Meta-analysis of trigger timing in normal responders undergoing GnRH antagonist ovarian hyperstimulation protocol
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SUBMITTER: Xie Q
PROVIDER: S-EPMC10913352 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo evaluate the effectiveness and safety of GnRH antagonist and GnRH agonist in supposed normal ovarian responders undergoing IVF.MethodsData from 6 databases were retrieved for this study. The RCTs of GnRH agonist and GnRH antagonist use during IVF-EF therapy for patients with supposed normal ovarian response were included. A meta-analysis was performed with Revman 5.1software.ResultsTwenty-three RCTs met the inclusion criteria. The number of stimulation days (mean difference (MD): -0.66, 95% confidence interval (CI): -1.04∼-0.27), Gn amount (MD: -2.92, 95% CI: -5.0∼-0.85), E2 values on the day of HCG (MD: -330.39, 95% CI: -510.51∼-150.26), Number of oocytes retrieved (MD: -1.33, 95% CI: -2.02∼-0.64), clinical pregnancy rate (odds ratio (OR): 0.87, 95% CI: 0.75-1.0), and ovarian hyperstimulation syndrome (OHSS) incidence (OR: 0.59, 95% CI: 0.42∼0.82) were significantly lower in GnRH antagonist protocol than GnRH agonist protocol. However, the endometrial thickness on the day of HCG (MD: -0.04, 95% CI: -0.23∼0.14), the ongoing pregnancy rate (OR: 0.87, 95% CI: 0.74∼1.03), live birth rate (OR: 0.89, 95% CI: 0.64∼1.24), miscarriage rate (OR: 1.17, 95% CI: 0.85∼1.61), and cycle cancellation rate (OR: 1.11, 95% CI: 0.90∼1.37) did not significantly differ between the 2 groups.ConclusionsDuring IVF treatment for patients with supposed normal responses, the incidence of OHSS were significantly lower, whereas the ongoing pregnancy and live birth rates were similar in the GnRH antagonist compared with the standard long GnRH agonist protocols.
| S-EPMC4162565 | biostudies-literature
Project description:BackgroundSynchronization of follicles is key to improving ovulation stimulation with the gonadotropin-releasing hormone (GnRH) antagonist protocol. GnRH antagonist administration in the early follicular phase can quickly decrease gonadotrophin (Gn) levels and achieve downregulation before stimulation, which may improves synchronization. A previous small randomized controlled study (RCT) showed that pretreatment with a GnRH antagonist for 3 days before stimulation may increase oocyte retrieval but cannot increase the pregnancy rate. This study investigated whether the GnRH antagonist pretreatment protocol in ovulatory women can increase the synchronization of follicles and pregnancy outcomes compared with the conventional GnRH antagonist protocol.MethodsThis RCT included 136 normal ovulatory women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Both groups were treated with recombinant follicle-stimulating hormone (r-FSH) and a flexible GnRH antagonist protocol. The women were randomized into two equal groups with or without GnRH antagonist administration from day 2 of the menstrual cycle for 3 days before stimulation. Our primary outcome was the number of retrieved oocytes. Secondary outcomes included the pregnancy rate and live birth rate.ResultsBoth groups had similar baseline characteristics. The number of retrieved oocytes in the study group was comparable to that in the control group (9.5 [8.0-13.0] vs. 11.0 [7.0-14.8], P = 0.469). There was no significant difference in the follicle size. The fertilization rate, number of good-quality embryos, implantation rate, pregnancy rate, ongoing pregnancy rate, live birth rate per embryonic transfer cycle, and miscarriage rate were similar between the two groups.ConclusionThis large RCT analysed GnRH antagonist pretreatment with the GnRH antagonist protocol applied to normal ovulatory women undergoing IVF/ICSI. The number of retrieved oocytes and pregnancy outcomes did not significantly vary.Trial registrationChinese Clinical Trial Registry, ChiCTR1800019730 . Registered 26 November 2018.
