HCG Trigger of GnRH Agonist-Induced Functional Ovarian Cysts Does Not Decrease Clinical Pregnancy Rate in GnRHa Pretreated Frozen Cycles: Evidence From a Retrospective Cohort Study

Background: GnRH agonist (GnRHa) pretreatment before the frozen-thawed embryo transfer (FET) was increasingly utilized. However, the incidence of GnRHa-induced functional ovarian cysts (FC) was inevitable. The feasibility and efficacy of HCG triggering GnRHa-induced FC are unknown.

Objective: The aim of the study was to investigate the effect of HCG triggering GnRHa-induced FC on FET outcomes.

Methods: A total of 657 HRT-FET cycles with GnRHa pretreatment were retrospectively analyzed. Patients were divided into the FC group and the no functional cysts (NC) group according to whether the patient developed FC (follicular diameter of ≥7 mm and E₂ of ≥100 pg/ml). Risk factors associated with the incidence of GnRHa-induced FC were determined by multivariate regression analysis. Pregnancy outcomes were compared between the FC group and the NC group. Propensity score matching (PSM) was performed to reduce the impact of confounding factors. Three multivariate regression models were performed to assess the association between HCG triggering GnRHa-induced FC and clinical pregnancy. Interactive analysis and subgroup analysis were also analyzed.

Results: The incidence rate of GnRHa-induced FC was 9.74%. Older age (aOR 1.10, 95% CI 1.05-1.15, p-value < 0.001) and lower BMI (aOR 0.81, 95% CI 0.71-0.93, p-value=0.002) are risk factors for GnRHa-induced FC. The implantation rate, clinical pregnancy rate (CPR), and miscarriage rate were not significantly different between the FC group and the NC group before or after PSM (p-value > 0.05). Multivariate logistic models showed that HCG triggering GnRHa-induced FC does not decrease CPR in the general population (p-value > 0.05). The effect of HCG triggering GnRHa-induced FC on clinical pregnancy is interactive with age (p-value for interaction: 0.003); HCG trigger is associated with significantly higher CPR than HRT-FET cycles without FC in patients ≥35 years (aOR 4.40, 95% CI 1.57-12.3, p-value = 0.005).

Conclusions: HCG triggering GnRHa-induced FC does not decrease the chance of clinical pregnancy in HRT-FET cycles pretreated with GnRHa.