GnRH agonist and GnRH antagonist protocols: comparison of outcomes among good-prognosis patients using national surveillance data

Implantation and live birth rates resulting from IVF cycles using gonadotropin-releasing hormone (GnRH) agonist and (GnRH) antagonist IVF protocols were compared among good-prognosis patients using the Centers for Disease Control and Prevention's National Assisted Reproductive Technology Surveillance System 2009–2010 data (n = 203,302 fresh, autologous cycles). Bivariable and multivariable analyses were conducted between cycles to compare outcomes. Cycles were restricted as follows: age younger than 35 years, maximum FSH less than 10 mIU/mL, first assisted reproduction technology cycle and FSH dose less than 3601 IU. A subgroup analysis including only elective single embryo transfer was also carried out. Among good-prognosis patients, the GnRH-agonist protocol was associated with a lower risk of cancellation before retrieval (4.3 versus 5.2%; P < 0.05) or transfer (5.5 versus 6.8%; P < 0.05), and a higher live birth rate per transfer (adjusted odds ratio [OR] 1.13, confidence interval [CI] 1.03 to 1.25) than the GnRH-antagonist group. Among the elective single embryo transfer group, the GnRH-agonist protocol was associated with a higher implantation rate (adjusted odds ratio [OR] 1.36, CI 1.08 to 1.73) and a higher live birth rate (adjusted OR 1.33, CI 1.07 to 1.66) compared with the GnRH-antagonist protocol. The GnRH-antagonist group had lower rates of ovarian hyperstimulation syndrome. Among good-prognosis patients, agonist protocols decreased cancellation risk and increased odds of implantation and live birth. Antagonist protocols may confer decreased risk of hyperstimulation.     

Precycle administration of GnRH antagonist and microdose HCG decreases clinical pregnancy rates without affecting embryo quality and blastulation

The outcome of a novel protocol utilizing precycle gonadotrophin-releasing hormone (GnRH) antagonist administration and LH activity support with microdose recombinant human chorionic gonadotrophin (HCG) was compared to GnRH agonist long protocol used in patients undergoing their first ICSI (n=707) or IVF (n=571) cycles, which had resulted in one or two blastocyst transfers. In GnRH antagonist cycles, cetrorelix acetate (3 mg) was administered s.c. 4 days before FSH stimulation and a repeat dose was given when the lead follicular diameter was 13-14 mm. LH support was provided by recombinant HCG (2.5 microg). Embryo progression and blastulation were evaluated using embryo progression indices and blastocyst quality scores. The tested protocol demonstrated reduced implantation and clinical pregnancy rates as compared with GnRH agonist long protocol, although the embryo progression and blastulation parameters and blastocyst quality were comparable among the groups. Logistic regression models further supported the significant negative impact of GnRH antagonist/microdose HCG protocol on clinical pregnancy rates in both ICSI and IVF patients. Assisted reproduction cycles with fresh blastocyst transfers utilizing precycle GnRH antagonist administration and microdose HCG support resulted in lower implantation and clinical pregnancy rates as compared with GnRH agonist cycles, although the embryo progression and blastulation parameters were comparable.     

The dynamics of endometrial growth and the triple layer appearance in three different controlled ovarian hyperstimulation protocols and their influence on IVF outcomes

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

Impact of high basal FSH/LH ratio in women with normal FSH levels on in vitro fertilization outcomes

Abstract

Basal luteinizing hormone (LH) levels have also been suggested to impact on ovarian responsiveness as well as basal follicular stimulating hormone (FSH) levels. The aim of this study was to compare the in vitro fertilization (IVF) outcomes according to cycle day 3 FSH/LH ratio and to assess the proper stimulation protocol between gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist protocols. The retrospective cohort study recruited a total of 1211 women having the laboratory values of FSH (<10?IU/L) and LH within 3 months before IVF. Patients were treated with GnRH agonist long or GnRH antagonist protocols and stimulated with recombinant FSH (rFSH). The number of total retrieved oocytes and mature oocytes, implantation rate, clinical pregnancy rate and ongoing pregnancy rate were analyzed between groups: Group I: FSH/LH?<?2 and Group II: FSH/LH?≥?2. The Group II had the small number of retrieved oocytes and mature oocytes compared to the Group I (p?=?0.000). Clinical and ongoing pregnancy rate were lower in Group II (p?=?0.006, 0.006, respectively). In comparison of each protocol within groups, Group II showed significantly low pregnancy rate when GnRH antagonist was administered. In women with normal FSH level, high day 3 FSH/LH ratio can present subclinically low ovarian reserve and be predictive of lower pregnancy outcomes in fresh IVF cycles, and the choice of GnRH agonist can be related to favorable IVF outcomes.     

