Effects of gonadotropin-releasing hormone antagonist (GnRH-ant) cessation on trigger day in a GnRH-ant protocol: a meta-analysis

J Obstet Gynaecol. 2025 Dec;45(1):2444496. doi: 10.1080/01443615.2024.2444496. Epub 2024 Dec 28.

Abstract

Background: The gonadotropin-releasing hormone antagonist (GnRH-ant) protocol is associated with few oocytes retrieved, few mature oocytes and poor endometrial receptivity. Omission of GnRH-ants on trigger day seems unlikely to induce preovulation and may improve outcomes in the GnRH-ant protocol. This study aimed to systematically evaluate the effects of GnRH-ant cessation on trigger day on in vitro fertilisation outcomes following the GnRH-ant protocol.

Methods: We searched PubMed, Ovid/MEDLINE, Wanfang, VIP, CNKI and ClinicalTrials.gov databases. The last search was conducted on 10 December 2023 in English or Chinese, without time limitations on the collection of studies from the databases. The references in these articles were manually searched. Randomised controlled trials (RCTs) and cohort studies aimed at assessing the effects of GnRH-ant cessation on trigger day using the GnRH-ant protocol were included. The eligible studies included at least one of the main outcomes: number of oocytes retrieved, proportion of mature oocytes, implantation rate or clinical pregnancy rate.

Results: Three studies with 1449 cycles were included. Cessation of GnRH-ant on trigger day improved the proportion of mature oocytes (odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.09-1.45, I2 = 0%) but did not affect the number of oocytes retrieved (mean difference [MD] = 0.50, 95% CI = -0.07 to 1.07, I2 = 47%), implantation rate (OR = 0.95, 95% CI = 0.69-1.30, I2 = 0%), clinical pregnancy rate (OR = 1.06, 95% CI = 0.71-1.58, I2 = 0%), endometrial thickness (MD = -0.09, 95% CI = -0.27 to 0.10, I2 = 0%) or cycle cancellation rate (OR = 0.64, 95% CI = 0.15-2.74, I2 = 0%).

Conclusions: Cessation of GnRH-ant on trigger day of the GnRH-ant protocol is suggested because it could improve the proportion of mature oocytes. However, further RCTs are required.

Keywords: GnRH antagonist; clinical outcomes; embryological outcomes; oocyte maturation; ovarian stimulation; trigger day.

Plain language summary

The gonadotropin-releasing hormone antagonist (GnRH-ant) protocol is widely used to treat patients undergoing in vitro fertilisation. However, this protocol is associated with fewer oocytes retrieved, fewer mature oocytes and poorer endometrial receptivity than the depot gonadotropin-releasing hormone agonist protocol. The omission of GnRH-ants on trigger day seems unlikely to induce preovulation and may improve outcomes in the GnRH-ant protocol. This meta-analysis was performed to systematically evaluate the effects of cessation of GnRH-ants on trigger day in in vitro fertilisation outcomes following the GnRH-ant protocol. The cessation of GnRH-ants on trigger day improved the proportion of mature oocytes. It does not compromise the number of oocytes retrieved, implantation rate, clinical pregnancy rate or induction of preovulation. GnRH-ants should be omitted on trigger day of the GnRH-ant protocol during controlled ovarian hyperstimulation.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review

MeSH terms

  • Female
  • Fertilization in Vitro / methods
  • Gonadotropin-Releasing Hormone* / antagonists & inhibitors
  • Hormone Antagonists / administration & dosage
  • Hormone Antagonists / therapeutic use
  • Humans
  • Oocyte Retrieval / methods
  • Ovulation Induction* / methods
  • Pregnancy
  • Pregnancy Rate*

Substances

  • Gonadotropin-Releasing Hormone
  • Hormone Antagonists