GnRH antagonist versus long GnRH agonist protocol in poor IVF responders: a randomized clinical trial

Objective

To compare the efficacy of the long GnRH agonist and the fixed GnRH antagonist protocols in IVF poor responders.

Study design

This was a randomized controlled trial performed in the Iakentro IVF centre, Thessaloniki, from January 2007 to December 2011, concerning women characterised as poor responders after having 0–4 oocytes retrieved at a previous IVF cycle. They were assigned at random, using sealed envelopes, to either a long GnRH agonist protocol (group I) or a GnRH antagonist protocol (group II).

Results

Overall 364 women fulfilled the inclusion criteria and were allocated to the two groups: finally 330 participated in our trial. Of these, 162 were treated with the long GnRH agonist protocol (group I), and 168 with the fixed GnRH antagonist protocol (group II). Numbers of embryos transferred and implantation rates were similar between the two groups (P = NS). The overall cancellation rate was higher in the antagonist group compared to the agonist group, but the difference was not significant (22.15% vs. 15.2%, P = NS). Although clinical pregnancy rates per transfer cycle were not different between the two groups (42.3% vs. 33.1%, P = NS), the clinical pregnancy rate per cycle initiated was significantly higher in the agonist compared to the antagonist group (35.8% vs. 25.6%, P = 0.03).

Conclusions

Although long GnRH agonist and fixed GnRH antagonist protocols seem to have comparable pregnancy rates per transfer in poor responders undergoing IVF, the higher cancellation rate observed in the antagonist group suggests the long GnRH agonist protocol as the first choice for ovarian stimulation in these patients.     

Low-dose GnRH antagonist protocol is as effective as the long GnRH agonist protocol in unselected patients undergoing in vitro fertilization and embryo transfer

ObjectiveThe present retrospective and controlled comparative study was designed to evaluate the pregnancy rate achieved using a modified, fixed, multiple-dose 0.125 mg gonadotropin-releasing hormone (GnRH) antagonist protocol with the long GnRH agonist protocol as the control group.Materials and methodsOne hundred and twenty unselected women between 30 and 40 years of age, in their first cycle of IVF/ICSI, with a baseline follicle-stimulating hormone (FSH) <10 IU and an antral follicle count >3 were assigned into two groups: (1) the study group received 0.125 mg of cetrorelix daily starting on Day 6 of stimulation; and (2) the control group received leuprolide daily starting in the mid-luteal phase of the preceding cycle. Both groups were given a flexible dose of recombinant FSH for stimulation. An ongoing pregnancy rate of more than 12 weeks was the primary outcome measure of the study.ResultsPrimary and secondary outcomes were comparable in both groups. A shorter duration of stimulation, a lower dosage of recombinant FSH consumption and a thinner endometrium on the day of human chorionic gonadotropin administration were all observed in the GnRH antagonist group.ConclusionA dosage of 0.125 mg GnRH antagonist protocol was effective for these unselected patients during IVF/ET.     

Progestin-primed ovarian stimulation versus GnRH antagonist protocol in poor responders: Risk of premature LH surge and outcome of oocyte retrieval

PurposeFor poor ovarian responders (PORs), gonadotropin-releasing hormone (GnRH) antagonist was commonly used for prevention of premature LH surge during controlled ovarian stimulation (COS) over the past two decades. The application of progestin-primed ovarian stimulation (PPOS) recently increased, but the role of PPOS for PORs was uncertain. We aimed to analyze the incidence of premature luteinizing hormone (LH) surge and the outcome of oocyte retrieval among PPOS and GnRH antagonist protocol for PORs.MethodsThis was a single-center retrospective study, which enrolled the PORs (defined by the Bologna criteria) undergoing COS with PPOS or flexible GnRH antagonist protocol during January 2018 to December 2021. We compared the incidence of premature LH surge (LH > 10 mIU/mL) and the outcome of oocyte retrieval between the PPOS group and the GnRH antagonist group.ResultsA total of 314 women were recruited, with 54 in the PPOS group and 260 in the GnRH antagonist group. The PPOS group had lower incidence of premature LH surges compared with the GnRH antagonist protocol group (5.6% vs 16.9%, P value 0.035). There was no significant difference between the two groups regarding the number of oocytes retrieved (3.4 vs 3.8, P value 0.066) and oocyte retrieval rates (88.9% vs 88.0%, P value 0.711).ConclusionCompared with PPOS, GnRH antagonist protocol had higher risk of premature LH surges for PORs but may not affect pregnancy rates. PPOS is suitable for oocyte or embryo cryopreservation, but should not totally replace GnRH antagonist protocol for patients undergoing in vitro fertilization (IVF).     

