cetrorelix and Infertility--Female

The use of cetrorelix within ovarian-stimulation protocols demonstrates several advantages compared with gonadotropin-releasing hormone (GnRH) agonist-containing protocols, which include, for example, significantly less time for analogue treatment and a reduction in the amount of gonadotropins needed. Furthermore, fewer side effects can be expected. There is no difference regarding endometrium quality and hormone profiles, and the results of assisted reproduction cycles are comparable. Cetrorelix also seems to be useful in the treatment of endometriosis which, in most cases, is an estrogen-dependent disease. Furthermore, fewer side effects occur with this agent (e.g., postmenopausal symptoms) and no estradiol add-back is needed. In the future, new nonpeptic GnRH antagonists are expected to be available for oral administration. Although they are still under investigation, these agents have the potential to improve patients' comfort and compliance.

Topics: Adult; Clinical Trials as Topic; Endometriosis; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Middle Aged

This article is a systematic review of the literature on utilization of gonadotrophin-releasing hormone antagonists (GnRH-ant) for ovarian stimulation for IVF in special patient groups. Summarized by meta-analysis are the data from randomized controlled trials (RCT) in which GnRH-agonist (GnRH-a) and GnRH-ant were compared (eight RCT for poor response, four RCT for PCOS). Also reviewed are the data from two RCT and 13 retrospective or observational trials in which patients at risk of ovarian hyperstimulation syndrome (OHSS) were triggered with GnRH-agonist instead of HCG. For poor responders, no differences in clinical outcomes were found, except a significantly higher number of cumulus-oocyte complexes in GnRH-antagonist multiple dose protocol as compared to GnRH-agonist long protocol (P=0.05). For PCOS patients, no differences in outcomes were found, except a significantly shorter duration of stimulation, when GnRH-antagonist multiple dose protocol and GnRH-agonist long protocol are compared (P<0.01). However, sample sizes are still small and power to detect subtle differences is therefore limited. For OHSS risk patients triggered with GnRH-agonist, reports on the efficacy of this measure vary in the literature. GnRH-agonist triggering appears to be associated with a reduction in the incidence of mild and moderate OHSS. For prevention of severe OHSS, as yet, only very limited evidence is available.

Topics: Drug Administration Schedule; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Odds Ratio; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome

Gonadotrophin-releasing hormone (GnRH) plays a key role in the secretion of gonadotrophins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which regulate steroidogenesis and folliculogenesis. Two GnRH antagonists, Cetrorelix and Ganirelix, deprived of histaminergic side-effects, have been introduced into ovarian stimulation protocols to prevent premature LH surges and proved their safety in clinical trials. At present, most of the published studies have not found significant differences in follicular recruitment, oocyte quality, and so on, except for a decrease in pregnancy and implantation rates in in vitro fertilization and embryo transfer (IVF-ET) cycles when the GnRH antagonist rather than the agonist was used. This decrease in pregnancy rates was in relation with a necessary learning curve of the physicians. Another possibility is the impact of the GnRH antagonist on endometrium through its GnRH receptor; this effect was cancelled after cryopreserved embryo transfers because the pregnancy rates were similar between GnRH antagonist and agonist in this case. GnRH antagonists were also interesting in poor responders and polycystic ovarian syndrome, where the agonists have not permitted to obtain the better results in IVF-ET cycles. Similarly, the GnRH antagonists could prevent the LH surge in the intrauterine insemination cycles.

Topics: Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Oocytes; Pregnancy; Reproductive Medicine

Topics: Amino Acid Sequence; Buserelin; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Infertility, Male; Male; Models, Biological

Topics: Embryo Transfer; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Ovulation; Pregnancy; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

Gonadotrophin-releasing hormone (GnRH) antagonists have recently been introduced into clinical practice. They appear to offer a promising alternative to the long-established GnRH agonist regimens for prevention of a premature LH surge during ovarian stimulation for assisted reproductive techniques. Clinical outcomes achieved with antagonists are comparable with those of a long GnRH agonist protocol, while treatment times and gonadotrophin requirements are reduced and safety is improved. In particular, the antagonists appear to be associated with a lower risk of ovarian hyperstimulation syndrome (OHSS) than do agonists. Patient surveys suggest a preference for antagonist over agonist treatment cycles. These benefits suggest that GnRH antagonists have the potential to replace agonists as the treatment of choice in ovarian stimulation for assisted reproductive techniques. Two agents, cetrorelix and ganirelix, are currently in clinical use. Cetrorelix is available in single- and multiple-dose formulations, offering increased flexibility compared with ganirelix.

Topics: Amino Acid Sequence; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Molecular Sequence Data; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Pregnancy; Pregnancy Outcome; Recombinant Proteins

The introduction of the gonadotrophin-releasing hormone(GnRH) antagonists offers new potential for in vitro fertilization (IVF) clinics. Compared with GnRH agonists, the use of the GnRH antagonists significantly reduces the dose of gonadotrophin and duration of treatment required, and also reduces unwanted side-effects. Patients also tend to prefer treatment with GnRH antagonists compared with agonists. The GnRH antagonists are useful in both good and poor responders, and there is some flexibility in treatment protocols. A single dose of GnRH antagonist may be used in patients who do not want or require more aggressive stimulation. Promising data indicate advantages of GnRH antagonists in terms of reduced incidence of ovarian hyperstimulation syndrome and reduced impairment of luteal function. It is anticipated that, as a result of further development of treatment protocols, pregnancy rates with the GnRH antagonists will become at least equivalent to those achieved with GnRH agonist protocols.

Topics: Clinical Trials, Phase III as Topic; Female; Gonadotropin-Releasing Hormone; Gonadotropins; Hormone Antagonists; Humans; Infertility, Female; Ovarian Hyperstimulation Syndrome; Ovulation Induction

Suppression of endogenous hormone production by gonadotrophin-releasing hormone (GnRH) agonists followed by controlled ovarian hyperstimulation (COH) with human gonadotrophins, especially the so-called 'long protocol' has developed from second-line into first-line therapy. Due to this attitude premature luteinization can be safely avoided, enhancing therapeutic efficacy. Recombinant preparations of human follicle stimulating hormone (FSH) have been proven to be effective within COH according to the long protocol. The high purity of these compounds may have clinical advantages. GnRH antagonists could be successfully introduced in COH protocols. Also, daily injections in the midcycle phase according to the 'Lübeck protocol', as single or only dual administrations around day 9 seem to abolish any premature LH rises. Due to their different pharmacological mode of action, based on a classic competitive receptor blockage GnRH antagonists avoid any flare-up period and allow ovarian stimulation to start within the spontaneous cycle. Pregnancy rates are comparable to those after long protocol stimulation. Combination of softer stimulation regimes like clomiphene citrate and low dose HMG with midcycle administration of GnRH antagonists may be the way to a cheap, safe and efficient ovarian stimulation. It seems to be high time for modest forms of ovarian stimulation, lowering burden and risk for our patients.

Topics: Female; Fertility Agents, Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Menotropins; Ovary; Ovulation Induction; Pregnancy; Pregnancy Rate; Recombinant Proteins

Studies testing the effectiveness of GnRH antagonists in controlled ovarian stimulation (COS) for intrauterine insemination (IUI) have provided controversial results. The present study was undertaken to evaluate, whether the use of a half of the conventional dose of the GnRH antagonist cetrorelix can be effective in increasing the successful rate of IUI cycles. Patients started COS with human menopausal gonadotropin (hMG) on day three of the menstrual cycle. Cetrorelix was started when at least one follicle of ≥14 mm, was detected at the ultrasound scan, according to the flexible multiple daily dose protocol, and continued until the trigger day with recombinant hCG. Patients adopting GnRH antagonist at low dose had a pregnancy rate (21.7%) that was significantly higher (p < 0.05) in comparison to women receiving hMG only (8.7%). These results suggest that adding a reduced dose of GnRH antagonist to the COS for IUI cycles significantly improves the outcome of the procedure.

Topics: Adult; Chorionic Gonadotropin; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Hospitals, University; Humans; Infertility, Female; Infertility, Male; Insemination, Artificial; Italy; Male; Menotropins; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Recombinant Proteins

In order to avoid the toxic effect of chemotherapy, it has been proposed to use GnRH agonist analogues (GnRHa) to inhibit the depletion of ovarian follicles. Nevertheless, there is controversy about its effectiveness. This clinical trial has been conducted with the aim to assess the protective effect of GnRH analogues on the reproductive capacity of women with malignancies or autoimmune diseases, which require chemotherapy.. Open phase ii single-center clinical trial. During chemotherapy, a total of 5 doses of GnRH antagonist analogue at a dose interval of 3 days and/or a monthly dose of GnRHa were administered. Hormonal determinations prior to the start of the CT treatment were conducted during treatment and at the end of it.. The inclusion of patients was prematurely concluded when incorporating the determination of anti-Müllerian hormone (AMH) as a parameter for assessing the ovarian reserve. Out of 38 patients, 23 (60.5%, 95%CI 43.4-76.0) had AMH values below normal following completion of treatment. An intermediate analysis was carried out observing that while most patients were recovering the menstrual cycle (86.6% 95%CI 71.9-95.6), they had reduced levels of AMH.. Although most patients recovered their menstrual cycles, the ovarian reserve, assessed by the concentration of AMH, decreased in many patients. Therefore, we can conclude that the concomitant treatment of chemotherapy and GnRH analogues does not preserve the loss of follicular ovarian reserve.

Topics: Adolescent; Adult; Anti-Mullerian Hormone; Antineoplastic Agents; Autoimmune Diseases; Biomarkers; Female; Fertility Agents, Female; Fertility Preservation; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Immunosuppressive Agents; Infertility, Female; Menstruation; Middle Aged; Neoplasms; Ovary; Triptorelin Pamoate; Ultrasonography; Young Adult

The aim of this randomized controlled trial (RCT) was to investigate whether IVF outcomes would differ between patients with POR who received three different gonadotropin doses with or without the addition of letrozole during ovulation stimulation.. Only those who fulfilled two of the three Bologna criteria were included to the study. 95 patients met the inclusion criteria and agreed to participate in the study. In the first group, 31 patients were treated with 450IU gonadotropins. In the second group, 31 patients were treated with 300IU gonadotropins. The third group comprised 33 patients and was treated with 150IU gonadotropins in combination with letrozole.. The results indicate that differences in doses of hMG and rFSH in patients with POR result in a similar number of retrieved MII and fertilized oocytes, similar fertilization rates, number of transferred embryos, implantation, cancelation, chemical, clinical, and ongoing pregnancy rates.. Increasing the dose of gonadotropins during ovulation stimulation is an intuitively appealing approach when the patient is a poor responder. However, increasing the dose does not necessarily improve the reproductive outcome. Using a mild stimulation with addition of letrozole was as effective as stimulation with higher doses of gonadotropins alone in this patient population.

