To investigate the efficacy of oral dydrogesterone for luteal phase support (LPS) in modified natural cycle frozen-thawed embryo transfers (mNC-FET) compared to micronized vaginal progesterone (MVP) gel.

This was a randomized, single-center, parallel controlled trial conducted at an ART and Reproductive Genetics Centre within a private hospital between January and August 2019. A total of 134 women, aged below 38, were assigned randomly to receive oral dydrogesterone (n=67) or MVP (n=67) for LPS in mNC-FET. The primary outcome was ongoing pregnancy rate (OPR) and secondary outcomes were clinical pregnancy and miscarriage rates, patients’ satisfaction and tolerability of oral and vaginal progesterone. A questionnaire was developed to compare patient satisfaction and side effect profiles.

There was no significant difference in demographic features such as female age, body mass index, AMH levels and fresh cycle characteristics between two groups (p>0.05). When mNC-FET outcomes were compared, OPR was 68.7 % in MVP gel group and 71.6 % in the dydrogesterone group respectively percentage difference, -2.99; 95 % CI: -17.96, 13.10) Biochemical and clinical pregnancy rates and biochemical and clinical miscarriage rates were also similar between two groups. A significantly higher patient tolerability score was present in the dydrogesterone arm (4.09 ± 0.96 vs 3.36 ± 1.23, p=0.001).

Our results suggest that oral dydrogesterone provides similar ongoing pregnancy rates compared to MVP gel as a LPS in mNC FET. Since dydrogesterone is an effective and easy-to-use option with fewer intolerable side effects including vaginal irritation, vaginal discharge, and preventing sexual intercourse, it can be used as LPS in mNC FET.