose of MSJ-0011 to a 5,000 IU IM Dose of Urinary Human Chorionic Gonadotropin in Inducing Ovulation in Japanese Women Diagnosed With An [NCT01653743] | Phase 3 | 81 participants (Actual) | Interventional | 2012-09-30 | Completed | ||
| Mechanisms of Increased Androgen Production Among Women With Polycystic Ovary Syndrome [NCT00989781] | 41 participants (Actual) | Interventional | 2009-09-30 | Completed | |||
| A Randomized, Assessor-blinded, Parallel Group, Multi-center, Non-inferiority Study Investigating the Efficacy and Safety of Highly Purified Urofollitropin for Injection Compared to Recombinant Human Follitropin Alfa for Injection in Controlled Ovarian St [NCT01922193] | Phase 3 | 263 participants (Actual) | Interventional | 2013-10-31 | Completed | ||
| Combined Letrozole-metformin-pioglitazone Versus Combined Clomiphene Citrate-metformin-pioglitazone in Clomiphene Citrate-resistant Women With Polycystic Ovary Syndrome [NCT01909141] | Early Phase 1 | 100 participants (Actual) | Interventional | 2013-08-31 | Completed | ||
| Phase III Investigator and Assessor Blinded 1:1 Randomized, Parallel-group Multicenter Study to Compare Efficacy and Safety of Two r-hFSH Formulations (AFOLIA vs Gonal-f® RFF) in Normal Ovulatory Women 35 to 42 Years Old Undergoing in Vitro Fertilization [NCT01687712] | Phase 3 | 1,100 participants (Actual) | Interventional | 2013-11-25 | Completed | ||
| A Randomized Controlled Study on Sequential Therapy of Kidney Tonifying and Blood Regulating Herbs to Improve the Success Rate of IVF-ET in Patients With Ovarian Reserve Dysfunction [NCT04842825] | Phase 3 | 200 participants (Anticipated) | Interventional | 2021-04-15 | Recruiting | ||
| A Prospective, Randomized Trial to Compare Mono-menotropins Protocol for Controlled Ovarian Stimulation (COS) Versus Recombinant Follicle Stimulating Hormone (rFSH) Protocol on Embryo Quality Parameters in IVF Patients [NCT02418533] | 109 participants (Actual) | Interventional | 2015-03-31 | Completed | |||
| Comparative Pharmacokinetics of AFOLIA and US Gonal-f® RFF Redi-ject After Single Subcutaneous Application. A Randomised, Open Label, 2-way Cross-over Study [NCT02459418] | Phase 1 | 42 participants (Actual) | Interventional | 2015-05-07 | Completed | ||
| Continuous Ovarian Stimulation in DUOSTIM Cycles. [NCT05815719] | Phase 4 | 30 participants (Anticipated) | Interventional | 2022-11-17 | Recruiting | ||
| Luteal Phase Ovarian Stimulation With Follitropin Delta and Dydrogesterone: a Randomized Cross Over Pilot Trial [NCT05521828] | 50 participants (Anticipated) | Interventional | 2023-04-01 | Recruiting | |||
| Nordics and Switzerland Prospective Multicentre Non-Interventional Observational Study to Assess the Pattern of Use of REKOVELLE® in Women Undergoing In Vitro Fertilisation (IVF) or Intracytoplasmic Sperm Injection (ICSI) Procedures in Routine Clinical Pr [NCT05499052] | 201 participants (Actual) | Observational | 2022-08-28 | Active, not recruiting | |||
| Assessment of Multiple Intrauterine Gestations From Ovarian Stimulation [NCT01044862] | Phase 3 | 900 participants (Actual) | Interventional | 2010-06-30 | Completed | ||
| Effects of Follicle-Stimulating Hormone Injection on Flow Mediated Dilation in Healthy Males [NCT04430621] | Phase 4 | 16 participants (Anticipated) | Interventional | 2020-07-01 | Recruiting | ||
| A Multi-Centre, Two-Arm, Interventional, Phase IV Study to Evaluate Tailoring of Recombinant FSH Treatment in Subjects With Chronic Anovulation Using the Gonal-f® Prefilled Pen in Women Undergoing Ovulation Induction [NCT01871532] | Phase 4 | 24 participants (Actual) | Interventional | 2013-07-31 | Terminated(stopped due to Study was terminated because of delays in sourcing replacement Investigational Medicinal Product for the study due to manufacturing delays.) | ||
| Impact of Step-down Approach During Late Follicular Phase in Recombinant FSH-stimulation Dosage for IVF on Progesterone Level on the Day of Final Oocyte Maturation [NCT03356964] | Early Phase 1 | 127 participants (Actual) | Interventional | 2017-11-23 | Completed | ||
| An Exploratory Study to Evaluate a Mixed Protocol of Menopur (Highly Purified Human Menopausal Gonadotropin) and REKOVELLE (Follitropin Delta) for Controlled Ovarian Stimulation in IVF (in Vitro Fertilization) [NCT03483545] | 160 participants (Actual) | Interventional | 2018-07-17 | Completed | |||
| French Prospective Multicentre Non-Interventional Study to Assess the Design of Use of REKOVELLE® in Women Undergoing In Vitro Fertilisation or Intracytoplasmic Sperm Injection Procedures in Routine Clinical Practice [NCT04503707] | 250 participants (Actual) | Observational | 2020-06-17 | Completed | |||
| An Efficacy and Safety Study of Corifollitropin Alfa Versus Daily Follitropin Beta for Controlled Ovarian Stimulation in Women 35-42 Years Old With a Body Weight ≥ 50 kg Undergoing IVF Treatment. [NCT02466204] | Phase 4 | 400 participants (Actual) | Interventional | 2015-06-01 | Completed | ||
| Fertility and Ovarian Reserve Function in the Patient With Inflammatory Bowel - a Cross-sectional Survey and Case Control Study [NCT03269916] | 80 participants (Anticipated) | Interventional | 2017-05-01 | Recruiting | |||
| Significance of the FSH Receptor Polymorphism p.N680S for the Efficacy of FSH Therapy of Idiopathic Male Infertility: a Pharmacogenetic Approach [NCT02349945] | Phase 2/Phase 3 | 88 participants (Actual) | Interventional | 2011-01-31 | Completed | ||
| Corifollitropin Alfa (Elonva) Versus Follitropin Beta in High Responders: A Randomized Controlled Trial [NCT02471677] | Phase 4 | 62 participants (Anticipated) | Interventional | 2015-09-30 | Not yet recruiting | ||
| An Open-label Trial Investigating the Pharmacokinetics of FE 999049 Given as a Single Subcutaneous Dose in Gonadotropin Down-regulated Healthy Chinese Women [NCT04150861] | Phase 1 | 24 participants (Actual) | Interventional | 2019-06-23 | Completed | ||
| Ovarian Function in Women With Polycystic Ovary Syndrome [NCT03252223] | Phase 4 | 33 participants (Actual) | Interventional | 2017-10-02 | Completed | ||
| Long Protocol and Freeze All Embryos vs Antagonist Protocol With Fresh Embryo Transfer in PCOS Patients Undergoing ICSI [NCT03118830] | Phase 4 | 204 participants (Actual) | Interventional | 2017-04-21 | Completed | ||
| Pregnancy and Neonatal Follow-up of Ongoing Pregnancies Established After Controlled Ovarian Stimulation in Clinical Trial 38819 for Org 36286 (Corifollitropin Alfa) [NCT00703014] | 541 participants (Actual) | Observational | 2006-07-13 | Completed | |||
| Follow-up Protocol to Collect the Outcome of Frozen-thawed Embryo Transfer Cycles After Cryopreservation of Embryos in Clinical Trial 107012 [NCT00702546] | 102 participants (Actual) | Observational | 2006-12-31 | Completed | |||
| A Phase III, Randomized, Controlled, Single-blind, Multicentre, Parallel Arm Trial to Assess the Efficacy and Safety of Pergoveris® (Follitropin Alfa and Lutropin Alfa) and GONAL-f® (Follitropin Alfa) for Multifollicular Development as Part of an Assisted [NCT02047227] | Phase 3 | 939 participants (Actual) | Interventional | 2014-01-31 | Completed | ||
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] | |||||||
Average Inhibin B Levels after treatment. (NCT00064987)
Timeframe: month 4 of GnRH treatment
| Intervention | pg/mL (Mean) |
|---|---|
| Group 1 (FSH) | 110 |
| Group 2 (GnRH) | 74 |
Average Follicle Stimulating Hormone levels after treatment. (NCT00064987)
Timeframe: month 4 of GnRH treatment
| Intervention | IU/L (Mean) |
|---|---|
| Group 1 (FSH) | 9.9 |
| Group 2 (GnRH) | 15.6 |
Participants actively seeking to conceive. (NCT00064987)
Timeframe: 24 months
| Intervention | Participants (Count of Participants) |
|---|---|
| Group 1 (FSH) | 4 |
| Group 2 (GnRH) | 1 |
Average testicular volume after treatment. (NCT00064987)
Timeframe: at baseline and month 4 of GnRH treatment
| Intervention | mL (Mean) | |
|---|---|---|
| Before Treatment | After Treatment | |
| Group 1 (FSH) | 1.1 | 9.3 |
| Group 2 (GnRH) | .8 | 6.6 |
Average Testosterone levels after treatment. (NCT00064987)
Timeframe: month 4 of GnRH treatment
| Intervention | ng/dL (Mean) |
|---|---|
| Group 1 (FSH) | 299 |
| Group 2 (GnRH) | 330 |
Average sperm count after treatment. (NCT00064987)
Timeframe: month 4 of GnRH treatment
| Intervention | 10^6 sperms/mL (Mean) |
|---|---|
| Group 1 (FSH) | 5.8 |
| Group 2 (GnRH) | 2.6 |
Average Luteinizing Hormone levels after treatment. (NCT00064987)
Timeframe: month 4 of GnRH treatment
| Intervention | IU/L (Mean) |
|---|---|
| Group 1 (FSH) | 12.7 |
| Group 2 (GnRH) | 16.5 |
Embryo implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100. As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects. (NCT00249834)
Timeframe: 35-42 days post r-hCG administration
| Intervention | Percent sacs per embryo (Mean) |
|---|---|
| Gonal-f 75 IU | 36.5 |
| Gonal-f 112.5 IU | 24.3 |
| Gonal-f 150 IU | 28.2 |
| Gonal-f 187.5 IU | 37.1 |
| Gonal-f 225 IU | 11.9 |
As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects. (NCT00249834)
Timeframe: up to end of stimulation cycle (approximately 31 days)
| Intervention | IU/day (Mean) |
|---|---|
| Gonal-f 75 IU | 84.4 |
| Gonal-f 112.5 IU | 114.7 |
| Gonal-f 150 IU | 153.6 |
| Gonal-f 187.5 IU | 186.5 |
| Gonal-f 225 IU | 223.3 |
The mean number of stimulation days were determined based on the treatment administration information collected in the case report form. Ovarian stimulation included time from first r-hFSH injection (stimulation Day) until day on which r-hCG was administered (r-hCG day). As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects. (NCT00249834)
Timeframe: up to end of stimulation cycle (approximately 31 days)
| Intervention | Days (Mean) |
|---|---|
| Gonal-f 75 IU | 12.5 |
| Gonal-f 112.5 IU | 11.0 |
| Gonal-f 150 IU | 10.6 |
| Gonal-f 187.5 IU | 11.0 |
| Gonal-f 225 IU | 11.5 |
Mean number of oocytes retrieved on the day of ovum pick up (OPU) was calculated. Oocyte retrieval was a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body. As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects. (NCT00249834)
Timeframe: Ovum pick up day (34 to 38 hours post r-hCG administration)
| Intervention | Oocytes (Mean) |
|---|---|
| Gonal-f 75 IU | 8.3 |
| Gonal-f 112.5 IU | 9.6 |
| Gonal-f 150 IU | 12.1 |
| Gonal-f 187.5 IU | 12.7 |
| Gonal-f 225 IU | 8.3 |
Number of subjects needing increase in dose, decrease in dose or increase and decrease both in dose were reported. As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects. (NCT00249834)
Timeframe: 6 days post r-hFSH treatment
| Intervention | subjects (Number) | ||
|---|---|---|---|
| Increase | Decrease | Increase and decrease both | |
| Gonal-f 112.5 IU | 3 | 0 | 3 |
| Gonal-f 150 IU | 3 | 1 | 0 |
| Gonal-f 187.5 IU | 1 | 2 | 0 |
| Gonal-f 225 IU | 0 | 1 | 0 |
| Gonal-f 75 IU | 7 | 0 | 2 |
As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects. (NCT00249834)
Timeframe: up to end of stimulation cycle (approximately 31 days)
| Intervention | Percentage of cycles (Number) | |
|---|---|---|
| Excessive response | Inadequate response | |
| Gonal-f 112.5 IU | 0.0 | 8.9 |
| Gonal-f 150 IU | 2.9 | 8.8 |
| Gonal-f 187.5 IU | 0.0 | 8.3 |
| Gonal-f 225 IU | 0.0 | 20.0 |
| Gonal-f 75 IU | 0.0 | 25.0 |
Overall pregnancy rate was defined as the percentage of subjects with serum beta-hCG levels greater than 10 IU/L. Clinical pregnancy rate was defined as the percentage of subjects with at least 1 ultrasound confirmed gestational sac, with or without foetal heart activity. Multiple pregnancy rate was defined as the percentage of subjects with more than 1 ultrasound confirmed gestational sac in the uterus with fetal heart activity. As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects. (NCT00249834)
Timeframe: 35-42 days post r-hCG administration
| Intervention | Percentage of subjects (Number) | ||
|---|---|---|---|
| Total pregnancy | Clinical pregnancy | Multiple pregnancy | |
| Gonal-f 112.5 IU | 18 | 14 | 2 |
| Gonal-f 150 IU | 16 | 12 | 4 |
| Gonal-f 187.5 IU | 16 | 12 | 3 |
| Gonal-f 225 IU | 2 | 2 | 0 |
| Gonal-f 75 IU | 17 | 15 | 3 |
As per statistical analysis plan, efficacy analysis were performed for only those dose groups (Gonal-f 75 IU, Gonal-f 112.5 IU, Gonal-f 150 IU, Gonal-f 187.5 IU and Gonal-f 225 IU) which included more than 5 subjects. (NCT00249834)
Timeframe: up to end of stimulation cycle (approximately 31 days)
| Intervention | International Units (IU) (Mean) |
|---|---|
| Gonal-f 75 IU | 1102.3 |
| Gonal-f 112.5 IU | 1287.2 |
| Gonal-f 150 IU | 1632.4 |
| Gonal-f 187.5 IU | 2043.8 |
| Gonal-f 225 IU | 2572.5 |
Measurement on day of human chorionic gonadotrophin (hCG) administration / ovulation induction. (NCT00257556)
Timeframe: Day 7 or 9 or 11 or 13
| Intervention | picomoles / liter (Mean) |
|---|---|
| Menotrophin | 6706.6 |
| Follitropin Alfa | 6268.3 |
Number of days stimulated with study drug until participant met the criteria for ovulation induction. Ovulation induction criteria is three follicles greater than or equal to 17 mm diameter as shown by pelvic ultrasound examination. (NCT00257556)
Timeframe: study days 1 - 13
| Intervention | days (Mean) |
|---|---|
| Menotrophin | 9.2 |
| Follitropin Alfa | 8.9 |
Number of participants who met human chorionic gonadotrophin (hCG) criterion, received an embryo transfer, tested positive with a serum pregnancy test 11-14 days after embryo transfer and had an ongoing pregnancy (defined as positive fetal heart action) at ≥ 9 weeks after the first positive pregnancy test. (NCT00257556)
Timeframe: Approx week 13; 9 weeks or more after the 1st positive pregnancy test
| Intervention | participants (Number) |
|---|---|
| Menotrophin | 14 |
| Follitropin Alfa | 13 |
Number of participants with different categories of number of embryos frozen. (NCT00257556)
Timeframe: Approximately study day 17
| Intervention | participants (Number) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| 0 embryos frozen | 1 embryo frozen | 2 embryos frozen | 3 embryos frozen | 4 embryos frozen | 5 embryos frozen | 6-8 embryos frozen | 9 embryos frozen | 10 embryos frozen | |
| Follitropin Alfa | 22 | 0 | 1 | 4 | 2 | 2 | 0 | 1 | 1 |
| Menotrophin | 16 | 1 | 2 | 1 | 4 | 0 | 0 | 0 | 0 |
Percentage of participants who had an ongoing pregnancy ≥ 9 weeks after the first positive pregnancy test, as indicated by positive fetal heart action. (NCT00257556)
Timeframe: Approx week 13; 9 weeks or more after the first positive pregnancy test
| Intervention | percentage of participants (Number) |
|---|---|
| Menotrophin | 37.8 |
| Follitropin Alfa | 33.3 |
Long term follow-up to determine the outcome of the pregnancy. (NCT00257556)
Timeframe: Approximately 10 months
| Intervention | participants (Number) | |||||
|---|---|---|---|---|---|---|
| Miscarriage | Pre-term: 1 live birth | Pre-term: 2 live births | Pre-term stillbirth | Full term: 1 live birth | Full term: 2 live births | |
| Follitropin Alfa | 4 | 1 | 3 | 1 | 6 | 2 |
| Menotrophin | 4 | 1 | 2 | 0 | 7 | 3 |
Number of participants with various categories of numbers of embryos transferred. (NCT00257556)
Timeframe: Approximately study day 17
| Intervention | participants (Number) | |||
|---|---|---|---|---|
| 0 embryos transferred | 1 embryo transferred | 2 embryos transferred | 3 embryos transferred | |
| Follitropin Alfa | 1 | 1 | 28 | 3 |
| Menotrophin | 0 | 3 | 21 | 0 |
The criterion for ovulation induction was three follicles ≥ 17 mm diameter as shown by pelvic ultrasound examination. Patients were assessed by pelvic ultrasound on the morning (prior to menotrophin or follitropin alfa administration) of Day 7 and, if appropriate, every 2 days thereafter (Days 9/11/13) until the criterion was met. (NCT00257556)
Timeframe: Day 7 and, if appropriate, every 2 days thereafter (Days 9/11/13)
| Intervention | participants (Number) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Did not meet criterion | 3 follicles ≥ 17 mm in diameter | 4 follicles ≥ 17 mm in diameter | 5 follicles ≥ 17 mm in diameter | 6 follicles ≥ 17 mm in diameter | 7 follicles ≥ 17 mm in diameter | 8 follicles ≥ 17 mm in diameter | 9 follicles ≥ 17 mm in diameter | 10 follicles ≥ 17 mm in diameter | 11-14 follicles ≥ 17 mm in diameter | 15 follicles ≥ 17 mm in diameter | 16 follicles ≥ 17 mm in diameter | |
| Follitropin Alfa | 3 | 11 | 10 | 10 | 1 | 0 | 3 | 0 | 0 | 0 | 1 | 0 |
| Menotrophin | 10 | 11 | 7 | 2 | 4 | 0 | 1 | 0 | 1 | 0 | 0 | 1 |
Number of participants with grouped by the number of oocytes retrieved. Oocytes were retrieved following ovulation induction by subcutaneous administration of human chorionic gonadotrophin (hCG) in the form of choriogonadotropin alfa at a dose of 250 micrograms once participants reached the criteria of at least three follicles with >= 17mm in diameter. (NCT00257556)
Timeframe: Approximately study day 15
| Intervention | participants (Number) | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0 oocytes retrieved | 1 oocyte retrieved | 2 oocytes retrieved | 3 oocytes retrieved | 4 oocytes retrieved | 5 oocytes retrieved | 6 oocytes retrieved | 7 oocytes retrieved | 8 oocytes retrieved | 9 oocytes retrieved | 10 oocytes retrieved | 11 oocytes retrieved | 12 oocytes retrieved | 13 oocytes retrieved | 14 oocytes retrieved | 15 oocytes retrieved | 16 oocytes retrieved | 17-18 oocytes retrieved | 19 oocytes retrieved | 20 oocytes retrieved | 21 oocytes retrieved | 22 oocytes retrieved | 23 oocytes retrieved | |
| Follitropin Alfa | 0 | 1 | 1 | 1 | 2 | 5 | 4 | 2 | 4 | 2 | 3 | 0 | 4 | 1 | 0 | 3 | 2 | 0 | 2 | 0 | 0 | 0 | 1 |
| Menotrophin | 1 | 1 | 3 | 3 | 2 | 2 | 4 | 2 | 2 | 2 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 |
Number of participants with various groupings of pronuclear oocytes retrieved 16-20 hours after insemination. (NCT00257556)
Timeframe: Approximately study day 15
| Intervention | participants (Number) | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 pronuclear stage oocyte | 2 pronuclear stage oocytes | 3 pronuclear stage oocytes | 4 pronuclear stage oocytes | 5 pronuclear stage oocytes | 6 pronuclear stage oocytes | 7 pronuclear stage oocytes | 8 pronuclear stage oocytes | 9 pronuclear stage oocytes | 10 pronuclear stage oocytes | 11 pronuclear stage oocytes | 12 pronuclear stage oocytes | 13 pronuclear stage oocytes | 14-16 pronuclear stage oocytes | 17 pronuclear stage oocytes | |
| Follitropin Alfa | 0 | 6 | 3 | 7 | 7 | 0 | 2 | 2 | 1 | 1 | 0 | 4 | 1 | 0 | 1 |
| Menotrophin | 1 | 8 | 1 | 2 | 4 | 1 | 2 | 2 | 1 | 1 | 2 | 0 | 0 | 0 | 0 |
Measurement performed on day of human chorionic gonadotrophin (hCG) administration/ovulation induction. (NCT00257556)
Timeframe: Day 7 or 9 or 11 or 13
| Intervention | millimeters (Mean) |
|---|---|
| Menotrophin | 11.7 |
| Follitropin Alfa | 11.0 |
Clinical pregnancy was defined as the presence of one or more fetal sac with fetal heart activity on the Day 35-42 post r-hCG ultrasound examination. Cumulative clinical pregnancy referred to all clinical pregnancy that occurred during all the 3 treatment cycles. (NCT00328926)
Timeframe: Day 35-42 post r-hCG administration day (end of stimulation cycle [approximately 21 days])
| Intervention | Percentage of participants (Number) |
|---|---|
| Luveris® 75 IU | 60.0 |
| Luveris® 25 IU | 33.3 |
| Placebo | 33.3 |
Ovulation was defined as a mid-luteal phase progesterone (P4) level greater than or equal to (>=) 10 nanogram per milliliter (ng/mL). Cumulative ovulation referred to all ovulations that occurred during all the 3 treatment cycles. (NCT00328926)
Timeframe: Recombinant human chorionic gonadotropin (r-hCG) administration day (end of stimulation cycle [approximately 21 days])
| Intervention | Percentage of participants (Number) |
|---|---|
| Luveris® 75 IU | 80.0 |
| Luveris® 25 IU | 33.3 |
| Placebo | 66.7 |
Clinical pregnancy was defined as the presence of one or more fetal sac with fetal heart activity on the Day 35-42 post r-hCG ultrasound examination. (NCT00328926)
Timeframe: Stimulation Day 1 up to clinical pregnancy (Day 35-42 post r-hCG administration day [end of stimulation cycle {approximately 21 days}])
| Intervention | Days (Median) |
|---|---|
| Luveris® 75 IU | 71 |
| Luveris® 25 IU | 51 |
| Placebo | 103 |
clinical pregnancy rate defined as the presence of gestation sac and heart beat. (NCT00335725)
Timeframe: 6 weeks after treatment start
| Intervention | percentage of treated patients (Number) |
|---|---|
| Fostimon | 30.1 |
| Gonal-F | 29.2 |
Total number of oocytes retrieved (NCT00335725)
Timeframe: 10 days after stimulation start
| Intervention | oocytes (Mean) |
|---|---|
| Fostimon | 10.9 |
| Gonal-f | 12.0 |
Oocytes were fertilized using Intra-cytoplasmic Sperm Injection (ICSI) technique which is an in-vitro fertilization procedure in which a single sperm is injected directly into an egg under a microscope. The appearance of 2PN is the first sign of successful fertilization as observed during in vitro fertilization, and is usually observed after ICSI. The zygote is then termed 2PN. (NCT00505752)
Timeframe: Ovum pick-up (OPU) day (34-38 hours post r-hCG administration day [end of stimulation cycle {approximately 21 days}])
| Intervention | 2PN oocytes (Mean) |
|---|---|
| AS900672-Enriched 50 Mcg | 7.0 |
| AS900672-Enriched 100 Microgram (Mcg) | 8.7 |
| AS900672-Enriched 150 Microgram (Mcg) | 9.2 |
| Follitropin Alfa 150 IU | 6.7 |
Clinical pregnancy was defined as the presence of one or more fetal sacs with fetal heart activity on the Day 35-42 post r-hCG ultrasound examination. (NCT00505752)
Timeframe: Day 35-42 post r-hCG administration day (end of stimulation cycle [approximately 21 days])
| Intervention | Percentage of participants (Number) |
|---|---|
| AS900672-Enriched 50 Mcg | 39.1 |
| AS900672-Enriched 100 Microgram (Mcg) | 40.8 |
| AS900672-Enriched 150 Microgram (Mcg) | 35.2 |
| Follitropin Alfa 150 IU | 43.8 |
Ovarian stimulation included from first dose of study drug on S1 until day on which r-hCG was administered (r-hCG day). (NCT00553514)
Timeframe: Stimulation Day 1 (S1) up to r-hCG administration day (end of stimulation cycle [approximately 14 days])
| Intervention | Days (Mean) |
|---|---|
| AS900672-Enriched 10 Mcg | 10.0 |
| AS900672-Enriched 20 Mcg | 11.8 |
| AS900672-Enriched 30 Mcg | 14.0 |
| AS900672-Enriched 40 Mcg | 10.8 |
| Follitropin Alfa 75 IU | 10.6 |
(NCT00553514)
Timeframe: Stimulation Day 7 (S7) up to r-hCG administration day (end of stimulation cycle [approximately 14 days])
| Intervention | Days (Mean) |
|---|---|
| AS900672-Enriched 10 Mcg | 6.6 |
| AS900672-Enriched 20 Mcg | 6.6 |
| AS900672-Enriched 30 Mcg | 7.7 |
| AS900672-Enriched 40 Mcg | 5.6 |
| Follitropin Alfa 75 IU | 5.5 |
(NCT00553514)
Timeframe: Stimulation Day 7 (S7) up to r-hCG administration day (end of stimulation cycle [approximately 14 days])
| Intervention | IU (Mean) |
|---|---|
| AS900672-Enriched 10 Mcg | 476.3 |
| AS900672-Enriched 20 Mcg | 493.8 |
| AS900672-Enriched 30 Mcg | 556.7 |
| AS900672-Enriched 40 Mcg | 398.9 |
| Follitropin Alfa 75 IU | 397.5 |
(NCT00553514)
Timeframe: Stimulation Day 5 (S5), S7 and r-hCG administration day (end of stimulation cycle [approximately 14 days])
| Intervention | Follicles (Mean) | |||||
|---|---|---|---|---|---|---|
| < 11 mm on S5 (n=12,12,12,12,13) | < 11 mm on S7 (n=12,12,13,12,12) | < 11 mm on r-hCG Day (n=5,6,7,6,7) | >= 11 mm on S5 (n=12,8,7,11,8) | >= 11 mm on S7 (n=11,9,7,11,11) | >= 11 mm on r-hCG Day (n=5,6,8,6,8) | |
| AS900672-Enriched 10 Mcg | 23.6 | 22.8 | 15.6 | 1.5 | 3.4 | 2.6 |
| AS900672-Enriched 20 Mcg | 28.7 | 27.2 | 11.7 | 0.0 | 0.2 | 2.5 |
| AS900672-Enriched 30 Mcg | 23.2 | 21.0 | 18.4 | 1.6 | 2.6 | 2.5 |
| AS900672-Enriched 40 Mcg | 20.9 | 21.3 | 18.7 | 2.8 | 2.8 | 1.8 |
| Follitropin Alfa 75 IU | 21.3 | 22.0 | 14.9 | 0.8 | 1.8 | 2.9 |
Ovulation was defined as a mid-luteal phase progesterone (P4) level >= 30 nanomole per liter (nmol/L) (10 nanogram per milliliter [ng/mL]). In the absence of a positive progesterone response, clinical pregnancy was also considered as evidence of ovulation. (NCT00553514)
Timeframe: Mid-luteal phase progesterone assessed 5-10 days or clinical pregnancy 35-42 days after recombinant human chorionic gonadotropin (r-hCG) administration day (end of stimulation cycle [approximately 14 days])
| Intervention | Percentage of participants (Number) |
|---|---|
| AS900672-Enriched 10 Mcg | 46.2 |
| AS900672-Enriched 20 Mcg | 46.2 |
| AS900672-Enriched 30 Mcg | 38.5 |
| AS900672-Enriched 40 Mcg | 33.3 |
| Follitropin Alfa 75 IU | 53.8 |
Clinical pregnancy was defined as the presence of one or more fetal sacs with fetal heart activity on the Day 35-42 post r-hCG ultrasound examination. (NCT00553514)
Timeframe: Day 35-42 post r-hCG administration day (end of stimulation cycle [approximately 14 days])
| Intervention | Percentage of participants (Number) |
|---|---|
| AS900672-Enriched 10 Mcg | 23.1 |
| AS900672-Enriched 20 Mcg | 0.0 |
| AS900672-Enriched 30 Mcg | 7.7 |
| AS900672-Enriched 40 Mcg | 16.7 |
| Follitropin Alfa 75 IU | 0.0 |
The fertilization rate is 100 times the number of fertilized 2 pro-nuclei (2PN) oocytes obtained, divided by the number of oocytes fertilized by IVF or ICSI (NCT00696800)
Timeframe: Up to 18 hours after start of fertilization (up to 1 year)
| Intervention | Percentage of fertilized oocytes (Mean) |
|---|---|
| 150 µg Corifollitropin Alfa | 66.0 |
| 200 IU recFSH | 67.6 |
The implantation rate is 100 times the number of gestational sacs assessed by USS after embryo transfer, divided by the number of embryos transferred. (NCT00696800)
Timeframe: Up to 6 weeks after embryo transfer (up to 1 year)
| Intervention | Percentage of gestational sacs (Mean) |
|---|---|
| 150 µg Corifollitropin Alfa | 36.2 |
| 200 IU recFSH | 32.2 |
Biochemical pregnancy was assessed for participants who had embryo transfer by measuring serum or urinary hCG. The pregnancy rate is 100 times the number of participants with pregnancies detected, divided by the number of participants assessed. (NCT00696800)
Timeframe: Two weeks after embryo transfer (up to 1 year)
| Intervention | Percentage of participants (Number) |
|---|---|
| 150 µg Corifollitropin Alfa | 54.2 |
| 200 IU recFSH | 50.0 |
The miscarriage rate is 100 times the number of miscarriages, divided by the number of clinical pregnancies assessed by USS. A clinical pregnancy is the presence of at least one gestational sac or confirmed by live birth. (NCT00696800)
Timeframe: Up to day of miscarriage (up to 1 year)
| Intervention | Percentage of participants (Number) |
|---|---|
| 150 µg Corifollitropin Alfa | 8.4 |
| 200 IU recFSH | 6.8 |
The miscarriage rate is 100 times the number of miscarriages, divided by the number of vital pregnancies assessed by USS. A vital pregnancy is the presence of at least one fetus with heart activity. (NCT00696800)
Timeframe: Up to day of miscarriage (up to 1 year)
| Intervention | Percentage of participants (Number) |
|---|---|
| 150 µg Corifollitropin Alfa | 2.3 |
| 200 IU recFSH | 2.0 |
Embryos obtained on Day 3 were categorized by their qualiity as follows: Grade 1: excellent: No fragmentation, 6-10 cells, and equal blastomere size taking the impact of cell division into account. Grade 2: good: < 20% fragmentation, 6-10 cells, and equal blastomere size taking the impact of cell division into account. Grade 3: fair: 20-50% fragmentation and/or less than 6 cells and/or multinucleation (if observed). Other Grade: Embryos that do not qualify as Grades 1, 2 or 3. Grades 1 and 2 are considered good quality. (NCT00696800)
Timeframe: Post fertilization Day 3 (up to 1 year)
| Intervention | Number of embryos (Mean) | |||||
|---|---|---|---|---|---|---|
| Total | Good Quality | Grade 1 | Grade 2 | Grade 3 | Other Grade | |
| 150 µg Corifollitropin Alfa | 8.4 | 4.7 | 2.6 | 2.1 | 2.4 | 1.4 |
| 200 IU recFSH | 7.5 | 4.5 | 2.5 | 2.0 | 2.0 | 1.1 |
After fertilization, the mean number of embryos transferred on Day 3 were assessed. Total and good quality embryos are presented, with good quality embryos, Grades 1 and 2, defined as the following: Grade 1: excellent: No fragmentation, 6-10 cells, and equal blastomere size taking the impact of cell division into account. Grade 2: good: < 20% fragmentation, 6-10 cells, and equal blastomere size taking the impact of cell division into account. (NCT00696800)
Timeframe: Post fertilization Day 3 (up to 1 year)
| Intervention | Number of embryos (Mean) | |
|---|---|---|
| Total | Good Quality | |
| 150 µg Corifollitropin Alfa | 1.7 | 1.4 |
| 200 IU recFSH | 1.7 | 1.4 |
Ovaries were assessed during stimulation by USS, and the mean number of follicles are categorized by their size. (NCT00696800)
Timeframe: On Day 5 of treatment (up to 1 year)
| Intervention | Number of follicles (Mean) | ||
|---|---|---|---|
| >=11 mm | >=15 mm | >=17 mm | |
| 150 µg Corifollitropin Alfa | 4.4 | 0.3 | 0.1 |
| 200 IU recFSH | 4.7 | 0.4 | 0.1 |
Ovaries were assessed during stimulation by USS, and the mean number of follicles are categorized by their size. (NCT00696800)
Timeframe: On Day 8 of treatment (up to 1 year)
| Intervention | Number of follicles (Mean) | ||
|---|---|---|---|
| >=11 mm | >=15 mm | >=17 mm | |
| 150 µg Corifollitropin Alfa | 12.8 | 5.0 | 2.1 |
| 200 IU recFSH | 11.6 | 5.2 | 2.5 |
Ovaries were assessed during stimulation by USS, and the mean number of follicles are categorized by their size. (NCT00696800)
Timeframe: Day of HCG treatment (up to 1 year)
| Intervention | Number of follicles (Mean) | ||
|---|---|---|---|
| >=11 mm | >=15 mm | >=17 mm | |
| 150 µg Corifollitropin Alfa | 16.0 | 9.6 | 5.7 |
| 200 IU recFSH | 13.9 | 8.7 | 5.6 |
The number of oocytes used for ICSI was assessed, and categorized based on their quality (NCT00696800)
Timeframe: Up to 36 hours after administration of hCG (up to 1 year)
| Intervention | Number of oocytes (Mean) | |||
|---|---|---|---|---|
| Total | Metaphase I | Metaphase II | Germinal vesicles | |
| 150 µg Corifollitropin Alfa | 13.8 | 1.1 | 10.8 | 1.4 |
| 200 IU recFSH | 12.2 | 0.9 | 9.2 | 1.7 |
Mean serum P levels are presented over one COS cycle: from Day 1 (Pre-dose) up to day of hCG treatment (NCT00696800)
Timeframe: Up to day of hCG treatment (up to 1 year)
| Intervention | nmol/mL (Mean) | |||