Topics: Adolescent; Adult; Dose-Response Relationship, Drug; Drug Therapy, Combination; Embryo Transfer; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Letrozole; Menotropins; Nitriles; Ovulation Induction; Pregnancy; Pregnancy Rate; Prospective Studies; Single-Blind Method; Treatment Outcome; Triazoles; Young Adult

In vitro fertilization (IVF) cycles are associated with a defective luteal phase. Although progesterone supplementation to treat this problem is standard practice, estrogen addition is debatable. Our aim was to compare pregnancy outcomes in 220 patients undergoing antagonist intracytoplasmic sperm injection (ICSI) cycles protocol. The patients were randomly assigned into two equal groups to receive either vaginal progesterone alone (90 mg once daily) starting on the day of oocyte retrieval for up to 12 weeks if pregnancy occurred or estradiol addition (2 mg twice daily) starting on the same day and continuing up to seven weeks (foetal viability scan). Primary outcomes were pregnancy and ongoing pregnancy rates per embryo transfer. Secondary outcomes were implantation and early pregnancy loss rates. Pregnancy rates showed no significant difference between group 1 (39.09%) and 2 (43.63%) (p value = 0.3). Similarly, both groups were comparable regarding ongoing pregnancy rate (32.7% group 1 and 36.3% group 2, p value = 0.1). Implantation rates showed no difference between group 1 (19.25%) and group 2 (23.44%) (p value = 0.2). Early pregnancy loss rates were comparable, with 6.3% and 7.2% in groups 1 and 2, respectively, (p value = 0.4). In conclusion, the addition of 4 mg estrogen daily to progesterone for luteal support in antagonist ICSI cycles is not beneficial for pregnancy outcome.

Topics: Adult; Estradiol; Female; Fertility Agents, Female; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Ovarian Follicle; Ovulation Induction; Progesterone; Recombinant Proteins; Sperm Injections, Intracytoplasmic; Treatment Outcome

Does 'metformin' reduce the incidence of ovarian hyperstimulation syndrome (OHSS) for women with polycystic ovary syndrome (PCOS) undergoing a GnRH antagonist assisted conception treatment cycle?. A short course of metformin does not reduce the incidence of OHSS for women with PCOS undergoing a GnRH antagonist treatment cycle.. Metformin does reduce the incidence of OHSS in a GnRH-agonist treatment cycle.. A randomised placebo-controlled trial (RCT) using metformin or placebo. Randomisation was blinded to both patient and investigator, using a random permuted blocks method with a 50:50 allocation ratio. The study was completed over 5 years (2009-2014) with 153 randomised patients. A sample size calculation based on the incidence of OHSS was completed prospectively suggesting a minimum of 146 recruits was required for the trial with a power of 80% and a type 1 error of 0.05.. All patients met the Rotterdam criteria for PCOS and were treated with a standard GnRH antagonist IVF/ICSI treatment cycle in a tertiary infertility clinic. The study medication was started prior to stimulation and continued to oocyte retrieval. Of the 153 patients, 77 received metformin and 76 placebo.. There was no reduction in the incidence of moderate-severe OHSS (Placebo (PLA) 12.2%, metformin (MET) = 16%, 95% CI -0.08-0.16, P = 0.66). There was no difference in total gonadotrophin dose (PLA = 1200, MET = 1200, 95% CI -118.67-118.67, P = 0.75), oocytes retrieved (PLA = 15, MET = 14, 95% CI -2.37-4.37, P = 0.66) or fertilisation rate (PLA = 60.7%, MET = 53.3%, 95% CI -0.96-14.94, P = 0.07). However, using metformin resulted in a reduced clinical pregnancy rate (CPR) per cycle started (PLA = 48.7%, MET = 28.6%, 95% CI 0.04-0.35, P = 0.02) and live birth rate (PLA = 51.6%, MET = 27.6%, 95% CI 0.05-0.40, P = 0.02). Furthermore, when ethnicity was taken into account there was a significant reduction in pregnancy outcome for the South Asian population irrespective of metformin or placebo use (CPR per cycle started, White Caucasian = 44.4%, South Asian = 19.4%; 95% CI 0.06-0.39, P = 0.01).. This study was only undertaken on an infertility population with PCOS with a limited duration of study medication use.. This is the first adequately powered RCT to assess the impact of metformin on OHSS in a high-risk group (women with PCOS) undergoing a GnRH antagonist cycle. It does not support the empirical prescribing of metformin as an adjunct to a GnRH antagonist treatment cycle.. None.. EudraCT number 2009-010952-81.. 21 September 2009.. 30 October 2009.

Topics: Adult; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Metformin; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Treatment Outcome

The aim of this study was to evaluate the outcomes of adding low-dose hCG (human chorionic gonadotropin), as an LH active supplement, to a GnRH antagonist protocol in patients undergoing assisted reproduction techniques. In this parallel-group randomized clinical trial, 137 infertile female outpatients aged 20 - 39 years were randomized into two groups: hCG group and non-hCG group. All patients received r-FSH (150-300 IU) and then a GnRH-antagonist, Cetrorelix (0.25 mg/day). Concomitantly with Cetrorelix, patients in the hCG group received low-dose hCG (200 IU daily), but the patients in the non-hCG group did not. 10,000 IU Urinary hCG (10,000 IU) was injected to all patients, and ICSI was performed after oocyte retrieval. The primary outcome of this study was comparing the pregnancy rates between two study groups. Other differences between two groups such as serum estradiol concentration, fertilization rate, etc. were considered as secondary outcomes. A total of 130 patients completed this trial. No significant difference was detected between pregnancy rates of the two groups (P=0.52) as well as the fertilization, implantation and ongoing pregnancy rates (P=0.11, P=0.75 and P=0.06 respectively). The only significant difference between two groups was a higher concentration of estradiol in the hCG-treated patients (P<0.05). HCG-treated patients experienced a shorter treatment duration and a lower r-FSH required dose than the non-hCG group, but none of these differences were statistically significant (P=0.19 and P=0.10, respectively). The findings of the current study did not support advantages of adding low-dose hCG to GnRH antagonist plus r-FSH protocol in an unselected population of patients. Well-designed trials with a larger sample size for specific patients' subgroups are warranted.

Topics: Adult; Chorionic Gonadotropin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Pregnancy; Pregnancy Rate; Reproductive Control Agents; Reproductive Techniques, Assisted; Retrospective Studies; Young Adult

This prospective study was designed to assess whether the use of GnRH antagonists can improve the success rate of controlled ovarian stimulation (COS) in intrauterine insemination (IUI) treatments.. Eighty patients were divided into two groups: GnRH antagonist group (Group A, n=40) and control group (Group B, n=40). Patients in Group B underwent COS with recombinant Follicle Stimulating Hormone (r-FSH, 50-75 IU/d) only, while patients in Group A were administered r-FSH (50-75 IU/d) plus cetrorelix (0.25 mg/d, starting when ≥ 2 follicles ≥ 14 mm were detected on ultrasound scan). In both groups a single insemination was performed 36 hours after human Chorionic Gonadotropin (hCG, 250 mcg) administration. The primary outcome was clinical Pregnancy Rate (PR). Secondary outcomes were ongoing PR, incidence of Premature Luteinization (PL), number of follicles with mean diameter ≥ 16 mm and between 11 and 15 mm on the day of hCG administration, miscarriage rate, cycle cancellation rate, total amount of r-FSH used and duration of treatment. Student's t test and Chi-square test were used (p < .05 statistically significant).. A total of 146 cycles were performed (Group A: n=72; Group B: n=74). A trend towards higher PR in Group A was detected, although it was not statistically significant (Clinical PR: 18.05% vs 10.81%). The number of follicles ≥ 16 mm was significantly increased in Group A. The incidence of both premature LH surge and premature luteinization (PL) was significantly higher in Group B. No significant differences were found in the duration of the stimulation protocol, and in the total amount of r-FSH administered.. The addition of GnRH antagonist in COS/IUI protocol significantly increases the number of mature follicles. However, this multifollicular recruitment is not linked to a significantly higher PR.

Topics: Adult; Chorionic Gonadotropin; Drug Therapy, Combination; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Insemination, Artificial; Luteinizing Hormone; Pilot Projects; Pregnancy; Pregnancy Rate

To compare the IVF outcomes of letrozole/antagonist and microdose GnRH agonist flare up protocols in poor ovarian responders undergoing intracytoplasmic sperm injection.. A randomized controlled trial was performed in patients with one or more previous failed IVF cycles in which four or less oocytes were retrieved when the gonadotrophin starting dose was at least 300 IU/day. Sixty patients were randomized by computer-generated list to receive either letrozole/antagonist (mild stimulation) n = 30 or GnRH-a protocol (microdose flare) n = 30.. Both groups were similar with respect to background and hormonal characteristics (age, duration of infertility, BMI, FSH, LH and E2). The clinical pregnancy rate per cycle was similar in both groups (13.3 vs. 16.6%; OR = 0.769; 95% CI = 0.185, 3.198). The doses of used gonadotropins and the number of stimulation days were significantly lower in the letrozole/antagonist protocol. The peak E2 level on the day of hCG, the endometrial thickness, the retrieved oocytes, the number of fertilized oocytes, the number of transferred embryos and the cancellation rate were statistically similar in both groups.. The letrozole/antagonist protocol is a cost-effective and patient-friendly protocol that may be used in poor ovarian responders for IVF/ICSI.

Topics: Adult; Aromatase Inhibitors; Drug Resistance; Egypt; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Letrozole; Leuprolide; Menotropins; Nitriles; Ovary; Ovulation Induction; Pregnancy; Pregnancy Rate; Sperm Injections, Intracytoplasmic; Triazoles

Attempting to compare the rates of premature luteinization (PL), clinical pregnancy, and cycle cancellation in ovulation induction-intrauterine insemination (OI-IUI) cycles with and without the GnRH antagonist, cetrorelix, a randomized-controlled trial was undertaken in which patients were randomized to one of two OI-IUI protocols. Those in the cetrorelix arm showed a significantly reduced rate of PL and no change in clinical pregnancy or cycle cancellation rate, leading to the conclusion that GnRH antagonists can decrease the rate of PL, but appear to have no effect on pregnancy or cycle cancellation in gonadotropin OI-IUI cycles.

Topics: Female; Gonadotropin-Releasing Hormone; Gonadotropins; Hormone Antagonists; Humans; Infertility, Female; Insemination, Artificial; Luteinization; Ovulation Induction; Pregnancy; Pregnancy Outcome

The current prospective randomized study was designed to test the efficacy of a low dose (0.125 mg/day) of the gonadotrophin-releasing hormone antagonist cetrorelix in preventing premature luteinizing hormone (LH) rise during controlled ovarian stimulation in comparison with the standard dose of 0.25 mg/day. Ovarian stimulation was started with 225 IU of recombinant follicle stimulating hormone (FSH) on day 2 of the menstrual cycle. Cetrorelix was injected daily from day 6 of gonadotropin administration. Blood was sampled from each woman on day 3 of ovarian stimulation and then daily from day 5 onward up to human chorionic gonadotropin administration for analysis of FSH, LH, progesterone, and estradiol. LH rise was defined as serum LH ≥ 10 mIU/ml. There were 40 patients receiving cetrorelix at 0.25 mg/day and 36 patients receiving cetrorelix at 0.125 mg/day. Premature LH rise was recorded in 10% of patients injecting antagonist at 0.25 mg/day and in 14% of patients administered with antagonist at 0.125 mg/day. These frequencies did not differ statistically. In conclusion, our results suggest that a cetrorelix dose of 0.125 mg/day is effective as the standard dose (0.25 mg/day) in preventing premature LH rise during controlled ovarian stimulation.