Replacing HMG/FSH by low-dose HCG to complete corifollitropin alfa stimulation reduces cost per clinical pregnancy: a randomized pragmatic trial

Research questionThe cost of IVF treatment remains high, among other factors because of the medication needed for ovarian stimulation. This study investigated the effect of using low-dose human chorionic gonadotrophin (HCG) for the second phase of follicular maturation after corifollitropin alfa induction, to replace the more expensive, either recombinant or human menopausal gonadotrophin (HMG), on the cost of ovarian stimulation.DesignOne hundred and five patients were randomly divided into two groups: patients in the HCG group (n = 50) received low-dose HCG from Day 7 until the diameter of at least three follicles reached 17 mm or more, while patients in the FSH group (n = 55) received conventional ovarian stimulation with highly purified HMG injections.ResultsThe clinical pregnancy rate in the HCG group was 38% higher than in the FSH group (number needed to treat, NNT = 13). The cost per pregnancy needed for ovarian stimulation was reduced from €4902 in the FSH group to €2684 in the HCG group. Hence, the cost of ovarian stimulation medication to obtain 10 pregnancies using the conventional FSH protocol is sufficient to attain 18 pregnancies when applying the low-dose HCG protocol.ConclusionThis study provides evidence that using HCG instead of HMG/FSH for ovarian stimulation results in a significant reduction in the cost of IVF with, at least, an equivalent pregnancy rate.     

Meta-analysis of GnRH antagonist protocols: do they reduce the risk of OHSS in PCOS?

This systematic review and meta-analysis investigated whether gonadotrophin-releasing hormone (GnRH) antagonist protocols reduce the risk of ovarian hyperstimulation syndrome (OHSS) in women with polycystic ovary syndrome undergoing IVF compared with the long agonist protocol. Searches were conducted on MEDLINE, EMBASE, Cochrane Library, National Research Register and ISI Conference Proceedings. Primary outcome was OHSS incidence. Secondary outcomes were total duration and dose of gonadotrophin, number of oocytes retrieved and clinical pregnancy and miscarriage rates. A total of 966 women were included in nine randomized controlled trials. There was inconsistency in definition, classification of severity and reporting of the OHSS rate. There was no difference in the incidence of severe OHSS in the antagonist group compared with the long agonist group (relative risk 0.61; 95% CI 0.23 to 1.64). However, when all moderate and severe OHSS cases were pooled, the antagonist protocol was associated with significantly lower risk of OHSS (relative risk 0.60; 95% CI 0.48-0.76; P<0.0001). A possible reduction in the incidence of severe OHSS with the GnRH antagonist protocol should be viewed with caution since the data is inconclusive. Larger randomized trials with adequate sample size and standardized definition, classification and diagnosis of OHSS remain necessary.     

卵巢高反应对体外受精-胚胎移植的影响

目的探讨体外受精-胚胎移植周期控制性超排卵（COH）中卵巢高反应对妊娠结局的影响。方法回顾性分析中山大学附属第二医院生殖中心1082个IVF／ICSI周期的临床资料，根据HCG注射日血E2〉11010pmol／L或获卵数〉15个定义为高反应组，HCG注射日血E2〉1835pmol／L，且获卵数5～15个为正常反应组，比较两组的妊娠结局。结果与正常反应组相比，高反应组获得的优质胚胎数显著增多（P〈0．001），但两者的受精率、卵裂率、胚胎种植率、临床妊娠率、流产率比较，差异无显著性（P〉0．05）。结论COH中卵巢高反应对妊娠结局无明显影响，但需注意预防卵巢过度刺激综合征的发生.     