|---|---|---|---|---|
| Day 1 (Pre-dose) (Cori. Alfa N=732; recFSH N=724) | Day 5 (Cori. Alfa N=725; recFSH N=722) | Day 8 (Cori. Alfa N=708; recFSH N=678) | Day of hCG (Cori. Alfa N=698; recFSH N=708) | |
| 150 µg Corifollitropin Alfa | 1.80 | 2.13 | 1.95 | 3.20 |
| 200 IU recFSH | 1.85 | 1.61 | 2.64 | 3.16 |
Mean serum FSH are presented over one Controlled Ovarian Stimulation (COS) cycle: from Day 1 (Pre-dose) up to the day of hCG treatment. (NCT00696800)
Timeframe: Up to day of hCG treatment (up to 1 year)
| Intervention | IU/L (Mean) | |||
|---|---|---|---|---|
| Day 1 (Pre-dose) (Cori. Alfa N=732; recFSH N=724) | Day 5 (Cori. Alfa N=725; recFSH N=722) | Day 8 (Cori. Alfa N=708; recFSH N=678) | Day of hCG (Cori. Alfa N=698; recFSH N=708) | |
| 150 µg Corifollitropin Alfa | 6.70 | 23.49 | 11.76 | 12.54 |
| 200 IU recFSH | 6.60 | 11.61 | 11.59 | 11.59 |
Mean serum Inhibin-B levels are presented over one COS cycle: from Day 1 (Pre-dose) up to day of hCG treatment (NCT00696800)
Timeframe: Up to day of hCG treatment (up to 1 year)
| Intervention | pg/mL (Mean) | |||
|---|---|---|---|---|
| Day 1 (Pre-dose) (Cori. Alfa N=736; recFSH N=724) | Day 5 (Cori. Alfa N=731; recFSH N=724) | Day 8 (Cori. Alfa N=713; recFSH N=679) | Day of hCG (Cori. Alfa N=704; recFSH N=710) | |
| 150 µg Corifollitropin Alfa | 52.78 | 488.54 | 578.21 | 608.35 |
| 200 IU recFSH | 52.95 | 493.86 | 642.27 | 612.19 |
Mean serum LH levels are presented over one COS cycle: from Day 1 (Pre-dose) up to the day of hCG treatment. (NCT00696800)
Timeframe: Up to day of hCG treatment (up to 1 year)
| Intervention | IU/L (Mean) | |||
|---|---|---|---|---|
| Day 1 (Pre-dose) (Cori. Alfa N=732; recFSH N=724) | Day 5 (Cori. Alfa N=725; recFSH N=722) | Day 8 (Cori. Alfa N=708; recFSH N=678) | Day of hCG (Cori. Alfa N=698; recFSH N=708) | |
| 150 µg Corifollitropin Alfa | 4.80 | 3.62 | 1.29 | 1.38 |
| 200 IU recFSH | 4.67 | 2.23 | 2.05 | 1.86 |
Mean serum E2 levels are presented over one COS cycle: from Day 1 (Pre-dose) up to the day of hCG treatment. (NCT00696800)
Timeframe: Up to day of hCG treatment (up to 1 year)
| Intervention | pmol/L (Mean) | |||
|---|---|---|---|---|
| Day 1 (Pre-dose) (Cori. Alfa N=732; recFSH N=724) | Day 5 (Cori. Alfa N=725; recFSH N=722) | Day 8 (Cori. Alfa N=708; recFSH N=678) | Day of hCG (Cori. Alfa N=698; recFSH N=708) | |
| 150 µg Corifollitropin Alfa | 126.13 | 1859.39 | 3700.92 | 5486.67 |
| 200 IU recFSH | 124.79 | 1392.97 | 3750.96 | 5154.88 |
Ovaries were assessed during stimulation by ultrasonographic investigation (USS), and the mean number of follicles are categorized by their size. (NCT00696800)
Timeframe: On Day 1 of treatment (up to 1 year)
| Intervention | Number of follicles (Mean) | ||
|---|---|---|---|
| >=11 mm | >=15 mm | >=17 mm | |
| 150 µg Corifollitropin Alfa | 0.1 | 0.0 | 0.0 |
| 200 IU recFSH | 0.1 | 0.0 | 0.0 |
Biochemical pregnancy was assessed by measuring serum or urinary hCG. Per attempt means that if a participant did not reach the stage of pregnancy assessment zero values were imputed. The pregnancy rate is 100 times the number of participants with pregnancies detected, divided by the number of participants assessed. (NCT00696800)
Timeframe: Two weeks after embryo transfer (up to 1 year)
| Intervention | Percentage of participants (Number) |
|---|---|
| 150 µg Corifollitropin Alfa | 48.1 |
| 200 IU recFSH | 46.9 |
An ongoing pregnancy is a fetus with heart activity at least 10 weeks after embryo transfer as assessed by Ultrasound Scan (USS) or Doppler or is confirmed by live birth. The ongoing pregnancy rate is 100 times the number of participants with an ongoing pregnancy after embryo transfer, divided by the total number of participants who started treatment. Calculations were made per attempt, meaning that participants who did not have embryo transfers were considered not pregnant. (NCT00696800)
Timeframe: Assessed at least 10 weeks after embryo transfer (up to 1 year)
| Intervention | Percentage of participants (Number) |
|---|---|
| 150 µg Corifollitropin Alfa | 39.0 |
| 200 IU recFSH | 38.1 |
Up to 36 hours after receiving hCG, cumulus-oocyte-complexes were retrieved. Mean numbers retrieved were calculated per attempt, meaning that if a participant did not reach this stage in In Vitro Fertilization (IVF) treatment, zero values were imputed. (NCT00696800)
Timeframe: Up to 36 hours after administration of hCG (up to 1 year)
| Intervention | Number of oocytes (Mean) |
|---|---|
| 150 µg Corifollitropin Alfa | 13.8 |
| 200 IU recFSH | 12.6 |
The amount of recFSH administered for a participant to reach 3 follicles >= 17 mm, starting from treatment Day 1 onwards. (NCT00696800)
Timeframe: From Day 1 to day of hCG treatment (up to 1 year)
| Intervention | IU (Median) |
|---|---|
| 150 µg Corifollitropin Alfa | 400 |
| 200 IU recFSH | 1800 |
The amount of recFSH administered for a participant to reach 3 follicles >= 17 mm, starting from treatment Day 8 onwards. (NCT00696800)
Timeframe: From Day 8 to Day of hCG treatment (up to 1 year)
| Intervention | IU (Median) |
|---|---|
| 150 µg Corifollitropin Alfa | 400 |
| 200 IU recFSH | 400 |
Prior to IVF the mean number of cumulus-oocyte-complexes used for IVF was assessed (NCT00696800)
Timeframe: Up to 36 hours after administration of hCG (up to 1 year)
| Intervention | Number of cumulus-oocyte complexes (Mean) |
|---|---|
| 150 µg Corifollitropin Alfa | 13.6 |
| 200 IU recFSH | 12.8 |
Ovulation rate was defined as the number of participants with confirmed ovulation (≥15 nmol/l serum progesterone eight days after the bolus injection of hCG) divided by the number of treated participants. Ovulation was also considered confirmed for participants who became pregnant, had an ectopic pregnancy or had a miscarriage. (NCT00697255)
Timeframe: 8 days after bolus injection of hCG (up to 28 days)
| Intervention | percentage of participants (Number) |
|---|---|
| Corifollitropin Alfa + recFSH | 40.0 |
| Corifollitropin Alfa + hCG | 33.3 |
Treatment was considered cancelled if no bolus injection of hCG was administrated. Reasons of treatment failure included Adverse Event (AE)/ Serious Adverse Event (SAE), insufficient ovarian response on stimulation day 13 (no follicle ≥12 mm), insufficient ovarian response after 7 days of hCG/recFSH treatment (no follicle ≥18 mm), and multifollicular growth (≥3 follicles ≥15 mm). (NCT00697255)
Timeframe: Up to 3 weeks after bolus injection of hCG (up to 41 days)
| Intervention | percentage of participants (Number) | ||
|---|---|---|---|
| Insufficient ovarian response | Multifollicular growth | Not growing of dominant follicle | |
| Corifollitropin Alfa + hCG | 33.3 | 0 | 33.3 |
| Corifollitropin Alfa + recFSH | 20.0 | 20.0 | 20.0 |
OHSS was classified on study based on a slightly modified WHO Scientific Group (1973) classification: Grade I (mild) = characterized by excessive steroid secretion and ovarian enlargement (5-7 cm). Abdominal discomfort, including abdominal pain, is present. Grade II (moderate) = characterized by distinct ovarian cysts (ovary size 8-10 cm), accompanied by abdominal pain and tension, nausea, vomiting, diarrhea. Grade III (severe) = characterized by enlarged cystic ovaries (ovary size >10 cm), accompanied by ascites and occasionally hydrothorax. Abdominal tension and pain may be severe. Pronounced hydrothorax together with an abdominal cavity filled with cysts and fluid elevating the diaphragm may cause severe breathing difficulties. Large quantities of fluid inside the cysts and in the peritoneal and pleural cavities cause haemoconcentration and increased blood viscosity. In rare cases, the syndrome may further be complicated by the occurrence of thromboembolic phenomena. (NCT00697255)
Timeframe: During In-Treatment Period (up to 14 weeks after first corifollitropin injection)
| Intervention | participants (Number) |
|---|---|
| Corifollitropin Alfa + recFSH | 0 |
| Corifollitropin Alfa + hCG | 0 |
A pregnancy test (serum or urinary hCG) was performed two to three weeks after bolus injection of hCG. In case of a positive pregnancy test vaginal and/or abdominal ultrasound scan was performed to confirm the pregnancy at 5 to 6 weeks after bolus injection of hCG and ≥10 weeks after bolus injection of hCG to confirm ongoing pregnancy. (NCT00697255)
Timeframe: At least 10 weeks after bolus injection of hCG (up to 13 weeks)
| Intervention | participants (Number) |
|---|---|
| Corifollitropin Alfa + recFSH | 0 |
| Corifollitropin Alfa + hCG | 1 |
The monofollicular rate was defined as the number of participants with monofollicular response (one follicle ≥18 mm and no other follicle ≥15 mm on the day of the bolus injection of hCG) divided by the number of the treated participants. (NCT00697255)
Timeframe: At day of bolus injection of hCG (up to 20 days)
| Intervention | percentage of participants (Number) |
|---|---|
| Corifollitropin Alfa + recFSH | 0 |
| Corifollitropin Alfa + hCG | 0 |
Monofollicular ovulation rate was defined as the number of participants with monofollicular response (one follicle ≥18 mm and no other follicle ≥15 mm on the day of the bolus injection of hCG) and confirmed ovulation (≥15 nmol/l serum progesterone eight days after the bolus injection of hCG) divided by the number of treated participants. Ovulation was also considered confirmed for participants who became pregnant, had an ectopic pregnancy or had a miscarriage. (NCT00697255)
Timeframe: 8 days after bolus injection of hCG (up to 28 days)
| Intervention | percentage of participants (Number) |
|---|---|
| Corifollitropin Alfa + recFSH | 0 |
| Corifollitropin Alfa + hCG | 0 |
Miscarriages were calculated per clinical pregnancy, meaning the presence of at least one gestational sac or confirmed by live birth. (NCT00702273)
Timeframe: After one or more FTET cycles, up to day of miscarriage (up to 1 year)
| Intervention | Percentage of participants (Number) |
|---|---|
| 150 µg Corifollitropin Alfa | 8.2 |
| 200 IU RecFSH | 17.6 |
A clinical pregnancy is the presence of at least gestational sac or confirmed by live birth. Clinical pregnancies were calculated per attempt, meaning if any stage of in vitro fertilization (IVF) treatment was not achieved, zero values were imputed. (NCT00702273)
Timeframe: After one or more FTET cycles, assessed at least 10 weeks after embryo transfer (up to 1 year)
| Intervention | Percentage of participants (Number) |
|---|---|
| 150 µg Corifollitropin Alfa | 43.5 |
| 200 IU RecFSH | 38.6 |
An ectopic pregnancy is where the embryo implants outside the uterus. Ectopic pregnancies were calculated per total number of participants started in FTET. (NCT00702273)
Timeframe: After one or more FTET cycles, assessed at least 10 weeks after embryo transfer (up to 1 year)
| Intervention | Percentage of participants (Number) |
|---|---|
| 150 µg Corifollitropin Alfa | 1.2 |
| 200 IU RecFSH | 0.6 |
An ongoing pregnancy is the presence of at least one fetus with heart activity at least 10 weeks after embryo transfer or confirmed at live birth. Ongoing pregnancies were calculated per attempt, meaning if any stage of IVF treatment was not achieved, zero values were imputed. (NCT00702273)
Timeframe: After one or more FTET, assessed at least 10 weeks after embryo transfer or at live birth (up to 1 year)
| Intervention | Percentage of participants (Number) |
|---|---|
| 150 µg Corifollitropin Alfa | 38.7 |
| 200 IU RecFSH | 30.7 |
An ongoing pregnancy is the presence of at least one fetus with heart activity at least 10 weeks after embryo transfer or confirmed by live birth.The cumulative ongoing pregnancy rate is 100 times the number of participants with an ongoing pregnancy either immediately after embryo transfer in base Trial P05787 (NCT00696800), or after one or more FTET cycles in follow-up Trial P05716 following cryopreservation, divided by the total number of participants that started treatment in base Trial P05787 (NCT00696800). Participants who did not have cryopreserved embryos, or embryo transfers in the FTET cycle(s), were considered 'not pregnant'. (NCT00702273)
Timeframe: Up to 1 year after embryo transfer in base trial P05787 (NCT00696800), and FTET cycles in follow up trial
| Intervention | Percentage of participants (Number) |
|---|---|
| 150 µg Corifollitropin Alfa | 47.2 |
| 200 IU RecFSH | 44.9 |
Miscarriages were calculated per vital pregnancy, meaning the presence of at least one fetus with heart activity. (NCT00702273)
Timeframe: After one or more FTET cycles, up to day of miscarriage (up to 1 year)
| Intervention | Percentage of participants (Number) |
|---|---|
| 150 µg Corifollitropin Alfa | 0 |
| 200 IU RecFSH | 0 |
A vital pregnancy is the presence of at least one fetus with heart activity. Vital pregnancies were calculated per attempt, meaning if any stage of IVF treatment was not achieved, zero values were imputed. (NCT00702273)
Timeframe: After one or more FTET cycles, assessed at least 10 weeks after embryo transfer (up to 1 year)
| Intervention | Percentage of participants (Number) |
|---|---|
| 150 µg Corifollitropin Alfa | 39.9 |
| 200 IU RecFSH | 31.8 |
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. (NCT00702338)
Timeframe: From ≥10 weeks after bolus injection of hCG (administered in study P05693) up to 12 weeks after birth on current follow-up study
| Intervention | participant (Number) |
|---|---|
| Corifollitropin Alfa + hCG FU-Infants | 2 |
The Take-Home Baby Rate was defined as the number of participants with an ongoing pregnancy in base study P05693 (NCT00697255) with at least one live born infant in the current follow-up study divided by the total number of participants treated in base study P05693. (NCT00702338)
Timeframe: From ≥10 weeks after bolus injection of hCG (administered in study P05693) up to time of birth on current follow-up study (up to 1 year)
| Intervention | percentage of participants (Number) |
|---|---|
| Corifollitropin Alfa + recFSH Mothers | 0.0 |
| Corifollitropin Alfa + hCG Mothers | 33.3 |
Take-Home Baby Rate was alternately defined ad hoc as the number of participants with an ongoing pregnancy in base study P05693 (NCT00697255) with at least one live born infant in the current follow-up study divided by the total number of participants who received bolus injection of hCG in the base study. (NCT00702338)
Timeframe: From ≥10 weeks after bolus injection of hCG (administered in study P05693) up to time of birth on current follow-up study (up to 1 year)
| Intervention | percentage of participants (Number) |
|---|---|
| Corifollitropin Alfa + recFSH Mothers | 0.0 |
| Corifollitropin Alfa + hCG Mothers | 100.0 |
An SAE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. (NCT00702338)
Timeframe: From ≥10 weeks after bolus injection of hCG (administered in study P05693) up to 12 weeks after birth on current follow-up study
| Intervention | participants (Number) |
|---|---|
| Corifollitropin Alfa + hCG FU-Infants | 2 |
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. (NCT00702338)
Timeframe: From ≥10 weeks after bolus injection of hCG (administered in study P05693) up to 1 day after birth on current follow-up study (up to 1 year)
| Intervention | participants (Number) |
|---|---|
| Corifollitropin Alfa + hCG Mothers | 1 |
An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. (NCT00702338)
Timeframe: From ≥10 weeks after bolus injection of hCG (administered in study P05693) up to 1 day after birth on current follow-up study (up to 1 year)
| Intervention | participants (Number) |
|---|---|
| Corifollitropin Alfa + hCG Mothers | 1 |
An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the study drug. (NCT00702520)
Timeframe: Up to 1 Year
| Intervention | Participants (Number) |
|---|---|
| Expectant Mothers Administered Corifollitropin Alpha 100 ug | 7 |
| Expectant Mothers Administered Corifollitropin Alpha 150 ug | 6 |
The take-home baby rate was calculated as the number of participants with a least one live born infant in the follow-up study (P05783, 38834, NCT00702520) relative to the number of participants treated with Corifollitropin alpha in the base study (P05788, 38833, NCT00702351). (NCT00702520)
Timeframe: Birth of a one or more live babies (Up to 1 year)
| Intervention | Percentage of participants (Number) |
|---|---|
| Expectant Mothers Administered Corifollitropin Alpha 100 ug | 28.0 |
| Expectant Mothers Administered Corifollitropin Alpha 150 ug | 33.3 |
"An AE or suspected adverse reaction is considered serious if, in the view of either the investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition." (NCT00702520)
Timeframe: Up to 1 Year
| Intervention | Participants (Number) |
|---|---|
| Infants From Mothers Administered Corifollitropin Alpha 100 ug | 6 |
| Infants From Mothers Administered Cori. Alpha 150 ug | 7 |
An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the study drug. (NCT00702520)
Timeframe: Up to 1 Year
| Intervention | Participants (Number) |
|---|---|
| Infants From Mothers Administered Corifollitropin Alpha 100 ug | 6 |
| Infants From Mothers Administered Cori. Alpha 150 ug | 11 |
"An AE or suspected adverse reaction is considered serious if, in the view of either the investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition." (NCT00702520)
Timeframe: Up to 1 Year
| Intervention | Participants (Number) |
|---|---|
| Expectant Mothers Administered Corifollitropin Alpha 100 ug | 2 |
| Expectant Mothers Administered Corifollitropin Alpha 150 ug | 2 |
An ongoing pregnancy is the presence of at least one fetus with heart activity at least 10 weeks after embryo transfer or confirmed at live birth. Ongoing pregnancies were calculated per attempt, meaning if any stage of IVF treatment was not achieved, zero values were imputed. (NCT00702546)
Timeframe: After one or more FTET, assessed at least 10 weeks after embryo transfer or at live birth (up to 1 year)
| Intervention | Percentage of participants (Number) |
|---|---|
| Corifollitropin Alfa 100 μg | 23.4 |
| recFSH 150 IU | 36.0 |
A clinical pregnancy is the presence of at least gestational sac or confirmed by live birth. Clinical pregnancies were calculated per attempt, meaning if any stage of in vitro fertilization (IVF) treatment was not achieved, zero values were imputed. (NCT00702546)
Timeframe: After one or more FTET cycles, assessed at least 10 weeks after embryo transfer (up to 1 year)
| Intervention | Percentage of participants (Number) |
|---|---|
| Corifollitropin Alfa 100 μg | 28.6 |
| recFSH 150 IU | 40.0 |
Cumulative ongoing pregnancy rate was defined as 100 times the number of participants with an ongoing pregnancy either immediately after embryo transfer in base study P05690 (NCT00702845) or after one or more FTET cycles in follow up study P05711 following cryopreservation, divided by the total number of subjects that started treatment in base study P05690. (NCT00702546)
Timeframe: Up to 1 year after embryo transfer in base trial P05690 (NCT00702845), and FTET cycles in follow up study P05711
| Intervention | Percentage of participants (Number) |
|---|---|
| Corifollitropin Alfa 100 μg | 32.1 |
| recFSH 150 IU | 41.4 |
An ectopic pregnancy is where the embryo implants outside the uterus. Ectopic pregnancies were calculated per total number of participants started in FTET. (NCT00702546)
Timeframe: After one or more FTET cycles, assessed at least 10 weeks after embryo transfer (up to 1 year)
| Intervention | Percentage of participants (Number) |
|---|---|
| Corifollitropin Alfa 100 μg | 1.3 |
| recFSH 150 IU | 0.0 |
A vital pregnancy is the presence of at least one fetus with heart activity. Vital pregnancies were calculated per attempt, meaning if any stage of IVF treatment was not achieved, zero values were imputed. (NCT00702546)
Timeframe: After one or more FTET cycles, assessed at least 10 weeks after embryo transfer (up to 1 year)
| Intervention | Percentage of participants (Number) |
|---|---|
| Corifollitropin Alfa 100 μg | 24.7 |
| recFSH 150 IU | 36.0 |
Miscarriages were calculated per vital pregnancy, defined as the presence of at least one fetus with heart activity as assessed by USS or Doppler, or confirmed by live birth. (NCT00702546)
Timeframe: After one or more FTET cycles, assessed at least 10 weeks after embryo transfer (up to 1 year)
| Intervention | Percentage of participants (Number) |
|---|---|
| Corifollitropin Alfa 100 μg | 0.0 |
| recFSH 150 IU | 0.0 |
Miscarriages were calculated per clinical pregnancy, defined as the presence of at least one gestational sac as assessed by USS or Doppler, or confirmed by live birth. (NCT00702546)
Timeframe: After one or more FTET cycles, assessed at least 10 weeks after embryo transfer (up to 1 year)
| Intervention | Percentage of participants (Number) |
|---|---|
| Corifollitropin Alfa 100 μg | 13.6 |
| recFSH 150 IU | 10.0 |
The Take-Home Baby Rate was defined as the number of participants with an ongoing pregnancy in base study P05690 with at least one live born infant during follow up relative to the number of participants treated in base study. (NCT00702624)
Timeframe: From approximately 10 weeks after ET in base study P05690 up to birth of infant (up to approximately 6 months)
| Intervention | Percentage of participants (Number) |
|---|---|
| Corifollitropin Alfa 100 μg Women | 23.5 |
| recFSH 150 IU Women | 34.4 |
An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. (NCT00702624)
Timeframe: Up to 12 weeks after birth
| Intervention | Live born infants (Number) |
|---|---|
| Corifollitropin Alfa 100 μg Follow-Up Infants | 30 |
| recFSH 150 IU Follow-Up Infants | 16 |
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. (NCT00702624)
Timeframe: Up to 12 weeks after birth
| Intervention | Live born infants (Number) |
|---|---|
| Corifollitropin Alfa 100 μg Follow-Up Infants | 37 |
| recFSH 150 IU Follow-Up Infants | 27 |
An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. (NCT00702624)
Timeframe: From approximately 10 weeks after ET in base study P05690 up to birth of infant (up to approximately 6 months)
| Intervention | Participants (Number) |
|---|---|
| Corifollitropin Alfa 100 μg Expectant Mothers | 38 |
| recFSH 150 IU Expectant Mothers | 21 |
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. (NCT00702624)
Timeframe: From approximately 10 weeks after ET in base study P05690 up to birth of infant (up to approximately 6 months)
| Intervention | Participants (Number) |
|---|---|
| Corifollitropin Alfa 100 μg Expectant Mothers | 48 |
| recFSH 150 IU Expectant Mothers | 35 |
A Biochemical Pregnancy was defined as a pregnancy proven by a biochemical pregnancy test. (Participants not having a positive biochemical pregnancy test result, but with an ultrasound showing at least one gestational sac were counted as having a biochemical pregnancy.) A Clinical Pregnancy was defined as the presence of at least one gestational sac as assessed by an USS scan. A Vital Pregnancy was considered the presence of at least one fetus with heart activity as assessed by USS. An Ongoing Pregnancy was defined as the presence of at least one fetus with heart activity at least 10 weeks after ET as assessed by USS or Doppler, or confirmed by live birth. (NCT00702845)
Timeframe: Up to 10 weeks after ET (up to a maximum of 14 weeks)
| Intervention | Participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Biochemical pregnancy, per attempt (n=268,128) | Biochemical pregnancy, per ET (n=246,121) | Clinical pregnancy, per attempt (n=268,128) | Clinical pregnancy, per ET (n=246,121) | Vital pregnancy, per attempt (n=268,128) | Vital pregnancy, per ET (n=246,121) | Ongoing pregnancy, per attempt (n=268,128) | Ongoing pregnancy, per ET (n=246,121) | |
| 100 μg Corifollitropin Alfa | 101 | 101 | 78 | 78 | 69 | 69 | 68 | 68 |
| 150 IU recFSH | 58 | 58 | 48 | 48 | 45 | 45 | 44 | 44 |
For each participant, the number of follicles ≥11 mm, ≥15 mm, and ≥17 mm, documented by ultrasonography on defined days during the treatment cycle, was calculated. (NCT00702845)
Timeframe: Predose up to day of hCG administration (up to a maximum total duration of 19 stimulation days, including day of hCG administration)
| Intervention | Follicles (Mean) | |||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Stimulation Day 1, >=11mm (n=266,124) | Stimulation Day 1, >=15mm (n=266,124) | Stimulation Day 1, >=17mm (n=266,124) | Stimulation Day 3, >=11mm (n=268,128) | Stimulation Day 3, >=15mm (n=268,128) | Stimulation Day 3, >=17mm (n=268,128) | Stimulation Day 5, >=11mm (n=267,128) | Stimulation Day 5, >=15mm (n=267,128) | Stimulation Day 5, >=17mm (n=267,128) | Stimulation Day 6, >=11mm (n=9,5) | Stimulation Day 6, >=15mm (n=9,5) | Stimulation Day 6, >=17mm (n=9,5) | Stimulation Day 7, >=11mm (n=30,12) | Stimulation Day 7, >=15mm (n=30,12) | Stimulation Day 7, >=17mm (n=30,12) | Stimulation Day 8, >=11mm (n=259,121) | Stimulation Day 8, >=15mm (n=259,121) | Stimulation Day 8, >=17mm (n=259,121) | Stimulation Day 9, >=11mm (n=185,76) | Stimulation Day 9, >=15mm (n=185,76) | Stimulation Day 9, >=17mm (n=185,76) | Stimulation Day 10, >=11mm (n=101,40) | Stimulation Day 10, >=15mm (n=101,40) | Stimulation Day 10, >=17mm (n=101,40) | Stimulation Day 11, >=11mm (n=38,14) | Stimulation Day 11, >=15mm (n=38,14) | Stimulation Day 11, >=17mm (n=38,14) | Stimulation Day 12, >=11mm (n=17,6) | Stimulation Day 12, >=15mm (n=17,6) | Stimulation Day 12, >=17mm (n=17,6) | Stimulation Day 13, >=11mm (n=5,4) | Stimulation Day 13, >=15mm (n=5,4) | Stimulation Day 13, >=17mm (n=5,4) | Stimulation Day 14, >=11mm (n=2,1) | Stimulation Day 14, >=15mm (n=2,1) | Stimulation Day 14, >=17mm (n=2,1) | Stimulation Day 15, >=11mm (n=1,1) | Stimulation Day 15, >=15mm (n=1,1) | Stimulation Day 15, >=17mm (n=1,1) | Day of hCG administration, >=11mm (n=266,127) | Day of hCG administration, >=15mm (n=266,127) | Day of hCG administration, >=17mm (n=266,127) | |
| 100 μg Corifollitropin Alfa | 0.0 | 0.0 | 0.0 | 0.6 | 0.0 | 0.0 | 4.7 | 0.3 | 0.0 | 7.6 | 1.8 | 0.7 | 11.9 | 4.5 | 1.8 | 11.8 | 5.0 | 2.0 | 13.4 | 6.9 | 2.6 | 13.9 | 7.4 | 3.6 | 13.9 | 7.7 | 3.9 | 12.7 | 6.8 | 3.5 | 17.0 | 10.6 | 4.4 | 13.5 | 10.5 | 6.0 | 7.0 | 4.0 | 2.0 | 14.9 | 9.4 | 5.3 |
| 150 IU recFSH | 0.0 | 0.0 | 0.0 | 0.5 | 0.0 | 0.0 | 4.1 | 0.3 | 0.0 | 8.6 | 4.0 | 1.8 | 9.2 | 3.3 | 1.1 | 10.6 | 5.1 | 2.4 | 11.1 | 6.0 | 2.6 | 13.0 | 7.5 | 4.0 | 11.6 | 7.1 | 3.8 | 9.3 | 5.2 | 2.7 | 10.3 | 6.3 | 4.0 | 3.0 | 0.0 | 0.0 | 4.0 | 4.0 | 3.0 | 12.9 | 8.5 | 5.1 |
Blood samples for assessment of serum P were taken prior to injection on Stimulation Day 1, Day 3, Day 5, Day 8, Day of hCG, Day of ET, at the visit two weeks after ET. (NCT00702845)
Timeframe: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
| Intervention | nmol/L (Median) | ||||||
|---|---|---|---|---|---|---|---|
| Stimulation Day 1 (pre-dose) (n=264,120) | Stimulation Day 3 (n=263,126) | Stimulation Day 5 (n=265,127) | Stimulation Day 8 (n=255,121) | Day of hCG injection (n=262,126) | Day of ET (n=242,121) | 2 weeks after ET (n=244,120) | |
| 100 μg Corifollitropin Alfa | 1.36 | 1.23 | 1.65 | 1.39 | 2.10 | 421.35 | 38.64 |
| 150 IU recFSH | 1.40 | NA | 1.28 | 2.03 | 2.39 | 333.90 | 51.99 |
"Embryo quality was rated Grade 1, 2, 3, or other. Grade 1 represented excellent quality; Grade 2 good quality; Grade 3 fair quality. Other grade embryos were those that did not qualify as Grade 1, 2, or 3." (NCT00702845)
Timeframe: Post fertilization Day 3 (up to a maximum of 2 days after hCG administration)
| Intervention | Number of embryos (Mean) | |||||
|---|---|---|---|---|---|---|
| Total (n=259,123) | Good quality | Grade 1 | Grade 2 | Grade 3 | Other | |
| 100 μg Corifollitropin Alfa | 7.2 | 3.4 | 1.7 | 1.8 | 2.8 | 1.0 |
| 150 IU recFSH | 6.2 | 3.0 | 1.4 | 1.6 | 2.4 | 0.7 |
The number of oocytes used for ICSI was assessed and categorized based on their quality (i.e., metaphase I oocytes, metaphase II oocytes, and germinal vesicles stage oocytes). (NCT00702845)
Timeframe: Up to 36 hours after administration of hCG
| Intervention | Number of oocytes (Mean) | |||
|---|---|---|---|---|
| Oocytes assessed prior to ICSI | Metaphase I oocytes | Metaphase II oocytes | Germinal vesicles stage oocytes | |
| 100 μg Corifollitropin Alfa | 12.7 | 0.8 | 10.7 | 1.1 |
| 150 IU recFSH | 9.9 | 0.7 | 7.8 | 1.3 |
Total duration of stimulation was defined as the number of days from first drug administration up to and including the Day of hCG administration. (NCT00702845)
Timeframe: One COS cycle (up to a maximum total duration of 19 stimulation days)
| Intervention | Days (Median) |
|---|---|
| 100 μg Corifollitropin Alfa | 9.0 |
| 150 IU recFSH | 9.0 |
Total dose of recFSH (IU) needed from Stimulation Day 8 onwards to reach the criterion for administration of hCG (at least 3 follicles >=17mm). (NCT00702845)
Timeframe: Stimulation Day 8 of COS cycle up to day of hCG administration (up to a maximum total duration of 19 stimulation days)
| Intervention | International Unit (IU) (Median) |
|---|---|
| 100 μg Corifollitropin Alfa | 300.0 |
| 150 IU recFSH | 275.0 |
Blood samples for assessment of serum LH were taken prior to injection on Stimulation Day 1, Day 3, Day 5, Day 8, Day of hCG, Day of ET, at the visit two weeks after ET. (NCT00702845)
Timeframe: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
| Intervention | IU/L (Median) | ||||||
|---|---|---|---|---|---|---|---|
| Stimulation Day 1 (pre-dose) (n=265,122) | Stimulation Day 3 (n=265,127) | Stimulation Day 5 (n=264,127) | Stimulation Day 8 (n=255,121) | Day of hCG injection (n=262,126) | Day of ET (n=242,121) | 2 weeks after ET (n=245,121) | |
| 100 μg Corifollitropin Alfa | 4.46 | 1.18 | 1.91 | 0.82 | 0.88 | NA | 2.38 |
| 150 IU recFSH | 4.12 | 1.46 | 1.49 | 1.60 | 1.30 | NA | 1.02 |
"A miscarriage, also known as a spontaneous abortion, was defined as the loss of a fetus without induction or instrumentation." (NCT00702845)
Timeframe: Up to 10 weeks after ET (up to a maximum of 14 weeks)
| Intervention | Participants (Number) | |
|---|---|---|
| Per clinical pregnancy (n=78,48) | Per vital pregnancy (n=69,45) | |
| 100 μg Corifollitropin Alfa | 10 | 1 |
| 150 IU recFSH | 4 | 1 |
Total dose of recFSH (IU) administered was defined as the total amount of recFSH needed by participants to reach the criterion for administration of hCG (at least 3 follicles >=17mm). (NCT00702845)