GnRH拮抗剂方案中HCG扳机时机对胚胎的影响

目的:探讨促性腺激素释放激素拮抗剂(GnRH antagonist)方案超促排卵过程中推迟人绒毛膜促性腺激素(HCG)扳机时机对胚胎质量及妊娠率等的影响。方法:回顾性分析2015年1月至12月在我院接受体外受精-胚胎移植(IVF-ET)助孕的不孕症患者183例,均采用GnRH拮抗剂促排方案,于月经周期第2天启用促性腺激素(Gn),当有卵泡平均直径达到14mm,加用GnRH拮抗剂。按照传统HCG扳机时机(有3个≥17mm卵泡)与推迟1天扳机分为2组:早期HCG组(149例)和晚期HCG组(34例),比较两组数据。结果:HCG扳机日,晚期HCG组≥15mm的卵泡数明显多于早期HCG组(P=0.026)。晚期HCG组Gn使用天数及Gn使用总量均明显高于早期HCG组(P=0.000,P=0.012)。妊娠结局方面,晚期HCG组较早期HCG组具有更高的妊娠率(76.00%vs 50.45%,P=0.020)。两组受精率、继续妊娠率、流产率、异位妊娠率均无显著差异(P0.05)。结论:GnRH拮抗剂促排方案中,适当推迟HCG扳机时间不影响胚胎质量和妊娠率,可以推行。     

Comparison of cryopreservation outcome with human pronuclear stage oocytes obtained by the GnRH antagonist, cetrorelix, and GnRH agonists

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.     

Comparable effectiveness using flexible single-dose GnRH antagonist (cetrorelix) and single-dose long GnRH agonist (goserelin) protocol for IVF cycles--a prospective, randomized study

This prospective randomized study compared the effectiveness of a flexible single-dose gonadotrophin-releasing hormone (GnRH) antagonist (cetrorelix) and a single-dose long GnRH agonist (goserelin) protocol for ovarian stimulation in IVF/intracytoplasmic sperm injection (ICSI) cycles. All patients from the waiting list were successively included in the study, pre-programmed with an oral contraceptive, and randomized into goserelin and cetrorelix groups. Depending on the date on which their menstrual period started, patients took oral contraceptives for one or two cycles. Ultimately, 236 patients in the first group received a single dose of depot preparation of goserelin and 224 patients received a single 3 mg dose of cetrorelix in the late follicular phase, when the mean follicle diameter exceeded 12 mm. The mean number of ampoules of FSH and the duration of stimulation was statistically significantly lower in the cetrorelix group than in the goserelin group (25.9 versus 34.5, and 9.6 versus 12.2 days, P < 0.01). The mean number of oocytes retrieved was similar (6.7 +/- 4.5 versus 7.2 +/- 4.6, NS). Similar results were observed in fertilization rates, blastulation rates and blastocyst transfer rates in both groups. Clinical pregnancy and delivery rates per cycle were higher in the goserelin group (34.3 and 30.1%) than in the cetrorelix group (31.9 and 28.3%), but the differences were not statistically significant. The flexible single-dose GnRH antagonist protocol is an advantageous alternative to the long GnRH agonist protocol, with similar efficacy, shorter duration, a significant reduction in the number of FSH ampoules used and without the menopause-like effects of the GnRH antagonist.     

