Use Of GnRH Agonist Trigger Research Articles

The use of GnRH-agonist trigger for the final maturation of oocytes in normal and low responders undergoing planned oocyte cryopreservation

Does GnRH-agonist trigger offer similar maturity rate (MR) in low and normal responders compared to high responders in women undergoing planned oocyte cryopreservation, for whom even a small risk of ovarian hyperstimulation syndrome (OHSS) may not be acceptable? GnRH-agonist is an appropriate choice for final maturation of oocytes in planned oocyte cryopreservation, regardless of response to stimulation or risk of ovarian hyperstimulation syndrome. Numerous studies have demonstrated the utility of GnRH-agonist trigger for the prevention of ovarian hyperstimulation in high-responder in vitro fertilization cycles. Limited data exist supporting its use in normal or low responders, or in non-infertile women undergoing planned oocyte cryopreservation. Retrospective cohort study of 1189 subjects including all planned oocyte cryopreservation cycles performed at a large, single center, oocyte cryopreservation program from April 2016 to December 2018. A total of 1680cycles were included in the study. A total of 57.1% (959/1680) utilized GnRH-agonist for trigger. Demographic and clinical data were collected from the medical record. Maturation rate was calculated for the entire cohort, and by trigger type, using the quotient of Metaphase II (MII) oocytes and retrieved oocytes. A sub-cohort of GnRH-agonist trigger cycles were categorized by peak estradiol (E2) levels and maturation rates compared between groups. Associations were made using Student's t test, ANOVA, Mann-Whitney U and Kruskal-Wallis, where appropriate. A sample size calculation for 90% power with a significance of 5% to detect non-inferiority of <0.05 from a 0.75 maturity rate between subjects with E2 > 3000pg/mL and E2 < 3000pg/mL demonstrated the need for at least 116cycles per group. Mean MR was 0.71 ± 0.19 overall, and 0.73 ± 0.18 in the sub-cohort of GnRH-agonist trigger cycles. A total of 611cycles (63.7%) had peak E2 < 3000, and 331 (34.5%) had E2 > 3000. No significant difference in maturity rate was noted between cycles with E2 levels >3000pg/mL and <3000pg/mL (0.72 ± 0.19 vs. 0.74 ± 0.14, P = 0.18), confirming the non-inferiority of maturity rates with GnRH-agonist triggers in cycles with peak E2 < 3000pg/mL. While lower mean oocytes retrieved and mean MII oocytes were associated with lower peak E2 levels, maturity rate did not significantly differ amongst E2 level groups. Cycles with E2 < 1000pg/mL had lower MR irrespective of trigger type. The retrospective nature cannot entirely exclude selection biases, confounding factors or additional variables that could not be accounted for or were not collected by the electronic medical record. Given the nature of planned oocyte cryopreservation, studies of ongoing pregnancy rates and birth outcomes will naturally be delayed. Lastly, the study population was limited to women undergoing planned oocyte cryopreservation; therefore, the results may not be generalizable to women undergoing in vitro fertilization. This is the first study specifically comparing the efficacy of GnRH-agonist in patients at lower risk for OHSS to those at high risk, as well the first study evaluating GnRH-agonist's efficacy specifically in planned oocyte cryopreservation cycles. Study support provided by departmental funds from the Center for Fertility Research and Education-Extend Fertility Medical Practice. BLM discloses personal fees from Ferring Pharmaceuticals and Merck KgAA, unrelated to the submitted work. C.S., M.G., L.R. and J.K. have nothing to disclose. N/A.

A quality management approach to controlled ovarian stimulation in assisted reproductive technology: the "Fischer protocol".