Topics: Adult; Drug Administration Schedule; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Luteinizing Hormone; Ovulation Induction; Prospective Studies

To assess the safety and efficacy of mixing cetrorelix with follitropin alfa (rFSH) in assisted reproductive technology.. Prospective, randomized study.. An IVF center in a teaching hospital.. One hundred forty patients undergoing intracytoplasmic sperm injection were randomized into mixed (M) or separate (S) injection groups.. In the M group, rFSH and cetrorelix were mixed immediately before administration, whereas in the S group, rFSH and cetrorelix were administered separately.. The primary efficacy end point was the incidence of premature LH surge. The secondary efficacy endpoints included estradiol levels on the day of hCG injection, numbers of oocytes obtained, implantation, and ongoing pregnancy rates. The safety endpoints included ovarian hyperstimulation syndrome, and adverse events related to injections including local tolerability.. Excluding eight patients who dropped out of the study, there were 66 patients in each group for analysis. Patients in the M group received significantly fewer injections than patients in the S group (9.1 vs. 13.9). Other outcome parameters, including incidences of premature LH surge, numbers of oocytes retrieved, fertilization, implantation, and ongoing pregnancy rates were similar between the two groups.. Cetrorelix and rFSH can be mixed together without compromising their reported safety and efficacy. This observation is in line with the reported safety and efficacy profile of the products listed in their current package inserts.

Topics: Adult; Drug Combinations; Drug Therapy, Combination; Female; Glycoprotein Hormones, alpha Subunit; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Ovarian Hyperstimulation Syndrome; Pregnancy; Prospective Studies; Reproductive Techniques, Assisted

To evaluate the efficacy of GnRH antagonist in comparison with the GnRH agonist protocol in OCP pretreated polycystic ovary syndrome (PCOs) patients undergoing their first ART cycle.. Prospective randomized controlled trial. University-based tertiary fertility center. Ninety-five PCOs patients under 35 years of age, with primary infertility were randomized to an ovarian stimulation protocol consisting of either. GnRh antagonist (study group) or GnRH agonist (control group) after pretreatment with OCP. Coasting or GnRH agonist Trigger was used when estradiol level > or =3,000 pgr/ml in the control and study group, respectively. Both groups received 800 mg vaginal progesterone and 4 mg oral estradiol valerate for luteal phase support.. There was no statistically significant difference in the age, body mass index, basal FSH, duration of infertility, the number of oocytes retrieved, the number of embryos transferred, Serum E2 levels on day of trigger, fertilization rate, chemical and clinical pregnancy rates between the two groups. None of the patients in the study group developed ovarian hyperstimulation syndrome (OHSS) compared with 22.2% of patients in the control group. Total duration of treatment and the number of HMG ampoules used were lower in the study group.. Antagonist protocol and GnRH agonist trigger for ovulation whenever necessary has a similar cycle outcome to the GnRH-agonist protocol in OCP pretreated PCOs patients, with significantly reduced risk of OHSS.

Topics: Adult; Buserelin; Contraceptives, Oral, Combined; Drug Administration Schedule; Drug Therapy, Combination; Ethinyl Estradiol-Norgestrel Combination; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Young Adult

To evaluate the appropriate controlled ovarian hyperstimulation (COH) protocol in patients with repeated IVF failures and poor embryo quality we compared the stimulation characteristics of ten cycles which included ultrashort flare GnRH agonist combined with flexible multidose GnRH antagonist with the patients' earlier failed IVF attempts. The use of ultrashort GnRH agonist/GnRH antagonist COH protocol resulted in a significantly higher number and proportion of top-quality embryos, with a consequent improvement in clinical pregnancy rate (50%).

Topics: Adult; Contraceptives, Oral; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Gonadotropins; Hormone Antagonists; Humans; Infertility, Female; Luteolytic Agents; Pregnancy; Pregnancy Rate; Treatment Failure; Treatment Outcome; Triptorelin Pamoate

To determine whether including a GnRH antagonist in controlled ovarian stimulation-intrauterine insemination cycles would increase pregnancy rates.. Prospective randomized study.. Private reproductive medicine clinic in Spain.. Three hundred sixty-seven women with primary or secondary infertility.. Patients were randomly assigned to controlled ovarian stimulation with recombinant FSH (75-150 IU/d) alone (controls, n = 183) or with recombinant FSH (75-150 IU/d) + the GnRH antagonist (0.25 mg/d), initiated when the recruited follicles were >or=16 mm (n = 184). A single insemination was performed, 36-38 hours after hCG (5,000 IU, IM), in both groups.. Follicular recruitment, pregnancy rates.. Numbers of mature follicles (2.4 +/- 1.3 vs. 1.3 +/- 1.09) and clinical pregnancy rates (23% vs. 11%) were statistically significantly higher in patients who were treated with GnRH antagonist than in those who were in the control group. The pregnancy rate was only higher in the antagonist group if more than one follicle sized >or=18 mm was present on the day that the hCG was given. A similar number of twin pregnancies occurred in both groups: two in the antagonist group and three in the control group. The antagonist group also had one triplet gestation.. Adding GnRH antagonist to controlled ovarian stimulation-intrauterine insemination cycles significantly increases pregnancy rates in multifollicular, but not monofollicular, cycles.

Topics: Adult; Chorionic Gonadotropin; Drug Administration Schedule; Drug Therapy, Combination; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Insemination, Artificial; Ovarian Follicle; Ovulation Induction; Pregnancy; Pregnancy Rate; Prospective Studies; Recombinant Proteins; Treatment Outcome

To determine whether a low initial dosage of cetrorelix acetate could prevent a premature luteinizing hormone (LH) surge in women undergoing controlled ovarian stimulation.. Treatment with a recombinant follicle stimulating hormone was started on Day 3 of the menstrual cycle, and 0.125 mg of cetrorelix was injected daily from Day 5 of the ovarian stimulation until the diameter of the dominant follicle reached at least 16 mm. The dosage was then doubled and maintained at 0.250 mg/day until the day before the injection of human chorionic gonadotropin.. There was a significant decrease in serum LH concentration 1 day after doubling the cetrorelix dosage, and the LH concentration remained low during the follicular phase. Clinical pregnancy occurred in 18 women (42.8%), with 2 intrauterine fetal deaths before the 12th week.. Increasing the cetrorelix dosage from 0.125 to 0.250 mg/day when the follicular size is appropriate can prevent a premature LH surge.

Topics: Adult; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Luteinizing Hormone; Ovulation Induction; Pregnancy; Treatment Outcome

To investigate the outcomes of intracytoplasmic sperm injection (ICSI) cycles after controlled ovarian hyperstimulation (COH) with GnRH antagonist or GnRH agonist (GnRH-a) in mild-to-moderate endometriosis and endometrioma.. Prospective randomize trial.. A private IVF center.. A total of 246 ICSI cycles in 246 patients were divided into three groups: women with mild-to-moderate endometriosis (n = 98); women who had ovarian surgery for endometrioma (n = 81); women with endometrioma and no history of previous surgery (n = 67).. Patients in each group were randomized to COH with either triptrolein or cetrorelix.. Clinical parameters, characteristics of COH, and ICSI results were analyzed.. Outcomes of COH with both GnRH antagonist and GnRH-a were similar in patients with mild-to-moderate endometriosis. Implantation rates were 15.9% vs. 22.6% and clinical pregnancy rates were 27.5% vs. 39% with GnRH antagonist and GnRH-a protocols, respectively, in patients who had ovarian surgery for endometrioma. Implantation rates were 12.5% vs. 14.8% and clinical pregnancy rates were 20.5% vs. 24.2% with GnRH antagonist and GnRH-a protocols, respectively, in patients with endometrioma and no history of ovarian surgery.. Considering the implantation and clinical pregnancy rates, COH with both GnRH antagonist and GnRH-a protocols may be equally effective in patients with mild-to-moderate endometriosis and endometrioma who did and did not undergo ovarian surgery.

Topics: Adult; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Ovulation Induction; Pregnancy; Pregnancy Rate; Sperm Injections, Intracytoplasmic; Triptorelin Pamoate

Coasting is the most popular modality for the prevention of ovarian hyperstimulation syndrome, but this procedure has not been evaluated in patients undergoing controlled ovarian hyperstimulation (COH) with GnRH antagonists. The impact of coasting in a cycle in which GnRH antagonist is used was evaluated in 29 women, and it was found that coasting did not deleteriously affect the outcome in high-responder patients undergoing COH with GnRH antagonists.

Topics: Adult; Drug Administration Schedule; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Outcome; Treatment Outcome

Suppression of endogenous LH production by mid-follicular phase GnRH-antagonist administration in controlled ovarian hyperstimulation protocol using recombinant (rec) FSH preparations void of LH activity may potentially affect ovarian response and the outcome of IVF treatment. The present study prospectively assessed the effect of using a combination of recFSH and recLH on ovarian stimulation parameters and treatment outcome in a fixed GnRH-antagonist multiple dose protocol.. 127 infertile patients with an indication for IVF or ICSI were recruited and randomized (using sealed envelopes) to receive a starting dose of either 150 IU recFSH (follitropin alpha) or 150 IU recFSH plus 75 IU recLH (lutropin alpha) for ovarian hyperstimulation. GnRH-antagonist (Cetrorelix) 0.25 mg was administered daily from stimulation day 6 onwards up to and including the day of the administration of recombinant HCG (chorion gonadotropin alpha). Gonadotropin dose adjustments were allowed from stimulation day 6 onwards, HCG was administered as soon as three follicles > or =18 mm were present. The primary outcome parameter was treatment duration until administration of HCG.. Exogenous LH did not shorten the time necessary to reach ovulation induction criteria. Serum estradiol (E(2)) and LH levels were significantly higher on the day of HCG administration in the recLH-supplemented group (1924.7 +/- 1256.4 vs 1488.3 +/- 824.0 pg/ml, P < 0.03), and 2.1 +/- 1.4 vs 1.4 +/- 1.5 IU/l, P < 0.01, respectively).. Except for higher E(2) and LH levels on the day of HCG administration, no positive trend in favour of additional LH was found as defined by treatment outcome parameters.

Topics: Adult; Chorionic Gonadotropin; Dose-Response Relationship, Drug; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Luteinizing Hormone; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Recombinant Proteins; Treatment Outcome

To compare the outcome of using gonadotropin-releasing hormone (GnRH) antagonists versus agonists in women with polycystic ovary disease (PCOD) who underwent controlled ovarian hyperstimulation (COH) for assisted reproductive techniques (ART).. A total of 129 patients with PCOD were randomly allocated to undergo COH with a GnRH antagonist (59 patients) and GnRH agonist (leuprolide acetate) (70 patients) to prevent a premature luteinizing hormone (LH) surge. Assisted fertilization following oocyte retrieval and embryo transfer was performed.. None of the cycles were cancelled due to a premature LH surge. There was no significant difference between the antagonist and agonist arms in the number of gonadotropin ampules consumed per cycle. However, in the antagonist arm a shorter duration of ovarian stimulation was recorded as compared to the agonist arm. Although similar numbers of oocytes was retrieved from both groups of patients, the quality of the oocytes, as measured by metaphase 2/total oocyte ratio, was lower in the antagonist arm as compared to the agonist arm. Pregnancy rates were 57.6% and 58.5% in the antagonist and agonist arms, respectively (p > 0.05). Implantation rates were not different (34.0% and 34.6%, respectively). The frequency of ovarian hyperstimulation syndrome also did not differ between the treatment groups (5% and 7.1%, respectively).. The size of our study, on a specific subgroup of patients, does not allow a reliable conclusion regarding ART outcomefollowing the use of a GnRH antagonist versus agonist. Nevertheless, the protocol with the antagonist gave results that were as good as those of the protocol with the agonist in this PCOD patient population.

