menotropins and cetrorelix

The gonadotrophin-releasing hormone (GnRH) antagonists Cetrorelix and Ganirelix have been used in recent years in clinical studies to prove that these compounds reliably prevent the onset of premature luteinizing hormone (LH) surges during ovarian stimulation. Cetrorelix has been applied in single and multiple dose protocols, while Ganirelix has until now only been used in the multiple dose protocol. In the latter protocol, ovarian stimulation is started on day 2 or 3 of the spontaneous cycle with human menopausal gonadotrophin or recombinant follicle stimulating hormone. Daily administration of the GnRH antagonist at its minimum effective dose (0.25 mg/day s.c.) occurs from the sixth day of stimulation onwards until ovulation induction by human chorionic gonadotrophin. In the single dose protocol, 3 mg of the GnRH antagonist Cetrorelix was injected on day 8 of the stimulation cycle. Both protocols have been proven to be safe and effective. Fertilization rates of >60% in in-vitro fertilization and >70% in intracytoplasmic sperm injection, as well as clinical pregnancy rates of approximately 30% per transfer, sound most promising. The incidence of a premature LH surge is below 2%. The incidence of severe ovarian hyperstimulation syndrome seems to be lower under antagonist treatment than in the long agonistic protocol. Treatment time is significantly shortened.

Topics: Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonadotropins; Hormone Antagonists; Humans; Menotropins; Ovulation Induction; Randomized Controlled Trials as Topic; Recombinant Proteins; Sperm Injections, Intracytoplasmic

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

Objective To compare the efficacy of three protocols for ovarian stimulation in patients with diminished ovarian reserve during in vitro fertilization (IVF) treatment. Methods This prospective randomized study enrolled patients with diminished ovarian reserve who underwent cycles of IVF or intracytoplasmic sperm injection. The patients were randomly divided into three groups: a modified gonadotrophin releasing hormone (GnRH) agonist protocol (group A); (ii) a mild stimulation protocol (group B); or (iii) an antagonist protocol (group C). Demographic characteristics, clinical variables and pregnancy outcomes were compared between the groups. Results A total of 116 patients were enrolled in the study: 54 in group A, 52 in group B and 60 in group C. Group B (32.69%) had a significantly higher cycle cancellation rate compared with groups A (11.11%) and C (16.67%). The early abortion rate of group C (44.44%) was significantly higher than group A (12.50%), but not significantly different from group B (16.67%). There were no significant differences in the clinical pregnancy rates and live birth rates among the three groups. Conclusion A modified GnRH agonist protocol achieved a comparable pregnancy rate to those of the mild stimulation protocol and antagonist protocol, whilst having lower cycle cancellation and early abortion rates.

Topics: Adult; Clinical Protocols; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Letrozole; Luteolytic Agents; Male; Menotropins; Ovarian Follicle; Ovarian Reserve; Ovulation Induction; Pregnancy; Pregnancy Rate; Prospective Studies; Sperm Injections, Intracytoplasmic; Treatment Outcome; Triptorelin Pamoate

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

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

To evaluate the feasibility of a long protocol of controlled ovarian stimulation prior to in vitro fertilization (IVF) and embryo transfer with a gonadotropin-releasing hormone (GnRH) antagonist used for pituitary and ovarian suppression.. Thirty patients undergoing IVF/intracytoplasmic sperm injection were randomized into two groups. The control group (n = 16) received a standard flexible GnRH antagonist protocol. Ovarian stimulation consisted of 225 IU/day of recombinant follicle-stimulating hormone for 5 days, followed by 225 IU/day of human menopausal gonadotropin until human chorionic gonadotropin (hCG) administration. The study group (n = 14) received 0.25 mg of GnRH antagonist daily for 7 days, thereafter, upon confirmation of pituitary and ovarian suppression, ovarian stimulation was commenced with the same protocol as used in the control group. Hormone and follicle dynamics, as well as laboratory characteristics and cycle outcome, were compared for both groups.. Both groups were comparable in baseline characteristics. Pituitary and ovarian suppression were effectively achieved in 12/14 patients in the study group. The duration of ovarian stimulation and gonadotropin consumption were similar in both groups, as was also the number and size of follicles on hCG day.. The results of our study confirm the feasibility of a long GnRH antagonist protocol. This regimen could become another option to optimize GnRH antagonist protocols, and should thus be further explored.

Topics: Adult; Dinoprostone; Feasibility Studies; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Menotropins; Oocyte Retrieval; Ovarian Follicle; Ovulation Induction; Pregnancy; Progesterone; Sperm Injections, Intracytoplasmic; Time Factors

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

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

Previous studies have shown that ovarian stimulation with clomiphene citrate (CC), human menopausal gonadotrophin (HMG), and multiple-dose gonadotrophin-releasing hormone (GnRH) antagonist is associated with a high rate of premature LH surge. This study assessed whether administration of the GnRH antagonist cetrorelix at an incremental dose or at a high dose (0.5mg) from the start could prevent premature LH surge. Couples with male factor or unexplained infertility who were going to undergo intrauterine insemination were randomized into two stimulation protocols. All women were stimulated with CC and HMG. In protocol A, cetrorelix was given at 0.25 mg per day when the leading follicles reached 14 mm, and increased to 0.5 mg when the leading follicles were 16 mm. With protocol B, cetrorelix was given at 0.5 mg per day when the leading follicles reached 14 mm. The primary outcome measure was the incidence of premature LH surge. Premature LH surge occurred in 21.6% of patients undergoing protocol A, and in 18.9% of patients undergoing protocol B. Cetrorelix at incremental dose or at 0.5 mg per day does not prevent premature LH surges associated with the CC/HMG/multiple-dose cetrorelix stimulation protocol.

