Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Assisted Reproduction and Genetics

27-04-2024 | Dydrogesterone | Assisted Reproduction Technologies

Impact of dydrogesterone use in cycles with low progesterone levels on the day of frozen embryo transfer

Authors: Jose Metello, Claudia Tomás, Pedro Ferreira, Isabel Natário, Samuel Santos-Ribeiro

Published in: Journal of Assisted Reproduction and Genetics

Login to get access

Abstract

Purpose

This study aims to evaluate whether the clinical outcomes of cycles with frozen embryo transfer (FET) in hormonal replacement treatment supplemented with dydrogesterone (DYD) following detection of low circulating levels of progesterone (P4) were comparable to the results of cycles with otherwise normal serum P4 values.

Methods

Extended analyses of a retrospective cohort that included FET cycles performed between July 2019 and March 2022 after a cycle of artificial endometrial preparation using valerate-estradiol and micronized vaginal P4 (400 mg twice daily). Whenever the serum P4 value was considered low on the morning of the planned transfer, 10 mg of DYD three times a day was added as a supplement. Only single-embryo transfers of a blastocyst were considered. The primary endpoint was live birth rate.

Results

Five-hundred thirty-five FET cycles were analyzed, of which 136 (25.4%) underwent treatment with DYD. There were 337 pregnancies (63%), 207 live births (38.6%), and 130 miscarriages (38.5%). The P4 values could be modeled by a gamma distribution, with a mean of 14.5 ng/ml and a standard deviation of 1.95 ng/ml. The variables female age on the day of FET, ethnicity, and weight were associated with a variation in the serum P4 values.
There were no differences in the results between cycles with or without the indication for DYD supplementation.