Topics: Adult; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fertilization in Vitro; Follow-Up Studies; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Leuprolide; Ovulation Induction; Pilot Projects; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Probability; Prospective Studies; Risk Assessment; Statistics, Nonparametric

To compare the efficacy of GnRH antagonist vs. GnRH agonist administration for controlled ovarian hyperstimulation (COH) in assisted reproduction.. A prospective, randomized trial.. Clinical research unit at a tertiary care medical center.. Sixty-five patients with unexplained infertility or mild male subfertility undergoing COH for IUI.. Twenty-nine women (group A) were randomized to receive 600 microg of busereline acetate per day starting in the midluteal phase of the cycle (long protocol), whereas 36 women (group B) were treated with 0.25 mg/d of the GnRH antagonist Cetrorelix starting from day 6 of the cycle. The starting dose of recombinant FSH was 150 IU in women of both groups. Insemination was performed 34 hours after hCG injection.. Clinical and successful ongoing pregnancy rate (PR), measurements of serum FSH, LH, E2, and P, number of recruited follicles, duration of stimulation period, and amount of gonadotropins used.. Women in group A required significantly more days of treatment (median: 12.0 vs. 9.0) and significantly more total units of recombinant FSH (median 1,800 vs. 1,550) as compared with the corresponding values of the antagonist group (group B). Serum FSH, LH, E2, and P were significantly higher on the antagonist group on days 2 and 6 of stimulation. However, these differences regress until the day of hCG administration.. The GnRH antagonists have facilitated short and simple treatment, and are particularly attractive for administration in women undergoing COH, achieving comparable PR with the long protocol regimen.

Topics: Adult; Chi-Square Distribution; Confidence Intervals; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Male; Oligospermia; Pregnancy; Prospective Studies; Statistics, Nonparametric

During IVF or ICSI cycles, ovarian hyperstimulation syndrome (OHSS) is a major problem. The aim of this prospective, multicentre, comparative study (using historical controls) was to assess the efficacy of a GnRH antagonist protocol in preventing OHSS in selected patients who had experienced OHSS or had been at risk of OHSS in their previous IVF/ICSI attempt.. Patients underwent a new cycle where the same gonadotrophin protocol was used [same dose of recombinant FSH (rFSH)] but a different protocol was used for pituitary desensitization: cetrorelix 0.25 mg multiple-dose antagonist instead of GnRH agonist long protocol. Cetrorelix 0.25 mg was administered daily, starting when the leading follicle reached a diameter of 14 mm. In other words, rFSH was administered in the new cycle according to the dosage and the step-up or step-down modalities used during the previous cycle, independently of ultrasound findings and serum estradiol (E(2)) levels. Eighty-seven patients entered the study. Out of the 87 cycles involving GnRH agonists, 49 (56.3%) were cancelled and out of the 87 involving GnRH antagonists 28 (32.2%) were cancelled [McNemar's test; 95% confidence interval (CI) -35.8% to -11.2%; P < 0.001]. After GnRH agonist cycles, we recorded 24 cases of OHSS (18 moderate and six severe; 27.6%), whereas after the GnRH antagonist cycles there were 10 cases of OHSS (nine moderate and one severe; 11.5%) (95% CI-26.4% to -5.7%; P = 0.006). There was a statistically significant reduction in the total number of follicles with a diameter >10 mm (Wilcoxon's test; Z = 6.1; P < 0.001) and of E(2) levels on the day of HCG administration (2538 versus 4322.4 pg/ml; P < 0.001) in the GnRH antagonist cycles versus GnRH agonist cycles. Twenty-nine patients had an embryo transfer in the first cycle (76.3% of oocyte retrievals) and 57 in the cycle using GnRH antagonist (96.6%). This 20.3% difference was also significant (Z-test; 95% CI 6.8-36.0%; P = 0.003). After the antagonist cycles, 18 pregnancies (20.7 per initiated cycle; 31.6% per embryo transfer) were obtained.. Although this study presents some limitations owing to the use of historical controls, our data show a favourable effect of GnRH antagonists in reducing the incidence of OHSS and the number of assisted fertilization cycles cancelled because of the risk of OHSS in high responder patients. As a consequence, GnRH antagonist plus gonadotrophin administration could also increase the percentage of oocyte retrievals and embryo transfers in this high risk group of patients.

Topics: Adult; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Incidence; Infertility, Female; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Outcome; Prospective Studies; Recombinant Proteins; Risk Factors; Sperm Injections, Intracytoplasmic

To compare the safety and efficacy of single-dose cetrorelix acetate (3 mg) and daily ganirelix acetate (0.25 mg) in the inhibition of premature LH surge in women undergoing cycle-programmed ovarian stimulation before Assisted Reproductive Technology (ART).. Prospective, open-label, randomized, comparative study.. Sixteen ART centers in the United States.. One hundred eighty-five infertile patients undergoing ART.. Single injection of cetrorelix (3 mg SC) or daily dose of ganirelix (0.25 mg SC) was administered when the lead follicle was > or =14 mm. Daily cetrorelix (0.25 mg) was administered if the criteria for hCG administration were not met 4 days after receiving 3 mg of cetrorelix.. Percentage of patients who did not have a premature LH surge, defined as LH <10 IU/L on the day of hCG administration. The IVF and embryo transfer (ET) outcomes were assessed.. No patient in either treatment group had a premature LH surge. There were no statistically significant differences between treatments for any IVF/intracytoplasmic sperm injection (ICSI) or ET outcomes, including pregnancy rate (PR). However, cetrorelix required significantly fewer injections than ganirelix. Similar safety profiles were observed.. Cetrorelix and ganirelix effectively prevented LH surges in oral contraceptive (OC) pill-programmed, flexible protocols, with similar safety profiles and PRs; however, cetrorelix required significantly fewer injections, increasing patient convenience.

Topics: Adult; Analysis of Variance; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Luteinizing Hormone; Pregnancy; Pregnancy Rate; Prospective Studies; Reproductive Techniques, Assisted

Patients with polycystic ovary syndrome (PCOS) may need a longer period of pituitary downregulation to suppress the elevated serum LH and androgen levels effectively during IVF treatment using the GnRH agonist long protocol. We proposed a stimulation protocol incorporating Diane-35 and GnRH antagonist (Diane/cetrorelix protocol) and compared it with the GnRH agonist long protocol for PCOS patients.. Part I of the study was an observational pilot study to evaluate the hormonal change as a result of the Diane/cetrorelix protocol (n = 26). Part II of the study was a prospective randomized study comparing the Diane/cetrorelix protocol (n = 25) and the GnRH agonist long protocol (n = 24). In the Diane/cetrorelix protocol, patients were pre-treated with three cycles of Diane-35, followed by 0.25 mg of cetrorelix on cycle day 3. From day 4, cetrorelix and gonadotrophin were administered concomitantly until the day of HCG injection.. Serum LH, estradiol and testosterone levels were suppressed comparably in both protocols at the start of gonadotrophin administration. Serum LH was suppressed at constant levels without a premature LH surge in the Diane/cetrorelix protocol. The clinical results for both protocols were comparable, with significantly fewer days of injection, lower amounts of gonadotrophin used and lower estradiol levels on the day of HCG injection following the Diane/cetrorelix protocol. Furthermore, there was no significant difference in clinical pregnancy outcome between the two stimulation protocols.. The Diane/cetrorelix protocol has a similar pregnancy outcome to the GnRH agonist long protocol for women with PCOS undergoing IVF treatment.

Topics: Adult; Androgen Antagonists; Cyproterone Acetate; Drug Combinations; Drug Therapy, Combination; Ethinyl Estradiol; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Hormones; Humans; Incidence; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pilot Projects; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Premedication

An open label, randomized, multi-centre study was performed to compare cetrorelix and leuprolide acetate for prevention of premature LH surge and to assess whether patients treated with cetrorelix benefit from addition of recombinant human (r-h)LH. Normo-ovulatory women (n = 74) undergoing ovarian stimulation prior to intracytoplasmic sperm injection were treated with leuprolide acetate (n = 25) before ovarian stimulation with recombinant human FSH (r-hFSH) or with cetrorelix 3 mg on stimulation day 7 (with (n = 25) or without (n = 24) r-hLH 150 IU on days 7-10). The main outcome measures were the number of metaphase II (MII) oocytes retrieved; secondary efficacy end-points; adverse events (AE) and other safety measures. There were no significant differences between groups for MII oocytes retrieved, duration of stimulation, total r-hFSH dose and pregnancy rates. The group treated with cetrorelix alone had a significantly lower concentration of oestradiol per follicle compared with the other groups. The majority of AE were mild to moderate in severity. Cetrorelix and leuprolide acetate appear to have comparable efficacy and safety, although cetrorelix has the advantage of typically requiring only one injection.

Topics: Adolescent; Adult; Drug Therapy, Combination; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Leuprolide; Luteinizing Hormone; Ovulation Induction; Pregnancy; Pregnancy Rate; Reproductive Techniques, Assisted

The objective of this study was to compare, in a centre with previous experience of gonadotrophin-releasing hormone (GnRH) antagonist use, single administration of a GnRH antagonist [cetrorelix (Cetrotide) 3 mg] with a single administration of a GnRH agonist [Decapeptyl Retard 3.75 mg] in patients undergoing assisted reproduction treatment (n = 307 and 364 respectively). GnRH agonist was administered on the first day of menses, while cetrorelix was administered when the largest follicle reached 14 mm. Ovarian stimulation was performed with recombinant human FSH (r-hFSH; 150-225 IU/day). Human chorionic gonadotrophin (HCG, 10,000 IU) was administered when at least two follicles reached a mean diameter > or =18 mm. Over 90% of patients in both groups reached the criteria for HCG administration and underwent oocyte retrieval and embryo transfer. Duration of FSH therapy (9.95 versus 11.25 days) and cumulative dose of r-hFSH (1604 versus 1980 IU) were significantly reduced (P < 0.01) in the cetrorelix 3 mg group. The number of oocytes retrieved was lower (8.5 versus 11.2; P < 0.01) with cetrorelix, but the number of embryos replaced was similar (2.2 versus 2.3; NS). The pregnancy rates per oocyte retrieval were the same, 24.5%, in the antagonist and agonist groups. This study indicates that although fewer oocytes are recovered, similar pregnancy rates can be achieved with a GnRH antagonist compared with a GnRH agonist. Additionally, a single dose of 3 mg cetrorelix was administered in 84% of patients, thus being simpler and more convenient for patients. Cetrorelix 3 mg may thus be proposed as a first choice for preventing both a premature LH surge and detrimental rises in LH during ovarian stimulation prior to assisted reproduction treatment.