High-dose recombinant LH add-back strategy using high-dose GnRH antagonist is an innovative protocol compared with standard GnRH antagonist

High daily doses of gonadotrophin-releasing hormone (GnRH) antagonists during the follicular phase of ovarian stimulation were associated with low implantation rates. To test if this occurred because of profound pituitary suppression, the pituitary response was suppressed with a high-dose GnRH antagonist and recombinant LH (rLH) was added back to correct the implantation rate. An open-label, randomized, controlled, prospective clinical study in 60 patients undergoing IVF was performed. GnRH antagonist was initiated on day 6 of stimulation (2 mg/day) together with 375 IU rLH, and maintained until the day of HCG administration. Controls received 0.25 mg/day GnRH antagonist. Fluctuating LH concentrations were present on days 3 and 6 in both groups. This strong fluctuation continued on day 8 and on the day of HCG administration in the control (low-dose) group, where 30% of patients had LH concentrations <1 IU/1 on the HCG day. The study (high-dose) group showed stable LH concentrations on day 8 and on the HCG day, with no LH surges. No clinical differences were found between groups. The LH add-back strategy (375 IU/day) rescued the adverse effects that high doses of GnRH imposed on implantation. These results suggest that rLH should be considered during ovarian stimulation with GnRH antagonist.     

High-dose recombinant LH add-back strategy using high-dose GnRH antagonist is an innovative protocol compared with standard GnRH antagonist

High daily doses of gonadotrophin-releasing hormone (GnRH) antagonists during the follicular phase of ovarian stimulation were associated with low implantation rates. To test if this occurred because of profound pituitary suppression, the pituitary response was suppressed with a high-dose GnRH antagonist and recombinant LH (rLH) was added back to correct the implantation rate. An open-label, randomized, controlled, prospective clinical study in 60 patients undergoing IVF was performed. GnRH antagonist was initiated on day 6 of stimulation (2 mg/day) together with 375 IU rLH, and maintained until the day of HCG administration. Controls received 0.25 mg/day GnRH antagonist. Fluctuating LH concentrations were present on days 3 and 6 in both groups. This strong fluctuation continued on day 8 and on the day of HCG administration in the control (low-dose) group, where 30% of patients had LH concentrations <1 IU/l on the HCG day. The study (high-dose) group showed stable LH concentrations on day 8 and on the HCG day, with no LH surges. No clinical differences were found between groups. The LH add-back strategy (375 IU/day) rescued the adverse effects that high doses of GnRH imposed on implantation. These results suggest that rLH should be considered during ovarian stimulation with GnRH antagonist.     

No association between endogenous LH and pregnancy in a GnRH antagonist protocol: part II, recombinant FSH

The association between endogenous LH concentrations during ovarian stimulation in a gonadotrophin-releasing hormone (GnRH) antagonist protocol and pregnancy likelihood was examined in a large combined analysis of individualized patient data obtained after treatment with recombinant FSH and a GnRH antagonist prior to IVF/intracytoplasmic sperm injection. Data from 1764 patients from six randomized controlled trials were pooled for retrospective analysis. Ongoing pregnancy and miscarriage rates for patients stratified by LH percentiles were assessed. Patients in the lowest LH quartile (< P25) were younger with a higher predicted ovarian reserve and response compared with patients in the highest quartile (> P75). With adjustment for identified predictive factors of pregnancy, estimated odds ratios (95% confidence interval) for ongoing pregnancy for LH categories < P25 versus ≥ P25, > P75 versus ≤ P75 and < P25 versus > P75 were 0.96 (0.75-1.22), 1.13 (0.88-1.45) and 0.89 (0.66-1.21) on stimulation day 8, and 0.96 (0.76-1.21), 1.03 (0.82-1.30) and 0.95 (0.72-1.26) on the day of human chorionic gonadotrophin, respectively. No significant differences in pregnancy or miscarriage rates between the LH categories were observed. Endogenous LH concentrations have no association with the likelihood of ongoing pregnancy in women undergoing ovarian stimulation using a recombinant FSH/GnRH antagonist protocol.     