Ovarian stimulation (OS) is crucial for pregnancy success in assisted reproductive technology (ART) treatments. The possibility of programming the OS cycle and oocyte pick-up (OPU) is advantageous to Fertility Centers operating under quality management systems (QMS) as it might increase efficiency and safety. Moreover, cycle programming is patient-centered as it might help IVF patients to most optimally manage domestic and work commitments. In this study, we describe the so-called "Fischer protocol" to IVF cycle programming and present the clinical results of using this approach in two independent Fertility Centers certified according to DIN EN ISO 9001 standards. Cycle programming was achieved in normo-ovulatory women with pretreatment administration of norethisterone acetate, followed by OS using individualized doses of recombinant human FSH and recombinant human LH in a fixed 2:1 ratio in association with a flexible GnRH antagonist regimen. The final oocyte maturation was attained with use of GnRH agonist trigger. The oocyte pick-ups (OPU) were scheduled approximately 40 days ahead of the programed OPU date. The cycle outcomes of 647 patients treated using the "Fischer protocol" in the Center where the method was developed (study center 1) are presented. The model was then tested at an independent Fertility Center (study center 2), and the first clinical results using the Fischer protocol in 216 patients are presented and compared with that of 516 patients undergoing conventional OS without cycle programming. The duration of ovarian stimulation was 9±1 day in all treated patients. No OPU was scheduled during weekends or had to be re-scheduled due to issues related to cycle programming. In the study center 1, the highest and lowest mean number of oocytes retrieved was 11.7 (95% confidence interval [CI]: 4.5-22.1) in patients of ≤30 years and 7.7 (95% CI: 1-19) in those aged 40 years and over. No cases of OHSS were recorded in this series. The mean number of embryos transferred was 1.5 and the overall clinical pregnancy rates (CPR) and live birth rates (LBR) were 52.7% and 43.5%, respectively. In the study center 2, patients treated using the Fisher protocol achieved statistically higher oocyte output rate (94.6% vs. 85.0%), number of oocytes retrieved (9.8±7.7 vs. 7.9±7.2), and blastulation rates (55.1% vs. 49.4%) than those treated using conventional OS. The CPR (50.6% vs. 41.1%) and LBR (44.7% vs. 33.2%) also favored the group of patients subjected to cycle programming using the Fisher protocol, although this data mainly resulted from the increased frequency of patients subjected to preimplantation genetic testing for aneuploidy (PGT-A). An optimal distribution of both clinical and laboratory workload was achieved by using the Fischer protocol. Moreover, oocyte pick-ups were eliminated on weekends and holidays without jeopardizing the quality of care provided to couples. The Fischer protocol is consistent with the quality management philosophy and focusses on improving the quality of care by increasing safety, efficacy, and patient-centeredness without harming treatment effectiveness.

Risk of ovarian torsion is reduced in GnRH agonist triggered freeze-all cycles: a retrospective cohort study

Ovarian torsion (OT) in IVF is rare, however, the consequences are significant, which include ovariotomy. In the present study, it was aimed for the first time to compare the incidence of OT between hCG triggered cycles with ICSI and fresh transfer and GnRH-agonist triggered cycles with the ICSI-freeze-all and frozen embryo transfer (FET). In total, 15,577 ICSI cycles performed between 2001 and 2016 were categorised into two groups (Group 1, n: 9978): cycles with controlled ovarian stimulation (COS) and hCG-triggered (Group 2, n: 5599) and COS, with GnRH-agonist only triggered and freeze-all. Thirteen patients (0.13%) were diagnosed with OT and corrected by laparoscopy (12) and laparotomy (1) in Group 1. One patient (0.018%) was diagnosed with OT and corrected by laparotomy in Group 2 (Group 1 vs. Group 2, p = .049). The incidence of severe ovarian hyperstimulation syndrome (OHSS) was 2.4% in Group 1 and 0.05% in Group 2 (p < .001). The use of freeze-all with GnRH agonist trigger in ART significantly reduced the incidence of OT and concomitantly OHSS, with no effect on the reproductive outcome.Impact StatementWhat is already known on this subject? Adnexal ovarian torsion (OT) is a well-known gynaecological event that constitutes a surgical emergency. Assisted reproduction technologies (ART) may result in ovarian conditions that predispose patients to ovarian hyperstimulation syndrome (OHSS) and torsion.What the results of this study add? The combined use of GnRH agonist trigger for final oocyte maturation after OS with freeze-all and frozen embryo transfer (FET) significantly reduces the incidence of OT, as well as OHSS.What the implications are of these findings for clinical practice and/or further research? The treatment strategy of GnRH agonist trigger with freeze-all significantly reduces the risks of adverse complications.

Final Oosit Matürasyonu İçin GnRH Agonist Tetikleme Kullanımında Güncel Yaklaşım

Final Oosit Matürasyonu İçin GnRH Agonist Tetikleme Kullanımında Güncel Yaklaşım

Strategies for the management of OHSS: Results from freezing-all cycles.

