Abstract
Study question
Do Gonadotropin-releasing hormone agonists (GnRHa) triggering improves oocyte maturation, clinical outcomes, and safety compared to human chorionic gonadotropin (hCG) triggering during controlled ovarian stimulation with an antagonist protocol?
Summary answer
The final triggering using GnRHa allows a higher number of retrieved and mature oocytes to be obtained with comparable clinical outcomes and lower OHSS risk.
What is known already
GnRHa represent an alternative to hCG for ovulation triggering after controlled ovarian stimulation with an antagonist protocol for IVF/ICSI. GnRHa triggering is thought to be more physiological due to the endogenous surges in LH and FSH levels. However, the benefit of GnRHa over hCG triggering on oocyte maturation remains controversial.
Study design, size, duration
A systematic review and meta-analysis of randomised controlled clinical trials. Searches were conducted from 01 January 1990 to 15 April 2020 on MEDLINE, EMBASE, the Cochrane Library, ClinicalTrials.gov and EudraCT, using the following search terms: ‘GnRH agonist’, ‘hCG’, ‘triggering’. Two independent reviewers carried out the study selection, the bias assessment using the RoB2 tool, and the data extraction according to Cochrane methods.
Participants/materials, setting, methods
The primary outcomes were the total number of retrieved oocytes and the number of mature oocytes. The main secondary outcomes were the number of embryos obtained, the clinical pregnancy rate, the early pregnancy loss rate, the live birth rate, and the incidence of ovarian hyperstimulation syndrome (OHSS). Random-effects meta-analysis was performed followed by prespecified sensitivity and subgroup analyses.
Main results and the role of chance
A total of 29 randomised controlled trials were included. The mean number of retrieved oocytes [difference in means (95% CI) 0.99 (0.21, 1.78); p = 0.01; n = 26] and of mature oocytes [0.68 (0.04, 1.33); p = 0.04; n = 12] were statistically significantly higher after GnRHa than after hCG triggering. A similar difference was observed for the number of embryos [0.94 (0.19, 1.68); p = 0.01; n = 10]. No differences in the clinical pregnancy rate [risk ratio 1.01 (0.90, 1.14); p = 0.83; n = 23], early pregnancy loss [1.27 (0.94, 1.71); p = 0.13; n = 16], and live birth rate [1.00 (0.77, 1.29); p = 0.97; n = 6] were noted. GnRHa was associated with a lower incidence of OHSS [odds ratio 0.25 (0.08, 0.74); p = 0.012; n = 20].
Limitations, reasons for caution
The validity of meta-analysis results depends mainly on the quality and the number of the published studies available.
Wider implications of the findings: In light of its safety and effectiveness, GnRHa should be the new standard for triggering in antagonist cycles, with dual triggering with hCG when the risk of OHSS is low and a fresh embryo transfer approach is used.
Trial registration number
NA
Increased risk of early pregnancy loss by profound suppression of luteinizing hormone during ovarian stimulation in normogonadotrophic women undergoing assisted reproduction