Comparing GnRH agonist long protocol and gnrh antagonist protocol in outcome the first cycle of ART

Purpose  

This prospective study evaluated the efficacy of gonadotropin-releasing hormone (GnRH) antagonist protocol in comparison with the GnRH agonist protocol in the first cycle of assisted reproductive technique (ART).     

Embryonic early-cleavage rate is decreased with aging in GnRH agonist but not inantagonist protocols

Purpose

The aim of this study was to evaluate the correlation between embryonic early-cleavage status and the age of patients receiving either a GnRH agonist long protocol or a GnRH antagonist protocol.

Methods

This retrospective study included 534 patients undergoing a fresh cycle of oocyte retrieval and day-3 embryo transfer. Of the 534 patients treated, 331 received a GnRH agonist long stimulation protocol (GnRH agonist group) for ovarian stimulation and 203 patients received a GnRH antagonist protocol (GnRH antagonist group).

Results

By logistic regression analysis, the rate of embryonic early-cleavage was significantly decreased with increasing age of women in the agonist (P < 0.001) but not in antagonist groups (P = 0.61). Based on the results of this study, maternal age is a critical factor for embryonic early-cleavage in agonist protocol but not in antagonist protocol. The results also showed that early-cleavage embryos were of better quality and resulted in a higher pregnancy rate than late-cleavage embryos in the GnRH agonist group. However, embryo quality and pregnancy rate was not significantly different between early and late cleavage embryos in the GnRH antagonist group.

Conclusions

We conclude that embryonic early-cleavage status is negatively correlated with aging in women receiving GnRH agonist long down-regulation but not in GnRH antagonist protocols. We also conclude that early cleavage of the zygote is not a reliable predictor for pregnancy potential using the GnRH antagonist protocol.     

Comparison of GnRH antagonist with long GnRH agonist protocol after OCP pretreatment in PCOs patients

Purpose  

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.     

GnRH antagonist versus follicular-phase single-dose GnRH agonist protocol in patients of normal ovarian responses during controlled ovarian stimulation

Objective: This study aims to explore the differences of the ovarian stimulation (OS) characteristics, laboratory, and clinical outcomes between follicular-phase single-dose gonadotropin-releasing hormone (GnRH) agonist protocol and GnRH antagonist protocol during controlled ovarian hyperstimulation (COH).

Methods: About 1883 consecutive IVF/ICSI fresh cycles of normal ovarian responders were retrospectively analyzed, with 1229 in the single-dose GnRH agonist protocol group and 654 in the GnRH antagonist protocol group at Reproductive Medical Center of Tongji Hospital from 1 January 2014 to 31 December 2017.

Results: The follicular-phase single-dose GnRH agonist group showed significantly more oocytes obtained, higher implantation rate and pregnancy rate, as well as lower luteinizing hormone (LH) level and estradiol (E2)/oocyte ratio on the day of human chorionic gonadotropin (hCG) administration. However, differences were not significant in meiosis II (MII) oocyte rate, two pronuclear zygote (2PN) embryo rate, viable embryo rate or high-quality embryo rate, compared with the GnRH antagonist group. Further comparison of clinical outcomes in the first frozen-thawed cycles did not show significant difference in either implantation or clinical pregnancy rate between the two protocol groups.

Conclusions: Follicular-phase single-dose GnRH agonist protocol may achieve better clinical outcomes in normal ovarian responders, which could be explained more by positive effect on endometrial receptivity rather than embryo quality.     

