The Effect of Intramuscular Human Chorionic Gonadotropin on Endometrial Preparation in Frozen-Thawed Embryo Transfer: A Randomized Clinical Trial.

Abstract

Objective: Experimental evidence suggests that the human endometrium expresses receptors for human chorionic gonadotropin (hCG), and activation of these receptors may enhance embryo implantation. Numerous studies have explored the effects of intrauterine hCG injection on embryo transfer (ET) outcomes; however, the impact of systemic hCG administration has been investigated in comparatively fewer studies. This study aimed to evaluate the effects of intramuscular administration of 5000 IU hCG on the outcomes of frozen-thawed ET in hormonal replacement cycles using a gonadotropin-releasing hormone (GnRH)-agonist protocol.

Materials and methods: This randomized controlled trial (RCT, registered April 22, 2021) was conducted at the ROYAN Institute, a tertiary referral center in Tehran, Iran, between July 2020 and August 2022. A total of 200 infertile women undergoing cleavage-stage frozen-thawed ET were enrolled. Inclusion criteria were age <40 years, body mass index <30 kg/m², and the availability of at least three frozen embryos of good or excellent quality. Participants were randomly assigned to either an intervention group receiving intramuscular hCG (5000 IU administered three times: 72 hours before ET, on the day of ET, and 72 hours after ET) or a control group without hCG.

Results: A total of 188 participants completed the trial (93 in the intervention group and 95 in the control group). No significant differences were observed in implantation rate (P=0.903), chemical pregnancy (P=0.912), clinical pregnancy (P=0.999), pregnancy complications (P=0.480), preterm labor (P=0.853), or live birth rate (P=0.233). However, the miscarriage rate was lower in the intervention group. This reduction approached significance per cycle (P=0.059) and reached statistical significance per pregnancy (P=0.011).

Conclusion: Intramuscular hCG administration in hormonal replacement cycles with a GnRH-agonist does not significantly affect overall frozen-thawed ET outcomes at the cleavage stage but may be associated with a lower miscarriage rate among those who achieve pregnancy (registration number: NCT04855383).