GnRH agonist for final oocyte maturation in GnRH antagonist co-treated IVF/ICSI treatment cycles. Systematic review & meta-analysis (original) (raw)
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KnE Medicine, 2016
Introduction. For decades, human chorionic gonadotropin (hCG) has been used for final oocyte maturation. It is proven to have highest life birth rate, comparing to gonadotropin releasing hormone (GnRH) agonist, but unfortunately it can increases the risk of developing ovarian hyper stimulation syndrome (OHSS). There is an ongoing debate over the optimal agent that can trigger final oocyte maturation in antagonist protocol, leading to higher IVF success rate without increasing the risk of OHSS. Objective. To compare IVF outcomes in patient using GnRH agonist trigger and hCG for final oocyte maturation. Method. A retrospective review of in vitro fertilization patient at Daya Medika Clinic and Yasmin Clinic. Result. 76 women were analyzed consist of 38 women using GnRH agonist and 38 women using hCG. We found no significant differences on biochemical pregnancy rate (24.00% and 20.51%) between two group, but there were significant differences on fertilization rate (67.72% and 61.32%), cleavage rate (95.04% and 88.92%) and blastocyst rate (13.90% and 7.38%). There was one patient developed OHSS in hCG group. Conclusion. GnRH agonists can be considered for use as a trigger final oocyte maturation in the antagonist protocol because some IVF outcomes data showed that GnRH agonists triggering were better than hCG without increasing the risk of OHSS.
GnRH agonist for triggering final oocyte maturation: time for a critical evaluation of data
Human Reproduction Update, 2012
Triggering final oocyte maturation with GnRH agonist during ovarian stimulation is feasible when inhibition of premature LH surge is performed with GnRH antagonists, and we aimed to systematically collate evidence on the clinical efficacy of GnRH agonist triggering in patients undergoing assisted reproduction in GnRH antagonist protocols. Twenty-three publications were identified by a comprehensive literature search that included PubMed, Embase and the Cochrane Library. Three publications out of 23 fulfilled the inclusion criteria for meta-analysis, which were (i) prospective, randomized controlled study design; (ii) stimulation with gonadotropins for induction of multifollicular development; (iii) suppression of endogenous LH by a GnRH antagonist; (iv) triggering of final oocyte maturation with GnRH agonist; (v) control group randomized to receive HCG for final oocyte maturation and (vi) any means of luteal phase support other than HCG. The participants were normoovulatory women undergoing IVF. The outcomes assessed were clinical pregnancy per randomized patient; number of oocytes retrieved; proportion of metaphase II oocytes; fertilization rate; embryo quality score; first trimester abortion rate; ovarian hyperstimulation syndrome (OHSS) incidence. Results are presented as combined standardized differences of the mean and combined odds ratios, as appropriate, with 95% confidence intervals. No significant difference was found for the number of oocytes retrieved (-0.94, -0.33-0.14), proportion of metaphase II oocytes (-0.03, -0.58-0.52), fertilization rate (0.15, -0.09-0.38) or embryo quality score (0.05, -0.18-0.29). No OHSS occurred in two of the studies, whereas in one study OHSS incidence was not reported. Thus from the available data, no conclusion can be drawn as regards OHSS incidence after GnRH agonist triggering. In comparison to HCG, GnRH agonist administration is associated with a significantly reduced likelihood of achieving a clinical pregnancy (0.21, 0.05-0.84; P = 0.03). The odds of first trimester pregnancy loss is increased after GnRH agonist triggering; however, the confidence interval crosses unity (11.51, 0.95-138.98; P = 0.05). In conclusion, the use of GnRH agonist to trigger final oocyte maturation in IVF, where inhibition of premature LH surge is achieved with GnRH antagonists, yields a number of oocytes capable to undergo fertilization and subsequent embryonic cleavage, which is comparable to that achieved with HCG. However, the likelihood of an ongoing clinical pregnancy after GnRH agonist triggering is significantly lower as compared to standard HCG treatment.