Timeframe: One COS cycle (up to a maximum total duration of 19 stimulation days)
| Intervention | International Unit (IU) (Median) |
|---|---|
| 100 μg Corifollitropin Alfa | 300.0 |
| 150 IU recFSH | 1350.0 |
Numbers of days treated with recFSH was defined as the total number of days participants received recFSH (excluding coasting days) until they reached the criterion for administration of hCG (at least 3 follicles >=17mm). (NCT00702845)
Timeframe: One COS cycle (up to a maximum total duration of 19 stimulation days)
| Intervention | Days (Median) |
|---|---|
| 100 μg Corifollitropin Alfa | 2.0 |
| 150 IU recFSH | 9.0 |
The primary efficacy parameter was defined as the number of cumulus-oocyte-complexes retrieved from participants in a controlled ovarian stimulation (COS) cycle for in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI). For participants who did not have cumulus-oocyte-complex retrieval, the number retrieved was set to zero. (NCT00702845)
Timeframe: One COS cycle with cumulus-oocyte-complex retrieval (up to a maximum total duration of 21 days)
| Intervention | Number of cumulus-oocyte-complexes (Mean) |
|---|---|
| 100 μg Corifollitropin Alfa | 13.3 |
| 150 IU recFSH | 10.6 |
The implantation rate was defined as 100 times the maximum number of gestational sacs as assessed by any ultrasound scan (USS) after ET divided by the number of embryos transferred (per participant), maximized to 100%. (NCT00702845)
Timeframe: Up to 6 weeks after ET within a treatment cycle (up to a maximum 10 weeks)
| Intervention | Percentage (Mean) |
|---|---|
| 100 μg Corifollitropin Alfa | 23.6 |
| 150 IU recFSH | 28.5 |
Fertilization rate, defined as 100 times the ratio of the number of fertilized 2 pronuclei (PN) oocytes obtained and the number of oocytes incubated, was tabulated for each treatment group. (NCT00702845)
Timeframe: Up to 10 weeks after ET
| Intervention | Percentage (Mean) |
|---|---|
| 100 μg Corifollitropin Alfa | 67.6 |
| 150 IU recFSH | 67.7 |
Blood samples for assessment of serum inhibin-B were taken prior to injection on Stimulation Day 1, Day 3, Day 5, Day 8, Day of hCG, Day of ET, at the visit two weeks after ET. (NCT00702845)
Timeframe: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
| Intervention | pg/mL (Median) | ||||||
|---|---|---|---|---|---|---|---|
| Stimulation Day 1 (pre-dose) (n=265,123) | Stimulation Day 3 (n=265,127) | Stimulation Day 5 (n=264,127) | Stimulation Day 8 (n=255,121) | Day of hCG injection (n=262,126) | Day of ET (n=242,121) | 2 weeks after ET (n=245,121) | |
| 100 μg Corifollitropin Alfa | 54.20 | 351.00 | 598.00 | 619.00 | 729.50 | 18.20 | 17.50 |
| 150 IU recFSH | 57.80 | 259.00 | 489.00 | 650.00 | 615.50 | 17.00 | NA |
Blood samples for assessment of serum FSH were taken prior to injection on Stimulation Day 1, Day 3, Day 5, Day 8, Day of hCG, Day of ET, at the visit two weeks after ET. (NCT00702845)
Timeframe: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
| Intervention | IU/L (Median) | ||||||
|---|---|---|---|---|---|---|---|
| Stimulation Day 1 (pre-dose) (n=265,122) | Stimulation Day 3 (n=265,127) | Stimulation Day 5 (n=265,127) | Stimulation Day 8 (n=255,121) | Day of hCG injection (n=262,126) | Day of ET (n=242,121) | 2 weeks after ET (n=245,121) | |
| 100 μg Corifollitropin Alfa | 6.46 | 26.30 | 19.50 | 10.10 | 11.50 | 2.52 | 4.46 |
| 150 IU recFSH | 6.51 | 9.18 | 10.20 | 10.30 | 10.65 | 1.32 | 1.90 |
Blood samples for assessment of serum E2 were taken prior to injection on Stimulation Day 1, Day 3, Day 5, Day 8, Day of hCG, Day of ET, at the visit two weeks after ET. (NCT00702845)
Timeframe: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
| Intervention | pmol/L (Median) | ||||||
|---|---|---|---|---|---|---|---|
| Stimulation Day 1 (pre-dose) (n=265,122) | Stimulation Day 3 (n=265,127) | Stimulation Day 5 (n=265,127) | Stimulation Day 8 (n=255,121) | Day of hCG injection (n=262,126) | Day of ET (n=242,121) | 2 weeks after ET (n=245,121) | |
| 100 μg Corifollitropin Alfa | 118.17 | 803.73 | 1901.06 | 2899.30 | 4440.70 | 3475.49 | 168.45 |
| 150 IU recFSH | 120.38 | 506.46 | 1295.51 | 3167.21 | 4440.70 | 3670.00 | 392.69 |
The take-home baby rate is 100 X the number of participants with an ongoing pregnancy in Base Trial P05787 (NCT00696800), from the Intent-to-Treat (ITT) group, with at least one live born infant relative to the number of participants in the Base Trial. (NCT00703014)
Timeframe: At least 10 weeks after embryo transfer in Base Trial P05787 up to birth in current follow up Trial (up to 1 year)
| Intervention | Percentage of Participants (Number) |
|---|---|
| Mothers Corifollitropin Alfa 150 µg | 35.6 |
| Mothers recFSH 200 IU | 34.4 |
The take-home baby rate is 100 X the number of participants with an ongoing pregnancy in Base Trial P05787 (NCT00696800), from the ITT group, with at least one live born infant relative to the number of participants from the Base Trial with embryo transfer. (NCT00703014)
Timeframe: At least 10 weeks after embryo transfer in Base Trial P05787 up to birth in current Follow Up Trial (up to 1 year)
| Intervention | Percentage of Participants (Number) |
|---|---|
| Mothers Corifollitropin Alfa 150 µg | 40.0 |
| Mothers recFSH 200 IU | 36.6 |
A SAE is any untoward medical occurrence that at any dose resulted in the following: death, was life threatening, required in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. (NCT00703014)
Timeframe: Up to one day following delivery (up to 1 year)
| Intervention | Participants (Number) |
|---|---|
| Mothers Corifollitropin Alfa 150 µg | 129 |
| Mothers recFSH 200 IU | 117 |
An AE is any untoward medical occurrence in a trial participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including laboratory finding), symptom, or disease temporally associated with the use of investigational medicinal product. (NCT00703014)
Timeframe: Up to one day following delivery (up to 1 year)
| Intervention | Participants (Number) |
|---|---|
| Mothers Corifollitropin Alfa 150 µg | 222 |
| Mothers recFSH 200 IU | 214 |
A SAE is any untoward medical occurrence that at any dose resulted in the following: death, was life threatening, required in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. (NCT00703014)
Timeframe: Up to 12 weeks following delivery (up to 1 year)
| Intervention | Participants (Number) |
|---|---|
| Infants Corifollitropin Alfa 150 µg | 106 |
| Infants recFSH 200 IU | 94 |
An AE is any untoward medical occurrence in a trial participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including laboratory finding), symptom, or disease temporally associated with the use of investigational medicinal product. (NCT00703014)
Timeframe: Up to 12 weeks following delivery (up to 1 year)
| Intervention | Participants (Number) |
|---|---|
| Infants Corifollitropin Alfa 150 µg | 164 |
| Infants recFSH 200 IU | 161 |
The number of embryos that were not transferred but instead were frozen for future use. (NCT00802360)
Timeframe: Approximately Day 24
| Intervention | embryos (Mean) |
|---|---|
| Menopur | 1.9 |
| Follistim | 1.6 |
"Number of participants with adverse events (AEs) that started after first treatment. Severity used a three point scale:~mild=awareness of signs/symptoms, but no disruption of usual activity moderate=event sufficient to affect usual activity (disturbing) severe=event causes inability to work or perform usual activities (unacceptable)~Relatedness to study treatment used a four point scale: unrelated, unlikely, possible, probable.~Seriousness refers to death, hospitalization, a life-threatening experience, persistent or significant disability/incapacity, or congenital anomaly." (NCT00802360)
Timeframe: Day 1 - week 12
| Intervention | participants (Number) | |||||
|---|---|---|---|---|---|---|
| With at least one adverse event | Mild or moderate adverse event | Severe adverse event | Serious adverse event | Unrelated or unlikely adverse event | Possibly or probably related adverse event | |
| Follistim/Endometrin | 18 | 18 | 2 | 1 | 17 | 7 |
| Follistim/Progesterone in Oil | 21 | 21 | 0 | 0 | 14 | 15 |
| Menopur/Endometrin | 20 | 20 | 1 | 0 | 15 | 10 |
| Menopur/Progesterone in Oil | 18 | 18 | 0 | 1 | 13 | 8 |
The number of embryos, morula and blastocytes transferred to the study participant on either day 3 or day 5 following fertilization. (NCT00802360)
Timeframe: Approximately Day 24
| Intervention | embryos (Mean) | ||
|---|---|---|---|
| Number of Embryos transferred | Number of Morula transferred | Number of Blastocytes transferred | |
| Follistim | 2.4 | 0.1 | 0.9 |
| Menopur | 2.1 | 0.0 | 0.9 |
The proportion of the number of oocytes inseminated (fertilized) of the total number of oocytes retrieved. (NCT00802360)
Timeframe: Approximately Day 19
| Intervention | proportion of oocytes retrieved (Mean) |
|---|---|
| Menopur | 0.3 |
| Follistim | 0.3 |
The ongoing pregnancy was defined as a positive fetal heart movement (motion) at approximately six weeks of gestation and confirmed in a follow-up pregnancy ultrasound. (NCT00802360)
Timeframe: Week 8 (Week 6 of gestation)
| Intervention | percentage of participants (Number) |
|---|---|
| Menopur/Endometrin | 45.2 |
| Menopur/Progesterone in Oil | 45.2 |
| Follistim/Endometrin | 42.9 |
| Follistim/Progesterone in Oil | 48.7 |
A count of participants whose discontinuation was clearly documented on the study completion/termination form as 1) due to cycle cancelled or 2) cycle cancellation for risk of ovarian hyperstimulation syndrome (OHSS). (NCT00802360)
Timeframe: Day 1 to Day 24
| Intervention | participants (Number) |
|---|---|
| Menopur/Endometrin | 0 |
| Menopur/Progesterone in Oil | 1 |
| Follistim/Endometrin | 1 |
| Follistim/Progesterone in Oil | 2 |
Clinical pregnancy is the confirmation of the presence of intrauterine gestational sacs on pregnancy ultrasound examination. (NCT00802360)
Timeframe: approximately week 7
| Intervention | participants (Number) |
|---|---|
| Menopur/Endometrin | 19 |
| Menopur/Progesterone in Oil | 19 |
| Follistim/Endometrin | 18 |
| Follistim/Progesterone in Oil | 20 |
Biochemical pregnancy is a positive β-hCG pregnancy test 12-14 days post embryo transfer. (NCT00802360)
Timeframe: approximately day 38 (Day 14 post embryo transfer)
| Intervention | participants (Number) |
|---|---|
| Menopur/Endometrin | 21 |
| Menopur/Progesterone in Oil | 20 |
| Follistim/Endometrin | 22 |
| Follistim/Progesterone in Oil | 23 |
The mean number of oocytes retrieved within 34-36 hours of human chorionic gonadotropin (hCG) administration. (NCT00802360)
Timeframe: Approximately Day 18
| Intervention | oocytes (Mean) |
|---|---|
| Menopur | 11.5 |
| Follistim | 13.8 |
The mean number of follicles observed in both ovaries at the last transvaginal ultrasound in the stimulation phase. (NCT00802360)
Timeframe: Day 15
| Intervention | follicles (Mean) |
|---|---|
| Menopur | 15.6 |
| Follistim | 16.2 |
A count of participants whose discontinuation was clearly documented on the study completion/termination form as cycle cancellation for risk of ovarian hyperstimulation syndrome (OHSS). (NCT00805935)
Timeframe: weeks 1-3
| Intervention | Participants (Number) | |
|---|---|---|
| Yes | No | |
| Follitropin Beta/Progesterone in Oil | 0 | 30 |
| Follitropin Beta/Progesterone Vaginal Insert | 1 | 27 |
| Menotropin/Progesterone in Oil | 0 | 27 |
| Menotropin/Progesterone Vaginal Insert | 1 | 24 |
"Number of participants with adverse events (AEs) that started after first treatment. Severity used a three point scale:~mild=awareness of signs/symptoms, but no disruption of usual activity moderate=event sufficient to affect usual activity (disturbing) severe=event causes inability to work or perform usual activities (unacceptable) Relatedness to study treatment used a four point scale: unrelated, unlikely, possible, probable.~Seriousness refers to death, hospitalization, a life-threatening experience, persistent or significant disability/incapacity, or congenital anomaly." (NCT00805935)
Timeframe: Week 1 to week12
| Intervention | Participants (Number) | |||||
|---|---|---|---|---|---|---|
| With at least one adverse event | With at least one mild or moderate adverse event | With at least one severe adverse event | With at least one serious adverse event | With at least one unrelated or unlikely AE | With at least one possibly or probably related AE | |
| Follitropin Beta/Progesterone in Oil | 14 | 14 | 0 | 0 | 13 | 6 |
| Follitropin Beta/Progesterone Vaginal Insert | 15 | 15 | 1 | 0 | 12 | 8 |
| Menotropin/Progesterone in Oil | 12 | 11 | 2 | 1 | 11 | 7 |
| Menotropin/Progesterone Vaginal Insert | 9 | 9 | 0 | 0 | 8 | 3 |
Clinical pregnancy is the confirmation of the presence of intrauterine gestational sacs on pregnancy ultrasound examination. (NCT00805935)
Timeframe: approximately Day 52
| Intervention | Percentage of participants (Number) |
|---|---|
| Menotropin/Progesterone Vaginal Insert | 56.0 |
| Menotropin/Progesterone in Oil | 33.3 |
| Follitropin Beta/Progesterone Vaginal Insert | 46.4 |
| Follitropin Beta/Progesterone in Oil | 66.7 |
The mean number of oocytes retrieved approximately 36 hours after hCG (Novarel®) administration and fertilized (by insemination or intra cytoplasmic sperm injection (ICSI)) according to site-specific procedures. (NCT00805935)
Timeframe: approximately day 18
| Intervention | Oocytes (Mean) |
|---|---|
| Menotropin | 13.0 |
| Follitropin Beta | 15.6 |
The mean number of follicles observed in both ovaries at the last transvaginal ultrasound in the stimulation phase. (NCT00805935)
Timeframe: approximately day 15
| Intervention | Follicles (Mean) |
|---|---|
| Menotropin | 27.7 |
| Follitropin Beta | 30.5 |
The fertilization rate for each participant was the percentage of the number of oocytes inseminated of the total number of oocytes retrieved. (NCT00805935)
Timeframe: approximately day 19
| Intervention | Percentage of oocytes retrieved (Number) |
|---|---|
| Menotropin | 17.1 |
| Follitropin Beta | 24.8 |
Biochemical pregnancy is a positive β-hCG pregnancy test 12-14 days post embryo transfer. (NCT00805935)
Timeframe: approximately day 38 (Day 14 post embryo transfer)
| Intervention | Percentage of participants (Number) |
|---|---|
| Menotropin/Progesterone Vaginal Insert | 60.0 |
| Menotropin/Progesterone in Oil | 55.6 |
| Follitropin Beta/Progesterone Vaginal Insert | 60.7 |
| Follitropin Beta/Progesterone in Oil | 73.3 |
The number of embryos that were not transferred but instead were frozen for future use. (NCT00805935)
Timeframe: approximately day 24
| Intervention | Embryos (Mean) |
|---|---|
| Menotropin | 1.9 |
| Follitropin Beta | 1.9 |
Blood tests were sent to a central laboratory to obtain hCG levels. (NCT00805935)
Timeframe: Day 6
| Intervention | mIU/ml (Mean) |
|---|---|
| Menotropin/Progesterone Vaginal Insert | 1.0 |
| Menotropin/Progesterone in Oil | 1.0 |
| Follitropin Beta/Progesterone Vaginal Insert | 1.0 |
| Follitropin Beta/Progesterone in Oil | 1.0 |
Estradiol monitoring during fertility therapy assesses follicular growth and is useful in monitoring the treatment. Blood tests sent to a central laboratory to obtain estradiol levels. (NCT00805935)
Timeframe: Day 6
| Intervention | pg/mL (Mean) |
|---|---|
| Menotropin/Progesterone Vaginal Insert | 354.6 |
| Menotropin/Progesterone in Oil | 268.2 |
| Follitropin Beta/Progesterone Vaginal Insert | 617.5 |
| Follitropin Beta/Progesterone in Oil | 550.5 |
Clinical pregnancy is the confirmation of the presence of intrauterine gestational sacs on pregnancy ultrasound examination. (NCT00805935)
Timeframe: approximately Day 65
| Intervention | Percentage of participants (Number) |
|---|---|
| Menotropin/Progesterone Vaginal Insert | 48.0 |
| Menotropin/Progesterone in Oil | 33.3 |
| Follitropin Beta/Progesterone Vaginal Insert | 46.4 |
| Follitropin Beta/Progesterone in Oil | 63.3 |
Blood tests were sent to a central laboratory to obtain progesterone levels. (NCT00805935)
Timeframe: approximately day 16
| Intervention | ng/mL (Mean) |
|---|---|
| Menotropin/Progesterone Vaginal Insert | 1.3 |
| Menotropin/Progesterone in Oil | 1.1 |
| Follitropin Beta/Progesterone Vaginal Insert | 1.7 |
| Follitropin Beta/Progesterone in Oil | 1.3 |
"The number of embryos, morulas and blastocysts transferred to the study participant on either day 3 or day 5 following fertilization. Embryos represent the earliest development stage and contain 2-8 cells.~Morulas, the next stage, continued cellular cleavage results in a 16-30 cell solid sphere. Morula further develop into blastocyst, which contains 70-100 cells in a hollow spherical shape." (NCT00805935)
Timeframe: approximately day 24
| Intervention | Embryos (Mean) | ||
|---|---|---|---|
| Number of embryos transferred | Number of morula transferred | Number of blastocyst transferred | |
| Follitropin Beta | 2.0 | 0.1 | 1.1 |
| Menotropin | 2.0 | 0.0 | 0.8 |
Implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100. (NCT00829244)
Timeframe: Day 35-42 Post-hCG
| Intervention | percent sacs per embryo (Mean) |
|---|---|
| GONAL-f ® CONSORT Calculator | 31.1 |
| GONAL-f ® Standard Treatment | 31.2 |
(NCT00829244)
Timeframe: Start of treatment until end of stimulation cycle (approximately 28 days)
| Intervention | IU (Mean) |
|---|---|
| GONAL-f ® CONSORT Calculator | 121.49 |
| GONAL-f ® Standard Treatment | 167.43 |
Mean number of oocytes retrieved on the day of ovum pick up (OPU) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body. (NCT00829244)
Timeframe: 34-38 hours post-recombinant human choriogonadotropin (hCG) (OPU)
| Intervention | oocytes (Mean) |
|---|---|
| GONAL-f ® CONSORT Calculator | 10.0 |
| GONAL-f ® Standard Treatment | 11.8 |
OHSS is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting. (NCT00829244)
Timeframe: Start of treatment until Day 15-20 Post-hCG
| Intervention | participants (Number) |
|---|---|
| GONAL-f ® CONSORT Calculator | 6 |
| GONAL-f ® Standard Treatment | 13 |
Biochemical pregnancy was defined as a pregnancy diagnosed only by the detection of hCG in serum and that does not develop into a clinical pregnancy. (NCT00829244)
Timeframe: Start of treatment until Day 15-20 Post-hCG
| Intervention | percentage of participants (Number) |
|---|---|
| GONAL-f ® CONSORT Calculator | 47.7 |
| GONAL-f ® Standard Treatment | 44.1 |
Clinical pregnancy is defined by the number of sacs and hearts with activity per ultrasound scan performed on Day 35-42 post-hCG. (NCT00829244)
Timeframe: Day 35-42 Post-hCG
| Intervention | percentage of participants (Number) |
|---|---|
| GONAL-f ® CONSORT Calculator | 36.0 |
| GONAL-f ® Standard Treatment | 35.5 |
(NCT00829244)
Timeframe: End of stimulation cycle (approximately 28 days)
| Intervention | nmol/L (Mean) |
|---|---|
| GONAL-f ® CONSORT Calculator | 5.41 |
| GONAL-f ® Standard Treatment | 4.88 |
(NCT00829244)
Timeframe: Start of treatment until end of stimulation cycle (approximately 28 days)
| Intervention | days (Mean) |
|---|---|
| GONAL-f ® CONSORT Calculator | 10.6 |
| GONAL-f ® Standard Treatment | 10.7 |
Number of participants with fetal sacs and fetal hearts (with activity) as seen on an ultrasound scan to confirm clinical pregnancy. (NCT00829244)
Timeframe: Day 35-42 Post-hCG
| Intervention | participants (Number) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Missing (fetal sacs and fetal hearts) | 0 (fetal sacs) | 1 (fetal sacs) | 2 (fetal sacs) | 3 (fetal sacs) | 0 (fetal hearts) | 1 (fetal hearts) | 2 (fetal hearts) | 3 (fetal hearts) | |
| GONAL-f ® CONSORT Calculator | 47 | 6 | 27 | 5 | 1 | 8 | 25 | 5 | 1 |
| GONAL-f ® Standard Treatment | 57 | 1 | 25 | 10 | 0 | 3 | 24 | 9 | 0 |
Pregnancy outcomes are live outcome (live infant) and non-live outcome (non-live infant) or unknown outcome (subject lost to follow-up). (NCT00829244)
Timeframe: up to 9 month (following the end of treatment)
| Intervention | participants (Number) | ||
|---|---|---|---|
| Live outcomes | Non-live outcomes | Unknown outcomes | |
| GONAL-f ® CONSORT Calculator | 24 | 2 | 5 |
| GONAL-f ® Standard Treatment | 25 | 3 | 5 |
Number of participants with cancelled cycles due to excessive or inadequate response was evaluated. An excessive response: greater than or equal to 25 oocytes which could put the participant at risk of OHSS; An inadequate response: defined as 3 or less follicles of greater than or equal to 12 millimeter (mm) developing following at least 7 days of GONAL-f® treatment. (NCT00829244)
Timeframe: Start of treatment until Day 15-20 post-hCG
| Intervention | Participants (Number) | |
|---|---|---|
| Inadequate response | Excessive response (Risk of OHSS) | |
| GONAL-f ® CONSORT Calculator | 9 | 1 |
| GONAL-f ® Standard Treatment | 5 | 6 |
(NCT00829244)
Timeframe: Start of treatment until end of stimulation cycle (approximately 28 days)
| Intervention | IU (Mean) |
|---|---|
| GONAL-f ® CONSORT Calculator | 1288.54 |
| GONAL-f ® Standard Treatment | 1809.95 |
Multiple pregnancy was defined as 2 or more fetal hearts with activity. (NCT00829244)
Timeframe: Day 35-42 Post-hCG
| Intervention | participants (Number) |
|---|---|
| GONAL-f ® CONSORT Calculator | 6 |
| GONAL-f ® Standard Treatment | 9 |
Fetal heart motion by transvaginal ultrasound (NCT00854373)
Timeframe: 6 weeks after embryo transfer
| Intervention | percentage of participants (Number) |
|---|---|
| Bravelle | 57 |
| Placebo | 46 |
Number of normally fertilized oocytes (2PNs) divided by the total number of oocytes collected (i.e., not just the number of inseminated MII oocytes). This accounted for the possibility of both an enhanced oocyte maturation and improved fertilization of the mature oocytes. This also permitted inclusion of both IVF and intracytoplasmic sperm injection (ICSI) cycles in a way that allowed for evaluation of collective fertilization rates (i.e., typically, the denominator in IVF in calculating fertilization rate is all eggs collected, but in ICSI it is calculated using only the number of MII oocytes injected). (NCT00854373)
Timeframe: 24 hours after IVF or intracytoplasmic sperm injection (ICSI)
| Intervention | percentage of oocytes (Mean) |
|---|---|
| Bravelle | 63 |
| Placebo | 55 |
Likelihood of obtaining an oocyte from a single mature-sized follicle on each ovary. (NCT00854373)
Timeframe: 36 hours after hCG trigger
| Intervention | percentage of follicles (Number) |
|---|---|
| Bravelle | 70 |
| Placebo | 57 |
17 hydroxyprogesterone levels (NCT00989781)
Timeframe: Baseline and 24 after hCG
| Intervention | Participants (Count of Participants) |
|---|---|
| NR-PCOS Women | 0 |
| HR-PCOS Women | 0 |
| Normal Women | 0 |
Change from baseline in 17-hydroxyprogesterone at 24 hours after hCG injection (NCT00989781)
Timeframe: Baseline and 24 hours after hCG
| Intervention | ng/ml (Mean) |
|---|---|
| NR-PCOS Women | 1.3 |
| HR-PCOS Women | 3 |
| Normal Women | 1.1 |
3-D ultrasound was not assessed; instead 2-D ultrasound was performed (NCT00989781)
Timeframe: baseline
| Intervention | Antral Follicle Count (Mean) |
|---|---|
| NR-PCOS Women | 64.4 |
| HR-PCOS Women | 49.3 |
| Normal Women | 31.8 |
(NCT00989781)
Timeframe: Baseline
| Intervention | ng/ml (Mean) |
|---|---|
| NR-PCOS Women | 16.0 |
| HR-PCOS Women | 6.7 |
| Normal Women | 5.3 |
17-hydroxyprogesterone response to ACTH infusion in women with PCOS and normal women. Response is reported as a single value generated by summing the data at end time frame. (NCT00989781)
Timeframe: Baseline and 1, 2, 3, 4, 5, and 6 hours after ACTH
| Intervention | ng/ml (Mean) |
|---|---|
| NR-PCOS Women | 6.0 |
| HR-PCOS Women | 8.1 |
| Normal Women | 6.2 |
(NCT01044862)
Timeframe: Participants were followed for the duration of their treatment and, if pregnant through 6 weeks post-delivery, up to 66 weeks
| Intervention | participants (Number) |
|---|---|
| Aromatase Inhibitors (AI) | 56 |
| Clomiphene Citrate (CC) | 70 |
| Follicle Stimulating Hormone (FSH) | 97 |
(NCT01044862)
Timeframe: Participants were followed for the duration of their treatment and, if pregnant through 6 weeks post-delivery, up to 66 weeks
| Intervention | number of multiples (Number) |
|---|---|
| Aromatase Inhibitors (AI) | 9 |
| Clomiphene Citrate (CC) | 8 |
| Follicle Stimulating Hormone (FSH) | 34 |
(NCT01044862)
Timeframe: Participants were followed for the duration of their treatment and, if pregnant through 6 weeks post-delivery, up to 66 weeks
| Intervention | participants (Number) |
|---|---|
| Aromatase Inhibitors (AI) | 85 |
| Clomiphene Citrate (CC) | 106 |
| Follicle Stimulating Hormone (FSH) | 140 |
(NCT01044862)
Timeframe: Participants were followed for the duration of their treatment and, if pregnant through 6 weeks post-delivery, up to 66 weeks
| Intervention | days (Mean) |
|---|---|
| Aromatase Inhibitors (AI) | 67.2 |
| Clomiphene Citrate (CC) | 67.4 |
| Follicle Stimulating Hormone (FSH) | 62.3 |
(NCT01071200)
Timeframe: Baseline (S8) until hCG day
| Intervention | Days (Mean) |
|---|---|
| FSH + rhLH | 4.6 |
| Follicle-stimulating Hormone (FSH) | 4.8 |
Mean number of oocytes retrieved on the day of ovum pick up (OPU) was counted. Oocyte retrieval is a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body. (NCT01071200)
Timeframe: 34-36 hours post-hCG (OPU)
| Intervention | oocytes (Mean) |
|---|---|
| FSH + rhLH | 7.0 |
| Follicle-stimulating Hormone (FSH) | 7.8 |
Total number of obtained embryos with maximum 3 inseminated oocytes was calculated. (NCT01071200)
Timeframe: Day 3 post-hCG (Embryo transfer [ET])
| Intervention | embryos (Number) |
|---|---|
| FSH + rhLH | 142 |
| Follicle-stimulating Hormone (FSH) | 158 |
OHSS is an exaggerated systemic response to ovarian stimulation characterized by a wide spectrum of clinical and laboratory manifestations. It is classified as mild, moderate or severe according to the degree of abdominal distention, ovarian enlargement and respiratory, haemodynamic and metabolic complications. (NCT01071200)
Timeframe: Baseline (S8) until 12-18 day post-hCG and/or Week 7
| Intervention | cycles (Number) |
|---|---|
| FSH + rhLH | 1 |
| Follicle-stimulating Hormone (FSH) | 0 |
Mean number of metaphase II oocytes was counted for participants undergoing ovum pick up for IntraCytoplasmic Sperm Injection (ICSI). ICSI is a procedure in which a single spermatozoon is injected into the oocyte cytoplasm. Metaphase II stage of the oocyte was classified as the time at which the first polar body was observed microscopically. Metaphase II oocytes are a sub-group of the total number of oocytes. (NCT01071200)
Timeframe: 34-36 hours post-hCG (OPU)
| Intervention | Metaphase II Oocytes (Mean) |
|---|---|
| FSH + rhLH | 5.1 |
| Follicle-stimulating Hormone (FSH) | 5.7 |
Fertilization rate was measured as the ratio between number of fertilized oocytes and number of inseminated oocytes (maximum 3). (NCT01071200)
Timeframe: 12-18 day post-hCG and/or Week 7
| Intervention | ratio (Mean) |
|---|---|
| FSH + rhLH | 0.85 |
| Follicle-stimulating Hormone (FSH) | 0.89 |
(NCT01071200)
Timeframe: Baseline (Stimulation day 8 [S8]) until hCG day
| Intervention | IU (Mean) | |
|---|---|---|
| Baseline (S8) | Baseline (S8) until hCG day | |
| Follicle-stimulating Hormone (FSH) | 703.3 | 318.5 |
| FSH + rhLH | 904.6 | 388.5 |
OHSS is an exaggerated systemic response to ovarian stimulation characterized by a wide spectrum of clinical and laboratory manifestations. It is classified as mild, moderate or severe according to the degree of abdominal distention, ovarian enlargement and respiratory, haemodynamic and metabolic complications. (NCT01071200)
Timeframe: Baseline (S8) until 12-18 day post-hCG and/or Week 7
| Intervention | participants (Number) | ||
|---|---|---|---|
| Mild OHSS | Moderate OHSS | Severe OHSS | |
| Follicle-stimulating Hormone (FSH) | 0 | 0 | 0 |
| FSH + rhLH | 0 | 1 | 0 |
(NCT01071200)
Timeframe: Baseline (S8) until hCG day
| Intervention | IU (Mean) | |
|---|---|---|
| Total FSH dose | Total r-hLH dose | |
| Follicle-stimulating Hormone (FSH) | 1595.0 | 0 |
| FSH + rhLH | 1434.0 | 575.9 |
(NCT01071200)
Timeframe: Baseline (S8) and hCG day
| Intervention | picogram/milliter (pg/mL) (Mean) | |
|---|---|---|
| Baseline (n = 59,59) | Change at hCG day (n = 40,47) | |
| Follicle-stimulating Hormone (FSH) | 518.9 | 1179.9 |
| FSH + rhLH | 516.1 | 1391.6 |
(NCT01071200)
Timeframe: 12-18 day post-hCG and/or Week 7
| Intervention | percentage of participants (Number) |
|---|---|
| FSH + rhLH | 29.9 |
| Follicle-stimulating Hormone (FSH) | 30.8 |
Implantation is the attachment and subsequent penetration by the zona-free blastocyst (usually in the endometrium) that starts five to seven days after fertilization. (NCT01071200)
Timeframe: 12-18 day post-hCG and/or Week 7
| Intervention | percentage of participants (Number) |
|---|---|
| FSH + rhLH | 13.38 |
| Follicle-stimulating Hormone (FSH) | 11.39 |
Clinical pregnancy is defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy. (NCT01071200)
Timeframe: 12-18 day post-hCG and/or Week 7
| Intervention | percentage of participants (Number) |
|---|---|
| FSH + rhLH | 23.9 |
| Follicle-stimulating Hormone (FSH) | 18.5 |
Embryo transfer is the procedure in which one or more embryos are placed in the uterus or Fallopian tube. (NCT01071200)
Timeframe: Day 3 post-hCG (ET)
| Intervention | embryos (Number) |
|---|---|
| FSH + rhLH | 60 |
| Follicle-stimulating Hormone (FSH) | 63 |
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. (NCT01075815)
Timeframe: Baseline up to 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])
| Intervention | participants (Number) |
|---|---|
| rFSH + rhLH | 19 |
| rFSH | 9 |
Ovarian stimulation included from first rFSH injection (S1) until day on which r-hCG was administered (r-hCG day). This period was divided into 2 parts: the first period in which 300 International Unit (IU) rFSH dose was constant and which covered from S1 to Day 4 of stimulation period (S4); the second period in which the rFSH dose could be adjusted depending on the ovarian response and which began on S4 and finished on the day on which the criteria for administration of r-hCG to induce the final follicular maturation were met. (NCT01075815)
Timeframe: S1 up to r-hCG day (end of stimulation cycle [approximately 28 days])
| Intervention | Days (Mean) |
|---|---|
| rFSH + rhLH | 9.7 |
| rFSH | 9.8 |