Conclusions

Live birth rate did not vary significantly in females with low and normal serum P4 levels on the day of FET when DYD was used as rescue therapy.
Appendix
Available only for authorised users
Literature
1.
European IVF-Monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE); Wyns C, De Geyter C, Calhaz-Jorge C, Kupka MS, Motrenko T, Smeenk J, Bergh C, Tandler-Schneider A, Rugescu IA, Vidakovic S, Goossens V. ART in Europe, 2017: results generated from European registries by ESHRE. Hum Reprod Open. 2021(3):hoab026. https://​doi.​org/​10.​1093/​hropen/​hoab026
2.
Groenewoud ER, Cohlen BJ, Macklon NS. Programming the endometrium for deferred transfer of cryopreserved embryos: hormone replacement versus modified natural cycles. Fertil Steril. 2018;109:768–74.CrossRefPubMed
3.
Yarali H, Polat M, Mumusoglu S, Yarali I, Bozdag G. Preparation of endometrium for frozen embryo replacement cycles: a systematic review and meta-analysis. J Assist Reprod Genet. 2016;33:1287–304.CrossRefPubMedPubMedCentral
4.
Nahoul K, Dehennin L, Jondet M, Roger M. Profiles of plasma estrogens, progesterone and their metabolites after oral or vaginal administration of estradiol or progesterone. Maturitas. 1993;16(3):185–202.CrossRefPubMed
5.
Paulson RJ, Collins MG, Yankov VI. Progesterone pharmacokinetics and pharmacodynamics with 3 dosages and 2 regimens of an effervescent micronized progesterone vaginal insert. J Clin Endocrinol Metab. 2014;99(11):4241–9.CrossRefPubMed
6.
Jing S, Li XF, Zhang S, Gong F, Lu G, Lin G. Increased pregnancy complications following frozen-thawed embryo transfer during an artificial cycle. J Assist Reprod Genet. 2019;36:925–33.CrossRefPubMedPubMedCentral
7.
Ernstad EG, Wennerholm UB, Khatibi A, Petzold M, Bergh C. Neonatal and maternal outcome after frozen embryo transfer: increased risks in programmed cycles. Am J Obstet Gynecol. 2019;221(2):126.e1-126.e18.CrossRef
8.
Blesa D, Ruiz-Alonso M, Simón C. Clinical management of endometrial receptivity. Semin Reprod Med. 2014;32:410–3.CrossRefPubMed
9.
Gellersen B, Brosens JJ. Cyclic decidualization of the human endometrium in reproductive health and failure. Endocr Rev. 2014;35:851–905.CrossRefPubMed
10.
11.
Yovich JL, Conceicao JL, Stanger JD, Hinchliffe PM, Keane KN. Mid-luteal serum progesterone concentrations govern implantation rates for cryopreserved embryo transfers conducted under hormone replacement. Reprod Biomed Online. 2015;31(2):180–91.CrossRefPubMed
12.
Basnayake SK, Volovsky M, Rombauts L, Osianlis T, Vollenhoven B, Healey M. Progesterone concentrations and dosage with frozen embryo transfers — what’s best? Aust N Z J Obstet Gynaecol. 2018;58(5):533–8.CrossRefPubMed
13.
Labarta E, Mariani G, Holtmann N, Celada P, Remohí J, Bosch E. Low serum progesterone on the day of embryo transfer is associated with a diminished se pregnancy rate in oocyte donation cycles after artificial endometrial preparation: a prospFETive study. Human Reprod. 2017;32(12):2437–42.CrossRef
14.
Brady PC, Kaser DJ, Ginsburg ES, Ashby RK, Missmer SA, Correia KF, Racowsky C. Serum progesterone concentration on day of embryo transfer in donor oocyte cycles. J Assist Reprod Genet. 2014;31:569–75.CrossRefPubMedPubMedCentral
15.
Alsbjerg B, Thomsen L, Elbaek HO, Laursen R, Povlsen BB, Haahr T, Humaidan P. Progesterone levels on pregnancy test day after hormone replacement therapy-cryopreserved embryo transfer cycles and related reproductive outcomes. Reprod BioMed Online. 2018;37(5):641–7.CrossRefPubMed
16.
Cédrin-Durnerin I, Isnard T, Mahdjoub S, Sonigo C, Seroka A, Comtet M, Herbemont C, Sifer C, Grynberg M. Serum progesterone concentration and live birth rate in frozen–thawed embryo transfers with hormonally prepared endometrium. Reprod Biomed Online. 2019;38(3):472–80.CrossRefPubMed
17.
Stanczyk FZ, Hapgood JP, Winer S, Mishell DR Jr. Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions, and clinical effFETs. Endocr Rev. 2013;34:171–208.CrossRefPubMed
18.
Rižner TL, Brožič P, Doucette C, Turek-Etienne T, Muller-Vieira U, Sonneveld E, van der Burg B, Bocker C, Husen B. SelFETivity and potency of the retroprogesterone dydrogesterone in vitro. Steroids. 2011;76:607–15.CrossRefPubMed
19.
Griesinger G, Tournaye H, Macklon N, Petraglia F, Arck P, Blockeel C, van Amsterdam P, Pexman-Fieth C, Fauser BC. Dydrogesterone: pharmacological profile and mechanism of action as luteal phase support in assisted reproduction. Reprod Biomed Online. 2019;38(2):249–59.CrossRefPubMed