A modified gonadotropin-releasing hormone (GnRH) antagonist protocol failed to increase clinical pregnancy rates in comparison with the long GnRH protocol

The purpose of this prospective randomized study was to compare stimulation characteristics and IVF outcomes of the standard long GnRH agonist protocol for ovarian stimulation with a modified GnRH antagonist protocol. Starting GnRH antagonist in a flexible protocol according to the size of the leading follicle, with simultaneous augmentation of 75 IU recombinant FSH, failed to increase clinical pregnancy rates.     

GnRH agonist versus GnRH antagonist in ovarian stimulation: is the emperor naked?

OBJECTIVE: The aim of the study was to evaluate the influence of type of GnRH-analog used during controlled ovarian hyperstimulation (COH) on the outcome of in vitro fertilization (IVF) cycles. PATIENTS AND METHODS: All consecutive women aged < or = 35 years admitted to our IVF unit from January 2001 to December 2004 were enrolled in the study. Only patients undergoing up to their third IVF cycle attempt were included. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryos transferred, and clinical pregnancy rate were compared between women given GnRH-agonist or GnRH-antagonist during COH. RESULTS: Four hundred and eighty-seven consecutive IVF cycles were evaluated, 226 in the agonist group and 261 in the antagonist group. A clinical pregnancy was achieved in 93 patients in the agonist group (pregnancy rate 41.2% per cycle) and 66 patients in the antagonist grup (pregnancy rate 25.3%); this difference was statistically significant (p < 0.01). The agonist group also used significantly more gonadotropin ampoules, required longer stimulation, and had higher estradiol levels on the day of human chorionic gonadotropin administration. CONCLUSION: The midluteal long GhRH-agonist suppressive protocol should be the protocol of choice in young patients in their first three IVF cycle attempts.     

Effectiveness of human menopausal gonadotropin versus recombinant follicle-stimulating hormone for controlled ovarian hyperstimulation in assisted reproductive cycles: a meta-analysis

OBJECTIVE: To compare the effectiveness of hMG and recombinant FSH after down-regulation for ovulation stimulation in assisted reproductive cycles. DESIGN: Meta-analysis. SETTING: Infertility centers providing assisted reproductive techniques. PATIENT(S): Two thousand thirty women undergoing IVF or ICSI. INTERVENTIONS: Ovarian hyperstimulation with hMG or recombinant FSH after down-regulation. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, ongoing pregnancy/live birth rate, gonadotropin dose used, oocytes retrieved, implantation rate, miscarriage rate, and multiple pregnancy rate. RESULT(S): Six randomized controlled trials were included. In all trials, the group of women treated with hMG had higher pregnancy rates. Pooling the five trials that used a long GnRH agonist protocol resulted in a higher clinical pregnancy rate for hMG compared with recombinant FSH (relative risk, 1.22 [95% CI, 1.03 to 1.44]). However, there was no evidence of a difference in rates of ongoing pregnancy or live birth per woman between hMG recipients and recombinant FSH recipients (relative risk, 1.20 [95% CI, 0.99 to 1.45]). No differences were found in gonadotropin dose used, oocytes retrieved, miscarriage rate, or multiple pregnancy rate. CONCLUSION(S): Use of hMG resulted in higher clinical pregnancy rates than did use of recombinant FSH in IVF/ICSI cycles after GnRH agonist down-regulation in a long 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.     

