Abstract
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?
Design
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.
Results
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).
Conclusions
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.
Keywords
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References
- Individualised luteal phase support in artificially prepared frozen embryo transfer cycles based on serum progesterone levels: a prospective cohort study.Hum. Reprod. 2021; 36: 1552-1560
- Comparable outcomes using oral dydrogesterone vs. micronized vaginal progesterone in frozen embryo transfer: a retrospective cohort study.Reprod. Sci. 2021; 28: 1874-1881
- Serum progesterone concentrations are reduced in obese women on the day of embryo transfer.Reprod. Biomed. Online. 2022; 45: 679-687
- Serum progesterone concentration and live birth rate in frozen-thawed embryo transfer with hormonally prepared endometrium.Reprod. Biomed. Online. 2019; 38: 472-480
- Low progesterone levels on the day before natural cycle frozen embryo transfer are negatively associated with live birth rates.Hum. Reprod. 2020; 35: 1623-1629
- Low serum progesterone the day prior to frozen embryo transfer of euploid embryos is associated with significant reduction in live birth rates.Gynecol. Endocrinol. 2019; 35: 439-442
- Culture and transfer of human blastocysts.Curr. Opin. Obstet. Gynecol. 1999; 11: 307-311
- Factors associated with serum progesterone concentrations the day before cryopreserved embryo transfer in artificial cycles.Reprod. Biomed. Online. 2020; 40: 797-804
- Dydrogesterone as an oral alternative to vaginal progesterone for IVF luteal phase support: a systematic review and individual participant data meta-analysis.PloS One. 2020; 15e0241044
- Oral dydrogesterone versus intravaginal micronized progesterone gel for luteal phase support in IVF: a randomized controlled trial.Hum. Reprod. 2018; 33: 2212-2221
- Dydrogesterone: pharmacological profile and mechanism of action as luteal phase support in assisted reproduction.Reprod. Biomed. Online. 2019; 38: 249-259
- A critical appraisal of safety data on dydrogesterone for the support of early pregnancy: a scoping review and meta-analysis.Reprod. Biomed. Online. 2022; 45: 365-373
- Terminology for pregnancy loss prior to viability: a consensus statement from the ESHRE early pregnancy special interest group.Hum. Reprod. 2015; 30: 495-498
- Low serum progesterone on the day of embryo transfer is associated with a diminished ongoing pregnancy rate in oocyte donation cycles after artificial endometrial preparation: a prospective study.Hum. Reprod. 2017; 32: 2437-2442
- Impact of low serum progesterone levels on the day of embryo transfer on pregnancy outcome: a prospective cohort study in artificial cycles with vaginal progesterone.Hum. Reprod. 2021; 36: 683-692
- Individualized luteal phase support normalizes live birth rate in women with low progesterone levels on the day of embryo transfer in artificial endometrial preparation cycles.Fertil. Steril. 2022; 117: 96-103
- Analysis of serum and endometrial progesterone in determining endometrial receptivity.Hum. Reprod. 2021; 36: 2861-2870
- Clinical factors associated with low serum progesterone levels on the day of frozen blastocyst transfer in hormonal replacement therapy cycles.Hum. Reprod. 2022; 37: 2570-2577
- Serum luteal phase progesterone in women undergoing frozen embryo transfer in assisted conception: a systematic review and meta-analysis.Fertil. Steril. 2021; 116: 1534-1556
- Dydrogesterone and 20α-dihydrodydrogesterone plasma levels on day of embryo transfer and clinical outcome in an anovulatory programmed frozen-thawed embryo transfer cycle: a prospective cohort study.Hum. Reprod. 2022; 37: 1183-1193
- Oral, vaginal or intramuscular progesterone in programmed frozen embryo transfer cycles: a pilot RCT.Reprod. Biomed. Online. 2022; 45: 1145-1151
- Secretory products of the corpus luteum and preeclampsia.Hum. Reprod. Update. 2021; 27: 651-672
- Dydrogesterone use during pregnancy: overview of birth defects reported since 1977.Early Hum. Dev. 2009; 85: 375-377
- Oral dydrogesterone for luteal support in frozen-thawed embryo transfer artificial cycles: a pilot randomized controlled trial.Asian Pac. J. Reprod. 2016; 5: 490-494
- Impact of different endometrial preparation protocols before frozen embryo transfer on pregnancy outcome: a review.Fertil. Steril. 2022; 118: 820-827
- Artificially prepared vitrified-warmed embryo transfer cycles are associated with an increased risk of pre-eclampsia.Reprod. Biomed. Online. 2022; 44: 915-922
- A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization.Hum. Reprod. 2017; 32: 1019-1027
- Impact of endometrial preparation on early pregnancy loss and live birth rate after frozen embryo transfer: a large multicenter cohort study (14 421 frozen cycles).Hum. Reprod. Open. 2022; 2022: hoac007
- Micronized progesterone plus dydrogesterone versus micronized progesterone alone for luteal phase support in frozen-thawed cycles (MIDRONE): a prospective cohort study.Hum. Reprod. 2021; 36: 1821-1831
- Progesterone supplementation in natural cycles improves live birth rates after embryo transfer of frozen-thawed embryos – a randomized controlled trial.Hum. Reprod. 2022; 37: 2366-2374
- Comparison of four protocols for luteal phase support in frozen-thawed embryo transfer cycles: a randomized clinical trial.Arch. Gynecol. Obstet. 2017; 295: 239-246
- The International Glossary on Infertility and Fertility Care, 2017.Hum. Reprod. 2017; 32: 1786-1801
Biography
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.
Article info
Publication history
Published online: February 23, 2023
Accepted:
February 17,
2023
Received in revised form:
February 15,
2023
Received:
November 29,
2022
Declaration: The authors report no financial or commercial conflicts of interest.Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
