Abstract

Background and Aims: Human chorionic gonadotropin (hCG) has been proposed as an intrauterine intervention around embryo transfer period due to its potential to enhance endometrium receptivity and implantation. Existing randomised controlled trials (RCTs) showed inconsistent findings and multiple meta-analyses on this topic showed high unexplained heterogeneity. Individual participant data meta-analysis (IPDMA) is considered the “gold standard” synthesis method due to its ability to standardise and harmonise the data reporting and analysis. In this IPDMA, we aimed to investigate the effectiveness and safety of intrauterine hCG before embryo transfer. Method: We searched Cochrane Gynaecology and Fertility Group Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase and PsycINFO without language restrictions up to November 2022. We included RCTs comparing intrauterine administration of hCG before embryo transfer versus placebo or no intervention in women undergoing IVF. The outcomes were live birth, clinical pregnancy and other fertility outcomes. We invited trial authors to share the de-identified IPD and established the IHABT collaboration. We performed a one-stage IPDMA as the main analysis. Results: Eight RCTs including IPD of 2338 participants were included. These RCTs were conducted in 6 different countries, with a dosage of intrauterine hCG between 500 IU and 1000 IU. In women undergoing IVF, compared to the control group, intrauterine administration of hCG before embryo transfer does not improve live birth rates (7 RCTs, 2245 participants, odds ratio [OR] 0.98, 95% confidence interval [CI] 0.82–1.17) or clinical pregnancy rates (8 RCTs, 2338 participants, OR 1.13, 95%CI 0.89–1.43). There was insufficient evidence of a difference between the two groups on any of the other fertility outcomes. Conclusion: Intrauterine administration of hCG does not improve live birth or clinical pregnancy rates in women undergoing IVF. Therefore, it should not be offered as an IVF add-on in clinical practice.

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