Reproductive BioMedicine Online, 2006
The study retrospectively evaluated the infl uence of triggering fi nal oocyte maturation with gonadotrophin-releasing hormone (GnRH) agonist on the outcome of IVF cycles. Four hundred and sixty consecutive women admitted to the IVF unit during a 4-year period were enrolled in the study. Ovarian stimulation characteristics and clinical pregnancy rate were compared between three groups: patients at risk of developing ovarian hyperstimulation syndrome (OHSS), undergoing either the long GnRH-agonist protocol (agonist group) or the fl exible multidose GnRH-antagonist protocol who received GnRH-agonist for fi nal oocyte maturation (antagonist-agonist group); and patients not at risk of developing severe OHSS undergoing the fl exible multidose GnRH-antagonist protocol who received human chorionic gonadotrophin (HCG) for fi nal oocyte maturation (antagonist-HCG group). Implantation and clinical pregnancy rates were lowest in the antagonist-agonist group despite the fact that no difference were was observed in fertilization rates between the groups. Moreover, the high-responder antagonist-agonist group required shorter stimulation and had higher numbers of oocytes retrieved as compared with the high-responder agonist-group. No case of severe OHSS was observed in the antagonist-agonist group. The use of fl exible multidose GnRH-antagonist protocol with GnRH-agonist for fi nal oocyte maturation, in high-responder patients, eliminates the risk of OHSS but results in decreased implantation and pregnancy rates.
Frontiers in Endocrinology, 2022
IntroductionThe choice of trigger drug for the controlled ovarian hyperstimulation (COH) protocol correlates with the outcome of in vitro fertilization/intracytoplasmic sperm injection embryo transfer (IVF/ICSI-ET). The co-administration of gonadotropin releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG), i.e., dual trigger, for final oocyte maturation, has received much attention in recent years. This trial was designed to determine whether a dual trigger approach by lengthening the time between trigger and ovum pick-up (OPU) improves the quantity and quality of mature oocytes/top-quality embryos and pregnancy outcomes in expected normal responders with a high immature oocyte rate.Methods and AnalysisWe propose a study at the Affiliated Hospital of Shandong University of Chinese Medicine. A total of 90 individuals undergoing COH use a fixed GnRH antagonist protocol. They will be assigned randomly into two groups according to the trigger method and timing: reco...
Journal of Assisted Reproduction and Genetics, 2017
Purpose The purpose this study is to investigate whether a double antagonist dose (0.25 mg/12 h) administered the day before hCG trigger is effective in preventing ovarian hyperstimulation syndrome (OHSS) in GnRH antagonist IVF/intracytoplasmic sperm injection (ICSI) cycles at risk for OHSS. Methods This is a prospective randomized control study, conducted from November 2012 to January 2016. A total of 194 patients undergoing a IVF/ICSI GnRH antagonist cycle that were at risk of OHSS and chose to proceed with embryo transfer and avoid cycle cancellation or embryo cryopreservation were allocated into two groups. The inclusion criteria consisted of a rapid rise of oestradiol ≥ 3500 pg/ml combined with ≥ 18 follicles > 11 mm in diameter without any mature follicle > 16 mm, in any day of stimulation. Overall, 97 patients (intervention group A) received a double dose of GnRH antagonist (0.25 mg/12 h) the day before hCG while 97 patients (control group B) did not. Recombinant FSH administration was tapered to 100 IU/24 h the day of the allocation in both groups. Results Incidence of early-onset moderate/severe OHSS was significantly lower in intervention group A compared to control group B (0 vs 12.37%, P < 0.001). Clinical pregnancy rate per cycle (50.52 vs 42.27%, P = 0.249) was not significantly different between the two groups. Oestradiol (3263.471 ± 1271.53 vs 5233 ± 1425.17, P < 0.001), progesterone (0.93 ± 0.12 vs 1.29 ± 0.14, P < 0.001) and luteinizing hormone (1.42 ± 0.31 vs 1.91 ± 0.33, P < 0.001) were significantly lower in group A the day of the hCG triggering. Conclusion The administration of a rescue double GnRH antagonist dose the day before hCG trigger may represent a safe alternative preventive strategy for early OHSS without affecting the reproductive outcomes. Trial registration number ISRCTN02750360
Journal of reproduction & infertility, 2012
The purpose of present study was to evaluate the role of pre-ovulatory GnRH agonist therapy on IVF outcomes in GnRH antagonist cycles. In this prospective study we recruited 100 infertile women undergoing IVF cycles with GnRH antagonists. The patients were assigned to two groups: Group A (the study group, n = 42) were assigned for receiving hCG + triptorelin for the final oocyte maturation and group B (the control group, n = 58) were assigned for only hCG. The t-test, chi-square (χ(2)), and Fisher's exact test were used for data analysis. A p < 0.05 was taken as statistically significant. The results are presented by mean± SD, and in percents (%). LH levels significantly (p < 0.001) increased in the study…