Topics: Adult; Clomiphene; Female; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Menotropins; Ovulation Induction

The aim of the study was to investigate the cause of the lower estradiol (E(2)) concentration in women treated with gonadotropin-releasing hormone (GnRH) antagonist compared with those treated with agonist protocol in in vitro fertilization (IVF). Thirty patients who were known low responders were prospectively randomized into two equal groups for IVF treatment. Group 1 used GnRH agonist (flare-up) protocol and group 2 used antagonist protocol. The results showed that serum luteinizing hormone (LH) levels were significantly higher in the agonist group during the folliculogenesis stage. Despite this higher LH, serum E(2) levels were significantly higher in the agonist group on cycle day 2 only, not on day 5 or day 9. The significantly higher E(2) level in the agonist group reappeared on the day of administration of human chorionic gonadotropin (hCG). The rate of folliculogenesis in the antagonist group was faster than in the agonist group; therefore their E(2) production should have been higher on hCG day. Furthermore, the rate of decline in E(2) after hCG administration was significantly higher in the antagonist group. These findings, along with the fact that both groups received exogenous LH (human menopausal gonadotropin) that should optimize steroidogenesis and make the difference in E(2) insignificant, enable us to conclude that GnRH antagonists have a suppressive effect on the production of E(2).

Topics: Adult; Buserelin; Chorionic Gonadotropin; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteal Phase; Luteinizing Hormone; Menotropins; Ovarian Follicle; Prospective Studies; Steroids

This study evaluates the efficacy of a stimulation protocol with clomiphene citrate (CC)/human menopausal gonadotropin (hMG)/cetrorelix and its effects on oocyte quality and endometrium. One hundred and twenty couples with male-factor infertility who were about to undergo their first intracytoplasmic sperm injection cycles were randomized into two groups. Sixty women were stimulated with the CC/hMG/cetrorelix protocol (cetrorelix group) and 60 received the buserelin long protocol (buserelin group). Fewer oocytes were recovered in the cetrorelix group than in the buserelin group (mean +/- standard deviation (SD): 11.1 +/- 4.0 vs. 17.3 +/- 5.8, p < 0.001); however, the percentages of metaphase II, metaphase I and germinal vesicle oocytes were similar between the two groups. Serum estradiol level was significantly lower in the cetrorelix than in the buserelin group (mean +/- SD: 2600.58 +/- 1189.11 vs. 3293.46 +/- 1221.49 pg/ml, p = 0.006), but the endometrial thickness was similar. The implantation rates (19.2% vs. 17.7%) and the pregnancy rates (41.7% vs. 40.0%) were similar between groups. The ampoules (mean +/- SD: 18.9 +/- 3.0 vs. 38.9 +/- 12.2, p < 0.001) and injections (mean +/- SD: 6.8 +/- 1.1 vs. 15.7 +/- 3.1, p < 0.001) of gonadotropin used were significantly lower in the cetrorelix group than in the buserelin group. No patients in either group developed a premature luteinizing hormone surge. The present study found no statistically significant difference between the two treatment modalities with regard to pregnancy rates.

Topics: Adult; Buserelin; Chorionic Gonadotropin; Clomiphene; Embryo Culture Techniques; Estradiol; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility, Male; Luteinizing Hormone; Male; Menotropins; Pregnancy; Sperm Injections, Intracytoplasmic; Treatment Outcome

The intrafollicular levels of IGF-I and epidermal growth factor (EGF) were studied in women undergoing controlled ovarian hyperstimulation using the multidose GnRH-antagonist protocol or the long agonist protocol, in an attempt to elucidate whether GnRH-antagonists affect the levels of the two growth factors. The follicular fluid concentration of IGF-I, EGF, estradiol and progesterone were detected in 68 women undergoing ovarian hyperstimulation for intracytoplasmic sperm injection (ICSI) cycles. There were no differences in intrafollicular concentrations of EGF and IGF-I in the two studied groups. Additionally, we found no correlation between the intrafollicular levels of IGF-I or EGF and the ICSI outcome. The intrafollicular levels of IGF-I were positively correlated with those of progesterone. In conclusion, the intrafollicular levels of IGF-I and EGF do not seem to be influenced by the stimulation protocol. The intrafollicular levels of both growth factors can not serve as prognostic markers for the ICSI outcome.

Topics: Adult; Epidermal Growth Factor; Estradiol; Female; Follicle Stimulating Hormone; Follicular Fluid; Gonadotropin-Releasing Hormone; Humans; Insulin-Like Growth Factor I; Menotropins; Ovulation Induction; Progesterone; Sperm Injections, Intracytoplasmic; Treatment Outcome; Triptorelin Pamoate

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

The introduction of GnRH antagonists such as cetrorelix acetate has made possible the simplification of ovarian stimulation. However, the most effective protocol for their administration has not yet been clearly defined.. Forty women with male-factor infertility undergoing 40 ICSI cycles were included in the study. Clomiphene citrate at 100 mg a day was given from cycle day 3 through day 7. hMG at 150 IU was given on cycle days 4, 6 and 8, and was adjusted from day 9 according to the follicular and hormone responses. Cetrorelix acetate at 2.5 mg was administered when the leading follicle reached 14 mm. The remaining 0.5 mg was divided into two 0.25 mg injections for possible later use. Serum FSH, LH, estradiol and progesterone levels were measured daily from the day of cetrorelix acetate injection until hCG was given.. Serum LH level was suppressed effectively for 4 days. Four patients (10%) needed one or two additional injections of 0.25 mg cetrorelix acetate. No premature LH surge was detected in any of the women treated. Sixteen women became pregnant (40%), of which 14 pregnancies (35%) were ongoing at the time of writing.. This study demonstrates that this new protocol is feasible for couples with male-factor infertility undergoing ICSI.