GnRH agonists and antagonists in assisted reproduction: pregnancy rate

Although gonadotrophin-releasing hormone (GnRH) antagonists offer many advantages when used in ovarian stimulation, their popularity is lower than expected. GnRH protocols are suspected to yield lower pregnancy rates compared with the long agonist protocol. In the current study, subgroup analyses from the German IVF registry (DIR) were performed to evaluate the hypothesis that GnRH antagonists are often used as second-line medication in patients with difficult medical conditions, and thus pregnancy rates may be biased. Consequently, pregnancy rates in the first six stimulation cycles (low rank cycles) were more favourable in the group treated according to the long protocol, while in the patient group requiring more stimulation cycles (high rank cycles; 7, 9 and 10), numerically higher pregnancy rates were achieved with GnRH antagonist protocols. On the other hand, in a patient collective with equal demographic and clinical features (<35 years, tubal infertility), the long and the GnRH antagonist protocols resulted in similar pregnancy rates, supporting the hypothesis that both stimulation protocols lead to equal results.     

Gonadotropin-releasing hormone antagonist protocol: a novel method of ovarian stimulation in poor responders.

OBJECTIVE: To estimate the efficacy of gonadotropin-releasing hormone (GnRH) antagonist 'Cetrorelix' in poor responders comparing with the standard long protocol. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.     

Luteal phase oestradiol administration in ovarian stimulation cycles with GnRH antagonist is comparable to the GnRH agonist (long) protocol

Purpose: The purpose of the study was to compare the effectiveness of GnRH antagonist with luteal phase estradiol administration to GnRH agonist cycles, long protocol. Methods: 55 IVF-ICSI patients received oestradiol in the luteal phase of the cycle, before a cycle with GnRH antagonist. Fifty-five patients submitted to IVF-ICSI with the use of agonist were allocated, age matched, as a control group (historical control). The primary outcome was the number of retrieved oocytes. Results: Patients were similar in terms of clinical characteristics. No differences were found in the number of oocytes retrieved (study group, 8.1 ± 4.7; control group, 7.4 ± 4.5) or in oocyte quality. Conclusions: We clearly demonstrated that the effectiveness of GnRH antagonist when combined with luteal phase estradiol is comparable to GnRH agonist cycles. Capsule Oestradiol associated to GnRH antagonist may increase the rates of oocytes causing reproductive results to be comparable to the results with the use of agonists.     

Reproductive outcome using a GnRH antagonist (cetrorelix) for luteolysis and follicular synchronization in poor responder IVF/ICSI patients treated with a flexible GnRH antagonist protocol

To investigate the possible beneficial effect of a new stimulation protocol (termed 'CRASH') on the outcome of poor responder patients, a multicentre, prospective longitudinal study including a total of 36 women undergoing 72 IVF/intracytoplasmic sperm injection (ICSI) cycles with patients serving as their own controls, was conducted. A poor responder patient was defined as a patient with four or fewer oocytes extracted from five or fewer follicles and with a total FSH consumption exceeding 2000 IU in a preceding long agonist down-regulation protocol. The CRASH protocol included 3 mg of the gonadotrophin-releasing hormone (GnRH) antagonist cetrorelix given in the late luteal phase on cycle day 23. Stimulation with recombinant human FSH (rhFSH) started on cycle day 2, followed by a flexible GnRH antagonist protocol. The results showed significantly more follicles (5.4 versus 3.5), oocytes (4.3 versus 2.4) and transferable embryos (1.8 versus 0.8) with the CRASH protocol as compared with the preceding long protocol (P < 0.005 in all cases). The implantation rate and pregnancy rate per transfer was 18.4 and 38.5% respectively, approaching the clinical outcome of normal responder patients. The CRASH protocol thus may constitute an attractive alternative to conventional protocols for low responder patients, improving their clinical outcome.     

