Dydrogesterone versus micronized vaginal progesterone for luteal phase support in artificial cycle frozen embryo...

The introduction of vitrification has markedly increased frozen embryo transfer (FET) cycles, driving efforts to optimize FET protocols. In artificial-cycle FET (AC-FET), micronized vaginal progesterone (MVP) is widely used for luteal phase support (LPS), though local side effects are common. Dydrogesterone (DYD), an oral selective progesterone receptor agonist, offers patient-friendly administration, but its efficacy in AC-FET remains uncertain.

In this single-centre trial (October 2021 - September 2023), women <41 years with normal BMI undergoing single blastocyst AC-FET were randomized (1:1) to DYD 10 mg three times daily (Group A) or MVP 200 mg twice daily (Group B). All received estradiol valerate for endometrial preparation. The primary outcome was ongoing pregnancy rate (OPR) at 12 weeks.

Of 167 screened, 150 were randomized (Group A: 73; Group B: 77). Baseline and cycle characteristics were comparable. Four women switched LPS post-randomization; both per-protocol and intention-to-treat analyses were performed. OPR was 31·5% with DYD vs 45·2% with MVP (p=0·09; difference -13%, 95% CI -38 to 12). ITT analysis was consistent (31·1% vs 44·7%).

Although not statistically significant, the results of this pilot prospective randomized controlled trial may have clinical implications and highlight the need for larger studies investigating the ideal dose and administration route of different LPS medications in AC-FET cycles. Given the differences in pharmacological profiles, varying dosages and more frequent administration of DYD may also warrant exploration.