Progesterone vaginal gel or combined medication for luteal-phase support of frozen-thawed embryo transfer cycles: single-centre, Chinese, randomized, open-label, pilot study.

Abstract

Objectives: This study aimed to explore potential differences in efficacy between vaginal progesterone (VPG) and VPG+oral progesterone (OPG) for luteal-phase support in hormone replacement therapy-frozen embryo transfer (HRT-FET) cycles.

Design: A single-centre, open-label, randomized controlled, phase IV pilot study.

Participants/materials, setting, methods: Infertile women aged 20-38 years undergoing HRT-FET cycles were included. Participants were randomized to VPG (n=86) or VPG+OPG (n=86). The primary efficacy endpoint was ongoing pregnancy at 10-12 weeks. Secondary efficacy endpoints included β-human chorionic gonadotropin (β-hCG) positivity, implantation rate, and clinical-pregnancy rate. Safety analyses included adverse events (AE) and vital signs.

Results: A higher ongoing pregnancy rate was observed with VPG+OPG (29.1%) versus VPG (18.8%); treatment difference 8.4% (90% confidence interval [CI] -2.2%, 19.0%). Numerical differences also favoured VPG+OPG over VPG for β-hCG positivity (0.9% [90% CI -10.8%, 12.7%]), implantation (10.4% [90% CI 0.5%, 21.3%]), and clinical pregnancy (10.1% [90% CI -0.8%, 21.1%]). Incidences of treatment-emergent AEs were comparable.

Limitations: The single-centre study was limited by a relatively small sample size which could have impacted the reported outcomes. Another limitation was the open-label design, which might have increased the risk of bias for subjective endpoints, such as AE reporting.

Conclusions: A higher ongoing pregnancy rate was observed with VPG+OPG vs VPG; however, a statistical conclusion cannot be reached considering the small sample size. These data suggest that a minimum daily progesterone dose, such as VPG 90 mg+OPG 20 mg reported here, or VPG 180 mg reported in other studies, may be required for successful outcomes following HRT-FET cycles.