Topics: Adult; Clomiphene; Drug Administration Schedule; Drug Therapy, Combination; Feasibility Studies; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Male; Luteinizing Hormone; Male; Menotropins; Ovulation Induction; Pregnancy; Pregnancy Rate; Sperm Injections, Intracytoplasmic

To evaluate the cost effectiveness of a clomiphene citrate (CC)/human menopausal gonadotropin (hMG)/GnRH antagonist protocol versus a long-acting GnRH agonist/hMG protocol.. One hundred eighty nine couples having their first trial of ICSI for male factor infertility were divided into two groups. Group I (no = 33) received CC 100-150 mg/day for five days starting from day 2 of the cycle and 150 IU of hMG/day on days 6-10. GnRH antagonist (Centrorelix) 0.25 mg/day was started when the leading follicle reached 16 mm in the absence of an LH surge. Group II (no = 156) received 0.1 mg Deacapeptyl/day as our standard long protocol.. Clinical pregnancy was observed in 8 out of the 33 cases in group I (24%) while in group II, 92 out of 156 achieved clinical pregnancy (59%), the difference was statistically significant (P = 0.019). The cost of medications/cycle was estimated to be 1110+/-492 E.P in group I, while it was 1928+/-456 E.P. in group II. However, the total cost per pregnancy was 19653 EP in group I and 10047 EP in group II.. The use of the clomid/hMG/antagonist protocol is not a cost effective strategy and should not be recommended in IVF-ICSI cycles.

Topics: Adult; Chorionic Gonadotropin; Clomiphene; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Male; Menotropins; Pregnancy; Pregnancy Rate; Sperm Injections, Intracytoplasmic; Triptorelin Pamoate

A prospective randomized feasibility study was carried out on 10 patients undergoing IVF treatment using a single-dose LHRH antagonist protocol (cetrorelix, Cetrotide) with clomiphene citrate in combination with either human menopausal gonadotrophin (HMG) (n = 5) or recombinant human FSH (rFSH) (n = 5). Both treatment-groups, HMG and rFSH, were comparable with regard to age (33.2 +/- 2.6 versus 34.4 +/- 4.0 years) BMI (23.2 +/- 2.6 versus 22.7 +/- 1.6) and cause of infertility. They yielded comparable results concerning gonadotrophin dose (19.8 +/- 8.7 versus 17.0 +/- 8.9), stimulation days (6.5 +/- 2.0 versus 5.8 +/- 1.9) and live births (one versus two). No premature LH surge (LH >10 IU/ml and progesterone >1 ng/ml) occurred. The overall baby take-home rate was 30%. In a small number of patients, cetrorelix could be shown to effectively prevent premature LH surges in stimulation protocols combining clomiphene with gonadotrophins with an excellent baby take-home rate per started cycle of 30%.

Topics: Adult; Clomiphene; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Hormones; Humans; Menotropins

With the recently introduced GnRH antagonists, soft stimulation protocols on the basis of clomiphene pretreatment should be possible as the pituitary remains fully sensitive at the beginning of the cycle.. A prospective trial was carried out on 107 patients undergoing IVF treatment using the multiple dose GnRH antagonist protocol (cetrorelix), clomiphene citrate, and either HMG (n = 54) or recombinant FSH (rFSH) (n = 53). Different stimulation protocols were used to find the most appropriate one for clinical application.. Both treatment groups, HMG and rFSH, yielded comparable results concerning gonadotrophin dose, stimulation days and pregnancy rate. A mean number of 6.34 +/- 4.4 metaphase II oocytes was retrieved and a mean number of 2.45 +/- 0.65 embryos was transferred. However, the overall rate of premature LH surges was 21.5% (defined as measurement of LH >10 IU/l and progesterone >1 ng/ml) which is unacceptable for clinical practice.. Increasing the daily cetrorelix dose from 0.25 to 0.5 mg might decrease the number of premature LH surges. Soft stimulation protocols with clomiphene should be used cautiously.

Topics: Adult; Clomiphene; Drug Combinations; Embryo Transfer; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Luteinizing Hormone; Menotropins; Metaphase; Oocytes; Ovulation Induction; Pregnancy; Pregnancy Rate; Prospective Studies; Recombinant Proteins; Time Factors; Tissue and Organ Harvesting

Luteinizing hormone (LH) is mandatory for the maintenance of the corpus luteum. Ovarian stimulation for IVF has been associated with a defective luteal phase. The luteal phases of two groups of patients with normal menstrual cycles and no endocrinological cause of infertility were retrospectively analysed in IVF cycles. Thirty-one infertile patients stimulated with human menopausal gonadotrophins (HMG) for IVF to whom the gonadotrophin-releasing hormone (GnRH) antagonist Cetrorelix 0.25 mg was also administered to prevent the LH surge (group I) were compared with 31 infertile patients stimulated with HMG alone (group II). Despite differences in the stimulation outcome, luteal LH serum concentrations were similar in the two groups. LH values dropped from 2.3 +/- 1 IU/l on the day of human chorionic gonadotrophin (HCG) administration to 1.1 +/- 0.7 IU/l on day HCG +2 in group I (P < 0.0001) and from 5.1 +/- 3 to 1.2 +/- 1.7 IU/l (P < 0.0001) in group II. In the mid-luteal phase, LH concentrations were low in both groups. Our results suggest that suppressed LH concentrations in the early and mid-luteal phase may not be attributed solely to the GnRH-antagonist administration. Pituitary LH secretion may be inhibited by supraphysiological steroid serum concentrations via long-loop feedback and/or by the central action of the exogenously administered HCG via a short-loop mechanism.