To compare the use of GnRH agonist (GnRHa) or hCG trigger in potential OHSS patients undergoing freeze-all programs. We also compared the clinical outcomes when fresh versus freeze-thawed embryo transfers were performed in cycles with a high number of retrieved oocytes. The study included potential OHSS patients who received GnRHa (n=74) or hCG (n=49) trigger. The protocols were compared with respect to the clinical outcomes. We also compared the clinical outcomes of cycles in which hCG trigger was used and more than 20 MII oocytes were retrieved when: fresh embryo transfer protocol (n=153) or freeze-all protocol (n=123) were performed. A decreased serum estradiol level, a decreased number of retrieved oocytes, an increased MII retrieved rate, and decreased fertilization rate was observed in the hCG when compared with the GnRHa group. No significant differences were noted concerning clinical outcomes. When fresh cycles were compared with frozen-thawed cycles, the estradiol serum level and the number of cryopreserved embryos were higher in the frozen-thawed cycles. The clinical pregnancy rate was higher among freeze-all cycles, as well as the implantation and cumulative pregnancy rates, when compared with fresh embryo transfer cycles. The use of GnRHa trigger may be a good alternative to prevent the OHSS in patients presenting an extreme ovarian response to COS, leading to similar clinical outcomes, when compared with the traditional hCG trigger. Moreover, our findings demonstrated that the strategy of freezing-all embryos not only decreases the risk of OHSS but also leads to a better pregnancy rate.

Hcg verus agonist trigger in donor oocyte cycles: does hCG have a place in current practice?

The use of GnRH agonist trigger has been shown to reduce OHSS. However in autologous ART, previous meta-analysis suggested GnRH agonist trigger might lower clinical outcomes when compared to hCG trigger. Reducing the risk of OHSS without compromising pregnancy outcomes is of paramount importance in donor oocyte ART. Thus we compared clinical outcomes between donors receiving hCG or GnRH agonist triggers.

Comparison of reproductive outcomes between trigger with hCG versus GnRH agonist in eggs donors cycle

The aim of this study is to compare the controlled ovarian stimulation (COS) protocols and their reproductive outcomes in donors using trigger with human chorionic gonadotropin (hCG) versus GnRH agonist (GnRHa) for In Vitro Fertilization (IVF) cycles of two private centers. Multicenter, Prospective and Comparative Analysis. A total of 66 consecutive cycles of COS in donors from two centers were reviewed. Two groups were formed: Group 1, donors with a luteal phase agonist protocol triggered with 10,000 IU of hCG, and Group 2 with an antagonist protocol using trigger with 0.8 ml of GnRHa (Lucrin Depot®3.75mg). ANOVA test was used for statistical analysis. Both groups were homogeneous for demographic characteristics and stimulation protocols (P=NS): donor age (22.4 ±2.0 vs. 23.7 ±2.2); receptor age (39.1 ±4.9 vs. 42 ±4.2); BMI (23.7 ±3.06 vs. 22.5±2.18); FSH day3 (5.05 ±1.55 vs. 5.95 ±0.97 mIU/ml); LH day3 (3.02 ±1.22 vs. 2.9 ± 1.13 mIU/ml); antral follicles (14.85 ±3.6 vs. 14.83 ±4.9); total doses of rFSH (1700 ±293.8 vs. 1643 ±393.2 IU). During the period of study was reported a single case of OHSS, and one case of ovarian torsion, in group 1. There were no complications in group 2. Reproductive outcomes are described in table 1.Tabled 1Table1. Ovarian stimulation outcomes by group.Group 1 (n=35)Group 2 (n=31)P valueE2 day 10 α2333 ± 147mIU/ml1810 ± 599 mIU/ml0.068Retrieved oocytes α15120.058Oocyte MII α12.510.80.185Embryo transfer α2.82.70.644Embryo transfer G142%54%0.734Gestational sac α1.61.30.662Implantation rate32%26%0.980Pregnancy rate61%54%0.244Ongoing pregnancy rate54%41%0.392α: Mean; G1: grade 1. Open table in a new tab α: Mean; G1: grade 1. Trigger with hCG remains the best option for final oocyte maturation. However, the use of GnRH agonist trigger after GnRH antagonist protocol is equally effective for oocyte maturation, fertilization and pregnancy in donor cycles. In addition it reduces the risk of OHSS and complications of stimulation in high risk patients (donors).