Total number of births per reporting group was calculated. (NCT01075815)
Timeframe: Up to 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])
| Intervention | births (Number) |
|---|---|
| rFSH + rhLH | 10 |
| rFSH | 9 |
(NCT01075815)
Timeframe: 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])
| Intervention | IU (Mean) |
|---|---|
| rFSH + rhLH | 2812.2 |
| rFSH | 2970.3 |
Poor response was defined as 3 or less follicles of greater than or equal to 12 mm developing following at least 7 days of study treatment. (NCT01075815)
Timeframe: Up to 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])
| Intervention | cycles (Number) |
|---|---|
| rFSH + rhLH | 4 |
| rFSH | 1 |
OHSS is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting. (NCT01075815)
Timeframe: Baseline up to 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])
| Intervention | participants (Number) |
|---|---|
| rFSH + rhLH | 1 |
| rFSH | 0 |
Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy. (NCT01075815)
Timeframe: 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])
| Intervention | participants (Number) |
|---|---|
| rFSH + rhLH | 10 |
| rFSH | 10 |
Number of mature oocytes retrieved per reporting group on the day of OPU (34-38 hours post r-hCG day (end of stimulation cycle [approximately 28 days]) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body. The nuclear maturity was evaluated based on the presence of a germinal vesicle (GV) or whether oocytes were in metaphase I (Meta-I) or II (Meta-II) stage. (NCT01075815)
Timeframe: 34-38 hours post r-hCG day (end of stimulation cycle [approximately 28 days])
| Intervention | mature oocytes (Number) |
|---|---|
| rFSH + rhLH | 234 |
| rFSH | 271 |
Oocytes were fertilized using Intra-cytoplasmic Sperm Injection (ICSI) technique which is an in-vitro fertilization procedure in which a single sperm is injected directly into an egg under a microscope. The appearance of two 2PN is the first sign of successful fertilization as observed during in vitro fertilization, and is usually observed after ICSI. The zygote is then termed 2PN. (NCT01075815)
Timeframe: 34-38 hours post r-hCG day (end of stimulation cycle [approximately 28 days])
| Intervention | 2PN oocytes (Number) |
|---|---|
| rFSH + rhLH | 128 |
| rFSH | 136 |
OHSS is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting. (NCT01075815)
Timeframe: Baseline up to 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])
| Intervention | cycles (Number) |
|---|---|
| rFSH + rhLH | 1 |
| rFSH | 0 |
Mean number of oocytes retrieved per reporting group on the day of OPU (34-38 hours post r-hCG day (end of stimulation cycle [approximately 28 days]) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body. (NCT01075815)
Timeframe: 34-38 hours post r-hCG day (end of stimulation cycle [approximately 28 days])
| Intervention | oocytes (Mean) |
|---|---|
| rFSH + rhLH | 5.9 |
| rFSH | 7.7 |
(NCT01075815)
Timeframe: r-hCG day (end of stimulation cycle [approximately 28 days])
| Intervention | follicles (Mean) |
|---|---|
| rFSH + rhLH | 7.7 |
| rFSH | 8.7 |
Implantation rate was measured as the number of gestational sacs observed, divided by the number of embryos transferred. (NCT01075815)
Timeframe: Day 35-42 post ovum pick-up (OPU) (34-38 hours post recombinant human choriogonadotropin day {end of stimulation cycle}[approximately 28 days])
| Intervention | sacs per embryo (Mean) |
|---|---|
| rFSH + rhLH | 0.2 |
| rFSH | 0.2 |
Embryos were graded according to Spanish Association for the Study of Reproductive Biology (ASEBIR) criteria into different categories: (A) optimal quality with maximum capacity for implantation, (B) good quality with a high capacity for implantation, (C) regular with low possibility of implantation and (D) poor quality with very little possibility of implantation. (NCT01075815)
Timeframe: Day 2-3 post OPU (34-38 hours post r-hCG day {end of stimulation cycle}[approximately 28 days])
| Intervention | embyros (Number) | ||
|---|---|---|---|
| A + B (good quality) | C + D (poor quality) | Total embryos | |
| rFSH | 65 | 73 | 138 |
| rFSH + rhLH | 69 | 56 | 125 |
Biochemical pregnancy was defined as a pregnancy diagnosed only by the detection of hCG in serum or urine and that does not develop into a clinical pregnancy. (NCT01075815)
Timeframe: 2 months after OPU (34-38 hours post r-hCG day {end of stimulation cycle} [approximately 28 days])
| Intervention | participants (Number) |
|---|---|
| rFSH + rhLH | 11 |
| rFSH | 10 |
(NCT01075815)
Timeframe: r-hCG day (end of stimulation cycle [approximately 28 days])
| Intervention | picogram/milliter (pg/mL) (Mean) |
|---|---|
| rFSH + rhLH | 1890.2 |
| rFSH | 1621 |
Number of oocytes retrieved per reporting group on the day of ovum pick-up (OPU) (34-38 hours post r-hCG day) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization (IVF) in order to remove oocytes from the ovary of the female participant, enabling fertilization outside the body. (NCT01079949)
Timeframe: Ovum pick-up (OPU) day (34-38 hours post r-hCG day [end of stimulation cycle {approximately 9 days}])
| Intervention | oocytes (Mean) |
|---|---|
| r-hFSH + r-hLH | 10 |
| r-hFSH | 10 |
(NCT01079949)
Timeframe: r-hCG day (end of stimulation cycle [approximately 9 days])
| Intervention | follicles (Mean) |
|---|---|
| r-hFSH + r-hLH | 8.6 |
| r-hFSH | 7.4 |
Oocytes were fertilized using ICSI technique which is an in-vitro fertilization procedure in which a single sperm is injected directly into an egg under a microscope. The appearance of 2PN is the first sign of successful fertilization as observed during in vitro fertilization, and is usually observed after ICSI. The zygote is then termed 2PN. Fertilized oocytes at stage higher then 2PN are those oocytes which consist more than 2 pronuclei like oocyte having 3 pronuclei termed as 3PN, oocyte having 4 pronuclei termed as 4PN. (NCT01079949)
Timeframe: Day 35-42 post r-hCG day (end of stimulation cycle [approximately 9 days])
| Intervention | oocytes (Number) |
|---|---|
| r-hFSH + r-hLH | 210 |
| r-hFSH | 210 |
Oocytes were fertilized using Intra-cytoplasmic Sperm Injection (ICSI) technique which is an in-vitro fertilization procedure in which a single sperm is injected directly into an egg under a microscope. The appearance of 2PN is the first sign of successful fertilization as observed during in vitro fertilization, and is usually observed after ICSI. The zygote is then termed 2PN. (NCT01079949)
Timeframe: OPU day (34-38 hours post r-hCG day [end of stimulation cycle {approximately 9 days}])
| Intervention | 2PN oocytes (Number) |
|---|---|
| r-hFSH + r-hLH | 203 |
| r-hFSH | 203 |
Ovarian Hyper Stimulation Syndrome (OHSS) is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting. (NCT01079949)
Timeframe: S1 to 1 month ± 1 week post r-hCG day (end of stimulation cycle [approximately 9 days])
| Intervention | cycles (Number) |
|---|---|
| r-hFSH + r-hLH | 0 |
| r-hFSH | 0 |
Implantation rate was measured as the number of gestational sacs observed, divided by the number of embryos transferred multiplied by 100. (NCT01079949)
Timeframe: Day 35-42 post OPU (34-38 hours post r-hCG day {end of stimulation cycle [approximately 9 days]})
| Intervention | percent sacs per embryo (Mean) |
|---|---|
| r-hFSH + r-hLH | 30 |
| r-hFSH | 20 |
(NCT01079949)
Timeframe: OPU day (34-38 hours post r-hCG day [end of stimulation cycle {approximately 9 days}])
| Intervention | nanogram/milliliter (ng/mL) (Mean) |
|---|---|
| r-hFSH + r-hLH | 5.9 |
| r-hFSH | 6.0 |
(NCT01079949)
Timeframe: OPU day (34-38 hours post r-hCG day [end of stimulation cycle {approximately 9 days}])
| Intervention | pg/mL (Mean) |
|---|---|
| r-hFSH + r-hLH | 454508.0 |
| r-hFSH | 349605.3 |
(NCT01079949)
Timeframe: r-hCG day (end of stimulation cycle [approximately 9 days])
| Intervention | picogram/milliter (pg/mL) (Mean) |
|---|---|
| r-hFSH + r-hLH | 1813.9 |
| r-hFSH | 1362.9 |
Number of mature oocytes retrieved per reporting group on the day of OPU (34-38 hours post r-hCG day) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body. The nuclear maturity is assessed based on the presence of a germinal vesicle (GV) or whether oocytes were in metaphase I (Meta-I) or II (Meta-II) stage or atretic. (NCT01079949)
Timeframe: OPU day (34-38 hours post r-hCG day [end of stimulation cycle {approximately 9 days}])
| Intervention | mature oocytes (Number) | |||
|---|---|---|---|---|
| Geminal vesicle (GV) | Meta-I | Meta-II | Atresic | |
| r-hFSH | 37 | 26 | 292 | 4 |
| r-hFSH + r-hLH | 60 | 44 | 275 | 10 |
Endometrial thickness measurement was performed on the day of r-hCG administration. (NCT01079949)
Timeframe: r-hCG day (end of stimulation cycle [approximately 9 days])
| Intervention | mm (Mean) |
|---|---|
| r-hFSH + r-hLH | 9.5 |
| r-hFSH | 8.8 |
Embryos were classified into 5 different grades (1 to 5) based on their capacity of implantation. Grade 1 embryos were those with best capacity of implantation and Grade 5 embryos were those with worst capacity of implantation. (NCT01079949)
Timeframe: Day 2-3 post OPU (34-38 hours post r-hCG day [end of stimulation cycle {approximately 9 days}])
| Intervention | embryos (Number) | ||||
|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | |
| r-hFSH | 39 | 35 | 49 | 13 | 70 |
| r-hFSH + r-hLH | 22 | 46 | 56 | 18 | 64 |
(NCT01079949)
Timeframe: OPU day (34-38 hours post r-hCG day [end of stimulation cycle {approximately 9 days}])
| Intervention | milli international unit (mIU)/mL (Mean) | ||
|---|---|---|---|
| LH levels at OPU | FSH levels at OPU | hCG levels at OPU | |
| r-hFSH | 2.0 | 9.0 | 136.2 |
| r-hFSH + r-hLH | 1.8 | 8.3 | 142.2 |
(NCT01079949)
Timeframe: Day 1 of stimulation period (S1) up to r-hCG day (end of stimulation cycle [approximately 9 days])
| Intervention | IU (Mean) |
|---|---|
| r-hFSH + r-hLH | 2916.1 |
| r-hFSH | 2861.7 |
Ovarian Hyper Stimulation Syndrome (OHSS) is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting. (NCT01079949)
Timeframe: S1 to 1 month ± 1 week post r-hCG day (end of stimulation cycle [approximately 9 days])
| Intervention | participants (Number) |
|---|---|
| r-hFSH + r-hLH | 0 |
| r-hFSH | 0 |
Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy. (NCT01079949)
Timeframe: Day 35-42 post r-hCG day (end of stimulation cycle [approximately 9 days])
| Intervention | participants (Number) |
|---|---|
| r-hFSH + r-hLH | 14 |
| r-hFSH | 12 |
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. (NCT01079949)
Timeframe: S1 to 1 month ± 1 week post r-hCG day (end of stimulation cycle [approximately 9 days])
| Intervention | participants (Number) |
|---|---|
| r-hFSH + r-hLH | 3 |
| r-hFSH | 0 |
Poor response was defined as 3 or less follicles of greater than or equal to 12 mm developing following at least 7 days of study treatment. (NCT01079949)
Timeframe: r-hCG day (end of stimulation cycle [approximately 9 days])
| Intervention | participants (Number) |
|---|---|
| r-hFSH + r-hLH | 1 |
| r-hFSH | 3 |
Ovarian stimulation included from first r-hFSH injection (S1) until day on which r-hCG was administered (r-hCG day). (NCT01079949)
Timeframe: Day 1 of stimulation period (S1) up to r-hCG day (end of stimulation cycle [approximately 9 days])
| Intervention | days (Mean) |
|---|---|
| r-hFSH + r-hLH | 9.4 |
| r-hFSH | 8.8 |
Multiple pregnancy is a pregnancy where more than one fetus develops simultaneously in the womb. There are two types of twinning-identical and fraternal. Identical twins represent the splitting of a single fertilized zygote (union of two gametes or male/female sex cells that produce a developing fetus) into two separate individuals. (NCT01081626)
Timeframe: Day 0 (first dose) up to Days 35-42 post hCG administration (end of stimulation cycle {less than or equal to [<=] 35 days})
| Intervention | participants (Number) |
|---|---|
| Chronic Low Dose (CLD) Protocol | 3 |
| Low Dose (LD) Protocol | 1 |
Multi-follicular development was defined as the development of more than 3 follicles >= 15 mm in diameter at or before Days 35-42 of stimulation period assessed by means of a transvaginal ultrasound scan. (NCT01081626)
Timeframe: Day 0 (first dose) up to Days 35-42 post hCG administration (end of stimulation cycle {less than or equal to [<=] 35 days})
| Intervention | participants (Number) |
|---|---|
| Chronic Low Dose (CLD) Protocol | 17 |
| Low Dose (LD) Protocol | 15 |
Participants who did not show any injection site reactions such as pain, redness, bruises, swelling and irritation were considered to have injection tolerability. (NCT01081626)
Timeframe: Day 0 (first dose) up to Days 35-42 post hCG administration (end of stimulation cycle {less than or equal to [<=] 35 days})
| Intervention | participants (Number) |
|---|---|
| Chronic Low Dose (CLD) Protocol | 54 |
| Low Dose (LD) Protocol | 54 |
Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy. (NCT01081626)
Timeframe: Day 0 (first dose) up to Days 35-42 post hCG administration (end of stimulation cycle {less than or equal to [<=] 35 days})
| Intervention | participants (Number) |
|---|---|
| Chronic Low Dose (CLD) Protocol | 19 |
| Low Dose (LD) Protocol | 18 |
Participants with cancelled cycles were those who did not achieve adequate follicular formation (at least 17 mm) for hCG administration. (NCT01081626)
Timeframe: End of stimulation cycle (less than or equal to [<=] 35 days)
| Intervention | participants (Number) |
|---|---|
| Chronic Low Dose (CLD) Protocol | 19 |
| Low Dose (LD) Protocol | 19 |
(NCT01081626)
Timeframe: End of stimulation cycle (less than or equal to [<=] 35 days)
| Intervention | Days (Mean) |
|---|---|
| Chronic Low Dose (CLD) Protocol | 13.68 |
| Low Dose (LD) Protocol | 12.85 |
Ease of use of Gonal-f® pen was assessed through a questionnaire consisting of 23 questions and the number of participants who responded to the questionnaire was recorded. (NCT01081626)
Timeframe: On hCG administration day (end of stimulation cycle {less than or equal to [<=] 35 days})
| Intervention | participants (Number) |
|---|---|
| Chronic Low Dose (CLD) Protocol | 58 |
| Low Dose (LD) Protocol | 75 |
AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. (NCT01081626)
Timeframe: Day 0 (first dose) up to Days 35-42 post hCG administration (end of stimulation cycle {less than or equal to [<=] 35 days})
| Intervention | participants (Number) |
|---|---|
| Chronic Low Dose (CLD) Protocol | 30 |
| Low Dose (LD) Protocol | 31 |
(NCT01081626)
Timeframe: End of stimulation cycle (less than or equal to [<=] 35 days)
| Intervention | participants (Number) |
|---|---|
| Chronic Low Dose (CLD) Protocol | 94 |
| Low Dose (LD) Protocol | 91 |
(NCT01081626)
Timeframe: End of stimulation cycle (less than or equal to [<=] 35 days
| Intervention | IU (Mean) |
|---|---|
| Chronic Low Dose (CLD) Protocol | 1119.41 |
| Low Dose (LD) Protocol | 1155.47 |
Mono-follicular development was defined as the development of only 1 follicle of greater than or equal to (>=) 17 millimeter (mm) diameter and no more than 2 other follicles larger than 14 mm in diameter at or before Days 35-42 of stimulation period assessed by means of a transvaginal ultrasound scan. (NCT01081626)
Timeframe: Day 0 (first dose) up to Days 35-42 post human chorionic gonadotropin [hCG] administration (end of stimulation cycle {less than or equal to [<=] 35 days})
| Intervention | percentage of participants (Number) |
|---|---|
| Chronic Low Dose (CLD) Protocol | 56.55 |
| Low Dose (LD) Protocol | 55.20 |
The average change was calculated by assessing the E2 levels on 4 timepoints until day 14 (day 1, day 5, day 10, day 14 [hCG administration day]). (NCT01084265)
Timeframe: up to Day 14
| Intervention | pg/mL per day (Mean) |
|---|---|
| Recombinant Human Luteinizing Hormone (Luveris) | 71.03 |
(NCT01084265)
Timeframe: Day 14
| Intervention | follicles (Mean) |
|---|---|
| Recombinant Human Luteinizing Hormone (Luveris) | 2.13 |
(NCT01084265)
Timeframe: Day 14
| Intervention | participants (Number) |
|---|---|
| Recombinant Human Luteinizing Hormone (Luveris) | 23 |
The three indices were defined as; Index 1: diameter of at least one follicle is greater than 17 mm; Index 2: serum oestradiol (E2) level in blood serum above 109 picogram/ milliliter (pg/mL) on human chorionic gonadotropin (hCG) injection day; Index 3: participant refuses to take hCG injection for the concern of ovarian hyperstimulation syndrome (OHSS) or participant is pregnant. A subset of these participants met Index 3. (NCT01084265)
Timeframe: Day 14
| Intervention | participants (Number) |
|---|---|
| Recombinant Human Luteinizing Hormone (Luveris) | 23 |
(NCT01084265)
Timeframe: Day 14
| Intervention | participants (Number) |
|---|---|
| Recombinant Human Luteinizing Hormone (Luveris) | 23 |
Participant refused to take hCG injection for the concern of OHSS or the participant was pregnant. (NCT01084265)
Timeframe: Day 14
| Intervention | participants (Number) | |
|---|---|---|
| Refused due to concern of OHSS | Refused due to pregnancy | |
| Recombinant Human Luteinizing Hormone (Luveris) | 0 | 10 |
AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. (NCT01084265)
Timeframe: Day 14
| Intervention | participants (Number) | |
|---|---|---|
| Adverse Events | Serious Adverse Events | |
| Recombinant Human Luteinizing Hormone (Luveris) | 0 | 0 |
Biochemical pregnancy was defined as a pregnancy diagnosed only by the detection of hCG in serum or urine and that does not develop into a clinical pregnancy. Clinical pregnancy was defined as a pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy. (NCT01084265)
Timeframe: Day 14
| Intervention | participants (Number) | |
|---|---|---|
| Biochemical Pregnancies | Clinical Pregnancies | |
| Recombinant Human Luteinizing Hormone (Luveris) | 1 | 9 |
(NCT01084265)
Timeframe: Day 14
| Intervention | follicles (Mean) |
|---|---|
| Recombinant Human Luteinizing Hormone (Luveris) | 3.57 |
Embryos were classified into 5 different grades (1 to 5) based on their capacity of implantation. Grade 1 embryos were those with best capacity of implantation and Grade 5 embryos were those with worst capacity of implantation. Mean number of embryos for each of the 5 grades were reported. (NCT01110707)
Timeframe: Day 2-3 post r-hCG administration
| Intervention | embryos (Mean) | ||||
|---|---|---|---|---|---|
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade 5 | |
| r-hFSH + r-hLH | 1.1 | 1.1 | 0.5 | 0.3 | 0.3 |
| r-hFSH Alone | 1.3 | 1.2 | 0.5 | 0.2 | 0.2 |
Mean number of follicles as per the following categories were presented: >=14 mm and less than (<) 16 mm; >=16 mm and <18 mm and >=18 mm. (NCT01110707)
Timeframe: r-hCG day (end of stimulation cycle [approximately 28 days])
| Intervention | Follicles (Mean) | ||
|---|---|---|---|
| >=14 mm and <16 mm | >=16 mm and <18 mm | >=18 mm | |
| r-hFSH + r-hLH | 2.2 | 2.3 | 4.0 |
| r-hFSH Alone | 2.1 | 2.7 | 3.7 |
Oocytes were fertilized using Intra-cytoplasmic Sperm Injection (ICSI) technique which is an in-vitro fertilization procedure in which a single sperm is injected directly into an egg under a microscope. The appearance of 2PN is the first sign of successful fertilization as observed during in vitro fertilization, and is usually observed after ICSI. The zygote is then termed 2PN. (NCT01110707)
Timeframe: 36 hours post r-hCG administration
| Intervention | 2PN oocytes (Mean) |
|---|---|
| r-hFSH + r-hLH | 3.1 |
| r-hFSH Alone | 3.3 |
If the subject was not administered with r-hCG and withdrew prematurely from the trail, it is considered as cycle cancellation (NCT01110707)
Timeframe: r-hCG day (end of stimulation cycle [approximately 28 days])
| Intervention | cycles (Number) |
|---|---|
| r-hFSH + r-hLH | 0 |
| r-hFSH Alone | 3 |
Mean number of M-II oocytes were calculated for subjects undergoing ovum pick up for Intra-cytoplasmic Sperm Injection (ICSI). ICSI is an in-vitro fertilization procedure in which a single sperm is injected directly into an egg under a microscope. Metaphase II stage of the oocyte was classified as the time at which the first polar body was observed microscopically. Metaphase II oocytes are a sub-group of the total number of oocytes. (NCT01110707)
Timeframe: 36 hours post r-hCG administration
| Intervention | M-II oocytes (Mean) |
|---|---|
| r-hFSH + r-hLH | 6.7 |
| r-hFSH Alone | 7.0 |
Oocyte retrieval is a technique used in in-vitro fertilization (IVF) in order to remove oocyte from the ovary of the female subject, enabling fertilization outside the body. (NCT01110707)
Timeframe: 36 hours post r-hCG administration
| Intervention | Oocytes (Mean) |
|---|---|
| r-hFSH + r-hLH | 8.3 |
| r-hFSH Alone | 8.9 |
Clinical pregnancy rate defined as the percentage of subjects with a ultrasound confirmation of a gestational sac, with or without fetal heart activity. (NCT01110707)
Timeframe: 35-42 days post r-hCG administration
| Intervention | Percentage of subjects (Number) |
|---|---|
| r-hFSH + r-hLH | 27.0 |
| r-hFSH Alone | 14.7 |
Embryo implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100. (NCT01110707)
Timeframe: 35-42 days post r-hCG administration
| Intervention | Percent sacs per embryo (Number) |
|---|---|
| r-hFSH + r-hLH | 18.1 |
| r-hFSH Alone | 11.3 |
(NCT01110707)
Timeframe: r-hCG day (end of stimulation cycle [approximately 28 days])
| Intervention | mm (Mean) |
|---|---|
| r-hFSH + r-hLH | 6.0 |
| r-hFSH Alone | 5.9 |
Number of embryos per blastocysts transferred (NCT01121666)
Timeframe: Day of embryo transfer, either 2, 3 or 5 days after oocyte retrieval
| Intervention | embryos per blastocysts transferred (Mean) |
|---|---|
| AFOLIA-150 (Follitropin Alfa) | 1.5 |
| Gonal-f® (Follitropin Alfa) | 1.6 |
Ongoing pregnancy per embryo transfer. Presence of at least one viable fetus 10 weeks after embryo transfer. (NCT01121666)
Timeframe: 10 weeks after embryo transfer
| Intervention | Ongoing pregnancies (Number) |
|---|---|
| AFOLIA-150 (Follitropin Alfa) | 22 |
| Gonal-f® (Follitropin Alfa) | 9 |
Ongoing pregnancy per embryo transfer. Presence of at least one viable fetus 10 weeks after embryo transfer. (NCT01121666)
Timeframe: Ten weeks after embryo transfer
| Intervention | Ongoing pregnancies (Number) |
|---|---|
| AFOLIA-150 (Follitropin Alfa) | 84 |
| Gonal-f® (Follitropin Alfa) | 51 |
"Good response was defined as patients with an oocyte retrieval of four or more oocytes" (NCT01121666)
Timeframe: Until child birth/miscarriage, up to the end of the study
| Intervention | Participants (Number) |
|---|---|
| AFOLIA-150 (Follitropin Alfa) | 217 |
| Gonal-f® (Follitropin Alfa) | 107 |
Number of patients with cycle cancellation was assessed. (NCT01121666)
Timeframe: Until child birth/miscarriage, up to the end of the study
| Intervention | Number of patients (Number) |
|---|---|
| AFOLIA-150 (Follitropin Alfa) | 13 |
| Gonal-f® (Follitropin Alfa) | 5 |
(NCT01121666)
Timeframe: Day 1, 2, 3 and 5 of OPU/fertilisation
| Intervention | Patients with cryopreservation (Number) |
|---|---|
| AFOLIA-150 (Follitropin Alfa) | 103 |
| Gonal-f® (Follitropin Alfa) | 55 |
"As soon as ovulation criteria were reached, HCG was given to trigger ovulation and 34-36 hours later, oocytes were retrieved. If criteria for ovulation triggering could not be reached by FSH stimulation on day 16, treatment was to be stopped.~The equivalence in the number of retrieved oocytes was tested using a pre-determined clinical equivalence margin of +/- 2.9 oocytes" (NCT01121666)
Timeframe: 34-36 hours after hCG administration and after maximum 16 days of r-hFSH treatment
| Intervention | Number of retrieved oocytes (Mean) |
|---|---|
| AFOLIA-150 (Follitropin Alfa) | 10.8 |
| Gonal-f® (Follitropin Alfa) | 10.6 |
"As soon as ovulation criteria were reached, HCG was given to trigger ovulation and 34-36 hours later, oocytes were retrieved. If criteria for ovulation triggering could not be reached by FSH stimulation on day 16, treatment was to be stopped.~The equivalence in the number of retrieved oocytes was tested using a pre-determined clinical equivalence margin of +/- 2.9 oocytes" (NCT01121666)
Timeframe: 34-36 hours after hCG administration and after maximum 16 days of r-hFSH treatment
| Intervention | Number of retrieved oocytes (Mean) |
|---|---|
| AFOLIA-150 (Follitropin Alfa) | 10.7 |
| Gonal-f® (Follitropin Alfa) | 10.4 |
Mean duration of stimulation was assessed. (NCT01121666)
Timeframe: At the day of hCG administration, up to 16 days
| Intervention | days (Mean) |
|---|---|
| AFOLIA-150 (Follitropin Alfa) | 10.6 |
| Gonal-f® (Follitropin Alfa) | 10.7 |
Patients with liveborn children (NCT01121666)
Timeframe: After childbirth with questionnaire
| Intervention | Patients with liveborn children (Number) |
|---|---|
| AFOLIA-150 (Follitropin Alfa) | 80 |
| Gonal-f® (Follitropin Alfa) | 51 |
Fertilisation rate was assessed (NCT01121666)
Timeframe: 1 day after ovum pick-up
| Intervention | percentage of oocytes (Mean) |
|---|---|
| AFOLIA-150 (Follitropin Alfa) | 66.1 |
| Gonal-f® (Follitropin Alfa) | 64.0 |
"Main embryo quality parameter mean number of blastomeres" (NCT01121666)
Timeframe: Day 2 of OPU/fertilisation
| Intervention | Number of blastomeres at day 3 (Mean) |
|---|---|
| AFOLIA-150 (Follitropin Alfa) | 6.6 |
| Gonal-f® (Follitropin Alfa) | 6.4 |
"Main embryo quality parameter absence of multinucleation observed." (NCT01121666)
Timeframe: Day 3
| Intervention | Percentage of absent multinucleation (Number) |
|---|---|
| AFOLIA-150 (Follitropin Alfa) | 93.6 |
| Gonal-f® (Follitropin Alfa) | 93.9 |
Presence of at least one intrauterine gestational sac. (NCT01121666)
Timeframe: Five to six weeks after oocyte retrieval
| Intervention | Clinical pregnancies (Number) |
|---|---|
| AFOLIA-150 (Follitropin Alfa) | 25 |
| Gonal-f® (Follitropin Alfa) | 10 |
Presence of at least one intrauterine gestational sac. (NCT01121666)
Timeframe: Five to six weeks after oocyte retrieval
| Intervention | Clinical pregnancies (Number) |
|---|---|
| AFOLIA-150 (Follitropin Alfa) | 90 |
| Gonal-f® (Follitropin Alfa) | 55 |
The nuclear maturity was assessed (Germinal vesicle, Metaphase I, Metaphase II). (NCT01121666)
Timeframe: After oocyte retrieval, 34 to 36 hours after hCG administration
| Intervention | Percentage of cells (Number) | ||
|---|---|---|---|
| Germinal vesicle | Metaphase I | Metaphase II | |
| AFOLIA-150 (Follitropin Alfa) | 9.5 | 7.2 | 83.4 |
| Gonal-f® (Follitropin Alfa) | 9.1 | 7.7 | 83.3 |
Defined as fetal sac per embryo transferred. (NCT01121666)
Timeframe: Five to six weeks after oocyte retrieval
| Intervention | Percentage of implantations (Number) |
|---|---|
| AFOLIA-150 (Follitropin Alfa) | 31.8 |
| Gonal-f® (Follitropin Alfa) | 36.7 |
The maturity of the cumulus oophorus was assessed. (NCT01121666)
Timeframe: After oocyte retrieval, 34 to 36 hours after hCG administration
| Intervention | Percentage of cumulus oophori (Number) | ||
|---|---|---|---|
| very mature | mature | immature | |
| AFOLIA-150 (Follitropin Alfa) | 9.1 | 75.7 | 14.5 |
| Gonal-f® (Follitropin Alfa) | 9.4 | 75.3 | 14.2 |
Number of patients with ovum pick-up (NCT01121666)
Timeframe: 34-36 hours after hCG administration
| Intervention | Participants (Number) | |
|---|---|---|
| day 2 | day 3 | |
| AFOLIA-150 (Follitropin Alfa) | 82 | 53 |
| Gonal-f® (Follitropin Alfa) | 36 | 28 |
The number and size of follicles 12 mm or over in diameter at day 8 of stimulation were evaluated as secondary end-point. (NCT01121666)
Timeframe: Day 8 of stimulation
| Intervention | Number of follicles (Mean) | ||
|---|---|---|---|
| ≥ 12 mm | ≥ 15 mm | ≥ 17 mm | |
| AFOLIA-150 (Follitropin Alfa) | 11.8 | 8.3 | 4.9 |
| Gonal-f® (Follitropin Alfa) | 11.1 | 7.7 | 4.5 |
The serum concentration of oestradiol was assessed at day 8 and the day of hCG administration. (NCT01121666)
Timeframe: Day 8 of stimulation and at the day of hCG administration (after max. 16 days of r-FSH treatment)
| Intervention | pmol/ L (Mean) | |
|---|---|---|
| Day of hCG administration | Day 8 | |
| AFOLIA-150 (Follitropin Alfa) | 8982.3 | 3958.9 |
| Gonal-f® (Follitropin Alfa) | 7704.2 | 3234.0 |
Total dose of r-hFSH required was assessed. (NCT01121666)
Timeframe: Day of hCG administration (after maximum 16 days of r-hFSH treatment)
| Intervention | IU (Mean) |
|---|---|
| AFOLIA-150 (Follitropin Alfa) | 1555.7 |
| Gonal-f® (Follitropin Alfa) | 1569.2 |
Number of patients with transferred blastocysts (NCT01121666)
Timeframe: At day 4 and 5
| Intervention | Participants (Number) | |
|---|---|---|
| day 4 | day 5 | |
| AFOLIA-150 (Follitropin Alfa) | 10 | 76 |
| Gonal-f® (Follitropin Alfa) | 2 | 46 |
The number of cumulus oocyte-complexes retrieved was summarized per treatment group and per attempt (= per started COS cycle). (NCT01144416)
Timeframe: Maximally 21 days after the start of study treatment.
| Intervention | Number of oocytes (Mean) |
|---|---|
| Single Injection of 150 µg SCH 900962/MK-8962 | 10.7 |
| Daily 300 IU recFSH | 10.3 |
"Grade II (moderate OHSS) is characterized by distinct ovarian cysts (ovary size 8-10 cm), accompanied by abdominal pain and tension, nausea, vomiting, diarrhea.~Grade III (severe OHSS) is characterized by enlarged cystic ovaries (ovary size >10 cm), accompanied by ascites and occasionally hydrothorax. Abdominal tension and pain may be severe. Pronounced hydrothorax together with an abdominal cavity filled with cysts and fluid elevating the diaphragm, may cause severe breathing difficulties. Large quantities of fluid inside the cysts and in the peritoneal and pleural cavities cause hemoconcentration and increased blood viscosity. In rare cases, the syndrome may further be complicated by the occurrence of thromboembolic phenomena." (NCT01144416)
Timeframe: Up to approximately 1 month after oocyte pick-up
| Intervention | participants (Number) |
|---|---|
| Single Injection of 150 µg SCH 900962/MK-8962 | 5 |
| Daily 300 IU recFSH | 10 |
Vital pregnancy was defined as the presence of at least 1 fetus with heart activity at least 35 days (≥5 weeks) after embryo transfer in the controlled ovarian stimulation (COS) treatment cycle (NCT01144416)
Timeframe: Vital pregnancy will be assessed by ultrasound at least 35 days after embryo transfer (with a timeframe of 35-42 days). Time from start of study treatment to embryo transfer is maximally 24 days.