GnRH agonist long protocol vs. a single 3-mg gnRH antagonist: a comparison of 2 protocols for pituitary down-regulation in oocyte donor-controlled ovarian hyperstimulation cycles

OBJECTIVE: To compare ovarian stimulation outcomes for 2 protocols of pituitary down-regulation in a group of fertile women. STUDY DESIGN: Retrospective outcome analysis of 35 healthy oocyte donors participating in a university-affiliated in vitro fertilization donor program from 1999 to 2004. Consecutive donor cycles were grouped according to the agent used for down-regulation (n = 27 GnRH agonist, n = 31 GnRH antagonist). Statistical analysis was performed using ANOVA, chi2 and Wilcoxon Rank Sum tests. RESULTS: Neither gonadotropin dosage, days of stimulation or number of oocytes retrieved per treatment cycle were statistically different between groups. The only significant embryo quality parameter was more grade D embryos in the GnRH antagonist (0.4 +/- 0.6) vs. GnRH agonist arm (0.0 +/- 0.2). The number of embryos transferred was significantly greater for the GnRH agonist (2.7 +/- 0.5) than GnRH antagonist arm (1.0 +/- 0.5), whereas implantation and clinical pregnancy rates were not significantly different between groups. No patient experienced the ovarian hyperstimulation syndrome. CONCLUSION: Since there was no significant difference in the biologic effects of the 2 protocols, the use of a 3-mg GnRH antagonist for down-regulation in a donor program is preferable to the long protocol because it requires only 1-2 injections for pituitary down-regulation.     

GnRH antagonist in IVF poor-responder patients: results of a randomized trial

The aim of this prospective study was to evaluate the efficacy of gonadotrophin-releasing hormone antagonist (GnRH) in comparison with the standard long protocol in poor-responder patients. Sixty patients with poor ovarian response in previous treatment cycles were randomized into two groups: group A (n = 30) was stimulated with a standard long protocol, and group B (n = 30) received GnRH antagonist. Vaginal ultrasound was performed to evaluate ovarian response. There was a significantly reduced duration of ovarian stimulation (9.8 +/- 0.8 versus 14.6 +/- 1.2, P = 0.001) in group B in comparison with group A, and a reduced number of ampoules was used in group B (49.3 +/- 4.3 versus 72.6 +/- 6.8, P = 0.0001). In group B, the number of oocytes retrieved was significantly higher than in group A (5.6 +/- 1.6 versus 4.3 +/- 2.2, P = 0.02) and there was an increased number of follicles with a diameter >15 mm at human chorionic gonadotrophin administration in group B (P = 0.0001). Fewer cycles were cancelled with the use of an antagonist protocol. Five pregnancies (17% for embryo transfer) were obtained with GnRH antagonist protocol and two (7% for embryo transfer) with GnRH agonist protocol.     

Use of GnRH antagonists in ovarian stimulation for assisted reproductive technologies compared to the long protocol

The use of GnRH antagonists has revolutionized ovarian stimulation for assisted reproduction. Two GnRH antagonists are clinically available, namely, cetrorelix and ganirelix. Several studies have directly compared these new stimulation protocols against the long GnRH agonist protocol. To evaluate whether there is a reduction in cases of ovarian hyperstimulation syndrome (OHSS) and/or a reduction in pregnancy rates, a meta-analysis was performed. There was a significant reduction of OHSS cases in the cetrorelix studies (odds ratio, OR, 0.23; 95% confidence interval, CI, 0.10-0.54), but no reduction for ganirelix (OR 1.13; 95% CI 0.24-5.31). The incidence of OHSS degree III cases was reduced in the cetrorelix protocols as compared to the long protocol to a nearly significant degree (OR 0.26; 95% CI 0.07-1.01). Ganirelix did not reduce the incidence of OHSS degree III at all (OR 1.08; 95% CI 0.27-4.38). The pregnancy rate per cycle was significantly lower in the ganirelix protocols than in the long protocol (OR 0.76; 95% CI 0.59-0.98). The studies using cetrorelix showed quite similar, not significantly different results for the antagonist and the long protocol groups for the pregnancy rate per cycle (OR 0.91; 95% Cl 0.68-1.22). From the data one can conclude that cetrorelix but not ganirelix will reduce the incidence of cases of OHSS and that cetrorelix but not ganirelix will result in the same pregnancy rates as the long protocol. Several possibilities to explain this phenomenon are discussed.