Human Reproduction, 2016
study question: Is the risk of severe ovarian hyperstimulation syndrome (OHSS) similar in a short GnRH antagonist and long GnRH agonist protocol in first cycle IVF/ICSI patients less than 40 years of age?. summary answer: There is an increased risk of severe OHSS in the long GnRH agonist group compared with the short GnRH antagonist protocol. what is known already?: In the most recent Cochrane review, the GnRH antagonist protocol was associated with a similar live birth rate (LBR), a similar ongoing pregnancy rate (OPR), and a lower incidence of OHSS (odds ratio (OR) ¼ 0.43 95% confidence interval (CI): 0.33-0.57) compared with the traditional GnRH agonist protocol. Previous trials comparing the two protocols mainly included selected patient populations, a limited number of patients and the applied OHSS criteria differed, making direct comparisons difficult. In two recent large meta-analyses, no significant differences in LBR (OR ¼ 0.86; 95% CI: 0.72-1.02) or in the incidence of severe OHSS were reported, while others found a lower LBR (OR ¼ 0.82; 95% CI: 0.68-0.97) and a reduced risk of severe OHSS using the GnRH antagonist protocol (OR ¼ 0.60; 95% CI: 0.40-0.88). study design, size, duration: Phase IV, dual-centre, open-label, RCT including 1050 women allocated to either short GnRH antagonist or long GnRH agonist protocol in a 1:1 ratio and enrolled over a 5-year period using a web-based concealed randomization code. This is a superiority study designed to detect a difference in severe OHSS, the primary outcome, between the two groups with a power of 80% and stratified for age, assisted reproductive technology (ART) clinic and planned fertilization procedure (IVF/ICSI). The secondary aims were to compare rates of mild and moderate OHSS, positive plasma (p)-hCG, ongoing pregnancy and live birth between the two arms. None of the women had undergone previous ART treatment. participants/materials, setting, methods: All infertile women referred for their first IVF/ICSI at two public fertility clinics, less than 40 years of age and with no uterine malformations were asked to participate. A total of 1099 subjects were randomized, including women with poor ovarian reserve, polycystic ovary syndrome and irregular cycles. A total of 49 women withdrew their consent, thus 1050 subjects were allocated to the GnRH antagonist (n ¼ 534) and agonist protocol (n ¼ 516), respectively. In total 1023 women started recombinant human follitropin-b (rFSH) stimulation, 528 in the GnRH antagonist group and 495 in the GnRH agonist group. All subjects were given a fixed rFSH dose of 150 IU or 225 IU according to age ≤36 years or .36 years, with the option to adjust dose at stimulation day 6. Clinical OHSS parameters were collected at oocyte retrieval, and Days 3 and 14 post-transfer. Ongoing pregnancy was determined by transvaginal ultrasonography at gestational weeks 7-9. In the intention-to-treat (ITT) analysis for reproductive outcomes, 1050 subjects were included. For the ITT analyses on OHSS 1023 subjects who started gonadotrophin stimulation were included. main results and the role of chance: The incidence of severe OHSS [5.1% (27/528) versus 8.9% (44/495) (difference in proportion percentage point (Dpp) ¼ 23.8pp; 95% CI: 27.1 to 20.4; P ¼ 0.02)] and moderate OHSS [10.2% (54/528) versus 15.6% (77/495) (Dpp ¼ 25.3pp; 95% CI: 29.6 to 21.0; P ¼ 0.01) ] was significantly lower in the GnRH antagonist group compared with the agonist group, respectively. In the GnRH antagonist and agonist group, respectively, 4.7% (25/528) versus 8.5% (42/495) women were seen
Journal of Assisted Reproduction and Genetics, 2008
Purpose To evaluate whether oocyte quality, implantation and pregnancy outcomes in in vitro fertilization (IVF)/ intra-cytoplasmic sperm injection (ICSI) are related to the duration of gonadotropin-releasing hormone (GnRH)antagonist use or the timing of its initiation. Methods Retrospective cohort study of 178 conventional IVF/ICSI cycles. All patients underwent ovarian stimulation with gonadotropins and GnRH-antagonist for pituitary down-regulation. Spearman correlations and logistic regression were used for statistical analysis. Results There was no correlation between the duration of use or the timing of initiation of GnRH-antagonist with oocyte quality or implantation and pregnancy outcomes. Oocyte quality was influenced by the peak estradiol. Implantation was influenced by the patient's age. Early pregnancy loss, by the endometrial thickness on human chorionic gonadotropin-day. Ongoing pregnancy was independent from the variables evaluated.