Topics: Adult; Estradiol; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Luteal Phase; Luteinizing Hormone; Menotropins; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone

The management of poor responders in IVF has always been a big problem. The ideal approach has yet to be formulated. In this study we aim to compare two alternative stimulation protocols. A total of 48 poor responder patients described from previous cycles were included and grouped into two: group I consisted of 24 patients in 24 cycles in which leuprolide acetate (40 microg s.c. per day) was initiated on cycle day 2 followed by exogenous gonadotrophins on cycle day 3; group II consisted of 24 patients in 24 cycles in which ovarian stimulation included gonadotrophin-releasing hormone (GnRH) antagonist (cetrorelix, 0.25 mg daily during late follicular phase) administration. While only the oestradiol concentrations on the day of HCG were lower in group II compared with group I, the clinical pregnancy and implantation rates among groups did not show any significance. The impact of these two regimens in ovarian stimulation of poor responders seem to be same and to establish these results further randomized studies with larger sample sizes are required.

Topics: Adult; Chorionic Gonadotropin; Embryo Implantation; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Follicular Phase; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Luteinizing Hormone; Menotropins; Middle Aged; Ovulation Induction; Pregnancy; Prospective Studies

To estimate the efficacy of gonadotropin-releasing hormone (GnRH) antagonist 'Cetrorelix' in poor responders comparing with the standard long protocol.. The study population consisted of 21 poor responders who underwent ICSI and treated with Cetrorelix according to the multiple-dose protocol and who were compared with 21 poor responders treated according to the long protocol and who also underwent ICSI. Patients in both groups were matched for chronological age, the number of follicles found by ultrasound at the retrieval day and cause of infertility. Fifteen patients of GnRH antagonist group were treated with the combination of GnRH antagonist with clomiphene citrate (CC) plus gonadotropins, while six patients were treated with the combination of GnRH antagonist plus gonadotropins, but without CC.. The use of GnRH antagonist in a multiple dose protocol gave a pregnancy rate of 14.28% which was in the range expected for patient with poor response, but with shorter treatment duration and with fewer ampoules of gonadotropins as compared with the use of a GnRH agonist protocol in a depot formulation. Within Cetrorelix group patients who received CC had a significant shorter duration of stimulation and needed fewer ampoules as compared with patients in the same group who did not receive CC.. A GnRH antagonist multiple dose protocol may be the protocol of choice for the treatment of poor responders. The use of GnRH antagonist Cetrorelix ended with significantly less ampoules of gonadotropins and a shorter duration of stimulation.

Topics: Adult; Chorionic Gonadotropin; Clomiphene; Female; Gonadotropin-Releasing Hormone; Humans; Menotropins; Ovulation Induction; Pregnancy; Sperm Injections, Intracytoplasmic; Treatment Outcome

To study the influence of an LHRH (luteinizing hormone releasing hormone) antagonist protocol (Cetrorelix) and the use of recombinant follicle-stimulating hormone (FSH) on the development of leukocytosis, compared to the use of urinary HMG (human menopausal gonadotrophin).. Prospective, randomized phase III clinical trial.. Infertility day clinic, Department of Gynecology and Obstetrics.. Thirty patients undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment following controlled ovarian stimulation using a multiple dose protocol and the LHRH antagonist Cetrorelix.. Differences in white blood cell (WBC) count before stimulation, during the follicular phase and in the midluteal phase.. Statistically significant increase in WBC count in the HMG group from the start of stimulation to the midluteal phase. No statistically significant increase in the recFSH group, but only a trend towards higher values was observed.. The development of a leukocytosis in controlled ovarian stimulation does not depend on the protocol used. Urinary gonadotrophins seem to have a greater potential to increase WBC count compared to recombinant gonadotrophins.

Topics: Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leukocytosis; Menotropins; Ovary; Prospective Studies; Recombinant Proteins

A total of 346 women with normal ovulatory function was stimulated with human menopausal gonadotrophins (HMG) to attain ovarian stimulation for IVF or intracytoplasmic sperm injection (ICSI). Stimulation with HMG started on cycle day 2 or 3. After 6 days of stimulation, Cetrorelix in its minimum effective multiple dose of 0. 25 mg/day, was administered daily until induction of ovulation. In total, 333 patients (96.2%) reached the day of HCG administration, and 324 (93.6%) underwent oocyte retrieval. A mean of 25.2 ampoules of HMG was applied for a mean of 10.4 days. Cetrorelix was administered for a mean time lapse of 5.7 days. The mean normal fertilization rate was 60% in the IVF group and 59% in the ICSI group. Seventy pregnancies were attained, reflecting an ongoing clinical pregnancy rate of 24% per transfer. The ongoing clinical implantation rate was 11.4%. Only three cases of raised luteinizing hormone (LH) (>/=10 IU/l) with increased progesterone secretion (>/=1 ng/ml) were observed after initiation of Cetrorelix administration, reflecting an incidence of premature luteinization of 0.9%. The abortion rate was 17%. The incidence of severe ovarian hyperstimulation syndrome (World Health Organization grade III) was as low as 0.6%.

Topics: Dose-Response Relationship, Drug; Embryo, Mammalian; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Luteinizing Hormone; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Prospective Studies

Concern about the use of gonadotrophin-releasing hormone (GnRH) agonists in ovarian stimulation of poor responder IVF patients has arisen from the claim that GnRH agonists might have a direct deleterious effect through their receptors on the ovary. In this study, we compared two ovarian stimulation protocols in which no GnRH agonists were used. In all, 40 patients with a poor response in previous treatment cycles were included. They were divided into two groups: group I (n = 20) received ovarian stimulation for 20 cycles, without the addition of either GnRH agonist or antagonist; while group II (n = 20) patients received ovarian stimulation for 20 cycles, including the administration of a GnRH antagonist (Cetrorelix, 0.25 mg daily) during the late follicular phase. There was no statistically significant difference between the groups for mean age, duration of infertility, baseline FSH concentration, cancellation rate, number of ampoules of gonadotrophin used, number of mature oocytes retrieved, oestradiol concentrations on the day of injection of human chorionic gonadotrophin (HCG), fertilization rate and number of embryos transferred. The clinical pregnancy and implantation rates in group II appeared higher than in group I, but were not significantly different (20 and 13.33% compared with 6.25 and 3.44% respectively). The addition of GnRH antagonists to ovarian stimulation protocols might be a new hope for poor responder IVF patients, but this report is preliminary and further controlled randomized prospective studies with larger sample sizes are required.