Topics: Adult; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Luteolytic Agents; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Triptorelin Pamoate

New gonadotrophin-releasing hormone (GnRH) antagonists, which allow suppression of luteinizing hormone (LH) surges, have recently become available. We compared in this study the results of a single administration of 3 versus 2 mg Cetrorelix in 65 patients undergoing ovarian stimulation and in-vitro fertilization (IVF). The GnRH antagonist (Cetrorelix) was non-randomly administered at a dose of 3 mg (34 patients) or 2 mg (32 patients) on day 8 of the stimulation cycle. In the case of slow follicular development, the injection was delayed until oestradiol reached 400 pg/ml. No difference was observed in the decrease in LH and in oestradiol secretion between the 3 and the 2 mg groups, but the LH secretion was suppressed for a shorter time in the 2 mg group. No LH surge was observed in the 3 mg group, while one surge (3%) and one significant rise in LH were observed in the 2 mg group. No significant difference was observed in IVF results in the two groups of patients. This study demonstrates that a single injection of 3 or 2 mg successfully prevents LH surges for at least 3 days in all the patients treated. The LH rises in the 2 mg group led us to choose the 3 mg dose as a safer dose in our single administration protocol.

Topics: Adult; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Ovulation Induction; Pregnancy

To examine the pituitary response in patients undergoing short-term application of the GnRH antagonist Cetrorelix in the mid-cycle phase for hypophysial suppression of premature LH surges within an IVF-program.. Twenty patients suffering from primary or secondary tubal infertility were stimulated with hMG from cycle day 2. From day 7 till ovulation induction Cetrorelix was administered in two different dose regimens (15 patients 3 mg s.c. daily; 5 patients 1 mg s.c. daily). Three hours before ovulation induction a GnRH test was performed using 25 micrograms of native GnRH and the pituitary response examined by measurement of the serum LH concentration after 30 min.. Premature LH surges could be avoided in the 3-mg group and in the 1-mg group, respectively. Due to this, none of the cycles had to be cancelled. Oestradiol profiles and ultrasound demonstrated a satisfactory follicular maturation. All patients showed pronounced suppression of the serum LH levels before ovulation induction. The mean increase of serum LH due to the performed GnRH test was 10 mIU/ml for the 3-mg group, while the average maximum in the 1-mg group was about 32.5 mIU/ml.. The pituitary response is preserved by the treatment with the GnRH antagonist Cetrorelix. The extent of suppression of the adenohypophysis, as expressed by the different reactions on GnRH test, can be modulated by the dosage administered. This should allow ovulation induction by GnRH or one of its agonists instead of hCG, which could be beneficial in patients at high risk of Ovarian Hyperstimulation Syndrome (OHSS) and those suffering from Polycystic Ovary Disease (PCOD).

Topics: Adult; Chorionic Gonadotropin; Estradiol; Fallopian Tube Diseases; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Kinetics; Luteinizing Hormone; Menotropins; Ovulation Induction; Pituitary Gland

Surges of luteinizing hormone (LH) that result in luteinization but occur prematurely with respect to the diameter of the leading follicle, prevent attempts to induce multiple follicular maturation for in-vitro fertilization (IVF) in a significant number of women. We examined the possibility of blocking premature LH surges by the administration of Cetrorelix, a potent antagonist of gonadotrophin-releasing hormone (GnRH), in a study including 20 patients, some of whom had previously shown premature LH surges. All patients were treated with human menopausal gonadotrophins (HMG) starting on day 2. From day 7 until the induction of ovulation by human chorionic gonadotrophin (HCG) the GnRH antagonist Cetrorelix was given daily. HCG was injected when the dominant follicle had reached a diameter of > or = 18 mm and oestradiol concentration was > 300 pg/ml for each follicle having a diameter of > 15 mm. Oocyte collection was performed 36 h later by transvaginal ultrasound puncture, followed by IVF and embryo transfer. The hormone profiles of these patients and the results of IVF and embryo transfer are comparable to those treated with GnRH agonists and HMG. However, less time and especially less HMG is needed in comparison to patients stimulated with a long agonist protocol. Hence, treatment with Cetrorelix proved to be much more comfortable for the patient. In this study we showed that combined treatment with gonadotrophins and the GnRH antagonist Cetrorelix is a promising method for ovarian stimulation in patients who frequently exhibit premature LH surges and therefore fail to complete treatment.

Topics: Adult; Chorionic Gonadotropin; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Luteinizing Hormone; Ovary; Ovulation Induction

To evaluate the effect of the GnRH antagonist on gonadotropin ovulation induction in women with PCOS.. A total of 175 intrauterine insemination (IUI) cycles in women with polycystic ovary syndrome (PCOS) were included in the study. Women in the control group (n = 87) underwent controlled ovarian stimulation (COS) with recombinant follicle stimulating hormone (r-FSH) only, while women in the study group (n = 88) were administered r-FSH plus cetrorelix.. As expected, the mean value of luteinizing hormone and progesterone, on the day of human chorionic gonadotropin administration were statistically significantly lower in patients receiving GnRH antagonist than the control group (p = 0.002). Premature luteinization occurred in only one of the patients in the GnRH antagonist group (1.1%) and in 15 of the 88 cycles in the control group (17.2%), showing a significant difference between the two groups (P = 0.001). The clinical pregnancy rate per cycle was higher in GnRH-antagonist group compared to the control group but the difference did not reach to a statistical significance (25% vs 14.9%, P = 0.096).. Adding GnRH-antagonist in COS/IUI cycles in women with PCOS resulted in a lower incidence of premature luteinization but did not improve pregnancy rates. However, owing to some benefits, antagonist therapy could be considered as a reasonable alternative to IVF in order to reduce PCOS patients'emotional distress.

Topics: Adult; Case-Control Studies; Chorionic Gonadotropin, beta Subunit, Human; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Insemination, Artificial; Luteinizing Hormone, beta Subunit; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Progesterone; Retrospective Studies; Young Adult

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Progestin-primed ovarian stimulation (PPOS) protocol, which used oral progestin to prevent premature luteinizing hormone (LH) surges in ovarian stimulation, has been proved to be effective and safe in patients with PCOS. The aim of the present study was to compare the efficacy of PPOS protocol with that of the traditional gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS. A total of 157 patients undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) were recruited into this study. The patients were divided into two groups by the stimulation protocols: the GnRH antagonist protocol group and the PPOS protocol group. There was no significant difference in the clinical characteristics between the two groups. Dose and duration of gonadotropin were higher in the PPOS protocol group. Estradiol levels on the day of human chorionic gonadotropin (hCG) administration were significantly lower in the PPOS protocol group. Fertilization rates and the number of good quality embryos were similar between the two groups. Remarkably, we found 6 patients with moderate ovarian hyperstimulation syndrome (OHSS) in the GnRH antagonist protocol group but 0 in the PPOS protocol group. A total of 127 women completed their frozen embryo transfer (FET) cycles. There were no significant differences between the two groups in terms of clinical pregnancy rate per transfer, implantation rate, first-trimester miscarriage rate and on-going pregnancy rate per transfer. To conclude, PPOS protocol decreased the incidence of OHSS without adversely affecting clinical outcomes in patients with PCOS.

Topics: Adult; Chorionic Gonadotropin; Embryo Transfer; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Gene Expression; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Male; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Progestins; Prospective Studies; Sperm Injections, Intracytoplasmic; Treatment Outcome

The long-acting corifollitropin alfa is comparable to FSH in terms of pregnancy outcomes in normal responders and poor responders. Corifollitropin alfa has never been studied in polycystic ovary syndrome (PCOS) patients because of concerns of excessive ovarian stimulation and ovarian hyperstimulation syndrome (OHSS). The purpose of the study was to evaluate if corifollitropin alfa can be used in PCOS patients.. Forty PCOS patients who were going to undergo in vitro fertilization were enrolled in this study. A single injection of corifollitropin alfa was administered on cycle day 2 or day 3. From stimulation day 8 onwards, daily FSH was administered until the day of final oocyte maturation. Cetrorelix was administered from stimulation day 5 to prevent premature LH surge. Final oocyte maturation was triggered by: acetate. All embryos were cryopreserved and replaced in subsequent cycles.. All 40 patients were subjected to oocyte retrieval, and none developed moderate or severe ovarian hyperstimulation syndrome (0%, 95% CI 0-0.088). For each patient, an average of 23.4 (±7.4; 95% CI 21.0-25.7) oocytes were retrieved and a mean of 11.7 (±6.4; 95% CI 9.6-13.8) embryos were frozen. Mean serum estradiol level on the day of GnRHa triggering was 7829.9 pg/ml (±3297; 95% CI 6775-8885). The cumulated ongoing pregnancy rate after 3 frozen-thawed embryo transfers was 75.0% (95% CI 61.6%-88.4%).. The results suggest that corifollitropin alfa/GnRH antagonist protocol can be used in PCOS patients, in combination with GnRHa triggering and embryo cryopreservation.

Topics: Adult; Cryopreservation; Embryo Transfer; Female; Fertilization in Vitro; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Oocyte Retrieval; Oocytes; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Proof of Concept Study; Prospective Studies

In this retrospective multicenter cohort study, women with congenital hypogonadotrophic hypogonadism (CHH) (n = 57) who underwent intra-cytoplasmic sperm injection in-between 2010-2014 were compared to age-matched controls with tubal factor infertility (n = 114) to assess ovarian stimulation cycle and pregnancy outcomes. Live birth rates (LBRs) per started cycle were 31.6 and 24.6% in CHH and controls groups, respectively (p = 0.36). Comparable success rates were also confirmed with the logistic regression analysis (OR: 1.44, 95% CI: 0.78-2.67, p = 0.24). Of the 57 women with CHH, 19 were stimulated with the gonadotropin-releasing hormone (GnRH) antagonist protocol, 13 with the long-GnRH-agonist protocol. Pituitary suppression (PS) was not employed in the remaining 25 cases. Compared to women with PS, women without PS had significantly higher embryo implantation rates (21.6 versus 52.6%, p = 0.03). Although there was a trend favoring no PS, LBRs (25.0 versus 40.0%, p = 0.26) per cycle were short of statistical significance. LBRs per cycle (57.1 versus 31.2%, p = 0.11) and miscarriage rates (11.1 versus 16.7%, p = 0.75) were similar between CHH women who were given estrogen + progesterone and progesterone alone to support the luteal phase. In conclusion, the optimal stimulation protocol appears to be exogenous gonadotropin stimulation alone, without PS, and progesterone-only luteal phase support in CHH patients.