| Intervention | percentage of participants (Number) |
|---|---|
| Single Injection of 150 µg SCH 900962/MK-8962 | 23.9 |
| Daily 300 IU recFSH | 26.9 |
The number of participants who started stimulation but did not undergo embryo transfer due to (S)AEs will be compared between the treatment groups. (NCT01144416)
Timeframe: Up to time of embryo transfer (maximum of 24 days after start of study drug)
| Intervention | participants (Number) |
|---|---|
| Single Injection of 150 µg SCH 900962/MK-8962 | 5 |
| Daily 300 IU recFSH | 6 |
The live-birth rate is the percentage of participants with at least 1 live born infant after an ongoing pregnancy in the controlled ovarian stimulation (COS)treatment cycle relative to the number of participants treated. (NCT01144416)
Timeframe: Approximately nine months after embryo transfer
| Intervention | Percentage of participants (Number) |
|---|---|
| Single Injection of 150 µg SCH 900962/MK-8962 | 21.3 |
| Daily 300 IU recFSH | 23.4 |
The cumulative vital pregnancy rate was defined as the number of participants with at least 1 vital pregnancy in a controlled ovarian stimulation (COS) cycle in Base Study P06029 or a frozen-thawed embryo transfer (FTET) in Follow Up Study P06031, divided by the total number of participants in each Full Analysis Set (FAS) treatment group. A vital pregnancy was defined as an intrauterine pregnancy with fetal heart tones assessed at least 35 days (≥5 weeks) after embryo transfer (ET). (NCT01146418)
Timeframe: Assessed at least 35 days after ET in COS cycle in Base Study P06029 or an FTET cycle in Follow-Up Study P06031 (up to 2 years)
| Intervention | Percentage of Participants (Number) |
|---|---|
| Corifollitropin Alfa 150 μg Women/Expectant Mothers | 31.1 |
| recFSH 300 IU Women/Expectant Mothers | 33.0 |
The cumulative live-birth rate was defined as the number of participants with at least 1 live birth after ET in a COS cycle in Base Study P06029 or an FTET in Follow-Up Study P06031, divided by the total number of participants in each FAS treatment group. (NCT01146418)
Timeframe: From approximately 10 weeks after ET in Base Study P06029 or FTET in Follow-Up Study P06031 up to time of delivery (up to 2 years)
| Intervention | Percentage of Participants (Number) |
|---|---|
| Corifollitropin Alfa 150 μg Women/Expectant Mothers | 28.2 |
| recFSH 300 IU Women/Expectant Mothers | 29.5 |
Subjects were provided with the information on Pen's utilization via training session and in the form of information brochure. Subjects assessed both the methods using the following responses: satisfactory, satisfactory, unsatisfactory and very unsatisfactory. (NCT01183143)
Timeframe: Up to 1 year
| Intervention | subjects (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Training Session: Very satisfactory | Training Session: Satisfactory | Training Session: Unsatisfactory | Training Session: Very unsatisfactory | Information brochure: Very satisfactory | Information brochure: Satisfactory | Information brochure: Unsatisfactory | Information brochure: Very unsatisfactory | |
| GONAL-f® | 89 | 95 | 5 | 1 | 95 | 89 | 9 | 2 |
Number of subjects whose stimulation with the IMP resulted in the birth of a baby were reported. (NCT01183143)
Timeframe: End of Gestation period, assessed up to a maximum of 1 year
| Intervention | subjects (Number) |
|---|---|
| GONAL-f® | 41 |
Pregnancy rate was defined as the percentage of subjects with diagnosis of pregnancy, who underwent OI/IUI. Clinical pregnancy: Evidence of pregnancy by clinical or ultrasound parameters at 12 weeks after fertilization. Biochemical pregnancy: Evidence of conception based only on biochemical data in the serum or urine before ultrasound evidence of a gestational sac. Ongoing pregnancy was defined when the pregnancy had completed 20 weeks of gestation. (NCT01183143)
Timeframe: Up to 20 Weeks of Gestation
| Intervention | Percentage of subjects (Number) | ||
|---|---|---|---|
| Clinical pregnancy | Biochemical pregnancy | Ongoing pregnancy | |
| GONAL-f® | 16.5 | 16.5 | 16.5 |
Investigator evaluated the use of GONAL-f® prefilled pen in subjects as very satisfactory, satisfactory and average satisfaction. (NCT01183143)
Timeframe: Up to 1 year
| Intervention | subjects (Number) | ||
|---|---|---|---|
| Very satisfactory | Satisfactory | Average satisfaction | |
| GONAL-f® | 101 | 93 | 1 |
Local tolerance at the GONAL-f ® injection site was assessed for the presence of pain, swelling/welt, redness, itch and haematoma. (NCT01183143)
Timeframe: Up to 1 year
| Intervention | subjects (Number) | ||||
|---|---|---|---|---|---|
| Pain | Swelling/welt | Redness | Itch | Haematoma | |
| GONAL-f® | 32 | 3 | 34 | 8 | 41 |
(NCT01183143)
Timeframe: End of Stimulation period (up to a maximum 26 days)
| Intervention | embryos (Mean) |
|---|---|
| GONAL-f® | 1.8 |
(NCT01183143)
Timeframe: Up to 26 days
| Intervention | International Units (IU) (Mean) | |
|---|---|---|
| Total dose | Daily dose | |
| GONAL-f® | 1527 | 149.5 |
Stimulation duration was defined as the duration (in days) for which subjects underwent GONAL-f® treatment. (NCT01183143)
Timeframe: Up to 1 year
| Intervention | days (Median) |
|---|---|
| GONAL-f® | 10 |
(NCT01183143)
Timeframe: Up to 1 year
| Intervention | subjects (Number) |
|---|---|
| GONAL-f® | 28 |
Number of subjects who self-administered the IMP were presented in this outcome measure. (NCT01183143)
Timeframe: Up to 1 year
| Intervention | subjects (Number) |
|---|---|
| GONAL-f® | 159 |
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerged or worsened relative to baseline (i.e. present at the initial study visit) during a clinical study with an investigational product, regardless of causal relationship and even if no investigational product has been administered. (NCT01183143)
Timeframe: Up to 1 year
| Intervention | subjects (Number) |
|---|---|
| GONAL-f® | 36 |
Oocytes were fertilized using Intra-cytoplasmic Sperm Injection (ICSI) technique which is an IVF procedure in which a single sperm is injected directly into an egg under a microscope. (NCT01185704)
Timeframe: Oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
| Intervention | percent fertilized oocytes (Mean) |
|---|---|
| Day 1 Protocol | 46.22 |
| Day 7 Protocol | 46.86 |
(NCT01185704)
Timeframe: Day 1
| Intervention | International unit/liter (IU/L) (Mean) | |
|---|---|---|
| LH levels (n=58, 62) | FSH levels (n=57, 59) | |
| Day 1 Protocol | 4.87 | 4.98 |
| Day 7 Protocol | 6.84 | 6.69 |
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. A Serious Adverse Event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. To avoid the participant/event combination double-count AEs and SAEs are reported separately. (NCT01185704)
Timeframe: Day 1 up to end of study (15 days post last administration of study drug)
| Intervention | participants (Number) | |
|---|---|---|
| AEs | SAEs | |
| Day 1 Protocol | 11 | 2 |
| Day 7 Protocol | 18 | 4 |
Oocyte retrieval is a technique used in in-vitro fertilization (IVF) in order to remove oocytes from the ovary of the female participant, enabling fertilization outside the body. Oocytes were classified into 4 different categories based on their quality: mature, fractured, immature and inseminated oocytes. (NCT01185704)
Timeframe: Oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
| Intervention | oocytes (Mean) | ||||
|---|---|---|---|---|---|
| Total number of oocytes | Mature oocytes | Fractured oocytes | Immature oocytes | Inseminated oocytes | |
| Day 1 Protocol | 7.48 | 2.52 | 0.09 | 0.98 | 3.06 |
| Day 7 Protocol | 8.11 | 3.72 | 0.11 | 1.38 | 4.52 |
(NCT01185704)
Timeframe: Day 1 up to r-hCG day (end of stimulation cycle [approximately 15 days])
| Intervention | international unit (IU) (Mean) |
|---|---|
| Day 1 Protocol | 1462.50 |
| Day 7 Protocol | 1221.35 |
(NCT01185704)
Timeframe: Day 1
| Intervention | nanomolar/liter (nmol/L) (Mean) |
|---|---|
| Day 1 Protocol | 0.83 |
| Day 7 Protocol | 0.97 |
(NCT01185704)
Timeframe: Day 1
| Intervention | pg/mL (Mean) |
|---|---|
| Day 1 Protocol | 30.42 |
| Day 7 Protocol | 68.79 |
Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It excludes ectopic pregnancy. (NCT01185704)
Timeframe: 10 weeks post r-hCG day (end of stimulation cycle [approximately 15 days])
| Intervention | percentage of participants (Number) |
|---|---|
| Day 1 Protocol | 20 |
| Day 7 Protocol | 20 |
Embryo transfer is the procedure in which one or more embryos are placed in the uterus. (NCT01185704)
Timeframe: Day 2-3 post Oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
| Intervention | transferred embryos (Mean) |
|---|---|
| Day 1 Protocol | 0.95 |
| Day 7 Protocol | 1.02 |
(NCT01185704)
Timeframe: r-hCG day (end of stimulation cycle [approximately 15 days])
| Intervention | follicles (Mean) |
|---|---|
| Day 1 Protocol | 3.55 |
| Day 7 Protocol | 2.49 |
Embryo is defined as the product of the zygote, two or three days after fertilization of the oocytes. (NCT01185704)
Timeframe: Day 2-3 post oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
| Intervention | embryos (Mean) |
|---|---|
| Day 1 Protocol | 3.18 |
| Day 7 Protocol | 3.60 |
Blastocyst is an embryo, five or six days after fertilization, with an inner cell mass, outer layer of trophectoderm and a fluid-filled blastocoele cavity. (NCT01185704)
Timeframe: Day 5-6 post oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
| Intervention | blastocysts (Mean) |
|---|---|
| Day 1 Protocol | 0.26 |
| Day 7 Protocol | 0.20 |
Implantation rate per reporting group was measured as the number of gestational sacs observed, divided by the number of embryos transferred multiplied by 100. (NCT01185704)
Timeframe: 5 weeks post oocytes retrieval day (36 +/- 2 hours post r-hCG day [end of stimulation cycle {approximately 15 days}])
| Intervention | percent sacs per embryo (Number) |
|---|---|
| Day 1 Protocol | 36.90 |
| Day 7 Protocol | 32.25 |
(NCT01185704)
Timeframe: r-hCG day (end of stimulation cycle [approximately 15 days])
| Intervention | picogram/milliliter (pg/mL) (Mean) |
|---|---|
| Day 1 Protocol | 1668.86 |
| Day 7 Protocol | 1672.80 |
(NCT01185704)
Timeframe: Day 0
| Intervention | nanogram/milliliter (ng/mL) (Mean) |
|---|---|
| Day 1 Protocol | 6.27 |
| Day 7 Protocol | 7.18 |
For this secondary endpoint, participants were considered to have ovulated if serum P4 level was more than or equal to 10 ng/mL on Day 6±1 or 9±1 during the post-treatment assessment period, or if the participant became clinically pregnant. (NCT01185782)
Timeframe: On Day 6±1 or 9±1 during post-treatment assessment period
| Intervention | percent ovulation (Number) |
|---|---|
| SJ-0021 | 71.3 |
| u-hFSH | 75.8 |
(NCT01185782)
Timeframe: Start of treatment period until Day 1 of post-treatment assessment period
| Intervention | participants (Number) |
|---|---|
| SJ-0021 | 117 |
| u-hFSH | 125 |
OHSS is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting. (NCT01185782)
Timeframe: Start of treatment period to post-treatment assessment period (Day 35-42)
| Intervention | participants (Number) |
|---|---|
| SJ-0021 | 10 |
| u-hFSH | 5 |
hCG cancellation criterion was defined as the presence of 4 or more ovarian follicles with a mean diameter greater than or equal to 16 mm. If the hCG cancellation criterion was met, the administration of hCG was withheld. Otherwise, a single intramuscular dose of hCG 5000 IU (Japanese Pharmacopoeia- JP) was administered within 24 hours of the last ultrasound examination. (NCT01185782)
Timeframe: Day 1 of post-treatment assessment period
| Intervention | percent hCG cancellation (Number) |
|---|---|
| SJ-0021 | 7.0 |
| u-hFSH | 7.6 |
Clinical pregnancy was defined as existence of at least one ultrasonography confirmed gestational sac in the uterus, with or without heartbeat. (NCT01185782)
Timeframe: Day 35-42 of post-treatment assessment period
| Intervention | percent clinical pregnancy (Number) |
|---|---|
| SJ-0021 | 17.1 |
| u-hFSH | 14.4 |
Biochemical pregnancy was defined as a positive pregnancy test (urinary beta-hCG test) on Day 28-31 of the post-treatment assessment period (NCT01185782)
Timeframe: Day 28-31 of post-treatment assessment period
| Intervention | percent biochemical pregnancy (Number) |
|---|---|
| SJ-0021 | 17.8 |
| u-hFSH | 15.2 |
AEs: Any untoward medical occurrence in the form of signs, clinically significant abnormalities in laboratory findings, diseases, symptoms, or worsening of complications. TEAEs: AEs that occur during treatment with the IMP. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. Participants who discontinued from the study due to AE were also recorded. (NCT01185782)
Timeframe: Pretrial observation period to post-treatment assessment period (Days 35-42)
| Intervention | participants (Number) | ||
|---|---|---|---|
| TEAEs | SAEs | Discontinuation due to AEs | |
| SJ-0021 | 69 | 1 | 0 |
| u-hFSH | 66 | 1 | 1 |
Total dose of IMP administered was defined as the cumulative dose administered from the start of treatment with IMP until the mean diameter of the dominant follicle reached 18 mm. (NCT01185782)
Timeframe: Start of treatment period until Day 1 of post-treatment assessment period
| Intervention | IU (Mean) |
|---|---|
| SJ-0021 | 959.29 |
| u-hFSH | 845.70 |
Dosing time length was calculated as number of days from the first administration of the IMP until the mean diameter of the dominant follicle was confirmed to have reached 18 mm. (NCT01185782)
Timeframe: Start of treatment period until Day 1 of post-treatment assessment period
| Intervention | days (Mean) |
|---|---|
| SJ-0021 | 13.1 |
| u-hFSH | 12.1 |
Single follicle maturation was defined as the presence of the dominant follicle with a mean diameter of 18 mm or greater without concurrent presence of other follicles of 14 mm or larger in diameter. (NCT01185782)
Timeframe: Start of treatment period until Day 1 of post-treatment assessment period
| Intervention | percent single follicle maturation (Number) |
|---|---|
| SJ-0021 | 33.3 |
| u-hFSH | 43.2 |
Participants were considered to have ovulated if serum progesterone (P4) level was greater than or equal to 5 nanogram (ng)/mL on Day 6±1 or 9±1 during the post-treatment assessment period, or if the participant became clinically pregnant. (NCT01185782)
Timeframe: On Day 6±1 or 9±1 days during post-treatment assessment period (Day 35-42 of post-treatment period for clinical pregnancy)]
| Intervention | percentage of participants (Number) |
|---|---|
| SJ-0021 | 79.1 |
| u-hFSH | 82.6 |
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. (NCT01297465)
Timeframe: Day 1 up to days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days])
| Intervention | participants (Number) |
|---|---|
| Gonal-f® Plus Pergoveris® | 26 |
| Pergoveris® | 23 |
(NCT01297465)
Timeframe: Day 1 up to r-hCG day (end of stimulation cycle [approximately 11 days])
| Intervention | IU (Mean) | |
|---|---|---|
| Total Dose | Mean Daily Dose | |
| Gonal-f® Plus Pergoveris® | 3292 | 307 |
| Pergoveris® | 3321 | 311 |
Biochemical pregnancy was defined as the pregnancy diagnosed only by the detection of human chorionic gonadotropin (hCG) in serum or urine and that does not develop into a clinical pregnancy. Participants with beta- hCG concentration greater than 10 international units per liter (IU/L) were considered as biochemical pregnant. (NCT01297465)
Timeframe: Days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days])
| Intervention | participants (Number) |
|---|---|
| Gonal-f® Plus Pergoveris® | 23 |
| Pergoveris® | 41 |
(NCT01297465)
Timeframe: Days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days])
| Intervention | beats per minute (bpm) (Mean) |
|---|---|
| Gonal-f® Plus Pergoveris® | 75.7 |
| Pergoveris® | 76.5 |
Implantation rate per reporting group was measured as the number of fetal sacs observed, divided by the number of embryos transferred multiplied by 100. (NCT01297465)
Timeframe: Days 35-42 post r-hCG day (end of stimulation cycle [approximately 11 days])
| Intervention | percent sacs per embryo (Mean) |
|---|---|
| Gonal-f® Plus Pergoveris® | 13.3 |
| Pergoveris® | 24.7 |
Number of fetal hearts with activity was evaluated by ultrasound scan (NCT01297465)
Timeframe: Days 35-42 post r-hCG day [end of stimulation cycle {approximately 11 days}])
| Intervention | fetal hearts (Mean) |
|---|---|
| Gonal-f® Plus Pergoveris® | 1.4 |
| Pergoveris® | 1.3 |
Number of fetal sacs with activity was evaluated by ultrasound scan (NCT01297465)
Timeframe: Days 35-42 post r-hCG day [end of stimulation cycle {approximately 11 days}])
| Intervention | fetal sacs (Mean) |
|---|---|
| Gonal-f® Plus Pergoveris® | 1.4 |
| Pergoveris® | 1.2 |
Multiple pregnancy was defined as the existence of more than one fetal sac with fetal heart activity. (NCT01297465)
Timeframe: Days 35-42 post r-hCG day (end of stimulation cycle [approximately 11 days])
| Intervention | participants (Number) |
|---|---|
| Gonal-f® Plus Pergoveris® | 6 |
| Pergoveris® | 8 |
The total number of oocytes retrieved per reporting group on the day of ovum pick-up (OPU) (34-38 hours post r-hCG day) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization (IVF) in order to remove oocytes from the ovary of the female participant, enabling fertilization outside the body. (NCT01297465)
Timeframe: OPU day (34-38 hours post r-hCG day [end of stimulation cycle {approximately 11 days}])
| Intervention | oocytes (Mean) |
|---|---|
| Gonal-f® Plus Pergoveris® | 10.9 |
| Pergoveris® | 9.7 |
(NCT01297465)
Timeframe: Day 1 up to r-hCG day (end of stimulation cycle [approximately 11 days])
| Intervention | days (Mean) |
|---|---|
| Gonal-f® Plus Pergoveris® | 10.6 |
| Pergoveris® | 10.6 |
Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy. Clinical pregnancy rate was reported as total clinical pregnancy rate, clinical pregnancy rate per cycle started and per embryo transfer [ET]). (NCT01297465)
Timeframe: Days 35-42 post r-hCG day (end of stimulation cycle [approximately 11 days])
| Intervention | percentage of participants (Number) | ||
|---|---|---|---|
| Total clinical pregnancy rate (n=97, 101) | Clinical pregnancy rate per cycle (n=97, 101) | Clinical pregnancy rate per ET (n=90, 93) | |
| Gonal-f® Plus Pergoveris® | 17.5 | 17.5 | 18.9 |
| Pergoveris® | 31.7 | 31.7 | 34.4 |
An excessive ovarian response: greater than or equal to 25 oocytes which could put the participant at risk of OHSS; An insufficient ovarian response: defined as 3 or less follicles of greater than or equal to 12 millimeter developing following at least 7 days of treatment. (NCT01297465)
Timeframe: S1 until Day 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days])
| Intervention | participants (Number) | |
|---|---|---|
| Insufficient ovarian response | Excessive ovarian response | |
| Gonal-f® Plus Pergoveris® | 1 | 0 |
| Pergoveris® | 1 | 1 |
Ovarian Hyper Stimulation Syndrome (OHSS) is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting. Early OHSS was defined as the onset of OHSS occurring within 9 days after oocyte retrieval and late OHSS was defined as the onset of OHSS occurring on or after day 10 from oocyte retrieval. (NCT01297465)
Timeframe: Days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days])
| Intervention | participants (Number) | |
|---|---|---|
| Early Ovarian hyperstimulation syndrome | Late Ovarian hyperstimulation syndrome | |
| Gonal-f® Plus Pergoveris® | 4 | 0 |
| Pergoveris® | 1 | 1 |
(NCT01297465)
Timeframe: Days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days])
| Intervention | millimeter of mercury ( mm Hg) (Mean) | |
|---|---|---|
| Systolic Blood Pressure | Diastolic Blood Pressure | |
| Gonal-f® Plus Pergoveris® | 118.9 | 74.8 |
| Pergoveris® | 121.2 | 76.8 |
Subject comprehension questionnaires were completed on Day 1 only by participants assigned to the Menopur and Bravelle treatment arm. On Day 1, the participant read the Mixing Instructions Guide on how to mix and administer the medications at home. The participant was given enough time to read and understand the instructions and ask any questions. The participant then completed the SCQ which consists of 7 questions with YES/NO answers, to self-gauge their understanding of drug administration procedures. Reported data represent the number of participants who answered the question YES. Gonadotropins are referred to as investigational medicinal product (IMP). (NCT01417195)
Timeframe: Day 1
| Intervention | participants (Number) | ||||||
|---|---|---|---|---|---|---|---|
| Overall mixing instructions | How to fill the syringe with saline solution | How to mix the first IMP vial with solution | How to mix additional vials of IMP in same syringe | How to inject the IMPs | How to store the IMPs | How to dispose of used vials, syringes, needles | |
| Menopur and Bravelle Combination | 60 | 60 | 60 | 60 | 60 | 60 | 60 |
"Participants assigned to the Menopur and Bravelle treatment arm prepared and self-administered her daily dose on Day 6 in the presence of the study coordinator or designee assessor. The assessor then completed a 7 question questionnaire with YES or NO answers to document their assessment of participant understanding of drug administration procedures. Reported data represent the number of participants for whom the assessor answered the question YES.~Gonadotropins are referred to as investigational medicinal product (IMP)." (NCT01417195)
Timeframe: Day 6
| Intervention | participants (Number) | ||||||
|---|---|---|---|---|---|---|---|
| Acknowledged understanding of mixing instructions | Filled the syringe with saline solution correctly | Mixed the first IMP vial with solution correctly | Mixed additional IMP in same syringe correctly | Injected the IMPs correctly | Acknowledged understanding of how to store IMPs | Disposed used vials, syringes, needles correctly | |
| Menopur and Bravelle Combination | 60 | 60 | 60 | 60 | 60 | 60 | 60 |
"Participants assigned to the Menopur and Bravelle treatment arm read the Mixing Instructions Guide on how to mix and administer the medications at home. Participants were given enough time to read and understand the instructions and ask any questions. After completing the SCQ, participants prepared and self-administered her assigned first daily dose in the presence of the study coordinator or designee assessor. The assessor then completed a 7 question questionnaire with YES or NO answers to document their assessment of participant understanding of drug administration procedures. Reported data represent the number of participants for whom the assessor answered the question YES.~Gonadotropins are referred to as investigational medicinal product (IMP)." (NCT01417195)
Timeframe: Day 1
| Intervention | participants (Number) | ||||||
|---|---|---|---|---|---|---|---|
| Acknowledged understanding of mixing instructions | Filled the syringe with saline solution correctly | Mixed the first IMP vial with solution correctly | Mixed additional IMP in same syringe correctly | Injected the IMPs correctly | Acknowledged understanding of how to store IMPs | Disposed used vials, syringes, needles correctly | |
| Menopur and Bravelle Combination | 60 | 60 | 60 | 60 | 60 | 60 | 60 |
A treatment-emergent AE was any AE occurring after start of investigational medicinal product (IMP) and within the time of residual drug effect, or a pretreatment AE or pre-existing medical condition that worsened in intensity after start of IMP and within the time of residual drug effect. The time of residual drug effect was the estimated period of time after the last dose of the IMP, where the effect of the product was still considered to be present based on pharmacokinetic, pharmacodynamic, or other IMP characteristics. (NCT01417195)
Timeframe: Day 1 up to Day 20
| Intervention | participants (Number) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Any TEAEs | Drug-related TEAEs | Severe TEAEs | Serious TEAEs | Drug-related Serious TEAEs | Any TEAEs resulting in study discontinuation | Participants who died | Participants with OHSS | Cycle cancellation due to OHSS | |
| Menopur Alone | 30 | 13 | 1 | 0 | 0 | 0 | 0 | 3 | 0 |
| Menopur and Bravelle Combination | 29 | 9 | 0 | 0 | 0 | 0 | 0 | 5 | 0 |
The fertilization rate was defined for each participant and calculated as the number of 2 pronuclei (fertilized) (2PN) oocytes divided by the total number of oocytes retrieved multiplied by 100. (NCT01417195)
Timeframe: approximately day 13 (16-20 hours post insemination by in vitro fertilization (IVF) insemination or intracytoplasmic sperm injection (ICSI))
| Intervention | percentage of oocytes retrieved (Mean) |
|---|---|
| Menopur and Bravelle Combination | 63.14 |
| Menopur Alone | 59.56 |
Subject comprehension questionnaires were repeated on Day 6 after 5 days of combination therapy by participants assigned to the Menopur and Bravelle treatment arm. The SCQ consists of 7 questions with YES/NO answers to self-gauge participants' understanding of drug administration procedures. Reported data represent the number of participants who answered the question YES. Gonadotropins are referred to as investigational medicinal product (IMP). (NCT01417195)
Timeframe: Day 6
| Intervention | participants (Number) | ||||||
|---|---|---|---|---|---|---|---|
| Overall mixing instructions | How to fill the syringe with saline solution | How to mix the first IMP vial with solution | How to mix additional vials of IMP in same syringe | How to inject the IMPs | How to store the IMPs | How to dispose of used vials, syringes, needles | |
| Menopur and Bravelle Combination | 60 | 60 | 60 | 60 | 60 | 60 | 60 |
Ovulation was defined as mid-luteal serum progesterone level of >= 9.4 ng/mL or clinical pregnancy. Clinical pregnancy was defined as the presence of at least a fetal sac on TVUS. (NCT01653743)
Timeframe: Mid-luteal phase progesterone assessed (Day 5 to 10) or clinical pregnancy (Day 35 to 42) post hCG treatment
| Intervention | percentage of subjects (Number) |
|---|---|
| MSJ-0011 | 96.3 |
| u-hCG | 88.9 |
Ovulation was defined as mid-luteal serum progesterone level of >= 5 ng/mL or clinical pregnancy. Clinical pregnancy was defined as the presence of at least a fetal sac on transvaginal ultrasound (TVUS). (NCT01653743)
Timeframe: Mid-luteal phase progesterone assessed (Day 5 to 10) or clinical pregnancy (Day 35 to 42) post hCG treatment
| Intervention | percentage of subjects (Number) |
|---|---|
| MSJ-0011 | 100 |
| u-hCG | 100 |
Percentage of subjects with clinical pregnancy was assessed. Clinical pregnancy was defined as the presence of at least a fetal sac on TVUS. (NCT01653743)
Timeframe: Day 35 to 42 post hCG treatment
| Intervention | percentage of subjects (Number) |
|---|---|
| MSJ-0011 | 29.6 |
| u-hCG | 33.3 |
Percentage of subjects with biochemical pregnancy was assessed. Biochemical pregnancy was defined as any miscarriage without any evidence of a fetal sac on TVUS on the Day 35 to 42 post hCG treatment, but with a positive serum β-hCG pregnancy test on Day 15 to 20 post hCG treatment (Beta-hCG level greater than [>] 10 IU/Liter) (NCT01653743)
Timeframe: Day 35 to 42 post hCG treatment
| Intervention | percentage of subjects (Number) |
|---|---|
| MSJ-0011 | 3.7 |
| u-hCG | 3.7 |
Endometrial thickness was measured using TVUS. (NCT01653743)
Timeframe: Day 5 to 7 post hCG treatment
| Intervention | millimeter (Mean) |
|---|---|
| MSJ-0011 | 11.6 |
| u-hCG | 12.4 |
Measurement of the number of subjects with detectable specific serum binding to FSH by surface Plasmon resonance during Cycle 2. (NCT01687712)
Timeframe: Immunogenicity samples were taken at baseline, Visit 5 (8 days after start of treatment), Visit 9 (5 days after the end of FSH treatment), Visit 10 (18 +/- 1 days after oocyte retrieval), and Visit 11 (42 +/- 1 days after embryo transfer).
| Intervention | Participants (Count of Participants) | ||||
|---|---|---|---|---|---|
| Baseline | Visit 5 | Visit 9 | Visit 10 | Visit 11 | |
| AFOLIA | 0 | 0 | 0 | 0 | 0 |
| Gonal-f® RFF | 0 | 0 | 0 | 0 | 0 |
The number of oocytes retrieved per subject, following hCG administration in Cycle 1. (NCT01687712)
Timeframe: Visit 8, 34-36 hours after hCG administration
| Intervention | Oocytes retrieved (Mean) |
|---|---|
| AFOLIA | 11.3 |
| Gonal-f® RFF | 11.2 |
The total dose of r-hFSH that subjects received during Cycle 1. (NCT01687712)
Timeframe: Measured at discretionary visits between Days 9 and 15 after FSH starts.
| Intervention | international unit (IU) (Mean) |
|---|---|
| AFOLIA | 3209.2 |
| Gonal-f® RFF | 3343.6 |
The number of days of r-hFSH stimulation a subject received during Cycle 1. (NCT01687712)
Timeframe: Measured at discretionary visits between Days 9 and 15 after FSH starts
| Intervention | days (Mean) |
|---|---|
| AFOLIA | 10.8 |
| Gonal-f® RFF | 11.0 |
The mean dose of r-hFSH that subjects received in a day during Cycle 1. (NCT01687712)
Timeframe: Measured at discretionary visits between Days 9 and 15 after FSH starts.
| Intervention | international unit (IU) (Mean) |
|---|---|
| AFOLIA | 292.1 |
| Gonal-f® RFF | 297.5 |
"Summary of AEs, including the number of subjects experiencing to following during Cycle 1:~At least one AE At least one treatment related AE At least one serious AE At least one AE leading to discontinuation of study drug At least one AE due to pregnancy complication" (NCT01687712)
Timeframe: Measured from the start of FSH treatment through to either the end FSH treatment + 30 days (up to 46 days) or to the last Telephone Follow-up / Live Birth Questionnaire on pregnancy outcome (if applicable) (up to 10 months).
| Intervention | Participants (Count of Participants) | ||||
|---|---|---|---|---|---|
| At least one AE | At least one treatment related AE | At least one serious adverse event | At least one AE leading to discontinuation | At least one AE due to pregnancy complication | |
| AFOLIA | 403 | 202 | 32 | 2 | 29 |
| Gonal-f® RFF | 391 | 197 | 31 | 1 | 30 |
Measurement of the number of subjects with detectable specific serum binding to FSH by surface Plasmon resonance during Cycle 3. (NCT01687712)
Timeframe: Immunogenicity samples were taken at baseline, Visit 5 (8 days after start of treatment), Visit 9 (5 days after the end of FSH treatment), Visit 10 (18 +/- 1 days after oocyte retrieval), and Visit 11 (42 +/- 1 days after embryo transfer).
| Intervention | Participants (Count of Participants) | ||||
|---|---|---|---|---|---|
| Baseline | Visit 5 | Visit 9 | Visit 10 | Visit 11 | |
| AFOLIA | 0 | 0 | 0 | 0 | 0 |
| Gonal-f® RFF | 0 | 0 | 0 | 0 | 0 |
Summary of the number of subjects with mild, moderate and severe OHSS. The total number of subjects with OHSS is also included. (NCT01687712)
Timeframe: Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10).
| Intervention | Participants (Count of Participants) | |||
|---|---|---|---|---|
| Total Number of Subjects with OHSS | Number of Subjects with Mild OHSS | Number of Subjects with Moderate OHSS | Number of Subjects with Severe OHSS | |
| AFOLIA | 13 | 6 | 5 | 2 |
| Gonal-f® RFF | 12 | 4 | 6 | 2 |
Summary of the number of subjects with mild, moderate and severe OHSS. The total number of subjects with OHSS is also included. (NCT01687712)
Timeframe: Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10).
| Intervention | Participants (Count of Participants) | |||
|---|---|---|---|---|
| Total Number of Subjects with OHSS | Number of Subjects with Mild OHSS | Number of Subjects with Moderate OHSS | Number of Subjects with Severe OHSS | |
| AFOLIA | 1 | 1 | 0 | 0 |
| Gonal-f® RFF | 3 | 1 | 2 | 0 |
Summary of the number of subjects with mild, moderate and severe OHSS. The total number of subjects with OHSS is also included. (NCT01687712)
Timeframe: Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10).
| Intervention | Participants (Count of Participants) | |||
|---|---|---|---|---|
| Total Number of Subjects with OHSS | Number of Subjects with Mild OHSS | Number of Subjects with Moderate OHSS | Number of Subjects with Severe OHSS | |
| AFOLIA | 0 | 0 | 0 | 0 |
| Gonal-f® RFF | 0 | 0 | 0 | 0 |
Dermal response to r-hFSH injection as assessed by the investigator and categorized according to severity of reaction (NCT01687712)
Timeframe: Measure recorded in the Patient Diary which is maintained through entire FSH treatment, from FSH through to Day 16 after start of FSH (16 days).
| Intervention | Participants (Count of Participants) | |||
|---|---|---|---|---|
| No evidence of irritation | Minimal erythema, barely perceptible | Definited Erythema, readily visible; minimal edema | Definite Edema | |
| AFOLIA | 28 | 2 | 0 | 1 |
| Gonal-f® RFF | 25 | 7 | 1 | 0 |
Measurement of the number of subjects with detectable specific serum binding to FSH by surface Plasmon resonance during Cycle 1. (NCT01687712)
Timeframe: Immunogenicity samples were taken at baseline, Visit 5 (8 days after start of treatment), Visit 9 (5 days after the end of FSH treatment), Visit 10 (18 +/- 1 days after oocyte retrieval), and Visit 11 (42 +/- 1 days after embryo transfer).
| Intervention | Participants (Count of Participants) | ||||
|---|---|---|---|---|---|
| Baseline | Visit 5 | Visit 9 | Visit 10 | Visit 11 | |
| AFOLIA | 1 | 1 | 1 | 1 | 0 |
| Gonal-f® RFF | 1 | 1 | 1 | 1 | 1 |
The immunogenicity potential of FSH in healthy volunteer will be assessed by analysing serum samples collected at different timepoints during two treatment cycle for oocytes donation: cycle 1, serum samples will be collected before treatment start (baseline), after 7-13 days and after 28 days of treatment; Cycle 2: serum samples will be collected before starting the second cycle (baseline 2), after 7-13 days and after 28 days of treatment. Cycle 1 and cycle 2 will be separated by a wash-out period of two months. (NCT01785095)
Timeframe: 4 months.