| S-EPMC8507211 | biostudies-literature
Project description:To determine if the GnRH antagonist protocol is effective in preventing ovarian hyperstimulation syndrome (OHSS) in potentially high responders.A total of 660 IVF-ET/ICSI cycles were retrospectively identified. The inclusion criterion was age ≤ 30 years. Cycles were divided into two groups: a GnRHa group and a GnRHant group. In the GnRHa group, the patients received one single injection of 1.0mg-1.3mg Triptorelin in previous mid-luteal phase. In the GnRHant group, a daily dose of 0.25 mg Cetrotide was initiated when a lead follicle obtained a mean diameter of 14 mm, continued up until the day of hCG administration. The duration of stimulation, total dose of Gn, implantation rate, pregnancy rate, and OHSS rate were compared.The duration of stimulation, E2 level on hCG day, numbers of oocytes retrieved, MII oocytes, and high-quality embryos in the GnRHa group were all significantly more than those in the GnRHant group. In the GnRHa group, 83.53% of cancelled fresh-transferred cycles were cancelled because of high risk of OHSS, which was significantly higher than that in the GnRHant group (43.55%, P<0.05). The incidence of OHSS in the GnRHa group was slightly higher than that in the GnRHant group. The implantation and clinical pregnancy rates in the GnRHa group were significantly higher than those in the GnRHant group (37.36% VS 19.25%, 62.78% VS 31.06%; P<0.05).Our study demonstrated that for potentially high responders, the GnRHant protocol can, to some extent, lower the cancellation and incidence rates of OHSS. The GnRHa protocol was superior to the GnRHant protocol in terms of implantation and clinical pregnancy rates.
| S-EPMC4607293 | biostudies-other
Project description:Study questionWhat is the threshold for the prediction of moderate to severe or severe ovarian hyperstimulation syndrome (OHSS) based on the number of growing follicles ≥ 11 mm and/or estradiol (E2) levels?Summary answerThe optimal threshold of follicles ≥11 mm on the day of hCG to identify those at risk was 19 for both moderate to severe OHSS and for severe OHSS. Estradiol (E2) levels were less prognostic of OHSS than the number of follicles ≥ 11 mm.What is known alreadyIn comparison to long gonadotropin-releasing hormone (GnRH) agonist protocols, the risk of severe OHSS is reduced by approximately 50% in a GnRH antagonist protocol for ovarian stimulation prior to in vitro fertilisation (IVF), while the two protocols provide equal chances of pregnancy per initiated cycle. Nevertheless, moderate to severe OHSS may still occur in GnRH antagonist protocols if human chorionic gonadotropin (hCG) is administered to trigger final oocyte maturation, especially in high responder patients. Severe OHSS following hCG trigger may occur with an incidence of 1-2% in a relatively young (aged 18 to 36 years) IVF population treated in a GnRH-antagonist protocol.Study design, size, durationFrom the Engage, Ensure and Trust trials, in total, 2,433 women who received hCG for oocyte maturation and for whom the number of follicles ≥ 11 mm and the level of E2 on the day of hCG administration were known were included in the analyses.Participants/materials, setting, methodsThe threshold for OHSS prediction of moderate and severe OHSS was assessed in women treated with corifollitropin alfa or daily recombinant follicle stimulation hormone (rFSH) in a gonadotropin-releasing hormone (GnRH)-antagonist protocol. Receiver operating characteristics curve analyses for moderate to severe OHSS and severe OHSS were performed on the combined dataset and the sensitivity and specificity for the optimal threshold of number of follicles ≥ 11 mm, E2 levels on the day of (hCG), and a combination of both, were determined.Main results and the role of chanceThe optimal threshold of follicles ≥ 11 mm on the day of hCG to identify those at risk of moderate to severe OHSS was 19 (sensitivity and specificity 62.3% and 75.6%, respectively) and for severe OHSS was also 19 (sensitivity and specificity 74.3% and 75.3%, respectively). The positive and negative predictive values were 6.9% and 98.6%, respectively, for moderate to severe OHSS, and 4.2% and 99.5% for severe OHSS.Limitations, reasons for cautionThis was a retrospective analysis of combined data from three trials following ovarian stimulation with two different gonadotropins.Wider implications of the findingsFor patients with 19 follicles or more ≥11 mm on the day of hCG, measures to prevent the development of OHSS should be considered. Secondary preventive measures include cycle cancellation or coasting, use of a GnRH agonist to trigger final oocyte maturation in place of hCG and a freeze all strategy.Trial registrationClinicalTrials.gov NCT00702845 NCT00696800 NCT00696878.
| S-EPMC4780699 | biostudies-literature
Project description:BackgroudTo investigate the effect of Luteinizing hormone (LH) level changes on the outcomes of controlled ovarian hyperstimulation (COH) and embryo transfer (ET) in gonadotropin-releasing hormone antagonist (GnRH-ant) protocol.MethodsA total of 721 patients undergoing GnRH-ant protocol COH for the first IVF/ICSI cycles were retrospectively analyzed. COH process were divided into 2 stages, before (stage 1) and after (stage 2) the GnRH-ant initiation, and each with 5 groups basing on LH levels: LH decreased more than 50% (groups A1, A2), decreased 25-50% (groups B1, B2), change less than 25% (groups C1, C2), increased 25-50% (groups D1, D2), and increased more than 50% (groups E1, E2).ResultsThere were no significant differences among groups of stage1 regarding COH and ET outcomes. For stage 2, the more obvious the decrease of LH level, the more the number of oocytes retrieved, mature oocytes, fertilized oocytes, embryos cleavaged and the numbers of embryo available (P < 0.05), but without significant differences regarding ET outcomes. We also found the freeze-all rate in Group A2 was higher (P < 0.001).ConclusionLH level changes before GnRH-ant addition were not related to COH and ET outcomes. LH level changes after the addition of GnRH-ant were related to the outcome of COH, and no significant differences were found relating to ET outcomes.
