Individualized luteal phase support using additional oral dydrogesterone in artificially prepared frozen embryo transfer cycles: is it beneficial?

Published:February 23, 2023DOI:


      Research question

      Does additional supplementation with oral dydrogesterone improve reproductive outcomes in patients with low serum progesterone concentrations on the day of frozen embryo transfer (FET) after artificial (HRT) endometrial preparation?


      Retrospective, single-centre cohort study including 694 unique patients performing single blastocyst transfer in an HRT cycle. For luteal phase support, intravaginal micronized vaginal progesterone (MVP, 400 mg twice daily) was administered. Serum progesterone concentrations were assessed prior to FET and outcomes were compared among patients with normal serum progesterone (≥8.8 ng/ml) continuing the routine protocol and patients with low serum progesterone (<8.8 ng/ml) who received additional oral dydrogesterone supplementation (10 mg three times daily) from the day after FET onwards. Primary outcome was live birth rate (LBR), with a multivariate regression model correcting for relevant confounders.


      Normal serum progesterone concentrations were observed in 547/694 (78.8%) of patients who continued only MVP as planned, whereas low (<8.8 ng/ml) serum progesterone concentrations were detected in 147/694 (21.2%) patients who received additional oral dydrogesterone supplementation on top of MVP from the day after FET onwards. LBR was comparable between both groups: 37.8% for MVP-only versus 38.8% for MVP+OD (P = 0.84). The multivariate logistic regression model indicated that LBR was not significantly associated with the investigated approaches (adjusted odds ratio 1.01, 95% confidence interval 0.69–1.47, P = 0.97).


      The current findings suggest that additional oral dydrogesterone supplementation in patients with low serum progesterone concentrations at the moment of transfer could have the potential to rescue reproductive outcomes in HRT–FET cycles. This field of research, however, remains hampered by the absence of randomized controlled trials.


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      Shari Mackens, MD, PhD, is a gynaecologist and medical director at the Centre for Reproductive Medicine (Brussels IVF) at the UZ Brussel, Belgium. She is a clinical professor at the Vrije Universiteit Brussel (VUB) with a specific interest in translational research focusing on the role of the endometrium in ART.
      Key message
      Additional supplementation with oral dydrogesterone in patients with low serum progesterone concentrations at the moment of transfer showed comparable reproductive outcomes to those with normal serum progesterone. This could have the potential to rescue outcomes in low progesterone HRT–FET cycles, but this field remains hampered by the absence of randomized controlled trials.