Topics: Adult; Chorionic Gonadotropin; Embryo Transfer; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Luteinizing Hormone; Menotropins; Ovulation Induction; Pregnancy; Pregnancy Outcome

To analyze the luteal phase of six patients undergoing controlled ovarian hyperstimulation (COH) with hMG and a new GnRH antagonist, Cetrorelix, without receiving luteal phase supplementation.. Phase II study involving the first six patients who did not receive luteal phase support.. Tertiary referral center.. Six healthy women undergoing COH for assisted reproductive techniques.. Oocyte retrieval was performed 36 hours after hCG administration, followed by embryo transfer 2 days later. No luteal phase supplementation was given.. Serum E2, progesterone, LH, and FSH concentrations were measured.. The length of the luteal phase was < or =12 days in three of the six patients. One of the patients in whom the luteal phase was >12 days had a low serum progesterone concentration (2.9 ng/mL) on day 10. Serum LH concentrations decreased after the preovulatory hCG injection in all patients. However, a progressive increase in LH was observed after day 7, reaching normal values.. Corpus luteum function seems to be impaired in cycles that are stimulated with hMG and the GnRH antagonist Cetrorelix.

Topics: Adult; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Luteal Phase; Luteinizing Hormone; Menotropins; Progesterone; Receptors, LHRH; Superovulation

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

We retrospectively compared neonatal sex after antagonist- versus long-stimulation protocols followed by fresh in vitro fertilization (IVF) or fresh intracytoplasmic sperm injection (ICSI) with either protocol. We reviewed data for 762 IVF/ICSI cycles in 2015, including 23 IVF procedures. We summarized sex outcomes in the entire cohort, and for the additional subgroups: embryo transfer day and number of embryos transferred, and number of oocytes recovered and maternal age. Among 169 live births for all protocols combined, 50.9% of babies were male, and we saw no difference between the antagonist versus long-stimulation groups (52.3% vs 48.3% male babies, respectively; P = .740). Our results also showed no significant difference in sex proportion when comparing IVF versus ICSI, although a higher proportion of babies were male with the antagonist-ICSI protocol. Differences between the additional subgroups were also neither clinically nor statistically significant.

Topics: Adult; Chorionic Gonadotropin; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infant, Newborn; Leuprolide; Male; Maternal Age; Menotropins; Oocytes; Retrospective Studies; Saudi Arabia; Sex Ratio; Socioeconomic Factors; Sperm Injections, Intracytoplasmic

The aim of the study was to assess the predictive value of vascular endothelial growth factor (VEGF), its soluble receptor - sVEGF-R1/sFlt1 and endocrine gland-derived vascular endothelial growth factor (EG-VEGF) concentrations in serum and follicular fluid (FF) for ovarian hyperstimulation syndrome (OHSS) in women undergoing controlled ovarian hyperstimulation (COH) protocols. Patients have been divided into 3 groups: control group on natural cycle, patients stimulated with GnRH agonist and patients stimulated with GnRH antagonist. The FF and serum concentrations of VEGF, EG-VEGF, sVEGF R1 and the expression of VEGF and EG-VEGF mRNA in GC in small and large follicles collected from patients were investigated. When we compared all patients in a trial, OHSS occurrence was correlated with higher level of sVEGF R1 and a lower level of VEGF in a follicular fluid from large follicles in a day of oocyte retrieval. The VEGF/sVEGF-R1 ratio for patients in COH groups, above which the risk of developing OHSS is very low (OR 0.1 (95% CI 0.01 - 0.29, P = 0.0006) was found to be 0.281 pg/ml, with AUC - 0.738, P = 0.042, (95% CI 0.656 - 0.82). High levels of sVEGF-R1 and low level of VEGF in FF on the day of oocyte retrieval correlate with OHSS regardless of the stimulation protocol.

Topics: Adult; Female; Fertilization in Vitro; Follicular Fluid; Gonadotropin-Releasing Hormone; Humans; Menotropins; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; RNA, Messenger; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor, Endocrine-Gland-Derived

Poor ovarian response to ovarian hyperstimulation is one of the biggest challenges in assisted reproduction technology. Although many stimulation protocols have been established to improve clinical outcomes in poor ovarian responders (PORs), which protocol is the most effective remains controversial. Luteal-phase ovarian stimulation (LPOS) has been used in normal ovarian responders with satisfactory outcomes. However, the efficacy of LPOS in PORs is unclear. This study aimed to compare the efficacy of LPOS and GnRH antagonist (GnRH-ant) in PORs.. The clinical parameters in PORs who received LPOS (50 cycles in 39 patients) or GnRH-ant (158 cycles in 123 patients) were compared.. Compared with those in the GnRH-ant group, the PORs in the LPOS group showed significantly fewer basal antral follicles (3.1 ± 2.2 vs. 4.1 ± 1.6, p < 0.001) and a higher in vitro fertilization rate. There were no significant differences in the numbers of retrieved oocytes and D3 transferable embryos between the two groups. However, the pregnancy rate in the LPOS group (46.4%) was significantly higher than that in the GnRH-ant group (25.8% overall; 22.9% from fresh embryos and 29.6% from frozen embryos). Moreover, 23 PORs in the LPOS group underwent oocyte retrieval twice in one cycle, and the numbers of retrieved oocytes and transferable embryos from the luteal phase were significantly higher than those from the follicular phase in the same menstrual cycle.. Compared with the GnRH-ant protocol, the LPOS protocol may be a better regime for PORs that can increase the numbers of retrieved oocytes and transferable embryos as well as the pregnancy rate.