Topics: Adult; Birth Rate; Cohort Studies; Embryo Transfer; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Infertility, Female; Live Birth; Ovulation Induction; Pregnancy; Sperm Injections, Intracytoplasmic; Treatment Outcome; Young Adult

We conducted an observational cohort study to evaluate whether drugs used for hypothalamic inhibition may impact thyroid function of infertile women scheduled for fresh nondonor in vitro fertilization/intracytoplasmic sperm injection treatment. We considered eligible for inclusion in the study only women with normal thyroid function (serum thyroid-stimulating hormone [TSH] range: 0.2-4.0 mIU/L, serum thyroxin values: 9-22 pmol/L) and negative personal history for previous thyroid disorders. According to which protocols were implemented to gain hypothalamic inhibition, patients were assigned to group A (70 women treated by long gonadotropin-releasing hormone [GnRH] agonist protocol) or to group B (86 women treated by flexible GnRH antagonist protocol). Before initiating controlled ovarian stimulation (COS), both groups were further stratified into 4 subgroups: A1 (46 of the 70 women) and B1 (61 of the 86 women) in women with a baseline TSH value <2.5 mIU/L, whereas those with a baseline value ≥2.5 mIU/L were assigned to groups A2 (24 of the 70 women) and B2 (25 of the 86 women). Prior to initiating stimulation (T-0), 17-β-estradiol (E(2)) and TSH serum values were dosed in all women and repeated on T-5 (day 5 of COS) and subsequently every 2 days until T-ov-ind (ovulation induction day) and T-pick-up (oocytes retrieval day). In case of detection of TSH levels above the cutoff, patients were screened for thyroxin and thyroid autoantibody serum values. In group A, E(2) at T-ov-ind was significantly increased compared to group B (P < .01), whereas TSH values showed an opposite trend (not significantly modified in group A, whereas significantly increased in group B; P < .001). A total of 64 women were found to have TSH values above the cutoff during COS: 7 in group A (11%) and 57 in group B (89%). Among them, 5 (71.4%) of the 7 in group A displayed hypothyroidism (and 4 of the 5 autoantibody positivity), whereas in group B, 6 (10.5%) of the 57 displayed hypothyroidism (and 2 of the 6 autoantibody positivity; P < .001). No pregnancies were observed in women with hypothyroidism, whereas in the 53 women with "isolated" increased TSH (normal T4, negative antibodies), we reported a 20.7% clinical pregnancy rate and a 54.5% ongoing pregnancy rate. Our preliminary data, despite requiring further confirmation, seem to suggest that the various drugs used for gaining hypothalamic control during COS could interfere through different mechanisms with physiological function

Topics: Adult; Cohort Studies; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Pregnancy; Pregnancy Outcome; Thyroid Gland; Thyrotropin; Triptorelin Pamoate

Human chorionic gonadotropin (hCG) is commonly used for final oocyte maturation in "in vitro fertilization" (IVF)-treatment cycles, however, the main important risk is development of severe ovarian hyperstimulation syndrome (OHSS). OHSS can almost be avoided by using gonadotrophin-releasing-hormone agonist for final oocyte maturation in an antagonist protocol. However, primarily this approach lead to a very poor reproductive outcome, despite the use of a standard luteal phase support. The reason seems to be severe luteolysis. Obviously, luteolysis post-gonadotropin-releasing-hormone-agonist (post-GnRH-a) trigger is individual specific, and not all patients will develop a complete luteolysis, as expected previously. Luteolysis can been reverted by the administration of hCG. Unprotected intercourse around the time of ovulation induction and oocyte retrieval can lead to a spontaneous conception in IVF treatment and, endogenous hCG, produced by the trophoblast, will rescue the corpora lutea. Therefore, one should not rely on complete luteolysis after GnRH-a triggering and, especially patients for egg donation and pre-implantation-genetic diagnosis for single gene disorder, have to be counselled to avoid unprotected intercourse.

Topics: Adult; Chorionic Gonadotropin; Corpus Luteum; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Luteal Phase; Luteolysis; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate

To evaluate the effects of an ovulation triggering agent, human chorionic gonadotropin (hCG), versus a gonadotropin-releasing hormone agonist (GnRHa) on early embryo development in vitro using a time-lapse system.. Retrospective analysis of a prospectively collected database. A total of 739 embryos from 152 infertile couples undergoing intracytoplasmic sperm injection cycles.. Embryo culture in a time-lapse incubator (EmbryoScope, Vitrolife, Göteborg, Sweden).. Embryo morphokinetic parameters.. In the 152 women, 252 embryos were derived from GnRHa-triggered cycles compared with 487 embryos derived from hCG-triggered cycles. Time-lapse analysis revealed that embryos from cycles triggered by a GnRHa cleaved faster than embryos derived from hCG-triggered cycles.. Triggering with a GnRHa in in vitro fertilization cycles affects embryo kinetics.

Topics: Adult; Azoospermia; Chorionic Gonadotropin; Embryo Culture Techniques; Embryonic Development; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Kinetics; Male; Ovarian Reserve; Ovulation Induction; Retrospective Studies; Sperm Injections, Intracytoplasmic; Time-Lapse Imaging; Triptorelin Pamoate

To determine whether the decrease in AMH levels during ovarian hyperstimulation for IVF occurs in patients with polycystic ovary syndrome (PCOS) and patients with low ovarian reserve (LOR), as in normal cycling women.. A cohort of 22 infertile patients treated in a single tertiary center with a GnRH-antagonist short protocol for IVF were prospectively included and divided into three groups: PCOS with hyperandrogenism (n=7), LOR (n=8) and control (n=7). Serum AMH levels were measured before and during FSH treatment, on the day of HCG administration, at the mid-luteal phase, and 14 days after embryo transfer. The three groups were compared using an ANOVA model in the case of continuous data and with Fisher's exact test when the data were discrete.. In the PCOS group, AMH levels increased at the beginning of the stimulation, but later decreased, until the mid-luteal stage. In the other two groups, AMH levels decreased throughout ovarian stimulation until the mid-luteal stage. In all groups, AMH levels returned to baseline levels two weeks after HCG administration, regardless of treatment outcome (pregnancy or not).. AMH levels decline during controlled ovarian hyperstimulation with a GnRH-antagonist short protocol in women with low and normal ovarian reserves. In contrast, in women with PCOS, an increase in AMH levels precedes this decline. These findings may support the hypothesis that androgens may play a role in AMH regulation in women.

Topics: Adult; Anti-Mullerian Hormone; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Hyperandrogenism; Infertility, Female; Luteal Phase; Ovarian Follicle; Ovarian Reserve; Ovulation Induction; Polycystic Ovary Syndrome

To examine whether patients with poor ovarian response (POR) during conventional IVF/intracytoplasmic sperm injection (ICSI) treatment cycle may benefit from a modified natural cycle (MNC)-IVF.. Cohort historic study.. Tertiary, university-affiliated medical center.. One hundred eleven patients with POR, defined according to the Bologna criteria, who underwent a subsequent MNC-IVF within 3 months of the previous failed conventional IVF/ICSI cycle. The elimination of bias in this selection, for the purposes of this study, was achieved by including only a subgroup of "genuine" poor responder patients, those who yielded up to three oocytes after controlled ovarian hyperstimulation (COH) with a minimal gonadotropin daily dose of 300 IU.. Modified natural cycle IVF protocol with GnRH antagonist (GnRH-a) supplementation. Gonadotropin-releasing hormone antagonist treatment was started when a follicle of 13 mm was present. Two to three ampules of hMG were coadministered daily during the GnRH-a treatment.. Live birth rate, pregnancy rate (PR), number of oocytes retrieved, and number of embryos transferred.. Live birth rate in "genuine" poor ovarian responders was <1%. Furthermore, in the subgroup of patients with POR who underwent a previous conventional IVF/ICSI cycle with a yield of only one oocyte, no pregnancies were achieved during the MNC-IVF cycle.. Modified natural cycle-IVF is of no benefit for genuine poor ovarian responders and the option of egg donation should be seriously considered for this population.

Topics: Adult; Drug Administration Schedule; Drug Therapy, Combination; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Live Birth; Menotropins; Ovary; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies; Sperm Injections, Intracytoplasmic; Treatment Outcome

The human androgen receptor (AR) gene contains a highly polymorphic CAG repeat sequence within exon 1. In-vitro studies have shown a relationship between CAG repeats in the AR gene and its transactivation potential. This variation in length may play a role in anovulatory infertility. The objective of this study was to investigate whether CAG polymorphism of the AR gene has a predictive value for ovarian reserve, response and cycle outcome in an egg donor programme. CAG length of the AR gene was determined in 147 oocyte donors. All donors underwent ovarian stimulation with a gonadotrophin-releasing hormone antagonist protocol (n = 355). No differences were reported in days of stimulation, gonadotrophin doses, and number of oocytes retrieved. Clinical outcomes were not affected by the CAG repeat length of the AR gene; the primary end-point, antral follicle count, was significantly affected (P < 0.05). In conclusion, in a population of fertile egg donors AR gene CAG polymorphism does not affect ovarian response to gonadotrophins. Antral follicle count was associated with the CAG polymorphism genotype. This suggests that genetic factors may increase susceptibility to poor ovarian reserve, and that AR gene genotype could play a role in the natural ovarian ageing process.

Topics: Adolescent; Adult; Female; Fertility Agents, Female; Genetic Association Studies; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Oocyte Donation; Ovarian Reserve; Ovary; Ovulation Induction; Polymorphism, Genetic; Receptors, Androgen; Retrospective Studies; Spain; Trinucleotide Repeat Expansion; Triptorelin Pamoate; Ultrasonography; Urofollitropin; Young Adult

Ovarian hyperstimulation syndrome (OHSS) is the most serious iatrogenic complication of IVF cycles. Although the development of effective treatment strategies for this syndrome is important, preventing OHSS is more crucial. Triggering ovulation with a gonadotrophin-releasing hormone (GnRH) agonist is one method used to avoid OHSS. In this paper, three patients who developed severe OHSS after undergoing GnRH agonist triggering and freezing of all embryos in a GnRH antagonist protocol are described. A review of the literature is also provided. This report highlights the ongoing risk of severe OHSS even after GnRH agonist triggering combined with freezing all embryos in GnRH antagonist cycles. Other prevention strategies might be considered for extreme hyper-responders.

Topics: Adult; Chorionic Gonadotropin; Cryopreservation; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy

The goal of this study was to assess the association between endometrial thickness on the chorionic gonadotropin (hCG) day and in vitro fertilization and embryo transfer (IVF-ET) outcome in normal responders after GnRH antagonist administration.. A retrospective cohort study was performed in normal responders with GnRH antagonist administration from January 2011-December 2013. Patients were divided into four groups according to endometrial thickness, as follows: <7 mm (group 1), > = 7- < 8 mm (group 2), > = 8- < 14 mm (group 3), and > =14 mm (group 4).. A total of 2106 embryo transfer cycles were analyzed. The pregnancy rate (PR) was 44.87%.The clinical pregnancy rate, ongoing pregnancy rate and the implantation rate (17.28%, 13.79%, 10.17%, respectively) were significantly lower in group 1 compared to the other three groups (p < 0.05). The miscarriage rate was higher in patients with endometrial thickness less than 7 mm. The clinical pregnancy rate, ongoing pregnancy rate and implantation rate were highest in patients with endometrial thickness higher than 14 mm, but showed no difference in patients with those of endometrial thickness between 8-14 mm.. There is a correlation between endometrial thickness measured on hCG day and clinical outcome in normal responders with GnRH antagonist administration. The pregnancy rate was lower in patients with endometrial thickness less than 7 mm compared with patients with endometrial thickness more than 7 mm.