A novel strategy of using corifollitropin alfa in the ultrashort gonadotropin-releasing hormone agonist (GnRHa) protocol in unselected patients: A patient-friendly alternative

ObjectiveTo compare the outcomes of in vitro fertilization (IVF) and fresh embryo transfer (ET) using corifollitropin alfa in ultrashort gonadotropin-releasing hormone agonist (GnRHa) protocol and GnRH antagonist protocol.Materials and methodsA total of 245 unselected patients undergoing IVF/fresh ET were enrolled between January 1 and December 31, 2017, including 135 treated with ultrashort GnRHa protocol and 110 treated with antagonist protocol. The primary outcomes were number of total injections and outpatient department (OPD) visits before ovulation triggering. The secondary outcomes were the duration of stimulation, dosage of additional gonadotropin for ovarian hyperstimulation, rates of pregnancy, clinical pregnancy, live birth, ovarian response, and ovarian hyperstimulation syndrome (OHSS) rate.ResultsPatients treated with ultrashort GnRHa required less additional gonadotropin, fewer total injections, but had better ovarian responses, including more oocytes retrieved, more metaphase II oocytes, and more blastocysts than those treated with antagonist did. A premature LH surge occurred only in six patients treated with antagonist protocol. The rates of pregnancy (37.0% vs. 43.6%), clinical pregnancy (25.2% vs. 34.6%), and live birth (19.3% vs. 30.0%) did not differ significantly between the two groups. The OHSS rate was similar in the two groups.ConclusionIn unselected patients using corifollitropin alfa, the ultrashort GnRHa protocol needed lower dose of additional gonadotropin and fewer injections but produced similar pregnancy outcomes than antagonist protocol did, suggesting that the ultrashort GnRHa protocol could be an alternative.     

Adding human menopausal gonadotrophin to antagonist protocols – is there a benefit?

The objective of this retrospective analysis was to compare the clinical outcomes of recombinant FSH (r-FSH) with combination r-FSH plus human menopausal gonadotrophin (HMG) protocols in a large private practice using a single IVF laboratory, from 2001 to 2003. Patients underwent ovarian stimulation by standard gonadotrophin-releasing hormone (GnRH) antagonist protocol using r-FSH or combination r-FSH plus HMG. When two or more follicles had attained a minimum mean diameter of 20 mm, follicular triggering was achieved with either recombinant HCG (r-HCG; Ovidrel, 250 microg s.c.) or urinary HCG (u-HCG; 10,000 IU i.m.). The main outcome measures were number of oocytes retrieved and clinical pregnancy rate. There was a lower percentage of cancelled cycles and an increased number of oocytes retrieved, mature oocytes, oocytes that fertilized, embryo that cleaved and a tendency towards higher clinical pregnancy rates in patients treated with r-FSH alone compared with those treated with r-FSH plus HMG. Patients treated with r-FSH plus HMG had lower miscarriage rates and the live birth rate was similar in both treatment groups. In conclusion, irrespective of age, using a treatment regimen consisting of a combination of HMG plus r-FSH was not beneficial compared with r-FSH alone in patients using a GnRH antagonist protocol.     

Antagonist rescue of agonist IVF cycle at risk of OHSS: a case series

We describe a series of in vitro fertilisation (IVF) long protocol cycles presenting a risk of ovarian hyperstimulation syndrome (OHSS) which were rescued with an antagonist at a university-based tertiary-care fertility centre. Nineteen IVF patients presenting a risk of OHSS during treatment with long protocol, between 2009 and November 2012 were included in the present study. After discussion of available options, the agonist was stopped and a daily gonadotropin-releasing hormone (GnRH) antagonist injection was initiated (“rescue protocol”) and maintained until ovulation trigger. Fourteen patients were triggered with human chorionic gonadotropin (hCG) and five with GnRH agonist bolus, yielding competent oocytes. Seventeen embryo transfers were performed in the fresh cycles. One patient developed moderate OHSS. There were eight clinical pregnancies after the fresh IVF cycle (42% per patient), and six further pregnancies after frozen-thawed cycles, resulting in a 73% cumulative clinical pregnancy rate within one year. We conclude that the “rescue protocol with antagonist” of the long IVF cycle with a high risk of OHSS allows us to carry on with the cycle, without compromising its success or the patient safety, thus broadening the possibility of applying the long protocol.     