Topics: Adult; Clomiphene; Embryo Transfer; Feasibility Studies; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Letrozole; Luteal Phase; Menotropins; Nitriles; Oocyte Retrieval; Ovarian Follicle; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies; Sperm Injections, Intracytoplasmic; Triazoles

To provide the best available evidence on the role of dehydroepiandrosterone (DHEA) treatment in improving the outcome of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in women with poor ovarian response (POR).. A randomized controlled trial conducted in Cairo University hospitals and Dar Al-Teb subfertility and assisted conception centre, Giza, Egypt. 140 women undergoing IVF/ICSI with POR according to the Bologna criteria were randomly divided into 2 equal groups. The study group received DHEA 25mg three times daily for 12 weeks before the IVF/ICSI cycles and the control group did not receive DHEA. Controlled ovarian stimulation (COH) was started on the second day of menstruation using human menopausal gonadotropins, cetrotide 0.25mg was started when the leading follicle reached 14mm. The main outcome measures were the clinical pregnancy rate, ongoing pregnancy rate, retrieved oocytes, fertilization rate, gonadotropins doses and COH days.. The DHEA group had significantly higher clinical pregnancy rate (32.8% vs 15.7%, p=0.029), ongoing pregnancy rate (28.5% vs 12.8%), retrieved oocytes (6.9±3 vs 5.8±3.1, p=0.03), fertilization rate (62.3±27.4 vs 52.2±29.8, p=0.039), significantly less gonadotropins doses (3383±717.5IU vs 3653.5±856IU, p=0.045) and COH days (11.6±1.8 vs 12.6±1.06, p=0.001).. DHEA increases the number of oocytes, fertilization rate, fertilized oocytes, and clinical pregnancy rate and ongoing pregnancy rate in women with POR according to the Bologna criteria. DHEA was well tolerated by the patients and was associated with less COH days and gonadotropins doses.. www.clinicaltrials.govNCT02151006.

Topics: Adult; Dehydroepiandrosterone; Egypt; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility; Menotropins; Oocyte Retrieval; Ovulation Induction; Pregnancy; Pregnancy Rate; Sperm Injections, Intracytoplasmic

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

To compare the results of IVF cycles after coasting in patients treated with a GnRH antagonist or GnRH agonist protocol.. A retrospective case-control study.. Infertility unit in a university-affiliated tertiary medical center.. The study group included all women less than 38 years old attending the IVF unit from 2000 to 2006 in whom coasting was used. Data on E(2) levels before and after coasting, duration of coasting, number of oocytes retrieved and fertilized, embryo quality, moderate-severe ovarian hyperstimulation syndrome (OHSS), and pregnancy were collected from the files and compared between GnRH agonist (n = 329) and GnRH antagonist (n = 45) cycles.. None.. Number of retrieved oocytes and pregnancy rates.. There were no between-group differences in cycle parameters. In the antagonist group, there was no need for more than 2 days of coasting. There was a significant decrease in the number of retrieved oocytes even in short periods of coasting in the antagonist group but not in the agonist group. On the day of hCG administration, E(2) levels dropped to a lower level in the antagonist cycles. The OHSS rate after coasting was 4.6% in the agonist group and 4.4% in the antagonist group. Corresponding pregnancy rates after coasting were 27.4% and 24.4%.. The same criteria for coasting can be applied in GnRH agonist as in GnRH antagonist cycles, with a similar IVF result.

Topics: Adult; Chorionic Gonadotropin; Drug Administration Schedule; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Menotropins; Oocyte Retrieval; Pregnancy; Pregnancy Rate; Retrospective Studies; Treatment Outcome; Triptorelin Pamoate

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

To investigate if the combination of clomiphene citrate, hMG, and cetrorelix (CC/hMG/cetrorelix protocol) can be applied to patients who had excessive response to GnRHa long protocol.. Fifty patients who coasted and failed to conceive in their first cycles stimulated with GnRHa long protocol were stimulated with CC/hMG/cetrorelix protocol. The peak serum estradiol levels, the need of coasting and prolonged coasting (>/=4 days), and the incidences of OHSS were compared.. The peak estradiol level was significantly lower with CC/hMG/cetrorelix protocol compared to GnRHa long protocol. With CC/hMG/cetrorelix protocol, only four patients (8%) needed coasting and no one coasted >/=4 days. In contrast, in the first cycles, 11 patients (22%) needed coasting >/=4 days. The incidence of moderate OHSS was significantly lower with CC/hMG/cetrorelix protocol.. The CC/hMG/cetrorelix protocol is an acceptable alternative protocol for patients who had excessive response to GnRHa long protocol.

Topics: Adult; Clomiphene; Drug Therapy, Combination; Embryo Transfer; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Prospective Studies; Sperm Injections, Intracytoplasmic; Superovulation; Treatment Outcome

Topics: Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility, Male; Male; Menotropins; Ovulation Induction; Recombinant Proteins; Sperm Injections, Intracytoplasmic; Spermatozoa; Triptorelin Pamoate; Zona Pellucida

The question of whether adjustment to body weight is necessary in in-vitro fertilization (IVF) cycles using GnRH antagonists is currently under discussion. Therefore, a data analysis of five prospective studies using either the single- or the multiple-dose antagonist protocol with cetrorelix (Cetrotide) was performed. The influence of stimulation procedure, gonadotrophins and body weight on pregnancy rate was evaluated in a linear logit model. The effect of the stimulation procedure and body weight on the cumulus-oocyte complex (COC) and follicle number was explored in an ANOVA model. Cetrorelix plasma concentrations were tested for any correlation with body weight. Baseline and outcome parameters in different body weight groups (<50 kg, 50-59 kg, 60-69 kg, 70-79 kg, > or =80 kg) were assessed for human menopausal gonadotrophin and recombinant human FSH stimulation separately. Cetrorelix plasma concentrations were correlated with body weight, but no influence of the type of stimulation or body weight on pregnancy rate was found. Body weight did not influence cetrorelix plasma concentrations. In contrast, body weight significantly influenced the number of retrieved COC as well as the number of follicles on the day of human chorionic gonadotrophin administration. Body weight does not influence the outcome of treatment in cetrorelix cycles.