| S-EPMC10464317 | biostudies-literature
Project description:ObjectiveTo evaluate the effectiveness and safety of gonadotropin-releasing hormone antagonist (GnRH-ant) protocol and gonadotropin-releasing hormone agonist (GnRH-a) long protocol in patients with normal ovarian reserve.MethodsWe searched the PubMed (1992-2016), Cochrane Library (1999-2016), Web of Science (1950-2016), Chinese Biomedical Database (CBM, 1979-2016), and China National Knowledge Infrastructure (CNKI, 1994-2016). Any randomized controlled trials (RCTs) that compared GnRH-ant protocol and GnRH-a long protocol in patients with normal ovarian reserve were included, and data were extracted independently by two reviewers. The meta-analysis was performed by Revman 5.3 software.ResultsTwenty-nine RCTs (6399 patients) were included in this meta-analysis. Stimulation days (mean difference (MD) [95% confidence interval (CI)] = -0.8 [-1.36, -0.23], P = 0.006), gonadotrophin (Gn) dosage (MD [95% CI] = -3.52 [-5.56, -1.48], P = 0.0007), estradiol (E2) level on the day of human chorionic gonadotrophin (HCG) administration (MD [95% CI] = -365.49 [-532.93, -198.05], P<0.0001), the number of oocytes retrieved (MD [95% CI] = -1.41 [-1.84, -0.99], P<0.00001), the embryos obtained (MD [95% CI] = -0.99 [-1.38, -0.59], P<0.00001), incidence of ovarian hyperstimulation syndrome (OHSS) (OR [95% CI] = 0.69 [0.57, 0.83], P<0.0001) were statistically significantly lower in GnRH-ant protocol than GnRH-a long protocol. However, the clinical pregnancy rate (OR [95% CI] = 0.90 [0.80, 1.01], P = 0.08), ongoing pregnancy rate (OR [95% CI] = 0.88 [0.77, 1.00], P = 0.05), live birth rate (OR [95% CI] = 0.95 [0.74, 1.09], P = 0.27), miscarriage rate (OR [95% CI] = 0.98 [0.69, 1.40], P = 0.93), and cycle cancellation rate (OR [95% CI] = 0.86 [0.52, 1.44], P = 0.57) showed no significant differences between the two groups.ConclusionGnRH-ant protocol substantially decreased the incidence of OHSS without influencing the pregnancy rate and live birth rate compared to GnRH-a long protocol among patients with normal ovarian reserve.
| S-EPMC5402978 | biostudies-literature
Project description:BackgroundThe aim of this study was to compare the efficacy of antagonist rescue protocol (replacing GnRH agonist with GnRH antagonist and reducing the dose of gonadotropins) combined with cabergoline versus cabergoline alone in the prevention of ovarian hyperstimulation syndrome (OHSS) in patients pretreated with GnRH agonist long protocol who were at high risk for OHSS.MethodsTwo hundred and thirty six patients were randomized in a 1:1 ratio to the cabergoline group or the antagonist rescue combined with cabergoline group. Both groups received oral cabergoline (0.5 mg/day) for eight days beginning on the day of HCG administration. In the antagonist rescue combined with cabergoline group, when the leading follicle reached 16 mm, GnRH agonist (triptorelin) was replaced with GnRH antagonist (cetrorelix acetate) and the dose of HP-uFSH was reduced to 75 IU/day. HCG (5,000 IU/I.M) was administered when the serum estradiol level dropped below 3500 pg/ml. The study was open label and the outcome assessors (laboratory staff and the doctor who performed oocyte retrieval) were blind to treatment allocation.ResultsThe incidence of moderate/severe OHSS was significantly lower in the antagonist rescue combined with cabergoline group [5.08 % Vs 13.56 %, P value =0.025, OR = 0.342, 95 % CI, 0.129-0.906]. Four cycles were cancelled in the cabergoline group. There were no significant differences between the groups with respect to the number of retrieved oocytes, metaphase II oocytes, high quality embryos and fertilization rate. Moreover, the implantation and pregnancy rates were comparable between both groups.ConclusionGnRH antagonist rescue protocol combined with cabergoline is more effective than cabergoline alone in the prevention of OHSS.Trial registrationClinical trial.gov ( NCT02461875 ).