In vitro fertilization program. Preliminary results

Three infertile couples were submitted to in vitro fertilization and uterine embryo transfer (IVF+ET) and 7 to in vitro fertilization and pronuclear stage tubal transfer (IVF+PROST). In order to programmed menstruation Norethisterone, 10 mg daily, were administered during the cycle preceding the one of controlled ovarian hyperstimulation. In order to inhibit endogenous production of FSH and LH, leuprolide acetate, a Gn-RH agonist, was injected subcutaneously 1 mg daily during 6 days and 0.5 mg fowardly from the luteal phase of the cycle proceeding the one of hyperstimulation until the day of HCG administration. To achieve superovulation pure FSH (Metrodine), HMG (Pergonal) and HCG (Endocorion) were used. Oocyte retrieval was performed through transvaginal puncture under ultrasonographic control. For oocyte and embryo identification and classification, spermatozoa separation and capacitation and gamete insemination and incubation procedures habitual techniques were employed. Pronuclear embryo tubal transfer was performed through a laparoscope 17 hours after insemination and embryo transfer to the uterine cavity after 48 hours. Nine of 10 patients responded to gonadotrophin hyperstimulation and were submitted to ovarian puncture. 69 oocytes (7, per patient) were obtained, 59 (81.15% of which were mature. 74.55% of the inseminated oocytes fertilized. Two patients got pregnant: one, submitted to IVF+PROST, presently has a multiple pregnancy with triplets and the second, submitted to IVF+UT, had a missed abortion at 8 weeks of pregnancy.     

Age-matched comparison of recombinant and urinary HCG for final follicular maturation

This age-matched retrospective analysis compared the clinical outcomes of recombinant human chorionic gonadotrophin (rHCG) and urinary HCG (uHCG) in patients undergoing fresh, nondonor IVF cycles. The patients underwent ovarian stimulation by standard gonadotrophin-releasing hormone (GnRH) agonist down-regulation or a GnRH antagonist protocol using recombinant FSH (rFSH) alone or in combination with human menopausal gonadotrophin. When two or more follicles had attained a mean diameter of 20 mm, follicular triggering was achieved with either Ovidrel (rHCG) 250 mug SC or uHCG 10,000 IU IM. Patients receiving rHCG were considered subjects, and they were age-matched in a 1:2 ratio to patients receiving uHCG, who were designated as controls. The main outcome measures were number of oocytes retrieved, number of mature oocytes obtained, number of oocytes fertilized and clinical pregnancy rates. A total of 273 subjects were age-matched and compared with 546 controls. Recombinant HCG had a minimal effect on the number of oocytes retrieved (13.4 versus 13.2), mature oocytes (10.5 versus 10.3) and oocytes fertilized (8.2 versus 7.8) compared with uHCG. Pregnancy (46.0 versus 45.2%) and clinical pregnancy rates (38.1 versus 36.8%) were similar for rHCG and uHCG. Recombinant HCG was as effective as uHCG for final follicular maturation in IVF cycles.     

GnRH antagonists

Ovarian stimulation is an important step in the success rate of in vitro fertilization (IVF) allowing multiple follicular growth, several oocytes and consequently more embryos. The combination of GnRH-antagonists (GnRH-ant) and gonadotrophins is now available for clinical use and represent a valid alternative to classical protocol with GnRH agonist. GnRH-antagonists induce a direct block of GnRH receptor with a rapid decrease in LH and FSH, preventing LH surge. Two protocols has been designed for assisted reproduction technology (ART) treatment: multiple-dose protocol and a single-dose. Both protocols are simply, efficacious, started in the late follicular phase and do not have side effects. A review of GnRH-antagonist applications in ART cycles are presented. Smaller doses of gonadotrophins, shorter stimulation period and lower ovarian hyperstimulation syndrome (OHSS) incidence are reported in literature using GnRH-antagonist compared to agonist. Triggering of ovulation, the use in polycystic ovarian syndrome (PCOS) and poor reponders patients are other interesting indication. Regarding to pregnancy rate and potentially adverse effects of drugs on endometrium or implantation needed more data.     