Topics: Body Weight; Cell Count; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Linear Models; Menotropins; Oocytes; Osmolar Concentration; Ovarian Follicle; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies; Tissue and Organ Harvesting; Treatment Outcome

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

To investigate the effect that clomiphene citrate exerts on luteinizing hormone (LH) concentrations in gonadotropin/gonadotropin-releasing hormone (GnRH) antagonist cycles.. Retrospective analysis.. Tertiary referral center.. Two groups of patients undergoing in vitro fertilization (IVF) were compared. In group I, 20 patients were stimulated with clomiphene citrate (CC) in combination with gonadotropins and 0.25 mg of Cetrorelix (ASTA Medica AG; Frankfurt am Main, Germany) and in group II, 20 patients were stimulated with gonadotropins and 0.25 mg of Cetrorelix.. Blood sampling was performed in the late follicular, periovulatory, early, mid, and late luteal phases.. Luteinizing hormone (LH), estradiol, and progesterone.. LH levels were significantly higher in group I than in group II on all the days studied. Progesterone serum concentrations were significantly higher in group II in the early luteal phase, but not in the follicular or the middle and late luteal phases.. LH concentrations are significantly higher in the follicular and luteal phases in cycles stimulated with CC, despite GnRH antagonist administration. This observation might have implications for the dose of GnRH antagonist needed to suppress LH in the follicular phase and questions the need for luteal-phase supplementation in cycles in which CC was used.

Topics: Adult; Chorionic Gonadotropin; Clomiphene; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Follicular Phase; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Luteal Phase; Luteinizing Hormone; Menotropins; Progesterone; Retrospective Studies

To evaluate the results of the use of GnRH antagonist (GnRHant) and GnRH analog (GnRHa) in two matched groups of unselected IVF/ICSI patients in a retrospective matched pair analysis.. Patients (n=52) were stimulated with human menopausal gonadotropin (hMG) and/or recombinant FSH (rFSH). In Group I (n=26) a daily dose of 0.25mg of Cetrorelix (GnRHant) was administered when follicles reached a diameter of > or = 14 mm. Patients in Group II (n=26) were first desensitized with GnRHa triptorelin long protocol, which was continued during the gonadotropins treatment until the induction of ovulation.. In both groups, serum LH levels remained low during the stimulation. The mean length of stimulation, and the dose of FSH required per patient were similar in both groups. The mean E2 level on day of hCG administration was significantly higher in the patients of Group II (2076+/-1430 versus 1145+/-605 pg/ml), however, a progressive increase in serum E2 concentration during the cycle was noted in both groups. A median of 5.38 and 6.34 mature oocytes per patient was obtained, and the fertilization rate was 59.3% in Group I and 63.6% in Group II. Pregnancy rate (PR) were better in Group II (15 versus 5%), and no severe or moderate ovarian hyperstimulation syndrome (OHSS) occurred.. GnRHant and GnRHa provide comparable results in unselected patients, while GnRHant allows a higher flexibility in the treatment.

Topics: Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility; Luteinizing Hormone; Menotropins; Ovarian Follicle; Ovulation Induction; Recombinant Proteins; Retrospective Studies; Sperm Injections, Intracytoplasmic

This retrospective study was performed to examine the implantation and pregnancy rates of frozen-thawed pronuclear stage oocytes obtained with the use of a GnRH antagonist, Cetrorelix (Cetrotide((R)) ASTA-Medica, Frankfurt/M, Germany) used in a multidose protocol with hMG, and to compare these results with those obtained after a conventional long GnRH analogue protocol (Decapeptyl-Depot, Ferring, Kiel, Germany). The study population consisted of 31 infertile couples with frozen-thawed pronuclear stage oocytes after ICSI treatment using the GnRH antagonist Cetrorelix (Cetrorelix((R))) and 31 infertile couples with frozen-thawed pronuclear stage oocytes after ICSI treatment using the long GnRH analogue protocol. Patients underwent ICSI after down regulation with a GnRH agonist (Decapeptyl) and stimulation with hMG, or a GnRH antagonist (Cetrorelix) and hMG. The supernumerary pronuclear stage oocytes were cryopreserved and transferred in a later mildly stimulated cycle. The implantation and pregnancy rates for frozen-thawed pronuclear stage oocytes derived from the GnRH antagonist compared with the GnRH agonist were 3.26% versus 3.73% (P=1.0000) and 8.33% versus 10.25% (P=1.0000), respectively. To our knowledge we report here the first pregnancies obtained by the transfer of cryopreserved pronuclear stage embryos generated from ICSI using a GnRH antagonist in the collecting cycle. The use of Cetrorelix in a multiple dose protocol in combination with hMG does not demonstrate a negative effect on viability, implantation potential or pregnancy outcome as compared to 2PN conceptuses obtained from a long GnRH agonist-hMG protocol.