| S-EPMC4869387 | biostudies-literature
Project description:In in vitro fertilization (IVF) cycles controlled ovarian hyperstimulation (COH) is established by gonadotropins in combination with gonadotropin-releasing hormone (GnRH) agonists or antagonists, to prevent premature luteinizing hormone (LH) surge. The aim of our study was to improve the understanding of gene expression profile of cumulus cells (CC) in terms of ovarian stimulation protocol and oocyte maturity. We applied Affymetrix gene expression profiling in CC of oocytes at different maturation stages using either GnRH agonists or GnRH antagonists. Two analyses were performed: the first involved CC of immature metaphase I (MI) and mature metaphase II (MII) oocytes where 359 genes were differentially expressed, and the second involved the two GnRH analogues where no differentially expressed genes were observed at the entire transcriptome level. A further analysis of 359 differentially genes was performed, focusing on anti-Müllerian hormone receptor 2 (AMHR2), follicle stimulating hormone receptor (FSHR), vascular endothelial growth factor C (VEGFC) and serine protease inhibitor E2 (SERPINE2). Among other differentially expressed genes we observed a marked number of new genes connected to cell adhesion and neurotransmitters such as dopamine, glycine and ?-Aminobutyric acid (GABA). No differential expression in CC between the two GnRH analogues supports the findings of clinical studies where no significant difference in live birth rates between both GnRH analogues has been proven.
| S-EPMC3474825 | biostudies-literature
Project description:A suggested explanation for the pituitary-suppressive effects of progestin-primed ovarian stimulation cycles (PPOS) is pituitary luteinizing hormone (LH) depletion with progestin exposure during the follicular phase. The GnRH agonist (GnRHa) trigger releases endogenous LH from the pituitary, and if the LH depletion theory is correct, the response to the agonist trigger would be dampened in PPOS cycles. In this study, we compared the performance of the GnRHa trigger after PPOS and GnRH antagonist ovarian stimulation cycles. All women who underwent ovarian stimulation with the GnRH antagonist or flexible PPOS (fPPOS) and received a GnRH agonist trigger were eligible for inclusion. Outcomes included number of metaphase-II (MII) oocytes retrieved per cycle, rates of empty follicle syndrome, maturation, fertilization, blastulation, and cumulative clinical pregnancy per stimulation cycle. During the screening period, there were 166 antagonists and 58 fPPOS cycles triggered with a GnRH agonist. Groups were matched for potential confounders using propensity score matching. Progestin-downregulated cycles had 19% high mature oocyte yield (median: 14 vs. 19 MII oocytes, P = 0.03). Cumulative ongoing pregnancy or live birth rates were estimated after matching for transferred embryo count, and rates were similar between GnRH antagonist and fPPOS group (57.0% vs. 62.1%, P = 0.68). However, the number of remaining blastocysts was higher in the fPPOS group (median: 5.0 vs. 6.0, P < 0.001). LH levels were higher in fPPOS cycles compared to GnRH antagonist cycles up to the trigger day (P < 0.001). After the GnRHa trigger, fPPOS cycles were associated with a steeper LH surge compared with antagonist cycles (P = 0.02). Higher endogenous gonadotropin levels through the stimulation period and an LH surge of higher magnitude following a GnRHa trigger suggest a milder pituitary suppression by fPPOS, which needs to be confirmed in larger samples. It appears that progestins do not deplete pituitary LH reserves and a GnRHa trigger is usable after PPOS in women with high ovarian reserve.
| S-EPMC9161281 | biostudies-literature
Project description:The purpose of this paper is to assimilate all data pertaining to the use of gonadotropin-releasing hormone (GnRH) antagonists in in vitro fertilization cycles after ovulation trigger to reduce the symptoms of ovarian hyperstimulation syndrome (OHSS). A systematic review of the literature was performed to identify all studies performed on the use of a GnRH antagonist in IVF cycle post-ovulation trigger with patients at high risk for OHSS. Ten studies were identified and reviewed. Descriptions of the studies and their individual results are presented in the following manuscript. Due to significant heterogeneity among the studies, it was not possible to perform a group analysis. The use of GnRH antagonists post-ovulation trigger for treatment of OHSS has been considered for almost 20 years, though research into its use is sparse. Definitive conclusions and recommendations cannot be made at this time, though preliminary data from these trials demonstrate the potential for GnRH antagonists to play a role in the treatment of OHSS in certain patient populations.
| S-EPMC5545220 | biostudies-other