| Intervention | participants (Number) |
|---|---|
| Follicle Stimulationg Hormone | 0 |
(NCT01785095)
Timeframe: after 2 weeks of treatment
| Intervention | IU (Mean) |
|---|---|
| First Cycle | 1911.1 |
| Second Cycle | 1984.4 |
the number of oocytes retrieved in the first cycle and in the second cycle are compared. (NCT01785095)
Timeframe: after 2 weeks of treatment
| Intervention | oocytes (Mean) |
|---|---|
| First Cycle | 13.4 |
| Second Cycle | 15.7 |
Two pharmacokinetic (PK) samples were collected per subject for the measurement of serum progesterone concentrations; 1st sample at Visit 2-2 (prior to hCG administration) and second sample during Visit 5 (Day 14+/-3, 7 hours after the morning of investigational medicinal product administration). (NCT01863680)
Timeframe: Visit 2-2 (Prior to hCG administration) and Visit 5 (Day 14+/-3)
| Intervention | nanogram per milliliter (ng/mL) (Mean) | |||
|---|---|---|---|---|
| Subjects with +ve serum beta-hCG: Visit 2-2 (n=44) | Subjects with +ve serum beta-hCG: Visit 5 (n=44) | Subjects with -ve serum beta-hCG: Visit 2-2 (n=77) | Subjects with -ve serum beta-hCG: Visit 5 (n=77) | |
| COL-1620 | 1.023 | 61.508 | 0.988 | 7.765 |
Clinical pregnancy was defined as the presence of a fetal sac on transvaginal ultrasound (TVUS) during Week 5 or the presence of an extra-uterine pregnancy (as confirmed during surgery or by 2 positive serum beta-human chorionic gonadotropin (beta-hCG) results from Week 5). The clinical pregnancy rate was calculated as number of subjects who were clinically pregnant divided by the number of subjects who had at least 1 embryo transferred. (NCT01863680)
Timeframe: Week 5 post embryo transfer (2-6 days after Ovum Pick-up [OPU])
| Intervention | Percentage of pregnancy/embryo transfer (Number) |
|---|---|
| COL-1620 | 28.5 |
Biochemical pregnancy was defined as any miscarriage without any evidence of a fetal sac on TVUS during Visit 6 (Week 5), but with a positive serum beta-hCG pregnancy test result at Visit 5 (Day 14+/-3). Biochemical pregnancy rate was calculated as the number of subjects who had no fetal sac observed during Visit 6 (Week 5) TVUS assessment or subjects who had a positive serum pregnancy test at Visit 5 (Day 14+/-3) and no data recorded at Visit 6 (Week 5) divided by the number of subjects who has at least 1 embryo transferred. (NCT01863680)
Timeframe: Week 5 post embryo transfer (2-6 days after Ovum Pick-up [OPU])
| Intervention | Percentage of pregnancy/embryo transfer (Number) |
|---|---|
| COL-1620 | 7.3 |
OHSS was defined as an exaggerated systemic response to ovarian stimulation characterized by a wide spectrum of clinical and laboratory manifestations, classified as mild, moderate or severe according to the degree of abdominal distention, ovarian enlargement and respiratory, hemodynamic and metabolic complications. (NCT01871532)
Timeframe: up to 42 days post hCG administration
| Intervention | subjects (Number) |
|---|---|
| Low Dose Gonal-f | 0 |
| Standard Low Dose Gonal-f | 0 |
(NCT01909141)
Timeframe: 3 months
| Intervention | mm (Mean) |
|---|---|
| Arm 1:Letrozole-pioglitazone -Metformin Group | 10.56 |
| Arm 2: Clomiphene Citrate-pioglitazone-metformin | 9.68 |
(NCT01909141)
Timeframe: 3 months
| Intervention | participants (Number) |
|---|---|
| Arm 1:Letrozole-pioglitazone -Metformin Group | 28 |
| Arm 2: Clomiphene Citrate-pioglitazone-metformin | 24 |
(NCT01909141)
Timeframe: 3 months
| Intervention | percentage of all cycles (Number) |
|---|---|
| Arm 1:Letrozole-pioglitazone -Metformin Group | 93 |
| Arm 2: Clomiphene Citrate-pioglitazone-metformin | 108 |
(NCT01909141)
Timeframe: 3 months
| Intervention | follicles (Mean) |
|---|---|
| Arm 1:Letrozole-pioglitazone -Metformin Group | 1.44 |
| Arm 2: Clomiphene Citrate-pioglitazone-metformin | 1.5 |
serum creatinine was measured at the end of the study period (after 3 months) in both groups. (NCT01909141)
Timeframe: 3 months
| Intervention | mg/dL (Mean) |
|---|---|
| Arm 1:Letrozole-pioglitazone -Metformin Group | 0.62 |
| Arm 2: Clomiphene Citrate-pioglitazone-metformin | 0.57 |
The proportion of subjects with early OHSS, early OHSS of moderate or severe grade, preventive interventions for early OHSS, early OHSS and/or preventive interventions for early OHSS, and early OHSS of moderate or severe grade and/or preventive interventions for early OHSS are presented. (NCT01956110)
Timeframe: ≤9 days after triggering of final follicular maturation
| Intervention | Percentage of subjects (Number) | ||||
|---|---|---|---|---|---|
| Early OHSS (any grade) | Early OHSS (moderate/severe) | Any preventive intervention | Early OHSS (any grade) / preventive interventions | Early OHSS (mod/severe) / preventive interventions | |
| FE 999049 | 2.6 | 1.4 | 2.3 | 4.7 | 3.6 |
| GONAL-F | 3.0 | 1.4 | 4.5 | 6.2 | 5.1 |
(NCT01956110)
Timeframe: Day of oocyte retrieval
| Intervention | Percentage of subjects (Number) | |
|---|---|---|
| <4 or >=15 oocytes retrieved | <4 or >=20 oocytes retrieved | |
| FE 999049 | 26.6 | 14.5 |
| GONAL-F | 31.3 | 18.4 |
Late OHSS was defined as OHSS with onset >9 days after triggering of final follicular maturation.The proportion of subjects with late OHSS, and late OHSS of moderate or severe grade are presented. (NCT01956110)
Timeframe: >9 days after triggering of final follicular maturation
| Intervention | Percentage of subjects (Number) | |
|---|---|---|
| Late OHSS (any grade) | Late OHSS (moderate/severe) | |
| FE 999049 | 0.9 | 0.8 |
| GONAL-F | 1.8 | 1.5 |
Fertilisation rate was defined as the number of oocytes with 2 pronuclei divided by the number of oocytes retrieved. (NCT01956110)
Timeframe: Day 1 after insemination
| Intervention | Percentage of oocytes (Mean) |
|---|---|
| FE 999049 | 56 |
| GONAL-F | 57 |
Number of oocytes in metaphase II prior to ICSI insemination is presented. (NCT01956110)
Timeframe: Prior to insemination
| Intervention | Number of oocytes (Mean) |
|---|---|
| FE 999049 | 7.4 |
| GONAL-F | 7.7 |
Ongoing pregnancy was defined as at least one intrauterine viable fetus 10-11 weeks after blastocyst transfer. (NCT01956110)
Timeframe: 10-11 weeks after blastocyst transfer
| Intervention | Percentage of subjects (Number) |
|---|---|
| FE 999049 | 30.7 |
| GONAL-F | 31.6 |
Ongoing implantation rate was defined as the number of intrauterine viable fetuses 10-11 weeks after transfer divided by number of blastocysts transferred. (NCT01956110)
Timeframe: 10-11 weeks after blastocyst transfer
| Intervention | Percentage (Number) |
|---|---|
| FE 999049 | 35.2 |
| GONAL-F | 35.8 |
(NCT01956110)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | Days (Mean) |
|---|---|
| FE 999049 | 8.9 |
| GONAL-F | 8.6 |
(NCT01956110)
Timeframe: Day of oocyte retrieval
| Intervention | Oocytes retrieved (Mean) |
|---|---|
| FE 999049 | 10.0 |
| GONAL-F | 10.4 |
Implantation rate was defined as the number of gestational sacs 5-6 weeks after transfer divided by number of blastocysts transferred. (NCT01956110)
Timeframe: 5-6 weeks after blastocyst transfer
| Intervention | Percentage (Number) |
|---|---|
| FE 999049 | 39.8 |
| GONAL-F | 41.3 |
Subjects self-assessed injection site reactions (redness, itching, pain, swelling and bruising) immediately, 30 minutes and 24 hours after each injection. The injection site reactions were assessed as none, mild, moderate and severe. The frequency of injection site reactions (mild, moderate or severe) based on all assessments performed is presented. (NCT01956110)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | Percentage of events (Number) |
|---|---|
| FE 999049 | 3.4 |
| GONAL-F | 3.5 |
Number of embryos (total and good-quality) on Day 3 are presented. A good-quality embryo was defined as an embryo with ≥6 blastomeres and fragmentation ≤20% on Day 3. (NCT01956110)
Timeframe: On day 3 after oocyte retrieval
| Intervention | Number of embryos (Mean) | |
|---|---|---|
| Number of embryos | Number of good-quality embryos | |
| FE 999049 | 5.4 | 4.2 |
| GONAL-F | 5.7 | 4.5 |
(NCT01956110)
Timeframe: Day of oocyte retrieval
| Intervention | Percentage of subjects (Number) | ||||
|---|---|---|---|---|---|
| Low response (<4 oocytes) | Moderate response (4-7 oocytes) | Targeted response (8-14 oocytes) | Hyperresponse (15-19 oocytes) | Severe hyperresponse (≥ 20 oocytes) | |
| FE 999049 | 8.0 | 30.1 | 43.3 | 12.1 | 6.5 |
| GONAL-F | 9.6 | 30.3 | 38.4 | 12.9 | 8.7 |
Proportion of subjects with cycle cancellation due to poor ovarian response, excessive ovarian response, and triggering with gonadotropin-releasing hormone (GnRH) agonist are presented. (NCT01956110)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | Percentage of subjects (Number) | ||
|---|---|---|---|
| Cycle cancelled due to poor ovarian response | Cycle cancelled due to excessive ovarian response | Triggering with GnRH agonist | |
| FE 999049 | 3.8 | 0 | 1.5 |
| GONAL-F | 2.7 | 0 | 3.5 |
(NCT01956110)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | Percentage of subjects (Number) |
|---|---|
| FE 999049 | 33.2 |
| GONAL-F | 36.8 |
The proportion of subjects with at least one treatment-induced anti-FSH antibody response at any time point. (NCT01956110)
Timeframe: Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose
| Intervention | Percentage of subjects (Number) |
|---|---|
| FE 999049 | 1.05 |
| GONAL-F | 0.76 |
Confirmed technical malfunction of administration pen. (NCT01956110)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | Percentage of subjects (Number) |
|---|---|
| FE 999049 | 0.15 |
| GONAL-F | 0.00 |
The total gonadotropin dose was recorded. (NCT01956110)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | µg of dose (Mean) |
|---|---|
| FE 999049 | 90 |
| GONAL-F | 103.7 |
Vital pregnancy was defined as at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after blastocyst transfer. (NCT01956110)
Timeframe: 5-6 weeks after blastocyst transfer
| Intervention | Percentage of subjects (Number) |
|---|---|
| FE 999049 | 31.7 |
| GONAL-F | 33.4 |
The subject self-assessed abdominal discomfort related to controlled ovarian stimulation using a VAS going from 0 mm (no abdominal discomfort) to 100 mm (worst imaginable abdominal discomfort). (NCT01956110)
Timeframe: End-of-stimulation and day of blastocyst transfer
| Intervention | Millimeter (Mean) | |
|---|---|---|
| End of stimulation visit | Transfer visit | |
| FE 999049 | 16.1 | 17.2 |
| GONAL-F | 15.9 | 16.1 |
Change in body weight from baseline to end-of-stimulation and from baseline to day of blastocyst transfer. (NCT01956110)
Timeframe: End-of-stimulation and day of blastocyst transfer
| Intervention | Kg (Mean) | |
|---|---|---|
| End of stimulation visit | Transfer visit | |
| FE 999049 | 0.3 | 0.0 |
| GONAL-F | 0.2 | 0.0 |
Change in maximum abdominal circumference from baseline to end-of-stimulation and from baseline to day of blastocyst transfer. (NCT01956110)
Timeframe: End-of-stimulation and day of blastocyst transfer
| Intervention | Centimeter (Mean) | |
|---|---|---|
| End of stimulation visit | Transfer visit | |
| FE 999049 | 0.3 | 0.6 |
| GONAL-F | 0.1 | -0.1 |
Number of blastocysts (total and good-quality) on Day 5 are presented. A good-quality blastocyst was defined as a blastocyst of grade 3BB or higher. (NCT01956110)
Timeframe: On day 5 after oocyte retrieval
| Intervention | Number of blastocytss (Mean) | |
|---|---|---|
| Number of blastocysts | Number of good-quality blastocysts | |
| FE 999049 | 3.3 | 2.0 |
| GONAL-F | 3.5 | 2.1 |
Participants self-assessed injection site reactions (redness, itching, pain, swelling and bruising) immediately, 30 minutes and 24 hours after each injection. The injection site reactions were assessed as none, mild, moderate and severe. The frequency of injection site reactions (mild, moderate or severe) based on all assessment performed is presented. (NCT01956123)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | Percentage of events (Number) |
|---|---|
| FE 999049 (COS Cycle 2) | 3.0 |
| GONAL-F (COS Cycle 2) | 2.4 |
| FE 999049 (COS Cycle 3) | 2.8 |
| GONAL-F (COS Cycle 3) | 2.3 |
Implantation rate was defined as the number of gestational sacs 5-6 weeks after transfer divided by number of blastocysts transferred. (NCT01956123)
Timeframe: 5-6 weeks after blastocyst transfer
| Intervention | Percentage (Number) |
|---|---|
| FE 999049 (COS Cycle 2) | 34.6 |
| GONAL-F (COS Cycle 2) | 30.6 |
| FE 999049 (COS Cycle 3) | 28.8 |
| GONAL-F (COS Cycle 3) | 32.2 |
Ongoing implantation rate was defined as the number of intrauterine viable fetuses 10-11 weeks after transfer divided by number of blastocysts transferred. (NCT01956123)
Timeframe: 10-11 weeks after blastocyst transfer
| Intervention | Percentage (Number) |
|---|---|
| FE 999049 (COS Cycle 2) | 28.7 |
| GONAL-F (COS Cycle 2) | 25.5 |
| FE 999049 (COS Cycle 3) | 25.0 |
| GONAL-F (COS Cycle 3) | 28.9 |
The proportion (percentage) of participants with at least one treatment-induced anti-FSH antibody response at any time point is presented. The cumulative incidences in COS cycle 2 and COS cycle 3 divided by participants in COS cycle 2 are presented. Participants with observations in both cycles are only counted once. (NCT01956123)
Timeframe: Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose
| Intervention | Percentage of participants (Number) |
|---|---|
| FE 999049 (COS Cycle 2) | 0.79 |
| GONAL-F (COS Cycle 2) | 0.38 |
The proportion (percentage) of participants with treatment-induced anti-FSH antibodies with neutralising capacity at any time point is presented. The cumulative incidences in COS cycle 2 and COS cycle 3 divided by participants in COS cycle 2 are presented. Participants with observations in both cycles are only counted once. (NCT01956123)
Timeframe: Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose
| Intervention | Percentage of participants (Number) |
|---|---|
| FE 999049 (COS Cycle 2) | 0.00 |
| GONAL-F (COS Cycle 2) | 0.00 |
Incidences of confirmed technical malfunction of administration pen are presented. (NCT01956123)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | Percentage of participants (Number) |
|---|---|
| FE 999049 (COS Cycle 2) | 0.0 |
| GONAL-F (COS Cycle 2) | 0.0 |
| FE 999049 (COS Cycle 3) | 0.0 |
| GONAL-F (COS Cycle 3) | 0.0 |
Vital pregnancy was defined as at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after blastocyst transfer. (NCT01956123)
Timeframe: 5-6 weeks after blastocyst transfer
| Intervention | Percentage of participants (Number) |
|---|---|
| FE 999049 (COS Cycle 2) | 29.4 |
| GONAL-F (COS Cycle 2) | 27.2 |
| FE 999049 (COS Cycle 3) | 27.4 |
| GONAL-F (COS Cycle 3) | 29.0 |
Ongoing pregnancy rate was defined as at least one intrauterine viable fetus 10-11 weeks after blastocyst transfer. (NCT01956123)
Timeframe: 10-11 weeks after blastocyst transfer
| Intervention | Percentage of participants (Number) |
|---|---|
| FE 999049 (COS Cycle 2) | 27.8 |
| GONAL-F (COS Cycle 2) | 25.7 |
| FE 999049 (COS Cycle 3) | 27.4 |
| GONAL-F (COS Cycle 3) | 28 |
The proportion (percentage) of participants with early OHSS, early OHSS of moderate or severe grade, preventive interventions for early OHSS, early OHSS and/or preventive interventions for early OHSS, and early OHSS of moderate or severe grade and/or preventive interventions for early OHSS are presented. (NCT01956123)
Timeframe: ≤9 days after triggering of final follicular maturation.
| Intervention | Percentage of participants (Number) | ||||
|---|---|---|---|---|---|
| Early OHSS (any grade) | Early OHSS (moderate/severe) | Any preventive intervention | Early OHSS (any grade) / preventive | Early OHSS (moderate/severe) / preventive | |
| FE 999049 (COS Cycle 2) | 0.8 | 0.0 | 1.6 | 2.0 | 1.6 |
| FE 999049 (COS Cycle 3) | 1.1 | 0.0 | 0.0 | 1.1 | 0.0 |
| GONAL-F (COS Cycle 2) | 2.3 | 1.9 | 1.9 | 3.8 | 3.8 |
| GONAL-F (COS Cycle 3) | 0.0 | 0.0 | 1.1 | 1.1 | 1.1 |
Late OHSS was defined as OHSS with onset >9 days after triggering of final follicular maturation. (NCT01956123)
Timeframe: >9 days after triggering of final follicular maturation
| Intervention | Percentage of participants (Number) | |
|---|---|---|
| Late OHSS (any grade) | Late OHSS (moderate/severe) | |
| FE 999049 (COS Cycle 2) | 0.4 | 0.0 |
| FE 999049 (COS Cycle 3) | 1.1 | 0.0 |
| GONAL-F (COS Cycle 2) | 0.8 | 0.8 |
| GONAL-F (COS Cycle 3) | 1.1 | 1.1 |
The proportion (percentage) of participants with treatment-induced anti-FSH antibodies, overall as well as with neutralising capacity, after one and after two repeated COS cycles is presented. (NCT01956123)
Timeframe: Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose
| Intervention | Percentage of participants (Number) | |
|---|---|---|
| Treatment-induced anti-FSH antibodies | Antibodies with neutralising capacity | |
| FE 999049 (COS Cycle 2) | 0.79 | 0.00 |
| FE 999049 (COS Cycle 3) | 1.05 | 0.00 |
| GONAL-F (COS Cycle 2) | 0.38 | 0.00 |
| GONAL-F (COS Cycle 3) | 1.08 | 0.00 |
Proportion (percentage) of participants with cycle cancellation due to poor ovarian response, excessive ovarian response, and triggering with gonadotropin-releasing hormone (GnRH) agonist are presented. (NCT01956123)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | Percentage of participants (Number) | ||
|---|---|---|---|
| Cycle cancelled due to poor ovarian response | Cycle cancelled due to excessive ovarian response | Triggering with GnRH agonist | |
| FE 999049 (COS Cycle 2) | 2.0 | 0.4 | 0.4 |
| FE 999049 (COS Cycle 3) | 2.1 | 0.0 | 0.0 |
| GONAL-F (COS Cycle 2) | 3.8 | 0.0 | 0.8 |
| GONAL-F (COS Cycle 3) | 2.2 | 0.0 | 1.1 |
Live birth rate was defined as the percentage of subjects with at least one live-born neonate. (NCT02047227)
Timeframe: Approximately 180 days following ongoing pregnancy determination (Day 365)
| Intervention | percentage of subjects (Number) |
|---|---|
| Pergoveris | 10.6 |
| GONAL-f | 11.7 |
Embryo implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100. (NCT02047227)
Timeframe: 35-42 days post r-hCG administration (Day 154)
| Intervention | percent sacs per embryo (Number) |
|---|---|
| Pergoveris | 14.7 |
| GONAL-f | 15.6 |
Clinical pregnancy rate defined as the percentage of subjects with a ultrasound confirmation of a gestational sac, with or without fetal heart activity. (NCT02047227)
Timeframe: 35-42 days post r-hCG administration (Day 154)
| Intervention | percentage of subjects (Number) |
|---|---|
| Pergoveris | 14.1 |
| GONAL-f | 16.8 |
Mean number of oocytes retrieved on the day of ovum pick up (OPU) was calculated. Oocyte retrieval was a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body. (NCT02047227)
Timeframe: At approximately 34 to 38 hours after r-hCG administration (Day 113)
| Intervention | oocytes (Mean) |
|---|---|
| Pergoveris | 3.3 |
| GONAL-f | 3.6 |
Biochemical pregnancy rate was defined as the percentage of subjects with a positive beta-hCG result from the serum pregnancy test. (NCT02047227)
Timeframe: 15 to 20 days post r-hCG administration (Day 132)
| Intervention | percentage of subjects (Number) |
|---|---|
| Pergoveris | 17.3 |
| GONAL-f | 23.9 |
Ongoing pregnancy rate was defined as the percentage of subjects with a ultrasound confirmation of at least one viable fetus (positive fetal heart beat). (NCT02047227)
Timeframe: 70 days after embryo transfer (Day 185)
| Intervention | percentage of subjects (Number) |
|---|---|
| Pergoveris | 11.0 |
| GONAL-f | 12.4 |
The AUC (0-t) was defined as the area under the serum concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration. Baseline-corrected AUC0-t (AUC0-t,adj) = AUC0-t - (baseline concentration * t). (NCT02317809)
Timeframe: Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 60, 72, 96 and 120 hours post-dose in each period
| Intervention | International units*hour/liter (IU*h/L) (Geometric Mean) |
|---|---|
| Liquid Pergoveris | 210.4 |
| Freeze-dried Pergoveris | 195.2 |
Baseline-corrected Cmax (Cmax,adj) = Cmax - baseline concentration (NCT02317809)
Timeframe: Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 60, 72, 96, 120 and 168 hours post-dose in each period
| Intervention | International units per liter (IU/L) (Geometric Mean) |
|---|---|
| Liquid Pergoveris | 47.92 |
| Freeze-dried Pergoveris | 42.55 |
Baseline-corrected Cmax (Cmax,adj) = Cmax - baseline concentration. (NCT02317809)
Timeframe: Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 60, 72, 96 and 120 hours post-dose in each period
| Intervention | International units per liter (IU/L) (Geometric Mean) |
|---|---|
| Liquid Pergoveris | 10.126 |
| Freeze-dried Pergoveris | 9.782 |
Transvaginal ultrasound (TVUS) was performed to determine the follicle size and number. (NCT02317809)
Timeframe: Day 1 (pre-dose) up to follow-up visit (Day 18) for IMP intervention periods
| Intervention | Subjects (Number) |
|---|---|
| Liquid Pergoveris | 0 |
| Freeze-dried Pergoveris | 0 |
(NCT02317809)
Timeframe: Day 1 post-IMP administration up to follow-up visit (Day 18) for IMP intervention periods
| Intervention | Subjects (Number) |
|---|---|
| Liquid Pergoveris | 0 |
| Freeze-dried Pergoveris | 0 |
(NCT02317809)
Timeframe: Day 1 pre-dose and Day 8 post-dose for IMP intervention periods.
| Intervention | Log Titers (Number) | |||
|---|---|---|---|---|
| Day 1: Subject 1 | Day 8: Subject 1 | Day 1: Subject 2 | Day 8: Subject 2 | |
| Freeze-dried Pergoveris | 1.7 | 1.0 | NA | NA |
| Liquid Pergoveris | 1.0 | 1.0 | 1.7 | 1.7 |
Clearance is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained is influenced by the fraction of the dose absorbed and was expressed as volume (Liter) per unit of time (hour). (NCT02317809)
Timeframe: Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 60, 72, 96, 120, 168 hours post-dose in each period for FSH; Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 60, 72, 96, 120 hours post-dose in each period for LH
| Intervention | Liter per hour (L/h) (Geometric Mean) | |
|---|---|---|
| Follicle-stimulating Hormone (n=22, 22) | Luteinizing Hormone (n=21, 22) | |
| Freeze-dried Pergoveris | 0.3091 | 2.238 |
| Liquid Pergoveris | 0.2673 | 2.082 |
The elimination rate constant was obtained from linear regression of the terminal phase of the log transformed concentration-time data. (NCT02317809)
Timeframe: Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 60, 72, 96, 120, 168 hours post-dose in each period for FSH; Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 60, 72, 96, 120 hours post-dose in each period for LH
| Intervention | Per Hour (1/hour) (Geometric Mean) | |
|---|---|---|
| Follicle-stimulating Hormone (n=22, 22) | Luteinizing Hormone (n=21, 22) | |
| Freeze-dried Pergoveris | 0.01963 | 0.05094 |
| Liquid Pergoveris | 0.01880 | 0.05542 |
Terminal half-life is the time measured for the concentration to decrease by one half. (NCT02317809)
Timeframe: Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 60, 72, 96, 120, 168 hours post-dose in each period for FSH; Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 60, 72, 96, 120 hours post-dose in each period for LH
| Intervention | Hour (h) (Geometric Mean) | |
|---|---|---|
| Follicle-stimulating Hormone (n=22, 22) | Luteinizing Hormone (n=21, 22) | |
| Freeze-dried Pergoveris | 35.31 | 13.608 |
| Liquid Pergoveris | 36.87 | 12.507 |
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired concentration. Apparent volume of distribution (Vz/F) is influenced by the fraction absorbed. (NCT02317809)
Timeframe: Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 60, 72, 96, 120, 168 hours post-dose in each period for FSH; Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 60, 72, 96, 120 hours post-dose in each period for LH
| Intervention | Liter (L) (Geometric Mean) | |
|---|---|---|
| Follicle-stimulating Hormone (n=22, 22) | Luteinizing Hormone (n=21, 22) | |
| Freeze-dried Pergoveris | 15.742 | 43.93 |
| Liquid Pergoveris | 14.219 | 37.57 |
(NCT02317809)
Timeframe: Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 60, 72, 96, 120, 168 hours post-dose in each period for FSH; Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 60, 72, 96, 120 hours post-dose in each period for LH
| Intervention | International units*hour/liter (IU*h/L) (Geometric Mean) | |
|---|---|---|
| Follicle-stimulating Hormone (n=22, 22) | Luteinizing Hormone (n=21, 22) | |
| Freeze-dried Pergoveris | 2912.1 | 201.1 |
| Liquid Pergoveris | 3366.6 | 216.1 |
An AE was any untoward medical occurrence in a subject, regardless of causal relationship with the treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs include both SAEs and non-serious AEs. (NCT02317809)
Timeframe: Day 1 post-IMP administration up to follow-up visit (Day 18) for IMP intervention periods
| Intervention | Subjects (Number) | |
|---|---|---|
| AEs | SAEs | |
| Freeze-dried Pergoveris | 14 | 0 |
| Liquid Pergoveris | 12 | 1 |
(NCT02317809)
Timeframe: Day 1 pre-dose and Day 8 post-dose for IMP intervention periods
| Intervention | Subjects (Number) | |||
|---|---|---|---|---|
| Day 1: Subjects with ADAs to FSH (n= 33, 31) | Day 8: Subjects with ADAs to FSH (n= 34, 31) | Day1: Subjects with NAbs to FSH (n= 34, 31) | Day8: Subjects with NAbs to FSH (n= 34, 31) | |
| Freeze-dried Pergoveris | 1 | 1 | NA | NA |
| Liquid Pergoveris | 2 | 2 | NA | NA |
(NCT02317809)
Timeframe: At follow-up visit (Day 49)
| Intervention | Subjects (Number) | |
|---|---|---|
| Subjects with ADAs for FSH (n= 33) | Subjects with NAbs for FSH (n= 34) | |
| All Subjects | 1 | NA |
(NCT02317809)
Timeframe: Day 1 pre-dose up to follow-up visit (Day 18) for IMP intervention periods
| Intervention | Subjects (Number) | |
|---|---|---|
| Subjects with ADAs to LH | Subjects with Neutralizing antibodies to LH | |
| Freeze-dried Pergoveris | 0 | NA |
| Liquid Pergoveris | 0 | NA |
Injection site was assessed by the study site staff for any local reaction (redness, swelling, bruising, and itching). Redness and bruising were scaled as None (no visible redness or bruising); Mild (less than or equal to [<=] 2.0 centimeters [cm] redness or bruising); Moderate (greater than [>] 2 to <=5.0 cm redness or bruising); Severe (>5.0 cm redness or bruising). Swelling was scaled as None (no swelling detected); Mild (palpable 'firmness' only); Moderate (<= 4 cm swelling); Severe (>4 cm swelling). Itching was scaled as None (no itching); Mild itching; Moderate itching and Severe itching. Only those scale categories which report at least 1 subject were presented. (NCT02317809)
Timeframe: 5 minutes, 1, 2, 4, 6, 12, and 24 hours post-dose in each period
| Intervention | Subjects (Number) | |||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No Bruising: Day 1, 5 min (n= 34, 31) | No Bruising: Day 1, 1 hour (n= 32, 31) | No Bruising: Day 1, 2 hour (n= 34, 31) | No Bruising: Day 1, 4 hour (n= 34, 30) | No Bruising: Day 1, 6 hour (n= 33, 30) | No Bruising: Day 1, 12 hour (n= 32, 30) | No Bruising: Day 1, 24 hour (n= 34, 28) | No Itching: Day 1, 5 min (n= 34, 31) | No Itching: Day 1, 1 hour (n= 32, 31) | No Itching: Day 1, 2 hour (n= 34, 31) | No Itching: Day 1, 4 hour (n= 34, 30) | No Itching: Day 1, 6 hour (n= 33, 30) | Mild Itching: Day 1, 6 hour (n= 33, 30) | No Itching: Day 1, 12 hour (n= 32, 30) | No Itching: Day 1, 24 hour (n= 34, 28) | No Redness: Day 1, 5 min (n= 34, 31) | Mild Redness: Day 1, 5 min (n= 34, 31) | No Redness: Day 1, 1 hour (n= 32, 31) | Mild Redness: Day 1, 1 hour (n= 32, 31) | No Redness: Day 1, 2 hour (n= 34, 31) | Mild Redness: Day 1, 2 hour (n= 34, 31) | No Redness: Day 1, 4 hour (n= 34, 30) | Mild Redness: Day 1, 4 hour (n= 34, 30) | No Redness: Day 1, 6 hour (n= 33, 30) | Mild Redness: Day 1, 6 hour (n= 33, 30) | No Redness: Day 1, 12 hour (n= 32, 30) | No Redness: Day 1, 24 hour (n= 34, 28) | No Swelling: Day 1, 5 min (n= 34, 31) | No Swelling: Day 1, 1 hour (n= 32, 31) | No Swelling: Day 1, 2 hour (n= 34, 31) | No Swelling: Day 1, 4 hour (n= 34, 30) | No Swelling: Day 1, 6 hour (n= 33, 30) | No Swelling: Day 1, 12 hour (n= 32, 30) | No Swelling: Day 1, 24 hour (n= 34, 28) | |
| Freeze-dried Pergoveris | 31 | 31 | 31 | 30 | 30 | 30 | 28 | 31 | 31 | 31 | 30 | 30 | 0 | 30 | 28 | 26 | 5 | 30 | 1 | 30 | 1 | 29 | 1 | 29 | 1 | 30 | 28 | 31 | 31 | 31 | 30 | 30 | 30 | 28 |
| Liquid Pergoveris | 34 | 32 | 34 | 34 | 33 | 32 | 34 | 34 | 32 | 34 | 34 | 32 | 1 | 32 | 34 | 30 | 4 | 30 | 2 | 34 | 0 | 34 | 0 | 33 | 0 | 32 | 34 | 34 | 32 | 34 | 34 | 33 | 32 | 34 |
The severity of pain was evaluated by the subject and recorded using a 100 millimeter (mm) visual analogue scale (VAS) ranging from 0 to 100, where 0 mm = no pain and 100 mm = worst possible pain. (NCT02317809)
Timeframe: 5 minutes, 1, 2, 4, 6, 12, and 24 hours post-dose in each period
| Intervention | mm (Mean) | ||||||
|---|---|---|---|---|---|---|---|
| Day 1, 5 min (n= 34, 31) | Day 1, 1 hour (n= 32, 31) | Day 1, 2 hour (n= 34, 31) | Day 1, 4 hour (n= 34, 30) | Day 1, 6 hour (n= 33, 30) | Day 1, 12 hour (n= 32, 30) | Day 1, 24 hour (n= 34, 29) | |
| Freeze-dried Pergoveris | 2.5 | 1.3 | 0.3 | 0.2 | 1.0 | 0.2 | 0.1 |
| Liquid Pergoveris | 1.9 | 0.2 | 0.2 | 0.1 | 0.2 | 0.2 | 0.1 |
Data was planned to be presented as per the sequence of treatment received. (NCT02317809)
Timeframe: Screening (up to 28 days), Day 1 (pre-dose) and Day 8 in Period 1, Day 1 (pre-dose), Day 8 and follow-up (Day 18) in Period 2
| Intervention | nanogram per liter (ng/L) (Mean) | |||||
|---|---|---|---|---|---|---|
| Screening (n= 17, 16) | Period 1: Day 1 (pre-dose) (n= 16, 17) | Period 1: Day 8 (n= 16, 17) | Period 2: Day 1 (pre-dose) (n= 14, 16) | Period 2: Day 8 (n= 13, 17) | Follow-up (Day 18) (n= 16, 17) | |
| First Freeze-dried Pergoveris, Then Liquid Pergoveris | 15.561 | 11.369 | 12.077 | 11.975 | 47.958 | 15.997 |
| First Liquid Pergoveris, Then Freeze-dried Pergoveris | 14.906 | 11.388 | 11.833 | 12.469 | 15.454 | 15.714 |
(NCT02317809)
Timeframe: Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 60, 72, 96, 120, 168 hours post-dose in each period for FSH; Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 60, 72, 96, 120 hours post-dose in each period for LH
| Intervention | Hour (h) (Median) | |
|---|---|---|
| Follicle-stimulating Hormone | Luteinizing Hormone | |
| Freeze-dried Pergoveris | 16.575 | 7.725 |
| Liquid Pergoveris | 23.983 | 8.000 |
(NCT02317809)
Timeframe: At follow-up visit (Day 49)
| Intervention | Log Titers (Number) |
|---|---|
| All Subjects | 1.0 |
The AUC (0-t) was defined as the area under the serum concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration. Baseline-corrected AUC0-t (AUC0-t,adj) = AUC0-t - (baseline concentration * t). (NCT02317809)
Timeframe: Pre-dose, 2, 4, 6, 7, 8, 9, 10, 12, 15, 18, 24, 36, 48, 60, 72, 96, 120 and 168 hours post-dose in each period
| Intervention | International units*hour/liter (IU*h/L) (Geometric Mean) |
|---|---|
| Liquid Pergoveris | 3187.4 |
| Freeze-dried Pergoveris | 2775.4 |
"Tmax was estimated for baseline corrected FSH in serum by noncompartmental methods using actual elapsed time from dosing. Baseline corrected concentrations were determined by subtracting the baseline concentration (collected immediately prior to dosing in that period) from the postdose concentration.~Geometric mean was not calculated for Tmax and the non-transformed results are presented are for all subjects who received active study drug and had Tmax estimated in both periods." (NCT02459418)
Timeframe: From 0 hours (predose) to 192 hours postdose.
| Intervention | hours (Median) |
|---|---|
| AFOLIA | 24.05 |
| Gonal-f® RFF | 16 |
"Cmax was estimated for baseline corrected FSH in serum by noncompartmental methods using actual elapsed time from dosing. Baseline corrected concentrations were determined by subtracting the baseline concentration (collected immediately prior to dosing in that period) from the postdose concentration.~Geometric mean baseline corrected FSH exposure results are presented for all subjects who received active study drug and had at least 1 measured and valid concentration at a scheduled PK time point after administration of AFOLIA or Gonal-f® RFF." (NCT02459418)
Timeframe: From 0 hours (predose) to 192 hours postdose.
