Retrospective cohort study and meta-analysis of individualized luteal phase support with additional oral dydrogesterone in artificially prepared frozen embryo transfer cycles.

PURPOSE: Does additional oral dydrogesterone (DYD) in luteal phase support enhance reproductive outcomes, in patients with low serum progesterone (P4) concentrations undergoing frozen-thawed embryo transfer (FET) with hormonal replacement therapy (HRT)? METHODS: This retrospective study analyzed 550 HRT cycles performed for FET between November 2020 and September 2023. Luteal phase support included micronized vaginal progesterone 400 mg twice daily. After two full day of progesterone administration, serum P4 levels were assessed: group 1 cycles with sufficient P4 levels continuing the routine protocol were compared to group 2 cycles with low serum P4 (< 11 ng/mL) who received additional oral DYD supplementation (10 mg three times daily). Primary outcome was live birth rate (LBR), with a multivariate regression analysis. A systematic review and meta-analysis of the current literature on DYD supplementation during HRT was also performed (PROSPERO registration number: CRD420250524058). RESULTS: Insufficient P4 levels were observed in 28.9% (159/550) of the studied cycles. LBR was comparable in both groups (24.16% [94/391] in group 1 and 27.22% [43/159] in group 2) and was not associated with the luteal support strategy (aOR 1.01, 95% CI [0.65-1.58], p = 0.96). In the meta-analysis, the ongoing pregnancy rate was similar in both groups (aOR 1.14, 95% CI [0.91-1.42]). CONCLUSIONS: Individualized luteal phase support with DYD supplementation in patients with low luteal serum P4 levels during an HRT cycle for FET achieves LBR comparable to those observed in patients with adequate serum P4 levels, both in this cohort study and in a complementary meta-analysis.