Intrauterine hCG flush prior to frozen embryo transfer and reproductive outcomes: a prospective cohort study

Intrauterine human chorionic gonadotropin (hCG) administration prior to embryo transfer has been explored as a method to improve embryo–endometrial synchrony, but clinical evidence remains inconsistent due to variations in dosage, timing, embryo stage, and cycle type. This study evaluated the clinical impact of a pre-transfer intrauterine hCG flush performed 48–72 h before frozen embryo transfer (FET) in hormonally prepared cycles. This prospective non-randomized cohort study included 200 women with primary infertility undergoing FET with at least one good-quality blastocyst. Participants were assigned either to the hCG flush group (n = 100) or a control group (n = 100). In the control group, 20 participants discontinued before FET for non-medical reasons, and one was lost to follow-up, leaving 79 for analysis. Outcomes included implantation rate, clinical pregnancy rate, live birth rate, miscarriage rate, multiple pregnancy rate, and procedure-related adverse events. Logistic regression generated odds ratios (ORs) with 95% confidence intervals (CIs). A p-value < 0.05 was considered significant. Baseline demographics and cycle parameters were comparable between groups (hCG flush vs. control group, respectively). Implantation rate did not differ significantly between the hCG flush and control groups (58.2% vs. 54.6%, respectively; p = 0.39). Clinical pregnancy rates were similarly comparable between the groups (73.0% vs. 79.7%, respectively; p = 0.88). The live birth rate was higher in the hCG group (70.0%) than the control group (62.0%), although not statistically significant (OR 1.51; 95% CI 0.76–2.99; p = 0.21). Multiple pregnancy rates were also comparable between hCG group and control group (15.0% and 24.0%, respectively, p = 0.18). However, a reduction in miscarriage rate was observed in the hCG group (3.0%) on comparing with the control group (16.4%) (p < 0.001). Pre-transfer intrauterine hCG administration 48–72 h before blastocyst-stage FET did not significantly influence implantation, clinical pregnancy, or live birth rates but was associated with miscarriage rate. These findings from this preliminary study suggest a potential biological effect of localized hCG exposure on early gestational maintenance and warrant confirmation through larger, multicentre randomized controlled studies.