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| AFOLIA | 0.4795 |
| Gonal-f® RFF | 0.3692 |
"AUC(0-last) was estimated for baseline corrected FSH in serum by noncompartmental methods using actual elapsed time from dosing. Baseline corrected concentrations were determined by subtracting the baseline concentration (collected immediately prior to dosing in that period) from the postdose concentration.~Geometric mean baseline corrected FSH exposure results are presented for all subjects who received active study drug and had at least 1 measured and valid concentration at a scheduled PK time point after administration of AFOLIA or Gonal-f® RFF." (NCT02459418)
Timeframe: From 0 (predose),0.5, 1, 3, 6, 9, 12, 16, 20, 21, 22, 23, 24, 25, 26, 27, 28, 48, 72, 96, 120, 144, 168 and 192 hours postdose.
| Intervention | nanograms*hours/mL (ng*h/mL) (Geometric Mean) |
|---|---|
| AFOLIA | 18.96 |
| Gonal-f® RFF | 10.47 |
"AUC(0-∞) was estimated for baseline corrected FSH in serum by noncompartmental methods using actual elapsed time from dosing. Baseline corrected concentrations were determined by subtracting the baseline concentration (collected immediately prior to dosing in that period) from the postdose concentration.~Geometric mean baseline corrected FSH exposure results are presented for all subjects who received active study drug and had at least 1 measured and valid concentration at a scheduled PK time point after administration of AFOLIA or Gonal-f® RFF." (NCT02459418)
Timeframe: From 0 hours (predose) to 192 hours postdose.
| Intervention | ng*h/mL (Geometric Mean) |
|---|---|
| AFOLIA | 27.88 |
| Gonal-f® RFF | 20.57 |
"Apparent terminal half-life was defined as ln2/apparent terminal rate constant (λz). λz is determined by linear regression of the terminal points of the log-linear concentration-time curve. Visual assessment was used to identify the terminal linear phase of the baseline corrected concentration-time profile. A minimum of 3 data points was used for determination.~Terminal half-life was estimated for baseline corrected FSH in serum by noncompartmental methods using actual elapsed time from dosing. Baseline corrected concentrations were determined by subtracting the baseline concentration (collected immediately prior to dosing in that period) from the postdose concentration.~Geometric mean baseline corrected FSH exposure results are presented for all subjects who received active study drug and had at least 1 measured and valid concentration at a scheduled PK time point after administration of AFOLIA or Gonal-f® RFF." (NCT02459418)
Timeframe: From 0 hours (predose) to 192 hours postdose.
| Intervention | hours (Geometric Mean) |
|---|---|
| AFOLIA | 20.4 |
| Gonal-f® RFF | 18.02 |
"Tmax was estimated for baseline corrected E2 in serum by noncompartmental methods using actual elapsed time from dosing. Baseline corrected concentrations were determined by subtracting the baseline concentration (collected immediately prior to dosing in that period) from the postdose concentration.~Geometric mean was not calculated for Tmax and the non-transformed results are presented are for all subjects who received active study drug and had Tmax estimated in both periods." (NCT02459418)
Timeframe: From 0 hours (predose) to 192 hours postdose.
| Intervention | hours (Median) |
|---|---|
| AFOLIA | 47.92 |
| Gonal-f® RFF | 27.5 |
"Cmax was estimated for baseline corrected E2 in serum by noncompartmental methods using actual elapsed time from dosing. Baseline corrected concentrations were determined by subtracting the baseline concentration (collected immediately prior to dosing in that period) from the postdose concentration.~Geometric mean baseline corrected E2 exposure results are presented for all subjects who received active study drug and had at least 1 measured and valid concentration at a scheduled PD time point after administration of AFOLIA or Gonal-f® RFF." (NCT02459418)
Timeframe: From 0 hours (predose) to 192 hours postdose.
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| AFOLIA | 28.03 |
| Gonal-f® RFF | 15.95 |
"AUC(0-last) was estimated for baseline corrected E2 in serum by noncompartmental methods using actual elapsed time from dosing. Baseline corrected concentrations were determined by subtracting the baseline concentration (collected immediately prior to dosing in that period) from the postdose concentration.~Geometric mean baseline corrected E2 exposure results are presented for all subjects who received active study drug and had at least 1 measured and valid concentration at a scheduled PD time point after administration of AFOLIA or Gonal-f® RFF." (NCT02459418)
Timeframe: From 0 hours (predose) to 192 hours postdose.
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| AFOLIA | 888 |
| Gonal-f® RFF | 570 |
The number of mature oocytes (MII stage of development) (NCT03088137)
Timeframe: From date of randomization up to 18 days
| Intervention | Number of mature oocytes (MII stage) (Mean) |
|---|---|
| Primapur (Follitropin Alfa) | 9.64 |
| Gonal-f (Follitropin Alfa) | 9.86 |
The number of dose adjustments during the ovarian hyperstimulation protocol (increment 25-50 IU) (NCT03088137)
Timeframe: From date of randomization up to 16 days
| Intervention | Participants (Count of Participants) |
|---|---|
| Primapur (Follitropin Alfa) | 13 |
| Gonal-f (Follitropin Alfa) | 11 |
The total number of retrieved oocytes at the day of ovum pick-up. No more than 37 hours from the introduction of the trigger of ovulation (hCG or GnRH-agonist). The equivalence in the number of retrieved oocytes was tested using a predetermined equivalence margin of +/- 3.4 oocytes. (NCT03088137)
Timeframe: From date of randomization up to 18 days
| Intervention | Number of retrieved oocytes (Mean) |
|---|---|
| Primapur (Follitropin Alfa) | 12.16 |
| Gonal-f (Follitropin Alfa) | 11.62 |
Biochemical pregnancy test: serum hCG more than 25 IU/l (days 12-17 after embryo transfer) (NCT03088137)
Timeframe: From date of randomization up to 42 days
| Intervention | Percentage of patients (%) (Number) |
|---|---|
| Primapur (Follitropin Alfa) | 34.7 |
| Gonal-f (Follitropin Alfa) | 36.7 |
Confirmation of clinical pregnancy: ultrasound detection of intrauterine gestational sac and heart activity (NCT03088137)
Timeframe: The 10th week after embryo transfer
| Intervention | Percentage of patients (%) (Number) |
|---|---|
| Primapur (Follitropin Alfa) | 26.5 |
| Gonal-f (Follitropin Alfa) | 32.7 |
The total dose of the follitropin alfa administrated during the ovarian hyperstimulation protocol (measured in International Units - IU) (NCT03088137)
Timeframe: From date of randomization up to 16 days
| Intervention | Total dose (IU) (Mean) |
|---|---|
| Primapur (Follitropin Alfa) | 1532.7 |
| Gonal-f (Follitropin Alfa) | 1517.9 |
The number of patients (and percentage) with embryo transfers on days 3 and 5 after ovum pick-up (NCT03088137)
Timeframe: From date of randomization up to 25 days
| Intervention | Participants (Count of Participants) | |
|---|---|---|
| Embryo transfer on day 3 (%) | Embryo transfer on day 5 (%) | |
| Gonal-f (Follitropin Alfa) | 9 | 40 |
| Primapur (Follitropin Alfa) | 11 | 38 |
The number of fertilised oocytes with the presence of two pronuclei: 2PN (NCT03088137)
Timeframe: From date of randomization up to 19 days
| Intervention | Number of oocytes with 2PN (Mean) |
|---|---|
| Primapur (Follitropin Alfa) | 8.127 |
| Gonal-f (Follitropin Alfa) | 8.764 |
The duration of ovarian hyperstimulation protocol (at the day of trigger of ovulation) (NCT03088137)
Timeframe: From date of randomization up to 16 days
| Intervention | Days (Mean) |
|---|---|
| Primapur (Follitropin Alfa) | 9.745 |
| Gonal-f (Follitropin Alfa) | 9.727 |
The number of follicles 16 mm or over in diameter at the day of hCG (or GnRH-agonist) administration (NCT03088137)
Timeframe: From date of randomization up to 16 days
| Intervention | Number of follicles (Mean) |
|---|---|
| Primapur (Follitropin Alfa) | 12.09 |
| Gonal-f (Follitropin Alfa) | 11.38 |
The number of patients with no response to follitropin alfa treatment (absence of growing follicles, no any oocytes obtained at the day of ovum pick-up) (NCT03088137)
Timeframe: From date of randomization up to 8 days
| Intervention | Participants (Count of Participants) |
|---|---|
| Primapur (Follitropin Alfa) | 0 |
| Gonal-f (Follitropin Alfa) | 0 |
The number of the ovarian hyperstimulation protocol cancellation (at the day of trigger of ovulation) (NCT03088137)
Timeframe: From date of randomization up to 16 days
| Intervention | Participants (Count of Participants) |
|---|---|
| Primapur (Follitropin Alfa) | 0 |
| Gonal-f (Follitropin Alfa) | 0 |
Defined as proportion of participants with early OHSS, early OHSS of moderate or severe grade, preventive interventions for early OHSS, early OHSS and/or preventive interventions for early OHSS, and early OHSS of moderate or severe grade and/or preventive interventions for early OHSS are presented. (NCT03228680)
Timeframe: Up to 9 days after triggering of final follicular maturation
| Intervention | percentage of participants (Number) | |||
|---|---|---|---|---|
| Early OHSS (any grade) | Early OHSS (moderate/severe) | Early OHSS (any grade) and/or preventive | Early OHSS (moderate/severe) and/or preventive | |
| FE 999049 (Follitropin Delta) | 10.0 | 6.5 | 10.6 | 7.6 |
| FOLLISTIM (Follitropin Beta) | 18.6 | 13.0 | 20.9 | 16.4 |
(NCT03228680)
Timeframe: ≤9 days after triggering of final follicular maturation
| Intervention | percentage of participants (Number) | ||
|---|---|---|---|
| Cycle cancellation | Triggering with GnRH agonist | Administration of dopamine agonist | |
| FE 999049 (Follitropin Delta) | 0 | 1.2 | 0.6 |
| FOLLISTIM (Follitropin Beta) | 1.1 | 1.1 | 1.7 |
(NCT03228680)
Timeframe: On the day of oocyte retrieval (up to 22 days after start of stimulation)
| Intervention | percentage of participants (Number) | ||
|---|---|---|---|
| AMH < 15 pmol/L (<4 oocytes retrieved) | AMH >= 15 pmol/L (>=15 oocytes retrieved) | AMH >= 15 pmol/L (>=20 oocytes retrieved) | |
| FE 999049 (Follitropin Delta) | 11.6 | 22.0 | 8.0 |
| FOLLISTIM (Follitropin Beta) | 12.3 | 42.0 | 19.0 |
(NCT03228680)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Cycle cancelled due to poor ovarian response | Cycle cancelled due to excessive ovarian response | |
| FE 999049 (Follitropin Delta) | 1.2 | 0 |
| FOLLISTIM (Follitropin Beta) | 0.6 | 1.1 |
Defined as proportion of participants grouped according to the number of oocytes retrieved. The proportion of participants with <4 oocytes (low response), 4-7 oocytes (moderate response), 8-14 oocytes (targeted response), 15-19 oocytes (hyperresponse) and ≥20 oocytes (severe hyperresponse) are presented. (NCT03228680)
Timeframe: On the day of oocyte retrieval (up to 22 days after start of stimulation)
| Intervention | percentage of participants (Number) | ||||
|---|---|---|---|---|---|
| Low response (<4 oocytes) | Moderate response (4-7 oocytes) | Targeted response (8-14 oocytes) | Hyperresponse (15-19 oocytes) | Severe hyperresponse (≥ 20 oocytes) | |
| FE 999049 (Follitropin Delta) | 8.3 | 36.1 | 40.8 | 10.1 | 4.7 |
| FOLLISTIM (Follitropin Beta) | 5.2 | 26.6 | 42.8 | 14.5 | 11.0 |
Defined as number of participants with at least one markedly abnormal changes in hematology parameters (as assessed by investigator) were reported. Hematology parameters included: red blood cells, white blood cells, red blood cells morphology, white blood cells morphology, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, platelets. (NCT03228680)
Timeframe: Up to 5-6 weeks after transfer
| Intervention | participants (Number) | ||
|---|---|---|---|
| Leukocytes (10^9/L) Normal to markedly high (>=16) | Hemoglobin (g/L) Normal to markedly low | Hematocrit (ratio) Normal to markedly low (>=0.56) | |
| FE 999049 (Follitropin Delta) | 0 | 0 | 0 |
| FOLLISTIM (Follitropin Beta) | 1 | 1 | 1 |
Defined as number of participants with at least one markedly abnormal finding in clinical chemistry parameters (as assessed by investigator) were reported. The clinical chemistry parameters included: alanine transaminase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), bicarbonate, bilirubin direct, bilirubin total, blood urea nitrogen, calcium, chloride, cholesterol total, creatinine, gamma-glutamyl transpeptidase, glucose, lactate dehydrogenase, phosphorus, potassium, sodium, total protein, uric acid. (NCT03228680)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | participants (Number) | |
|---|---|---|
| ALT (IU/L): Normal to markedly high (>3xULN) | AST (IU/L): Normal to markedly high (>3xULN) | |
| FE 999049 (Follitropin Delta) | 0 | 0 |
| FOLLISTIM (Follitropin Beta) | 1 | 1 |
The frequency of participants with total AEs and AEs by categories of intensity (mild, moderate, severe) are presented. An AE was any untoward medical occurrence in a participants participating in clinical trial. The intensity of AE was classified using the following 3-point scale: mild = awareness of signs or symptoms, but no disruption of usual activity); moderate = event sufficient to affect usual activity (disturbing); or severe = inability to work or perform usual activities (unacceptable). (NCT03228680)
Timeframe: From signed informed consent up to 5-6 weeks after transfer
| Intervention | Participants (Number) | |||
|---|---|---|---|---|
| Any AE | Mild AE | Moderate AE | Severe AE | |
| FE 999049 (Follitropin Delta) | 73 | 69 | 8 | 0 |
| FOLLISTIM (Follitropin Beta) | 92 | 86 | 12 | 1 |
Number of embryos (total and good-quality) on Day 5 are presented. The quality evaluation of blastocysts consisted of assessment of three parameters, as per the Gardner & Schoolcraft system: blastocyst expansion and hatching status (graded: 1-6), inner cell mass (graded: A-D) and trophectoderm (graded: A-D). A good-quality blastocyst was defined as a blastocyst of grade 3BB or higher. (NCT03228680)
Timeframe: Day 5 after oocyte retrieval (up to approximately 26 days after start of stimulation)
| Intervention | Blastocysts (Mean) | |
|---|---|---|
| Number of blastocysts | Number of good-quality blastocysts | |
| FE 999049 (Follitropin Delta) | 3.1 | 2.3 |
| FOLLISTIM (Follitropin Beta) | 4.2 | 3.0 |
The presence of of injection site reactions (redness, itching, pain, swelling and bruising) immediately, 30 minutes and 24 hours after the injection are presented. The injection site reactions were assessed as none, mild, moderate and severe. The number of injection site reactions (mild, moderate or severe) based on all assessments performed is presented. (NCT03228680)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | events (Number) | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Any mild injection site reaction | Any moderate injection site reaction | Any severe injection site reaction | Mild redness | Moderate redness | Severe redness | Mild itching | Moderate itching | Severe itching | Mild pain | Moderate pain | Severe pain | Mild swelling | Moderate swelling | Severe swelling | Mild bruising | Moderate bruising | Severe bruising | |
| FE 999049 (Follitropin Delta) | 271 | 7 | 1 | 140 | 2 | 0 | 4 | 1 | 0 | 19 | 1 | 0 | 6 | 0 | 0 | 102 | 3 | 1 |
| FOLLISTIM (Follitropin Beta) | 719 | 19 | 0 | 174 | 0 | 0 | 5 | 0 | 0 | 411 | 16 | 0 | 10 | 0 | 0 | 119 | 3 | 0 |
The median and inter-quartile range (IQR) of FSH and LH levels on stimulation Day 6 are presented. (NCT03228680)
Timeframe: At Day 6 of stimulation
| Intervention | IU/L (Median) | |
|---|---|---|
| FSH | LH | |
| FE 999049 (Follitropin Delta) | 15.4 | 2.6 |
| FOLLISTIM (Follitropin Beta) | 14.7 | 2.8 |
The median and IQR of FSH and LH levels at end-of-stimulation are presented. (NCT03228680)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | IU/L (Median) | |
|---|---|---|
| FSH | LH | |
| FE 999049 (Follitropin Delta) | 14.3 | 1.6 |
| FOLLISTIM (Follitropin Beta) | 16.4 | 1.4 |
Vital pregnancy was defined as at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after transfer. (NCT03228680)
Timeframe: 5-6 weeks after transfer (up to approximately 3 months after start of stimulation)
| Intervention | percentage of participants (Number) |
|---|---|
| FE 999049 (Follitropin Delta) | 23.5 |
| FOLLISTIM (Follitropin Beta) | 21.5 |
(NCT03228680)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | IU (Mean) |
|---|---|
| FOLLISTIM (Follitropin Beta) | 1499 |
(NCT03228680)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | μg (Mean) |
|---|---|
| FE 999049 (Follitropin Delta) | 83.5 |
(NCT03228680)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | percentage of participants (Number) |
|---|---|
| FE 999049 (Follitropin Delta) | 0 |
| FOLLISTIM (Follitropin Beta) | 0 |
"Defined as proportions of participants with late OHSS (including OHSS of moderate/severe grade).~Late OHSS was defined as OHSS with onset >9 days after triggering of final follicular maturation. The proportion of participants with late OHSS, and late OHSS of moderate or severe grade are presented. All OHSS cases were graded as mild, moderate, or severe." (NCT03228680)
Timeframe: >9 days after triggering of final follicular maturation
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Late OHSS (any grade) | Late OHSS (moderate/severe) | |
| FE 999049 (Follitropin Delta) | 1.2 | 0.6 |
| FOLLISTIM (Follitropin Beta) | 1.1 | 1.1 |
Clinical pregnancy was defined as at least one gestational sac 5-6 weeks after transfer. (NCT03228680)
Timeframe: 5-6 weeks after transfer (up to approximately 3 months after start of stimulation)
| Intervention | percentage of participants (Number) |
|---|---|
| FE 999049 (Follitropin Delta) | 25.3 |
| FOLLISTIM (Follitropin Beta) | 23.7 |
The fertilization rate was defined as the number of oocytes with 2 pronuclei divided by the number of oocytes retrieved. (NCT03228680)
Timeframe: Day 1 after oocyte retrieval (up to approximately 22 days after start of stimulation)
| Intervention | percentage of fertilized oocytes (Mean) |
|---|---|
| FE 999049 (Follitropin Delta) | 54.5 |
| FOLLISTIM (Follitropin Beta) | 57.1 |
Implantation rate was defined as the number of gestational sacs 5-6 weeks after transfer divided by the number of blastocysts transferred. (NCT03228680)
Timeframe: 5-6 weeks after transfer (up to approximately 3 months after start of stimulation)
| Intervention | % of sacs/blastocysts transferred (Number) |
|---|---|
| FE 999049 (Follitropin Delta) | 31.9 |
| FOLLISTIM (Follitropin Beta) | 29.8 |
Defined as the number of follicles observed in both ovaries at the last TVUS in the stimulation phase (end-of-stimulation). (NCT03228680)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | Follicles (Mean) |
|---|---|
| FE 999049 (Follitropin Delta) | 14.9 |
| FOLLISTIM (Follitropin Beta) | 16.3 |
Defined as the number of follicles observed in both ovaries at the last transvaginal ultrasound (TVUS) in the stimulation phase (on stimulation Day 6). (NCT03228680)
Timeframe: At Day 6 of stimulation
| Intervention | Follicles (Mean) |
|---|---|
| FE 999049 (Follitropin Delta) | 12.8 |
| FOLLISTIM (Follitropin Beta) | 13.3 |
The number of oocytes retrieved was recorded at the oocyte retrieval visit. (NCT03228680)
Timeframe: 36h (± 2h) after triggering of final follicular maturation (On day of oocyte retrieval)
| Intervention | Oocytes retrieved (Mean) |
|---|---|
| FE 999049 (Follitropin Delta) | 9.3 |
| FOLLISTIM (Follitropin Beta) | 10.5 |
(NCT03228680)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | Days (Mean) |
|---|---|
| FE 999049 (Follitropin Delta) | 8.9 |
| FOLLISTIM (Follitropin Beta) | 8.8 |
Defined as positive serum beta-hCG test 13-15 days after transfer. (NCT03228680)
Timeframe: 13-15 days after transfer (up to approximately 1.5 months after start of stimulation)
| Intervention | percentage of participants (Number) |
|---|---|
| FE 999049 (Follitropin Delta) | 29.4 |
| FOLLISTIM (Follitropin Beta) | 29.4 |
Defined as number of participants with at least one markedly abnormal finding in clinical chemistry parameters (as assessed by investigator) were reported. The clinical chemistry parameters included: alanine transaminase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), bicarbonate, bilirubin direct, bilirubin total, blood urea nitrogen, calcium, chloride, cholesterol total, creatinine, gamma-glutamyl transpeptidase, glucose, lactate dehydrogenase, phosphorus, potassium, sodium, total protein, uric acid. (NCT03228680)
Timeframe: Up to 5-6 weeks after transfer
| Intervention | participants (Number) |
|---|---|
| FE 999049 (Follitropin Delta) | 0 |
| FOLLISTIM (Follitropin Beta) | 0 |
Defined as number of participants with at least one markedly abnormal changes in hematology parameters (as assessed by investigator) were reported. Hematology parameters included: red blood cells, white blood cells, red blood cells morphology, white blood cells morphology, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, platelets. (NCT03228680)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | participants (Number) |
|---|---|
| FE 999049 (Follitropin Delta) | 0 |
| FOLLISTIM (Follitropin Beta) | 0 |
(NCT03228680)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | percentage of participants (Number) |
|---|---|
| FE 999049 (Follitropin Delta) | 7.6 |
| FOLLISTIM (Follitropin Beta) | 11.3 |
"Defined as size characteristics of follicles at end-of-stimulation.~Average size of 3 largest follicles has been presented in this endpoint." (NCT03228680)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | mm (Mean) |
|---|---|
| FE 999049 (Follitropin Delta) | 19.2 |
| FOLLISTIM (Follitropin Beta) | 19.4 |
The median and IQR of Inhibin A levels at end-of-stimulation are presented. (NCT03228680)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | ng/L (Median) |
|---|---|
| FE 999049 (Follitropin Delta) | 323.8 |
| FOLLISTIM (Follitropin Beta) | 390.3 |
The median and IQR of estradiol levels at end-of-stimulation are presented. (NCT03228680)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | pmol/L (Median) |
|---|---|
| FE 999049 (Follitropin Delta) | 6517.0 |
| FOLLISTIM (Follitropin Beta) | 7438.8 |
The median and IQR of estradiol levels on stimulation Day 6 are presented. (NCT03228680)
Timeframe: At Day 6 of stimulation
| Intervention | pmol/L (Median) |
|---|---|
| FE 999049 (Follitropin Delta) | 2277.1 |
| FOLLISTIM (Follitropin Beta) | 2680.0 |
The median and IQR of progesterone levels at end-of-stimulation are presented. (NCT03228680)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | nmol/L (Median) |
|---|---|
| FE 999049 (Follitropin Delta) | 2.5 |
| FOLLISTIM (Follitropin Beta) | 3.1 |
"Defined as size characteristics of follicles on stimulation Day 6.~Average size of 3 largest follicles has been presented in this endpoint." (NCT03228680)
Timeframe: At Day 6 of stimulation
| Intervention | mm (Mean) |
|---|---|
| FE 999049 (Follitropin Delta) | 12.7 |
| FOLLISTIM (Follitropin Beta) | 12.8 |
The median and IQR of progesterone levels on stimulation Day 6 are presented. (NCT03228680)
Timeframe: At Day 6 of stimulation
| Intervention | nmol/L (Median) |
|---|---|
| FE 999049 (Follitropin Delta) | 1.7 |
| FOLLISTIM (Follitropin Beta) | 1.7 |
Number of embryos (total and good-quality) on Day 3 are presented. A good-quality embryo was defined as an embryo with ≥6 blastomeres and fragmentation ≤20% on Day 3. (NCT03228680)
Timeframe: Day 3 after oocyte retrieval (up to approximately 24 days after start of stimulation)
| Intervention | Embryo (Mean) | |
|---|---|---|
| Number of embryo | Number of good-quality embryo | |
| FE 999049 (Follitropin Delta) | 5.8 | 3.9 |
| FOLLISTIM (Follitropin Beta) | 7.0 | 4.6 |
The median and IQR of Inhibin A levels on stimulation Day 6 are presented. (NCT03228680)
Timeframe: At Day 6 of stimulation
| Intervention | ng/L (Median) |
|---|---|
| FE 999049 (Follitropin Delta) | 113.1 |
| FOLLISTIM (Follitropin Beta) | 129.8 |
The median and IQR of inhibin B levels at end-of-stimulation are presented. (NCT03228680)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | ng/L (Median) |
|---|---|
| FE 999049 (Follitropin Delta) | 686.0 |
| FOLLISTIM (Follitropin Beta) | 734.5 |
The median and IQR of inhibin B levels on stimulation Day 6 are presented. (NCT03228680)
Timeframe: At Day 6 of stimulation
| Intervention | ng/L (Median) |
|---|---|
| FE 999049 (Follitropin Delta) | 570.5 |
| FOLLISTIM (Follitropin Beta) | 686.0 |
Blood samples for analysis of circulating concentrations of LH were drawn. The median and IQR of LH levels at end-of-stimulation are presented. (NCT03296527)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | IU/L (Median) |
|---|---|
| FE 000049 (Follitropin Delta) | 1.8 |
| GONAL-F (Follitropin Alfa) | 2.0 |
Grouped according to the number of oocytes retrieved. Participants with cycle cancellation due to poor ovarian response are included in the <4 oocytes group. (NCT03296527)
Timeframe: On the day of oocyte retrieval
| Intervention | percentage of participants (Number) | ||||
|---|---|---|---|---|---|
| <4 (low response) | 4 -7 (moderate response) | 8-14 (targeted response) | 15-19(hyperresponse) | >=20 (severe hyperresponse) | |
| FE 000049 (Follitropin Delta) | 11.3 | 23.0 | 46.7 | 12.9 | 6.1 |
| GONAL-F (Follitropin Alfa) | 4.7 | 22.3 | 42.6 | 16.2 | 14.2 |
For each participant the reason for each cycle cancellation was recorded. Embryo transfer cancellation due to adverse events, such as ovarian hyperfunction, OHSS and progesterone increased in participants with embryos available for transfer, were considered as transfer cancellations due to excessive response / OHSS risk. (NCT03296527)
Timeframe: End-of-stimulation visit (up to 20 days) or transfer visit
| Intervention | percentage of participants (Number) | |||
|---|---|---|---|---|
| Cycle cancellation due to poor response | Cycle cancellation due to excessive response | Transfer cancellation due to excessive ovarian response/ OHSS risk | Cycle cancellation: poor/excessive response, or transfer cancellation excessive response/OHSS risk | |
| FE 000049 (Follitropin Delta) | 3.4 | 0 | 5.2 | 8.6 |
| GONAL-F (Follitropin Alfa) | 0.8 | 0 | 12.4 | 13.1 |
For each participant the reason for cycle cancellation will be recorded. (NCT03296527)
Timeframe: Up to 20 stimulation days
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Adverse event (including immune-related adverse events) | Technical malfunctions of the administration pen | |
| FE 000049 (Follitropin Delta) | 0 | 0 |
| GONAL-F (Follitropin Alfa) | 0.2 | 0 |
Early OHSS was defined as OHSS with onset ≤9 days after triggering of final follicular maturation. Classification of grade was according to Golan's classification system, and all OHSS cases were graded as mild, moderate or severe. (NCT03296527)
Timeframe: Up to 9 days after triggering of final follicular maturation
| Intervention | percentage of participants (Number) | ||||
|---|---|---|---|---|---|
| Early OHSS (any grade) | Early OHSS (moderate/severe) | Any preventive intervention | Early OHSS (any grade) and/or preventive interventions | Early OHSS (moderate/severe) and/or preventive interventions | |
| FE 000049 (Follitropin Delta) | 4.0 | 3.6 | 1.2 | 5.0 | 4.6 |
| GONAL-F (Follitropin Alfa) | 6.5 | 4.7 | 3.5 | 9.6 | 7.8 |
Extreme ovarian response defined as <4, ≥15 or ≥ 20 oocytes retrieved. Participants with cycle cancellation due to poor ovarian response are included as <4 oocytes retrieved. (NCT03296527)
Timeframe: Oocyte retrieval visit
| Intervention | percentage of participants (Number) | |
|---|---|---|
| <4 or >=15 oocytes retrieved | <4 or >=20 oocytes retrieved | |
| FE 000049 (Follitropin Delta) | 30.3 | 17.4 |
| GONAL-F (Follitropin Alfa) | 35.1 | 18.9 |
Blood samples for analysis of circulating concentrations of Inhibin B were drawn. The median and IQR of inhibin B levels on stimulation Day 6 are presented. (NCT03296527)
Timeframe: On stimulation Day 6
| Intervention | ng/L (Median) |
|---|---|
| FE 000049 (Follitropin Delta) | 740.0 |
| GONAL-F (Follitropin Alfa) | 901.0 |
Blood samples for analysis of circulating concentrations of Inhibin B were drawn. The median and IQR of inhibin B levels at end-of-stimulation are presented. (NCT03296527)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | ng/L (Median) |
|---|---|
| FE 000049 (Follitropin Delta) | 1020.0 |
| GONAL-F (Follitropin Alfa) | 1101.0 |
Blood samples for analysis of circulating concentrations of inhibin A. The median and IQR of inhibin A levels on stimulation Day 6 are presented. (NCT03296527)
Timeframe: On stimulation Day 6
| Intervention | ng/L (Median) |
|---|---|
| FE 000049 (Follitropin Delta) | 107.9 |
| GONAL-F (Follitropin Alfa) | 129.1 |
Blood samples for analysis of circulating concentrations of inhibin A were drawn. The median and IQR of inhibin A levels at end-of-stimulation are presented. (NCT03296527)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | ng/L (Median) |
|---|---|
| FE 000049 (Follitropin Delta) | 361.7 |
| GONAL-F (Follitropin Alfa) | 447.4 |
Blood samples for analysis of circulating concentrations of FSH were drawn. The median and IQR of FSH levels at oocyte retrieval are presented. (NCT03296527)
Timeframe: At oocyte retrieval
| Intervention | IU/L (Median) |
|---|---|
| FE 000049 (Follitropin Delta) | 5.6 |
| GONAL-F (Follitropin Alfa) | 5.5 |
Blood samples for analysis of circulating concentrations of FSH were drawn. The median and IQR of FSH levels at end-of-stimulation are presented. (NCT03296527)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | IU/L (Median) |
|---|---|
| FE 000049 (Follitropin Delta) | 11.3 |
| GONAL-F (Follitropin Alfa) | 12.2 |
Blood samples for analysis of circulating concentrations of FSH were drawn. The median and IQR of FSH levels on stimulation Day 6 are presented. (NCT03296527)
Timeframe: On stimulation Day 6
| Intervention | IU/L (Median) |
|---|---|
| FE 000049 (Follitropin Delta) | 11.6 |
| GONAL-F (Follitropin Alfa) | 11.2 |
Blood samples for analysis of circulating concentrations of estradiol were drawn. The median and IQR of estradiol levels on stimulation Day 6 are presented. (NCT03296527)
Timeframe: On stimulation Day 6
| Intervention | pmol/L (Median) |
|---|---|
| FE 000049 (Follitropin Delta) | 2240.7 |
| GONAL-F (Follitropin Alfa) | 2885.9 |
Blood samples for analysis of circulating concentrations of estradiol were drawn. The median and IQR of estradiol levels at end-of-stimulation are presented. (NCT03296527)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | pmol/L (Median) |
|---|---|
| FE 000049 (Follitropin Delta) | 7429.3 |
| GONAL-F (Follitropin Alfa) | 9055.8 |
Investigator-requested decreases and increases of the gonadotropin dose were captured during the stimulation period. (NCT03296527)
Timeframe: Up to 20 stimulation days
| Intervention | percentage of participants (Number) |
|---|---|
| FE 000049 (Follitropin Delta) | 57.1 |
| GONAL-F (Follitropin Alfa) | 55.3 |
Blood samples were collected for the analysis of haematology parameter including: Haemoglobin. (NCT03296527)
Timeframe: From screening up to end-of-trial (approximately 5.5 months)
| Intervention | g/L (Mean) |
|---|---|
| FE 000049 (Follitropin Delta) | -2.9 |
| GONAL-F (Follitropin Alfa) | -1.7 |
Blood samples were collected for the analysis of haematology parameter including: Haematocrit. (NCT03296527)
Timeframe: From screening up to end-of-trial (approximately 5.5 months)
| Intervention | Ratio (Mean) |
|---|---|
| FE 000049 (Follitropin Delta) | -0.012 |
| GONAL-F (Follitropin Alfa) | -0.008 |
Blood samples were collected for the analysis of haematology parameter including: Erythrocytes. (NCT03296527)
Timeframe: From screening up to end-of-trial (approximately 5.5 months)
| Intervention | 10^12 cells/L (Mean) |
|---|---|
| FE 000049 (Follitropin Delta) | -0.13 |
| GONAL-F (Follitropin Alfa) | -0.09 |
Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular volume. (NCT03296527)
Timeframe: From screening up to end-of-trial (approximately 5.5 months)
| Intervention | Femtoliters (Mean) |
|---|---|
| FE 000049 (Follitropin Delta) | 0.0 |
| GONAL-F (Follitropin Alfa) | 0.1 |
Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular haemoglobin concentration. (NCT03296527)
Timeframe: From screening up to end-of-trial (approximately 5.5 months)
| Intervention | mmol/L (Mean) |
|---|---|
| FE 000049 (Follitropin Delta) | 0.2 |
| GONAL-F (Follitropin Alfa) | 0.1 |
Standardised Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs). (NCT03296527)