Topics: Abortion, Spontaneous; Adult; China; Chorionic Gonadotropin; Cohort Studies; Embryo Transfer; Endometrium; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Organ Size; Pregnancy; Pregnancy Maintenance; Pregnancy Rate; Retrospective Studies; Sperm Injections, Intracytoplasmic; Ultrasonography

To investigate the influence of duration of gonadotropin (Gn) administration on the clinical outcome of in vitro fertilization embryo transfer (IVF-ET).. A total of 3 221 cycles of short protocol or antagonist protocol in our center from January 2012 to December 2012 were included in the retrospective study. According to the different duration of Gn administration, all patients were divided into group A (≤7 days, n=58) and group B (>7 days, n=3 163). The different clinical parameters, such as age, duration of infertility, body mass index (BMI), basis estradiol (E2), follicle-stimulating hormone (FSH), the number of antral follicle, the number of oocytes, endometrium thickness, fertility rate, good quality embryo rate, impatation rate and clinical pregnancy rate were compared between the two groups.. There was no significant difference in age, duration of infertility, BMI, basis E2, FSH, the number of antral follicle between the two groups. The number of oocytes in group A was fewer than that in group B [(8.2±5.6)vs.(12.1±8.3), P=0.009]; endometrium thickness on the day of HCG in group A was thinner than that in group B [(9.9±2.1) mm vs.(10.4±1.6) mm,P=0.002]. There was no significant difference in fertility rate, good quality embryo rate, impatation rate and clinical pregnancy rate (36.2% vs. 33.6%, P>0.05). There was no significant difference in clinical pregnancy rate between the two groups in short protocol (33.3% vs. 27.2%, P>0.05). In the same way, there was no significant difference in clinical pregnancy rate between the two groups in antagonist protocol (37.5% vs. 36.6%, P> 0.05).. Although short duration of gonadotropin administration in short protocol and antagonist protocol has association with fewer number of oocytes, it may not affect the outcome of IVF-ET.

Topics: Adult; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Infertility, Female; Middle Aged; Ovulation Induction; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Retrospective Studies; Time Factors; Triptorelin Pamoate

The impact of endometrial growth to the triple layer, endometrial thickness, and echogenicity on IVF outcomes was investigated in the study. A retrospective analysis of 583 ICSI patients was conducted: 385 with a long GnRH agonist protocol, 114 with a short GnRH agonist, and 84 with a GnRH antagonist protocol. The progression of endometrial growth to the appearance of the triple layer, endometrial thickness, and echogenicity was compared between protocols. At least one high quality blastocyst was transferred in a double embryo transfer. The time of the appearance of the endometrial triple layer was statistically significant for the pregnancy rate only in the GnRH antagonist protocol. The endometrial thickness on the day of the appearance of the triple layer had a statistically significant influence on the pregnancy rate in the GnRH antagonist and in the long GnRH agonist protocols. The highest pregnancy rate for the long GnRH agonist and the GnRH antagonist protocols was observed when the endometrium thickness was 12-13 mm (61.6% and 58.8%, respectively). The endometrial echogenicity had a significant influence on the pregnancy rate only in the long GnRH agonist protocol. Endometrial features could be helpful parameters in IVF outcomes in particular controlled ovarian hyperstimulation protocols.

Topics: Adult; Endometrium; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Male; Ovulation Induction; Poland; Pregnancy; Pregnancy Outcome; Retrospective Studies; Sperm Injections, Intracytoplasmic; Triptorelin Pamoate; Ultrasonography; Young Adult

To assess the characteristics of progesterone (Prog) changes in women with a subtle Prog rise in recombinant follicle-stimulating hormone (r-FSH) and GnRH antagonist cycles.. We enrolled 233 patients undergoing controlled ovarian hyperstimulation with r-FSH and GnRH antagonist for IVF or ICSI. A subtle Prog rise 1 day before hCG administration was defined as a Prog value of > or =1.2 ng/ml.. 100 of 233 cycles (42.9%) showed a subtle Prog rise in this study. The mean serum Prog levels and area under curve (AUC) in the group with Prog > or =1.2 ng/ml was significantly higher than that in the Prog <1.2 ng/ml group on cycle day 8 (1.17 +/- 0.4 and 0.80 +/- 0.3 ng/ml, respectively, for Prog level, p = 0.003; 571 +/- 123 and 763 +/- 250 for AUC, p = 0.001), and remained significantly higher until the day of hCG administration. Moreover, 55% of the patients on cycle day 9, 65% on cycle day 10, 75% on cycle day 11 and 85% on cycle day 12 in the Prog > or =1.2 ng/ml group have a serum Prog level of > or =1.2 ng/ml.. A subtle Prog rise may occur as early as cycle day 8 in r-FSH/GnRH antagonist cycles.

Topics: Adult; Chorionic Gonadotropin; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Ovulation Induction; Pregnancy; Pregnancy Outcome; Progesterone; Recombinant Proteins; Young Adult

Reproductive function following chemotherapy is of increasing importance given that survival rates are improving. We assessed whether a gonadotropin-releasing hormone antagonist (GnRHant; cetrorelix) could promote ovarian protection against damage due to chemotherapy.. Forty-two female Wistar rats were used in this study. Animals were divided into four groups: group I (n=9) received placebo twice; group II (n=12) received placebo+cyclophosphamide (CPA); group III (n=12) received GnRHant+CPA; and group IV (n=9) received GnRHant+placebo. After medication, the estrous cycle was studied through vaginal smears. Rats were mated, pregnancy was documented and the number of live pups evaluated. Afterwards, rat ovaries were removed and prepared for histological studies. The ovarian cross-sectional area was measured and follicles were counted.. Cyclic changes in vaginal smears were observed in all but one animal after treatment, but group II had a significantly lower rate of animals with proestrus or estrus (p<0.01). The offspring was markedly reduced by CPA treatment (group II, 3.00+/-1.33 pups vs. group I, 11.44+/-0.78 pups, p<0.01) and this effect was partly reversed by pre-treatment with GnRHant (group III, 7.00+/-1.31 pups). The ovarian cross-sectional area was not significantly different between groups, neither was the number of individual follicle types. However, rats in Group IV had a higher total number of ovarian follicles than those in the control group (17.1+/-1.22 vs. 10.9+/-0.70, p<0.05).. The use of a GnRHant before CPA chemotherapy provided protection of fertility.

Topics: Animals; Antineoplastic Agents; Cell Count; Cyclophosphamide; Drug Administration Schedule; Drug Evaluation, Preclinical; Female; Fertility; Gonadotropin-Releasing Hormone; Hormone Antagonists; Infertility, Female; Neoplasms; Ovary; Placebos; Pregnancy; Pregnancy Rate; Rats; Rats, Wistar

In an attempt to evaluate the influence of the GnRH analogue used during controlled ovarian hyperstimulation (COH) on the outcome of IVF cycles of polycystic ovary syndrome (PCOS) patients, we studied 152 IVF cycles. The PCOS patients undergoing COH using the GnRH agonist protocol (n = 50) showed a significantly higher pregnancy rate (36% vs. 19.6%, respectively), compared with the GnRH antagonist protocol (n = 102).

Topics: Adult; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Luteolytic Agents; Oocyte Retrieval; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Retrospective Studies; Treatment Outcome; Triptorelin Pamoate

To determine if the choice of gonadotropin releasing hormone antagonist influences subsequent pregnancy rates in women with diminished egg reserve.. Retrospective determination of pregnancy rates following embryo transfer in women with day 3 FSH >12 mIU/ml using lower dose gonadotropin stimulation regimen.. Though no significant differences were found there was a trend for lower pregnancy rates with ganirelix vs cetrorelix.. The trend for lower pregnancy rates with ganirelix vs. cetrorelix seen in women with diminished egg reserve is consistent with the findings of a study performed in women with normal egg reserve using a normal gonadotropin stimulation regimen. It is not clear if the adverse effect is on the endometrium or the embryo.

Topics: Adult; Embryo Transfer; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Maternal Age; Ovarian Follicle; Pregnancy; Pregnancy Outcome; Retrospective Studies

To compare follicular fluid (FF) anti-Müllerian hormone (AMH) and inhibin B concentrations for GnRH agonist (GnRH-a) and GnRH antagonist cycles and to determine the correlations between FF AMH or inhibin B concentrations and controlled ovarian hyperstimulation (COH) outcomes.. Prospective comparative study.. University hospital.. Eighty-seven women who underwent COH cycles, either in the GnRH-a long-protocol group (n = 43) or the GnRH antagonist multiple-dose flexible-protocol group (n = 44).. Follicular fluid was obtained from dominant follicles during oocyte retrieval, and FF AMH, inhibin B, E(2), and P concentrations were measured. Serum levels of AMH and inhibin B also were assessed on the day of oocyte retrieval.. Follicular fluid AMH and inhibin B concentrations.. Concentrations of serum AMH and inhibin B and of FF AMH, inhibin B, E(2), and P were similar in the two groups. Follicular fluid AMH levels were found to be significantly correlated with age, gonadotropin dose, number of follicles on hCG day, and number of oocytes retrieved.. Our results suggest that there is no significant difference in follicular microenvironment in terms of AMH and inhibin B secretion between GnRH-a and GnRH antagonist protocols and that FF AMH is a marker that reflects ovarian reserve and response to COH.

Topics: Adult; Age Factors; Anti-Mullerian Hormone; Biomarkers; Chorionic Gonadotropin; Dose-Response Relationship, Drug; Drug Administration Schedule; Embryo Implantation; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Follicular Fluid; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Inhibins; Oocyte Retrieval; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Prospective Studies; Treatment Outcome; Triptorelin Pamoate

While performing the mild ovarian stimulation protocol with a GnRH antagonist, the pregnancy rate was compared between the groups, which were divided by the degree that the luteinizing hormone (LH) level decreased.. Patients aged 27 to 42years (36.1 +/- 3.79) underwent 308 IVF cycles who opted for IVF via the mild ovarian stimulation protocol began clomiphene citrate on day 3 and recombinant FSH on day 5. A GnRH antagonist was administered when the dominant follicle reached 14mm. Serum LH was measured at the time of GnRH antagonist administration and at the time of hCG injection. The pregnancy rate and implantation rate were compared between 50 cycles in which the LH level dropped less than one-third and the control (LH level within 1/3).. The pregnancy rate for the group in which the LH level fell less than one third was 18%. Conversely, the pregnancy rate for the control group was 39%. The implantation rate was 18% for the less than one-third group and 26% for the control group. Both the pregnancy rate and the implantation rate for the group in which the LH level fell less than one-third were significantly lower than that of control (p < 0.02).. When performing the mild ovarian stimulation protocol, serum LH should be followed. If the serum LH level is less than one-third at the time of hCG injection, both the pregnancy rate and implantation rate are significantly lower.

Topics: Adult; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Gonadotropins; Hormone Antagonists; Humans; Infertility, Female; Luteinizing Hormone; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies; Treatment Outcome

To determine if ovulation and pregnancy could be achieved in a case of amenorrhea, estrogen deficiency, and markedly elevated serum follicle stimulating hormone (FSH) through reduction of the serum FSH by a gonadotropin releasing hormone antagonist.. A 37-year-old woman with hypergonadotropic secondary amenorrhea related to two courses of chemotherapy with alkylating agents and abdominal radiation therapy (Hodgkin's disease and breast cancer) was treated with cetrorelix in an attempt to induce ovulation by lowering elevated serum FSH and hopefully restore sensitivity of the few remaining follicles by restoring down-regulated FSH receptors. She was monitored with serum estradiol (E2), FSH, luteinizing hormone (LH), progesterone (P) levels and sonography.. As the serum FSH dropped the serum E2 rose and peaked at 200 pg/ml after ten days of cetrotide. She conceived in that cycle. A viable ongoing pregnancy with appropriate ultrasound findings was demonstrated 40 days from conception.. This is the first case description of successful ovulation and pregnancy following induction of ovulation with the GnRH antagonist cetrorelix. The possibility exists that the ovulation was spontaneous but it seems unlikely. It has been estimated that the chance of spontaneous ovulation and pregnancy in cases of premature ovarian failure is 1:9,200.