Topics: Abortion, Spontaneous; Cryopreservation; Embryo Implantation; Embryo Transfer; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility; Menotropins; Oocytes; Pregnancy; Pregnancy Outcome; Retrospective Studies; Sperm Injections, Intracytoplasmic; Triptorelin Pamoate

Natural cycles were abandoned in in-vitro fertilization (IVF) embryo transfer, due to premature luteinizing hormone (LH) surges--and subsequent high cancellation rates. In this study, we investigated the administration of a new gonadotrophin-releasing hormone antagonist (Cetrorelix) in the late follicular phase of natural cycles in patients undergoing IVF and intracytoplasmic sperm injection (ICSI). A total of 44 cycles from 33 healthy women [mean age 34.1 +/- 1.4 (range 26-36) years] were monitored, starting on day 8 by daily ultrasound and measurement of serum concentrations of oestradiol, LH, follicle stimulating hormone (FSH) and progesterone. When plasma oestradiol concentrations reached 100-150 pg/ml, with a lead follicle between 12-14 mm diameter, a single injection (s.c.) of 0.5 mg (19 cycles) or 1 mg (25 cycles) Cetrorelix was administered. Human menopausal gonadotrophin (HMG; 150 IU) was administered daily at the time of the first injection of Cetrorelix, and repeated thereafter until human chorionic gonadotrophin (HCG) administration. Four out of 44 cycles were cancelled (9.0%). No decline in follicular growth or oestradiol secretion was observed after Cetrorelix administration. A total of 40 oocyte retrievals leading to 22 transfers (55%) was performed. In 10 cycles (25%), no oocyte was obtained. Fertilization failure despite ICSI occurred in six cycles (15%). In two patients the embryo was arrested at the 2 pronuclear (PN) stage. The stimulation was minimal (4.7 +/- 1.4 HMG ampoules). A total of seven clinical pregnancies was obtained (32.0% per transfer, 17.5% per retrieval), of which five are ongoing. Thus, a spontaneous cycle and the GnRH antagonist Cetrorelix in single dose administration could represent a first-choice IVF treatment with none of the complications and risks of current controlled ovarian hyperstimulation protocols, and an acceptable success rate.

Topics: Adult; Chorionic Gonadotropin; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Follicular Phase; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Male; Luteinizing Hormone; Male; Menotropins; Microinjections; Pregnancy; Progesterone

The luteal phase hormonal profile and the clinical outcome of 69 patients undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) after ovarian stimulation with human menopausal gonadotrophin (HMG) and the gonadotrophin-releasing hormone (GnRH) antagonist Cetrorelix were analysed. Twenty-four patients received Cetrorelix 0.5 mg (group I) while in 45 patients Cetrorelix 0.25 mg was administered (group II). Human chorionic gonadotrophin (HCG) was used as luteal support. Nine clinical pregnancies were obtained in group I (37.5%) and 12 in group II (26. 6%). These results were not significantly different. Serum progesterone and oestradiol concentrations did not differ between the two groups either in pregnant or non-pregnant patients. An expected decrease of the same hormones was observed 8 days after the pre-ovulatory HCG injection in non-pregnant women. With regard to serum luteinizing hormone concentrations, a decrease was observed 2 days after the pre-ovulatory HCG injection and was maintained at almost undetectable levels throughout the entire luteal phase in both conception and non-conception cycles of group I and group II. This study demonstrates that different doses of GnRH antagonist do not have any impact on the luteal phase of IVF/ICSI cycles when hormonal support is given.

Topics: Abortion, Spontaneous; Adult; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Luteal Phase; Luteinizing Hormone; Menotropins; Microinjections; Ovulation Induction; Pregnancy; Pregnancy Outcome; Pregnancy, Multiple; Pregnancy, Tubal; Retrospective Studies; Twins

The premature LH surge in ART programs seems to be avoided by daily administration of the GnRH-antagonist Cetrorelix during the midcycle phase in controlled ovarian hyperstimulation with hMG. The dosage necessary for sufficient suppression of the pituitary gland is not yet defined.. To elucidate this question three daily dosages (3, 1, 0.5 mg) were administered and the hormone profiles obtained as well as the number of oocytes retrieved, the fertilization rate, and the consumption of HMG were compared.. No premature LH surge could be observed at any of the three dosages administered. Both gonadotropins were deeply suppressed. The fertilization rates of the oocytes obtained were 45.3% in the 3-mg group, 53.1% in the 1-mg group, and 67.7% in the 0.5-mg group. The average uses of hMG ampoules were 30 in the 3-mg group, 27 in the 1-mg group, and 26 in the 0.5-mg group.. Cetrolix, 0.5 mg/day, administered during the midcycle phase of controlled ovarian hyperstimulation with hMG is enough to prevent completely the premature LH surge. Perhaps even lower dosages would be sufficient. Regarding fertilization rates and use of hMG, the lower dosage seems to be the most favorable.

Topics: Adolescent; Adult; Estradiol; Female; Fertility; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility; Luteinizing Hormone; Menotropins; Ovary; Progesterone

A third generation gonadotrophin-releasing hormone antagonist (Cetrorelix) was used during ovarian stimulation in 32 patients undergoing assisted reproduction, in order to prevent the premature luteinizing hormone (LH) surge. In all patients, ovarian stimulation was carried out with two or three ampoules of human menopausal gonadotrophin (HMG), starting on day 2 of the menstrual cycle. In addition, 0.5 mg of Cetrorelix was administered daily from day 6 of HMG treatment until the day of ovulation induction by human chorionic gonadotrophin (HCG). A significant drop in plasma LH concentration was observed within a few hours of the first administration of Cetrorelix (P < 0.005). Moreover, no LH surge was detected at any point in the treatment period in any of the 32 patients. A mean oestradiol concentration of 2111 +/- 935 ng/l was observed on the day of the HCG administration, indicating normal folliculogenesis. Like LH, progesterone concentration also dropped within a few hours of the first administration of Cetrorelix (P < 0.005). A 0.5 mg daily dose of Cetrorelix prevented a premature LH surge in all the 32 patients treated.

Topics: Adult; Cytoplasm; Female; Fertilization in Vitro; Follicular Phase; Gonadotropin-Releasing Hormone; Hormone Antagonists; Hormones; Humans; Male; Menotropins; Menstrual Cycle; Microinjections; Oocytes; Spermatozoa; Treatment Outcome