Which luteal phase support is better for each IVF stimulation protocol to achieve the highest pregnancy rate? A superiority randomized clinical trial

In vitro fertilization (IVF) cycles generate abnormalities in luteal-phase sex steroid concentrations and this represent an important limiting factor to achieve a good pregnancy rate. Although there are evidences about the usefulness of luteal phase support (LPS) after IVF cycles, no consensus exist about the best dose and way of progesterone (PG) administration, the advantages of estradiol (E2) supplementation and which IVF protocol could benefit from one more than other LPS scheme. Aim of the study was to assess the best LPS (low-dose PG, high-dose PG, high-dose PG and E2 supplementation) to achieve the highest clinical/ongoing pregnancy rate according to stimulation protocol, E2 at ovulation induction, endometrial thickness at pick-up and women’s age. We conducted a randomized trial on 360 women undergoing IVF (180 treated by long-GnRH agonist, 90 by short-GnRH agonist and 90 by short-GnRH antagonist protocol) and stimulated by recombinant follicle-stimulating hormone alone. Our data demonstrated that high-dose PG is better than low-dose to increase both clinical and ongoing pregnancy rate. E2 supplementation are mandatory in case of short-GnRH antagonist protocol and strongly suggested in all protocols when E2_max <5?nmol/l and endometrial thickness <10?mm. In long-GnRH agonist protocols, as well as in patients >35 years, the real advantages of E2 supplementation remain debatable and require further confirmation.     

Retrospective comparison of GnRH agonist trigger with HCG trigger in GnRH antagonist cycles in anticipated high-responders

All IVF-ICSI cycles carried out between October 2009 and October 2012 using GnRH agonist (GnRHa) ovulation trigger (n = 62) followed by a single dose of HCG plus progesterone and oestradiol in the luteal phase because of anticipated ovarian hypertsimulation were retrospectively compared with historic control cycles using HCG trigger (n = 29) and standard luteal phase support. Women's mean age, body mass index, anti-Müllerian hormone, FSH, LH, starting and total stimulation dose, number of follicles, oocytes, embryos, fertilization, implantation, polycystic ovary syndrome, ICSI, live birth and ongoing pregnancy rates per embryo transfer were similar (GnRHa 40.7% versus HCG 35.0%). For each started cycle, GnRHa resulted in 11.4% higher (statistically non-significant) live birth and ongoing pregnancy rate (OR 1.73, CI 0.64 to 4.69), with a similar difference for double-embryo transfers (OR 1.62, CI 0.44 to 6.38) and less need for freezing all embryos (9.7% versus 27.6%; P = 0.04). Incidence of mild-to-moderate OHSS was 16.2% with GnRHa trigger and 31.0% with HCG trigger) and no severe OHSS in the former. The addition of single low-dose HCG in the luteal phase after GnRHa trigger for suspected high-responders reduced the incidence of OHSS with good clinical outcomes, compared with HCG trigger.     

Gonadotrophin-releasing hormone antagonists for assisted conception: a Cochrane review

Gonadotrophin-releasing hormone (GnRH) antagonists suppress gonadotrophin secretion resulting in dramatic reduction in treatment cycle duration. Assuming comparable clinical outcomes, these benefits may justify changing the standard long GnRH agonist protocol to GnRH antagonist regimens. To evaluate the evidence, databases (e.g. Cochrane Library, MEDLINE, EMBASE) were electronically searched, hand searches were performed, and manufacturers in the field were contacted. Twenty-seven randomized controlled trials (RCT) fulfilled inclusion criteria for comparison of GnRH antagonist with long GnRH agonist protocol. Clinical pregnancy rate and ongoing pregnancy/live-birth rate were significantly lower in the antagonist group (P = 0.009; OR = 0.83, 95% CI 0.72-0.95 and P = 0.02; OR = 0.82, 95% CI 0.68-0.97 respectively). Conversely, incidence of severe OHSS was significantly reduced with the antagonist protocol (P = 0.01; OR = 0.60, 95% CI 0.40-0.88), and interventions to prevent OHSS were administered more frequently in the agonist group (P = 0.03; OR = 0.43, 95% CI 0.20-0.92). Concluding, GnRH antagonist protocols are short, simple, with good clinical outcomes and significant reduction in severe OHSS incidence and gonadotrophin amount; however, the lower pregnancy rate compared with the GnRH agonist long protocol necessitates counselling subfertile couples before recommending change from GnRH agonist to antagonist.