Topics: Adult; Antineoplastic Agents; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Ovulation Induction; Pregnancy; Pregnancy Outcome; Primary Ovarian Insufficiency

In modified natural cycle IVF (MNC-IVF), treatment is aimed at using the one follicle that spontaneously develops to dominance, using a GnRH-antagonist together with gonadotrophins in the late follicular phase only. The MNC-IVF is of interest because of its low-risk and patient-friendly profile. The effect of application of MNC-IVF preceding standard IVF with ovarian stimulation on overall results is unknown.. This single-center cohort study provides follow-up of an earlier study in which nine cycles of MNC-IVF were offered to 268 patients. Ongoing pregnancy rates and live birth rates, as well as time-to-pregnancy after controlled ovarian stimulation-IVF (COS-IVF) following MNC-IVF, were evaluated.. Actual observed cumulative ongoing pregnancy rates and live birth rates after sequential treatment with MNC-IVF followed by COS-IVF were 51.5 (95% CI: 45.4-57.6) and 50.0% (95% CI: 43.9-56.1) per patient, of which 8.0 and 6.7% were twins. Median time to ongoing pregnancy was 28.8 weeks. Including treatment-independent pregnancies, cumulative ongoing pregnancy rate was 56.7% (95% CI: 50.7-62.8).. Sequential treatment with MNC-IVF followed by COS-IVF does not appear to compromise overall success rates, while twin pregnancy rate is low. Because of its patient-friendly and low-risk profile, it seems appropriate to perform MNC-IVF preceding COS-IVF.

Topics: Adult; Birth Weight; Cohort Studies; Female; Fertilization in Vitro; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Humans; Infant, Newborn; Infertility, Female; Ovulation Induction; Pregnancy; Pregnancy Rate; Pregnancy, Multiple; Twins

Cytotoxic treatment can cause early loss of ovarian function associated with loss of fertility in younger women. To investigate if co-treatment with a combination of gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist may be useful in preserving ovarian function and fertility in younger women during chemotherapy, we prospectively observed nine young patients receiving different chemotherapies for various malignant diseases and other severe medical conditions who also received simultaneous GnRH agonist and GnRH antagonist. Mean age of the patients was 26.56 +/- 8.78 years, all were < or =35 years old. Eight (88.9%) patients regained normal basal hormonal profile within 3 - 6 months after the completion of chemotherapy. Median level of follicle-stimulating hormone, luteinizing hormone and estradiol was 6.3 +/- 8.8 U/l, 8.2 +/- 25.4 U/l and 118.0 +/- 130.8 pg/ml, respectively. Eight (88.9%) patients resumed spontaneous menses within 3 - 11 months following discontinuation of chemotherapy. Two (22.2%) patients conceived: one spontaneously, and the second following induction of ovulation by injection of gonadotropins. It seems that combined usage of GnRH agonist and GnRH antagonist during chemotherapy may be useful in preserving ovarian function and fertility in a group of young females receiving chemotherapy treatment.

Topics: Adolescent; Adult; Age Factors; Antineoplastic Agents; Case-Control Studies; Drug Therapy, Combination; Female; Gonadotropin-Releasing Hormone; Goserelin; Hormone Antagonists; Humans; Infertility, Female; Lymphoma; Ovary; Prospective Studies

A subtle rise in serum progesterone during the late follicular phase in patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles is a frequent event that can decrease implantation and pregnancy rates in controlled ovarian hyperstimulation (COH) protocols that use a gonadotropin-releasing hormone (GnRH) antagonist. The aim of the present study was to evaluate the prevalence and effect of the subtle progesterone rise during COH with single-dose GnRH antagonist in combination with clomiphene citrate (CC) and human menopausal gonadotropins (hMG) in IVF or ICSI cycles. Ninety-five women undergoing COH with CC, hMG and a single 2.5 mg dose of the GnRH antagonist, cetrorelix, were enrolled in the study. Patients were grouped according to serum progesterone level on the day of human chorionic gonadotropin (hCG) administration (P < 1.2 ng/ml or P >/= 1.2 ng/ml). The incidence of a subtle progesterone rise was 54.7% (52/95). The group with P >/= 1.2 ng/ml had significantly higher serum levels of luteinizing hormone (p = 0.002) and estradiol (p < 0.001) on the day of hCG injection than the group with P < 1.2 ng/ml, and more oocytes were retrieved (p = 0.001). However, there was no significant difference in fertilization, clinical pregnancy or implantation rate between the two groups. In conclusion, a subtle progesterone rise during the late follicular phase is common but not associated with pregnancy outcome.

Topics: Adult; Clomiphene; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Menotropins; Ovulation Induction; Progesterone; Sperm Injections, Intracytoplasmic

The aim of the study was to investigate whether controlled ovarian hyperstimulation (COH) using multi-dose gonadotropin-releasing hormone (GnRH) antagonist results in a lesser degree of systemic inflammation than the GnRH-agonist long protocol.. Prospective, observational study.. Blood was drawn three times during the COH cycle from patients undergoing the long GnRH-agonist protocol (agonist group) (n = 12) or the multi-dose GnRH-antagonist protocol (antagonist group) (n = 15): the day on which adequate suppression was obtained (agonist group), or day 2 or 3 of the menstrual cycle and before gonadotropin treatment (antagonist group) (Day-0); the day of or prior to administration of human chorionic gonadotropin (Day-hCG); and the day of ovum pick-up (Day-OPU). Levels of sex steroids and serum C-reactive protein (CRP) were compared between the two study groups among the three time points.. While no between-group differences were observed in patient age or ovarian stimulation characteristics, a significantly higher number of oocytes were retrieved in the antagonist compared with the agonist group. In both groups, serum CRP levels were significantly higher on Day-OPU than on Day-hCG and Day-0. While serum CRP levels were higher on Day-hCG than Day-0, the difference was statistically significant only for the agonist group (p < 0.05). Moreover, Day-OPU serum CRP levels were significantly higher in the agonist than in the antagonist subgroup.. COH using the multi-dose GnRH-antagonist protocol yields a lesser degree of systemic inflammation, as reflected by CRP levels, than the GnRH-agonist long protocol.

Topics: Adult; C-Reactive Protein; Drug Administration Schedule; Estradiol; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Inflammation; Luteolytic Agents; Oocyte Retrieval; Ovulation Induction; Patient Selection; Progesterone; Prospective Studies; Triptorelin Pamoate

To compare the agonist flare-up and antagonist protocols in the management of poor responders to the standard long down-regulation protocol.. Retrospective comparative study.. Assisted conception center.. One hundred thirty-four patients undergoing IVF/ intracytoplasmic sperm injection (ICSI) treatment, who responded poorly to the standard long down-regulation protocol in their first treatment cycle. In the second cycle, 77 received short flare-up agonist and 57 received antagonist protocol. We analyzed the outcome of the second cycle.. Peak serum E(2) was assayed on the day of hCG administration.. Cycle cancellation rate due to poor ovarian response.. There was no cycle cancellation in the flare-up protocol and 7% cancellation rate in the antagonist protocol due to lack of response. A significantly higher number of patients had embryo transfer in the flare-up protocol. There was no difference in pregnancy rate (PR) between the two groups.. Both the flare-up and the antagonist protocols significantly improved the ovarian response of known poor responders. However, a significantly higher cycle cancellation rate and less patients having embryo transfer in the antagonist group tips the balance in favor of the flare-up protocol.

Topics: Adult; Buserelin; Drug Resistance; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Pregnancy; Pregnancy Outcome; Retrospective Studies; Sperm Injections, Intracytoplasmic

The present retrospective study evaluated the outcome of frozen-thaw cycles with oocytes obtained either during a multiple dose protocol of cetrorelix, or after the use of a gonadotrophin-releasing hormone (GnRH) agonist. A total of 101 subfertile couples were included. These couples had a total of 222 transfers of frozen-thawed pronuclear oocytes after IVF/intracytoplasmic sperm injection (ICSI) treatment. According to the stimulation protocol during various cycles, four groups were established: cetrorelix/recombinant FSH (recFSH) (69 cycles), cetrorelix/human menopausal gonadotrophin (HMG) (10 cycles), GnRH-agonist/recFSH (71 cycles) and GnRH-agonist/HMG (72 cycles). The transfer cycles were mildly stimulated with transdermal oestradiol. No statistically significant difference was seen among the four groups regarding post-thaw survival rate, cumulative embryo score, implantation rate and pregnancies. Frozen-thawed pronuclear oocytes obtained with the use of cetrorelix give satisfactory implantation and pregnancy rates, similar to those obtained with a GnRH-agonist. These results do not depend on the gonadotrophins (HMG or recFSH) used in the collecting cycle.

Topics: Cryopreservation; Embryo Implantation; Estradiol; Estrogens; Female; Fertilization in Vitro; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Male; Menotropins; Oocytes; Ovulation Induction; Pregnancy; Pregnancy Outcome; Recombinant Proteins; Retrospective Studies; Sperm Injections, Intracytoplasmic

Applicability of the GnRH-antagonist Cetrorelix within controlled ovarian hyperstimulation (COH) to avoid the premature LH-surge should be examined.. 35 patients suffering from tubal infertility were stimulated for In Vitro Fertilization (IVF) by human menopausal gonadotrophins (HMG) and concomitant administration of Cetrorelix in different dosages (3 mg, 1 mg, 0,5 mg).. No premature LH-surge could be observed.. Short term administration of the GnGR-antagonists avoids the occurrence of a premature LH-surge.

Topics: Adult; Dose-Response Relationship, Drug; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infant, Newborn; Infertility, Female; Luteinizing Hormone; Ovulation Induction; Pregnancy

Surges of LH in serum, which result in luteinization, but occur prematurely with respect to the diameter of the leading follicle, frustrate attemps to induce multiple follicular maturation for in-vitro fertilisation in a number of women. We examined the possibility of blocking premature LH-surges by the administration of Cetrorelix, a potent antagonist of gonadotrophin releasing hormone. Twenty patients, who had repeatedly shown premature LH surges, were treated with human menopausal gonadotrophins from the 2nd day onwards. From the 7th day until the induction of ovulation by HCG, the GNRH-antagonist Cetrorelix was given daily. HCG was injected when the dominant follicle had reached the diameter of at least 18 mm and oestradiol levels were above 300 pg for each follicle and more than 15 mm. Oocyte collection was performed 36 hours later by transvaginal ultrasound puncture, followed by IVF and embryo transfer. The hormone profiles of these patients and the results of in-vitro fertilisation and embryo transfer are discussed. It could be demonstrated in this study, that combined treatment with gonadotrophins and the GNRH-antagonist seems to be a promising method for ovarian stimulation in patients, who frequently exhibit premature LH discharges and therefore fail to complete treatment.

Topics: Adult; Chorionic Gonadotropin; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Luteinizing Hormone; Ovulation Induction; Pregnancy