Timeframe: From screening up to end-of-trial (approximately 5.5 months)
| Intervention | events (Number) |
|---|---|
| FE 000049 (Follitropin Delta) | 0 |
| GONAL-F (Follitropin Alfa) | 0 |
Defined as number of gestational sacs 5-6 weeks after transfer divided by number of embryos transferred. (NCT03296527)
Timeframe: 5-6 weeks after transfer
| Intervention | percentage of sacs/embryos transferred (Number) |
|---|---|
| FE 000049 (Follitropin Delta) | 35.6 |
| GONAL-F (Follitropin Alfa) | 31.3 |
Assessed by the participant during the stimulation period. Participants assessed the injection site reactions (redness, pain, itching, swelling and bruising) three times daily: immediately after the injection, 30 minutes after the injection and 24 hours after the injection. (NCT03296527)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | percentage of participants (Number) |
|---|---|
| FE 000049 (Follitropin Delta) | 23.2 |
| GONAL-F (Follitropin Alfa) | 21.6 |
The number of oocytes retrieved was recorded at the oocyte retrieval visit. (NCT03296527)
Timeframe: On the day of oocyte retrieval (36 h [±2h] after triggering of final follicular maturation)
| Intervention | oocytes retrieved (Mean) |
|---|---|
| FE 000049 (Follitropin Delta) | 10.0 |
| GONAL-F (Follitropin Alfa) | 12.4 |
Any adverse event occurring after start of IMP and before the end-of-trial visit, or a pre-treatment adverse event or pre-existing medical condition that worsens in intensity after start of IMP and before the end-of-trial visit was considered treatment-emergent, and is presented for this endpoint. (NCT03296527)
Timeframe: From screening up to end-of-trial (up to approximately 5.5 months)
| Intervention | percentage of participants (Number) |
|---|---|
| FE 000049 (Follitropin Delta) | 46.3 |
| GONAL-F (Follitropin Alfa) | 43.1 |
Calculated by start dates and end dates. (NCT03296527)
Timeframe: Up to 20 stimulation days
| Intervention | days (Mean) |
|---|---|
| FE 000049 (Follitropin Delta) | 9.2 |
| GONAL-F (Follitropin Alfa) | 8.7 |
Defined as number of intrauterine viable fetuses 10-11 weeks after transfer divided by number of embryos transferred. (NCT03296527)
Timeframe: 10-11 weeks after transfer
| Intervention | % of viable fetus/embryos transferred (Number) |
|---|---|
| FE 000049 (Follitropin Delta) | 30.7 |
| GONAL-F (Follitropin Alfa) | 25.8 |
Defined as at least one intrauterine viable fetus 10-11 weeks after transfer. (NCT03296527)
Timeframe: 10-11 weeks after transfer
| Intervention | percentage of participants (Number) |
|---|---|
| FE 000049 (Follitropin Delta) | 31.3 |
| GONAL-F (Follitropin Alfa) | 25.7 |
The percentage of MII oocytes to oocytes retrieved for participants where all oocytes were inseminated using intracytoplasmic sperm injection (ICSI) are presented. (NCT03296527)
Timeframe: Prior to insemination
| Intervention | percentage of oocytes (Mean) |
|---|---|
| FE 000049 (Follitropin Delta) | 79.5 |
| GONAL-F (Follitropin Alfa) | 77.8 |
Defined as positive βhCG test 13-15 days after transfer. (NCT03296527)
Timeframe: 13-15 days after transfer
| Intervention | percentage of participants (Number) |
|---|---|
| FE 000049 (Follitropin Delta) | 41.7 |
| GONAL-F (Follitropin Alfa) | 35.3 |
"Grouped according to occurrence of biochemical pregnancy, spontaneous abortion, vanishing twin or ectopic pregnancy (with and without medical/surgical intervention).~Frequency of early pregnancy losses are presented." (NCT03296527)
Timeframe: End-of-trial
| Intervention | percentage of participants (Number) |
|---|---|
| FE 000049 (Follitropin Delta) | 25.0 |
| GONAL-F (Follitropin Alfa) | 27.2 |
Defined as pregnancy with more than one fetus. Among participants with ongoing pregnancy, percentage of participants with twin pregnancies are presented. (NCT03296527)
Timeframe: End-of-trial
| Intervention | percentage of participants (Number) |
|---|---|
| FE 000049 (Follitropin Delta) | 7.7 |
| GONAL-F (Follitropin Alfa) | 9.9 |
Late OHSS was defined as OHSS with onset >9 days after triggering of final follicular maturation. The proportion of participants with late OHSS, and late OHSS of moderate or severe grade are presented. All OHSS cases were graded as mild, moderate, or severe. (NCT03296527)
Timeframe: After 9 days post triggering of final follicular maturation
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Late OHSS (Any grade) | Late OHSS (Moderate/severe) | |
| FE 000049 (Follitropin Delta) | 4.0 | 3.6 |
| GONAL-F (Follitropin Alfa) | 2.0 | 1.8 |
The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation or end-of-trial values for alanine aminotransferase, aspartate aminotransferase, bicarbonate, calcium, phosphate. (NCT03296527)
Timeframe: End-of-stimulation visit and end-of-trial visit
| Intervention | percentage of participants (Number) | |||||
|---|---|---|---|---|---|---|
| Alanine aminotransferase (IU/L) (End-of-stimulation) | Aspartate aminotransferase (IU/L) (End-of-stimulation) | Phosphate (mmol/L) (End-of-stimulation) | Alanine aminotransferase (IU/L) (End-of-trial) | Bicarbonate (mmol/L) (End-of-trial) | Calcium (mmol/L) (End-of-trial) | |
| FE 000049 (Follitropin Delta) | 0.2 | 0 | 0.2 | 0.4 | 1.3 | 0 |
| GONAL-F (Follitropin Alfa) | 0.2 | 0.2 | 0.0 | 0.6 | 0.8 | 0.2 |
The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation and end-of-trial values for leukocytes and lymphocytes/leukocytes. (NCT03296527)
Timeframe: End-of-stimulation visit and end-of-trial visit
| Intervention | percentage of participants (Number) | |||
|---|---|---|---|---|
| Leukocytes (10^9 cells/L) (End-of-stimulation) | Lymphocytes/leukocytes (%) (End-of-stimulation) | Leukocytes (10^9 cells/L) (End-of-trial) | Lymphocytes/leukocytes (%) (End-of-trial) | |
| FE 000049 (Follitropin Delta) | 0.7 | 0.4 | 0.7 | 0.6 |
| GONAL-F (Follitropin Alfa) | 0 | 0.2 | 0 | 0 |
Measured by presence of anti-FSH antibodies. (NCT03296527)
Timeframe: Up to 28 days after end of the stimulation period
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Treatment-induced anti-FSH antibodies (Overall) | Treatment-induced anti-FSH antibodies with neutralizing capacity | |
| FE 000049 (Follitropin Delta) | 1.40 | 0 |
| GONAL-F (Follitropin Alfa) | 0.98 | 0 |
Counted by ultrasound for the right and left ovary for each participant. (NCT03296527)
Timeframe: At end-of-stimulation (up to 20 stimulation days)
| Intervention | mm (Mean) | ||
|---|---|---|---|
| Largest follicle (mm) | Average follicle size (mm) | Average size of 3 largest follicles (mm) | |
| FE 000049 (Follitropin Delta) | 19.8 | 15.0 | 18.6 |
| GONAL-F (Follitropin Alfa) | 19.8 | 15.1 | 18.7 |
Counted by ultrasound for the right and left ovary for each participant. (NCT03296527)
Timeframe: On stimulation Day 6
| Intervention | mm (Mean) | ||
|---|---|---|---|
| Largest follicle (mm) | Average follicle size (mm) | Average size of 3 largest follicles (mm) | |
| FE 000049 (Follitropin Delta) | 13.1 | 11.5 | 12.5 |
| GONAL-F (Follitropin Alfa) | 13.2 | 11.6 | 12.6 |
Blood samples were collected for the analysis of clinical chemistry parameter including: Direct bilirubin, Bilirubin, Creatinine, Urate. (NCT03296527)
Timeframe: From screening up to end-of-trial (approximately 5.5 months)
| Intervention | umol/L (Mean) | |||
|---|---|---|---|---|
| Direct bilirubin | Bilirubin | Creatinine | Urate | |
| FE 000049 (Follitropin Delta) | -0.3 | -1.3 | -3.4 | -18.8 |
| GONAL-F (Follitropin Alfa) | -0.2 | -1.0 | -3.5 | -17.9 |
Blood samples for analysis of circulating concentrations of LH were drawn. The median and inter-quartile range (IQR) of LH levels on stimulation Day 6 are presented. (NCT03296527)
Timeframe: On stimulation Day 6
| Intervention | IU/L (Median) |
|---|---|
| FE 000049 (Follitropin Delta) | 2.6 |
| GONAL-F (Follitropin Alfa) | 3.1 |
Blood samples for analysis of circulating concentrations of progesterone were drawn. The median and IQR of progesterone levels at end-of-stimulation are presented. (NCT03296527)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | nmol/L (Median) |
|---|---|
| FE 000049 (Follitropin Delta) | 2.4 |
| GONAL-F (Follitropin Alfa) | 3.2 |
Blood samples for analysis of circulating concentrations of progesterone were drawn. The median and IQR of progesterone levels on stimulation Day 6 are presented. (NCT03296527)
Timeframe: On stimulation Day 6
| Intervention | nmol/L (Median) |
|---|---|
| FE 000049 (Follitropin Delta) | 1.7 |
| GONAL-F (Follitropin Alfa) | 1.9 |
Defined as at least one gestational sac 5-6 weeks after transfer. (NCT03296527)
Timeframe: 5-6 weeks after transfer
| Intervention | percentage of participants (Number) |
|---|---|
| FE 000049 (Follitropin Delta) | 36.1 |
| GONAL-F (Follitropin Alfa) | 31.2 |
The fertilization rate was defined as the number of oocytes with 2 pronuclei divided by the number of oocytes retrieved. (NCT03296527)
Timeframe: On Day 1 after oocyte retrieval
| Intervention | percentage of fertilized oocytes (Mean) |
|---|---|
| FE 000049 (Follitropin Delta) | 63.5 |
| GONAL-F (Follitropin Alfa) | 63.9 |
Defined as at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after transfer. (NCT03296527)
Timeframe: 5-6 weeks after transfer
| Intervention | percentage of participants (Number) |
|---|---|
| FE 000049 (Follitropin Delta) | 32.3 |
| GONAL-F (Follitropin Alfa) | 28.0 |
Calculated by start dates, end dates and daily dose of IMP. (NCT03296527)
Timeframe: Up to 20 stimulation days
| Intervention | microgram of dose (Mean) |
|---|---|
| FE 000049 (Follitropin Delta) | 77.5 |
| GONAL-F (Follitropin Alfa) | 109.9 |
Incidences of technical malfunctions of the administration pen were recorded. (NCT03296527)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | percentage of participants (Number) |
|---|---|
| FE 000049 (Follitropin Delta) | 0.4 |
| GONAL-F (Follitropin Alfa) | 0 |
Blood samples were collected for the analysis of clinical chemistry parameters including: Bicarbonate, Blood urea nitrogen, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium and Sodium. (NCT03296527)
Timeframe: From screening up to end-of-trial (approximately 5.5 months)
| Intervention | mmol/L (Mean) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Bicarbonate | Blood urea nitrogen | Calcium | Chloride | Cholesterol | Glucose | Phosphate | Potassium | Sodium | |
| FE 000049 (Follitropin Delta) | -0.83 | -0.27 | -0.010 | -0.3 | 0.218 | -0.01 | 0.037 | 0.03 | -1.8 |
| GONAL-F (Follitropin Alfa) | -0.72 | -0.23 | 0.000 | -0.3 | 0.260 | -0.01 | 0.023 | 0.04 | -1.7 |
Blood samples were collected for the analysis of haematology parameters including: Basophils/leukocytes, Eosinophils/leukocytes, Lymphocytes/leukocytes, Monocytes/leukocytes and Neutrophils/leukocytes. (NCT03296527)
Timeframe: From screening up to end-of-trial (approximately 5.5 months)
| Intervention | percentage (Mean) | ||||
|---|---|---|---|---|---|
| Basophils/leukocytes | Eosinophils/leukocytes | Lymphocytes/leukocytes | Monocytes/leukocytes | Neutrophils/leukocytes | |
| FE 000049 (Follitropin Delta) | -0.01 | -0.01 | -2.05 | -0.16 | 2.20 |
| GONAL-F (Follitropin Alfa) | 0.02 | -0.07 | -1.39 | -0.04 | 1.50 |
Blood samples were collected for the analysis of haematology parameters including: Leukocytes and Platelets. (NCT03296527)
Timeframe: From screening up to end-of-trial (approximately 5.5 months)
| Intervention | 10^9 cells/L (Mean) | |
|---|---|---|
| Leukocytes | Platelets | |
| FE 000049 (Follitropin Delta) | 1.161 | 19.9 |
| GONAL-F (Follitropin Alfa) | 0.996 | 23.8 |
The intensity of immune-related adverse event was classified using the following 3-point scale: mild = awareness of signs or symptoms, but no disruption of usual activity; moderate = event sufficient to affect usual activity (disturbing); or severe = inability to work or perform usual activities (unacceptable). (NCT03296527)
Timeframe: From screening up to end-of-trial (approximately 5.5 months)
| Intervention | events (Number) | ||
|---|---|---|---|
| Mild | Moderate | Severe | |
| FE 000049 (Follitropin Delta) | 0 | 0 | 0 |
| GONAL-F (Follitropin Alfa) | 0 | 0 | 0 |
Blood samples were collected for the analysis of clinical chemistry parameters including: Alanine aminotransferase, Alkaline phosphatase, Aspartate aminotransferase and Gamma glutamyl transferase. (NCT03296527)
Timeframe: From screening up to end-of-trial (up to approximately 5.5 months)
| Intervention | IU/L (Mean) | |||
|---|---|---|---|---|
| Alanine aminotransferase | Alkaline phosphatase | Aspartate aminotransferase | Gamma glutamyl transferase | |
| FE 000049 (Follitropin Delta) | 3.9 | -2.9 | 0.7 | 1.1 |
| GONAL-F (Follitropin Alfa) | 4.6 | -2.7 | 1.2 | 1.1 |
Blood samples were collected for the analysis of clinical chemistry parameters including: Albumin and Protein. (NCT03296527)
Timeframe: From screening up to end-of-trial (approximately 5.5 months)
| Intervention | g/L (Mean) | |
|---|---|---|
| Albumin | Protein | |
| FE 000049 (Follitropin Delta) | -2.0 | -2.3 |
| GONAL-F (Follitropin Alfa) | -1.6 | -1.5 |
Blood samples were collected for the analysis of haematology parameter including: Erythrocyte mean corpuscular haemoglobin. (NCT03296527)
Timeframe: From screening up to end-of-trial (approximately 5.5 months)
| Intervention | picogram (Mean) |
|---|---|
| FE 000049 (Follitropin Delta) | 0.3 |
| GONAL-F (Follitropin Alfa) | 0.2 |
Blood samples were collected for the analysis of clinical chemistry parameter including: Lactate dehydrogenase. (NCT03296527)
Timeframe: From screening up to end-of-trial (approximately 5.5 months)
| Intervention | U/L (Mean) |
|---|---|
| FE 000049 (Follitropin Delta) | -3.0 |
| GONAL-F (Follitropin Alfa) | -0.9 |
The intensity of adverse event was classified using the following 3-point scale: mild = awareness of signs or symptoms, but no disruption of usual activity; moderate = event sufficient to affect usual activity (disturbing); or severe = inability to work or perform usual activities (unacceptable). (NCT03296527)
Timeframe: From screening up to end-of-trial (up to approximately 5.5 months)
| Intervention | percentage of participants (Number) | ||
|---|---|---|---|
| Mild adverse events | Moderate adverse events | Severe adverse events | |
| FE 000049 (Follitropin Delta) | 40.1 | 7.4 | 3.6 |
| GONAL-F (Follitropin Alfa) | 37.8 | 5.9 | 1.8 |
Assessed by the participant during the stimulation period as mild, moderate or severe. Participants are tabulated according to the highest severity of their reported injection site reactions. (NCT03296527)
Timeframe: End-of-stimulation (up to 20 stimulation days)
| Intervention | percentage of participants (Number) | ||
|---|---|---|---|
| Mild injection site reaction | Moderate injection site reaction | Severe injection site reaction | |
| FE 000049 (Follitropin Delta) | 21.6 | 1.6 | 0 |
| GONAL-F (Follitropin Alfa) | 21.2 | 0.4 | 0 |
Number of embryos (total and good-quality) on Day 3 are presented. A good-quality embryo was defined as an embryo with ≥6 blastomeres and ≤20% fragmentation, without signs of multinucleation. (NCT03296527)
Timeframe: On Day 3 after oocyte retrieval
| Intervention | embryos (Mean) | |
|---|---|---|
| Number of embryos | Number of good-quality embryos | |
| FE 000049 (Follitropin Delta) | 7.0 | 4.1 |
| GONAL-F (Follitropin Alfa) | 8.7 | 5.2 |
Counted by ultrasound for the right and left ovary for each participant. (NCT03296527)
Timeframe: At end-of-stimulation (up to 20 stimulation days)
| Intervention | number of follicles (Mean) | |||
|---|---|---|---|---|
| Follicles >= 10 mm | Follicles >= 12 mm | Follicles >= 15 mm | Follicles >= 17 mm | |
| FE 000049 (Follitropin Delta) | 12.4 | 10.3 | 6.5 | 4.1 |
| GONAL-F (Follitropin Alfa) | 14.2 | 11.9 | 7.5 | 4.5 |
Counted by ultrasound for the right and left ovary for each participant. (NCT03296527)
Timeframe: On stimulation Day 6
| Intervention | number of follicles (Mean) | |||
|---|---|---|---|---|
| Follicles >= 10 mm | Follicles >= 12 mm | Follicles >= 15 mm | Follicles >= 17 mm | |
| FE 000049 (Follitropin Delta) | 5.4 | 2.3 | 0.3 | 0.1 |
| GONAL-F (Follitropin Alfa) | 6.4 | 2.9 | 0.3 | 0.0 |
"Area under curve (AUC), Time frame: From 0 (predose), 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 120, 168 and 192 hours postdose.~Blood samples to study the pharmacokinetics are to be collected via a venous catheter, which is placed by means of vein puncture before any injection of r-hFSH. Blood sampling were carried out at certain time points according to the specified scheme: - 20 minutes (20 minutes before the drug injection), 0 hours (immediately prior to injection), and 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 120, 168, and 192 hours after each injection of the drug product." (NCT03857230)
Timeframe: 0-192 hours
| Intervention | mIU*h/ml (Geometric Mean) |
|---|---|
| Primapur | 1202.85 |
| Gonal-F | 1241.01 |
Elimination rate constant (Kel): Time frame: From 0 (predose), 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 120, 168 and 192 hours postdose. (NCT03857230)
Timeframe: 0-192 hours
| Intervention | 1/h (Mean) |
|---|---|
| Primapur | 0.01 |
| Gonal-F | 0.01 |
Terminal half-life (T1/2), Time frame: From 0 (predose), 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 120, 168 and 192 hours postdose. (NCT03857230)
Timeframe: 0-192 hours
| Intervention | hours (Geometric Least Squares Mean) |
|---|---|
| Primapur | 70.78 |
| Gonal-F | 71.71 |
Maximum serum concentration (Cmax), Time frame: From 0 (predose), 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 120, 168 and 192 hours postdose. (NCT03857230)
Timeframe: 0-192 hours
| Intervention | mIU/ml (Geometric Mean) |
|---|---|
| Primapur | 14.32 |
| Gonal-F | 16.00 |
Time to reach a maximum serum concentration (Tmax), Time frame: From 0 (predose), 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 120, 168 and 192 hours postdose. (NCT03857230)
Timeframe: 0-192 hours
| Intervention | hours (Mean) |
|---|---|
| Primapur | 18.70 |
| Gonal-F | 19.22 |
(NCT04150861)
Timeframe: At -1, -0.5 and 0 hour predose, and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 48 hours, and 3, 4, 5, 6, 7, 8, and 9 days postdose
| Intervention | Liter (Geometric Mean) |
|---|---|
| Follitropin Delta (FE 999049) 12 μg | 25.5 |
| Follitropin Delta (FE 999049) 18 μg | 20.8 |
| Follitropin Delta (FE 999049) 24 μg | 25.4 |
Area under the concentration-time curve from dosing to infinity. (NCT04150861)
Timeframe: At -1, -0.5 and 0 hour predose, and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 48 hours, and 3, 4, 5, 6, 7, 8, and 9 days postdose
| Intervention | h*ng/mL (Geometric Mean) |
|---|---|
| Follitropin Delta (FE 999049) 12 μg | 41.3 |
| Follitropin Delta (FE 999049) 18 μg | 62.9 |
| Follitropin Delta (FE 999049) 24 μg | 83.1 |
AUCt is defined as the area under the serum concentration-time curve from dosing up to time t, where t is the last time point at which the concentration is above the lower limit of quantification. (NCT04150861)
Timeframe: At -1, -0.5 and 0 hour predose, and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 48 hours, and 3, 4, 5, 6, 7, 8, and 9 days postdose
| Intervention | h*ng/mL (Geometric Mean) |
|---|---|
| Follitropin Delta (FE 999049) 12 μg | 36.4 |
| Follitropin Delta (FE 999049) 18 μg | 56.6 |
| Follitropin Delta (FE 999049) 24 μg | 74.6 |
The injection site reactions (redness, pain, itching, swelling, and bruising) will be assessed by the investigator after injection, 30 minutes, and 24 hours after administration of the IMP. Each injection site reaction will be assessed as none, mild, moderate, or severe. (NCT04150861)
Timeframe: Immediately, 30 minutes, and 24 hours after administration
| Intervention | Participants (Count of Participants) |
|---|---|
| Follitropin Delta (FE 999049) 12 μg | 0 |
| Follitropin Delta (FE 999049) 18 μg | 0 |
| Follitropin Delta (FE 999049) 24 μg | 0 |
An AE is any untoward medical occurrence in a participant participating in a clinical trial. Number of participants with any AE (serious or non-serious) and type of AEs ( mild, moderate, severe) are presented. (NCT04150861)
Timeframe: From signed informed consent until the end-of-trial visit (Day 28)
| Intervention | Participants (Count of Participants) | ||||
|---|---|---|---|---|---|
| Adverse events (AEs) | Serious AEs | Mild AEs | Moderate AEs | Severe AEs | |
| Follitropin Delta (FE 999049) 12 μg | 5 | 0 | 5 | 0 | 0 |
| Follitropin Delta (FE 999049) 18 μg | 4 | 0 | 3 | 1 | 0 |
| Follitropin Delta (FE 999049) 24 μg | 3 | 0 | 3 | 0 | 0 |
Maximum concentration observed in serum. (NCT04150861)
Timeframe: At -1, -0.5 and 0 hour predose, and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 48 hours, and 3, 4, 5, 6, 7, 8, and 9 days postdose
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| Follitropin Delta (FE 999049) 12 μg | 0.388 |
| Follitropin Delta (FE 999049) 18 μg | 0.677 |
| Follitropin Delta (FE 999049) 24 μg | 0.825 |
Number of participants with clinically significant abnormal changes in ECG are presented. (NCT04150861)
Timeframe: At screening, on Day -1, at 12, 24, 48 hours postdose, and at the follow-up visit (Day 11)
| Intervention | Participants (Count of Participants) |
|---|---|
| Follitropin Delta (FE 999049) 12 μg | 0 |
| Follitropin Delta (FE 999049) 18 μg | 0 |
| Follitropin Delta (FE 999049) 24 μg | 1 |
Number of participants with clinically significant abnormal changes in vital signs (systemic blood pressures, heart rate and body temperature) are presented. (NCT04150861)
Timeframe: At screening, on Day -1, at 12, 24, 48 hours postdose, and at the follow-up visit (Day 11)
| Intervention | Participants (Count of Participants) |
|---|---|
| Follitropin Delta (FE 999049) 12 μg | 0 |
| Follitropin Delta (FE 999049) 18 μg | 0 |
| Follitropin Delta (FE 999049) 24 μg | 0 |
(NCT04150861)
Timeframe: On Day 1 predose, Day 7, and Day 28
| Intervention | Participants (Count of Participants) |
|---|---|
| Follitropin Delta (FE 999049) 12 μg | 0 |
| Follitropin Delta (FE 999049) 18 μg | 0 |
| Follitropin Delta (FE 999049) 24 μg | 0 |
(NCT04150861)
Timeframe: At -1, -0.5 and 0 hour predose, and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 48 hours, and 3, 4, 5, 6, 7, 8, and 9 days postdose
| Intervention | hour (Geometric Mean) |
|---|---|
| Follitropin Delta (FE 999049) 12 μg | 58.6 |
| Follitropin Delta (FE 999049) 18 μg | 50.5 |
| Follitropin Delta (FE 999049) 24 μg | 60.9 |
Time of maximum observed concentration in serum. (NCT04150861)
Timeframe: At -1, -0.5 and 0 hour predose, and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 48 hours, and 3, 4, 5, 6, 7, 8, and 9 days postdose
| Intervention | hour (Median) |
|---|---|
| Follitropin Delta (FE 999049) 12 μg | 24.0 |
| Follitropin Delta (FE 999049) 18 μg | 24.0 |
| Follitropin Delta (FE 999049) 24 μg | 24.0 |
Number of participants with clinically significant abnormal findings in laboratory parameters (clinical chemistry, haematology, urinalysis) are presented. (NCT04150861)
Timeframe: At screening, on Day -1 and Day 3, and at the follow-up visit (Day 11)
| Intervention | Participants (Count of Participants) | ||
|---|---|---|---|
| Clinical Chemistry | Haematology | Urinalysis | |
| Follitropin Delta (FE 999049) 12 μg | 2 | 0 | 0 |
| Follitropin Delta (FE 999049) 18 μg | 1 | 1 | 1 |
| Follitropin Delta (FE 999049) 24 μg | 1 | 0 | 0 |
(NCT04150861)
Timeframe: At -1, -0.5 and 0 hour predose, and at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 48 hours, and 3, 4, 5, 6, 7, 8, and 9 days postdose
| Intervention | Liter/hour (Geometric Mean) |
|---|---|
| Follitropin Delta (FE 999049) 12 μg | 0.301 |
| Follitropin Delta (FE 999049) 18 μg | 0.286 |
| Follitropin Delta (FE 999049) 24 μg | 0.289 |
"Mean dose of follitropin alpha biosimilar for ovarian stimulation.~Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646)." (NCT04854707)
Timeframe: From date of start of ovarian stimulation with follitropin alpha up to 16 days
| Intervention | IU (International Units) (Mean) |
|---|---|
| Mixed Protocols: Recombinant and Urinary-derived Gonadotropins and Antagonists/Agonists of GnRH | 1672 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists/Agonists of GnRH | 1919 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists of GnRH | 1952 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Agonist of GnRH | 1711 |
| The Overall Protocols | 1825 |
"Ongoing clinical pregnancy per embryo transfer (detection of gestational sac and heartbeat from 6 weeks after transfer), n (ongoing pregnancy rate per transfer with known outcome, %).~Due to delayed embryo transfers, the analysed population for Ongoing clinical pregnancy per embryo transfer was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2007 embryo transfers (1542 with known outcome); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2213 embryo transfers (1800 with known outcome); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 1809 embryo transfers (1466 with known outcome) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 404 embryo transfers (334 with known outcome)." (NCT04854707)
Timeframe: At least 6 weeks after embryo transfer
| Intervention | Percetnage of patients (%) (Number) |
|---|---|
| Mixed Protocols: Recombinant and Urinary-derived Gonadotropins and Antagonists/Agonists of GnRH | 39.3 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists/Agonists of GnRH | 37.6 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists of GnRH | 37.9 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Agonist of GnRH | 35.9 |
| The Overall Protocols | 38.4 |
"The total number of retrieved oocytes at the day of ovum pick-up. No more than 37 hours from the introduction of the ovulation inducer (HCG or GnRH-agonist).~Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646)." (NCT04854707)
Timeframe: From date of start of ovarian stimulation with follitropin alpha up to 15 days
| Intervention | The total number of retrieved oocytes (Mean) |
|---|---|
| Mixed Protocols: Recombinant and Urinary-derived Gonadotropins and Antagonists/Agonists of GnRH | 8.6 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists/Agonists of GnRH | 10.3 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists of GnRH | 10.5 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Agonist of GnRH | 9.6 |
| The Overall Protocols | 9.5 |
"Fertilization rate (FR) is percentage of transformation of oocytes into two pronuclei (presence of two pronuclei: zygotes with 2PN).~Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646)." (NCT04854707)
Timeframe: From date of start of ovarian stimulation with follitropin alpha up to 16 days
| Intervention | zygotes with 2PN (Mean) |
|---|---|
| Mixed Protocols: Recombinant and Urinary-derived Gonadotropins and Antagonists/Agonists of GnRH | 5.8 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists/Agonists of GnRH | 7.2 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists of GnRH | 7.3 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Agonist of GnRH | 5.7 |
| The Overall Protocols | 6.1 |
"Mature oocytes (MII stage of development).~Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646)." (NCT04854707)
Timeframe: From date of start of ovarian stimulation with follitropin alpha up to 15 days
| Intervention | Number of mature oocytes (Mean) |
|---|---|
| Mixed Protocols: Recombinant and Urinary-derived Gonadotropins and Antagonists/Agonists of GnRH | 6.7 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists/Agonists of GnRH | 7.7 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Antagonists of GnRH | 7.6 |
| Monoprotocols: Follitropin Alpha Biosimilar Only and Agonist of GnRH | 6.7 |
| The Overall Protocols | 6.8 |
| Substance | Relationship Strength | Studies | Trials | Classes | Roles |
|---|---|---|---|---|---|
| buserelin Buserelin: A potent synthetic analog of GONADOTROPIN-RELEASING HORMONE with D-serine substitution at residue 6, glycine10 deletion, and other modifications. | 2.04 | 1 | 0 | oligopeptide | |
| enclomiphene Enclomiphene: The trans or (E)-isomer of clomiphene. | 4.33 | 1 | 1 | ||
| anandamide anandamide : An N-acylethanolamine 20:4 resulting from the formal condensation of carboxy group of arachidonic acid with the amino group of ethanolamine. | 2.25 | 1 | 0 | endocannabinoid; N-acylethanolamine 20:4 | human blood serum metabolite; neurotransmitter; vasodilator agent |
| menotropins Menotropins: Extracts of urine from menopausal women that contain high concentrations of pituitary gonadotropins, FOLLICLE STIMULATING HORMONE and LUTEINIZING HORMONE. Menotropins are used to treat infertility. The FSH:LH ratio and degree of purity vary in different preparations. | 6.18 | 6 | 2 | ||
| trelstar Triptorelin Pamoate: A potent synthetic long-acting agonist of GONADOTROPIN-RELEASING HORMONE with D-tryptophan substitution at residue 6. | 2.1 | 1 | 0 | ||
| cetrorelix cetrorelix: LHRH antagonist. cetrorelix : A synthetic ten-membered oligopeptide comprising N-acetyl-3-(naphthalen-2-yl)-D-alanyl, 4-chloro-D-phenylalanyl, 3-(pyridin-3-yl)-D-alanyl, L-seryl, L-tyrosyl, N(5)-carbamoyl-D-ornithyl, L-leucyl, L-arginyl, L-prolyl, and D-alaninamide residues coupled in sequence. A gonadotrophin-releasing hormone (GnRH) antagonist, it is used for treatment of infertility and of hormone-sensitive cancers of the prostate and breast. | 2.1 | 1 | 0 | oligopeptide | antineoplastic agent; GnRH antagonist |
| Condition | Indicated | Relationship Strength | Studies | Trials |
|---|---|---|---|---|
| Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. | 0 | 9.78 | 12 | 8 |
| Azoospermia A condition of having no sperm present in the ejaculate (SEMEN). | 0 | 2.17 | 1 | 0 |
| Sterility, Male [description not available] | 0 | 2.21 | 1 | 0 |
| Infertility, Male The inability of the male to effect FERTILIZATION of an OVUM after a specified period of unprotected intercourse. Male sterility is permanent infertility. | 0 | 2.21 | 1 | 0 |
| Sterility, Female [description not available] | 0 | 6.67 | 4 | 3 |
| Infertility, Female Diminished or absent ability of a female to achieve conception. | 0 | 6.67 | 4 | 3 |
| Hypergonadotropic Hypogonadism [description not available] | 0 | 4.41 | 1 | 1 |
| Hypogonadism Condition resulting from deficient gonadal functions, such as GAMETOGENESIS and the production of GONADAL STEROID HORMONES. It is characterized by delay in GROWTH, germ cell maturation, and development of secondary sex characteristics. Hypogonadism can be due to a deficiency of GONADOTROPINS (hypogonadotropic hypogonadism) or due to primary gonadal failure (hypergonadotropic hypogonadism). | 0 | 4.41 | 1 | 1 |
| Reproductive Sterility [description not available] | 0 | 6.45 | 4 | 4 |
| Infertility A reduced or absent capacity to reproduce. | 0 | 6.45 | 4 | 4 |
| Edema-Proteinuria-Hypertension Gestosis [description not available] | 0 | 2.15 | 1 | 0 |
| Pre-Eclampsia A complication of PREGNANCY, characterized by a complex of symptoms including maternal HYPERTENSION and PROTEINURIA with or without pathological EDEMA. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease. | 0 | 2.15 | 1 | 0 |
| Cardiac Failure [description not available] | 0 | 2.15 | 1 | 0 |
| Extravascular Hemolysis [description not available] | 0 | 2.15 | 1 | 0 |
| Blood Clot [description not available] | 0 | 2.15 | 1 | 0 |
| Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION. | 0 | 2.15 | 1 | 0 |
| Hemolysis The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. | 0 | 2.15 | 1 | 0 |
| Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. | 0 | 2.15 | 1 | 0 |
| Ovarian Hyperstimulation Syndrome, Familial Gestational Spontaneous [description not available] | 0 | 4.68 | 3 | 2 |
| Ovarian Hyperstimulation Syndrome A complication of OVULATION INDUCTION in infertility treatment. It is graded by the severity of symptoms which include OVARY enlargement, multiple OVARIAN FOLLICLES; OVARIAN CYSTS; ASCITES; and generalized EDEMA. The full-blown syndrome may lead to RENAL FAILURE, respiratory distress, and even DEATH. Increased capillary permeability is caused by the vasoactive substances, such as VASCULAR ENDOTHELIAL GROWTH FACTORS, secreted by the overly-stimulated OVARIES. | 0 | 4.68 | 3 | 2 |
| Polycystic Ovarian Syndrome [description not available] | 0 | 5.31 | 2 | 2 |
| Polycystic Ovary Syndrome A complex disorder characterized by infertility, HIRSUTISM; OBESITY; and various menstrual disturbances such as OLIGOMENORRHEA; AMENORRHEA; ANOVULATION. Polycystic ovary syndrome is usually associated with bilateral enlarged ovaries studded with atretic follicles, not with cysts. The term, polycystic ovary, is misleading. | 0 | 5.31 | 2 | 2 |