20.
Griesinger G, Blockeel C, Tournaye H. Oral dydrogesterone for luteal phase support in fresh in vitro fertilization cycles: a new standard? Fertil Steril. 2018;109(5):756–62.CrossRefPubMed
21.
Rashidi BH, Ghazizadeh M, Nejad EST, et al. Oral dydrogesterone for luteal support in frozen-thawed embryo transfer artificial cycles: a pilot randomized controlled trial. Asian Pac J Reprod. 2016;5:490–4.CrossRef
22.
Griesinger G, Blockeel C, Kahler E, Pexman-Fieth C, Olofsson JI, Driessen S, Tournaye H. 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;15(11):e0241044.CrossRefPubMedPubMedCentral
23.
Ott J, Egarter C, Aguilera A. Dydrogesterone after 60 years: a glance at the safety profile. Gynecol Endocrinol. 2021;20:1–9.
24.
Metello J, Tomás C, Ferreira P, Bravo I, Branquinho M, Santos-Ribeiro S. Impact of plasmatic progesterone on the day of frozen embryo transfer in hormone-induced cycles. Rev Bras Ginecol Obstet. 2021;43(8):608–61.CrossRefPubMedPubMedCentral
25.
Metello J, Tomas C, Ferreira P, Santos-Ribeiro S. The addition of dydrogesterone after frozen embryo transfer in hormonal substituted cycles with low progesterone levels. Rev Bras Ginecol Obstet. 2022Oct;44(10):930–7.CrossRefPubMedPubMedCentral
26.
27.
Labarta E, Mariani G, Paolelli S, Rodriguez-Varela C, Vidal C, Giles J, Bellver J, Cruz F, Marzal A, Celada P, Olmo I, Alama P, Remohi J, Bosch E. Impact of low serum progesterone levels on the day of embryo transfer on pregnancy outcome: a prospFETive cohort study in artificial cycles with vaginal progesterone. Human Reprod. 2021;36(3):683–92.CrossRef
28.
Gaggiotti-Marre S, Martinez F, Coll L, Garcia S, Álvarez M, Parriego M, Barri PN, Polyzos N, Coroleu B. 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(5):439–42.CrossRefPubMed
29.
González-Foruria I, Gaggiotti-Marre S, Álvarez M, Martínez F, García S, Rodríguez I, Coroleu B, Polyzos N. Factors associated with serum progesterone concentrations the day before cryopreserved embryo transfer in artificial cycles. RBMO. 2020;40(6):797–804.
30.
Levy T, Yairi Y, Bar-Hava I, Shalev J, Orvieto R, Ben-Rafael Z. Pharmacokinetics of the progesterone-containing vaginal tablet and its use in assisted reproduction. Steroids Progestins Progesterone Recept Modulators Progesterone Antagonists. 2000;65:645–9.
31.
Labarta E, Mariani G, Rodríguez-Varela C, Bosch E. Individualized luteal phase support normalizes live birth rate in female with low progesterone levels on the day of embryo transfer in artificial endometrial preparation cycles. Fertil Steril. 2022;117(1):96–103.CrossRefPubMed
32.
Álvarez M, Gaggiotti-Marre S, Martínez F, Coll L, García S, González-Foruria I, Rodríguez I, Parriego M, Polyzos N, Coroleu B. Individualised luteal phase support in artificially prepared frozen embryo transfer cycles based on serum progesterone levels: a prospFETive cohort study. Human Reprod. 2021;36(6):1552–60.CrossRef
33.
Neumann K, Masuch A, Vonthein R, Depenbusch M, Schultze-Mosgau A, Eggersmann T, Griesinger G. Dydrogesterone and 20α-dihydrodydrogesterone plasma levels on day of embryo transfer and clinical outcome in an anovulatory programmed frozen-thawed embryo transfer cycle: a prospFETive cohort study. Hum Reprod. 2022;37(6):1183–93.CrossRefPubMed
34.
Vuong L, Pham T, Le K, Ly T, Ho Le, Nguyen D, Ho V, Dang V, Phung T, Norman R, Mol B, Ho T. Micronized progesterone plus dydrogesterone versus micronized progesterone alone for luteal phase support in frozen-thawed cycles (MIDRONE): a prospFETive cohort study. Human Reprod. 2021;36(7):1821–31.CrossRef
35.
Mackens S, Pais F, Drakopoulos P, Amghizar S, Roelens C, Van Landuyt L, Tournaye H, De Vos M, Blockeel C. Individualized luteal phase support using additional oral dydrogesterone in artificially prepared frozen embryo transfer cycles: is it beneficial? Reprod Biomed Online. 2023Jun;46(6):939–45.CrossRefPubMed
36.
González-Foruria I, García S, Álvarez M, Racca A, Hernández M, Polyzos NP, Coroleu B. Elevated serum progesterone levels before frozen embryo transfer do not negatively impact reproductive outcomes: a large retrospective cohort study. Fertil Steril. 2023;120(3 Pt 2):597–604.CrossRefPubMed
37.
Queisser-Luft A. Dydrogesterone use during pregnancy: overview of birth defects reported since 1977. Early Hum Dev. 2009;85(6):375–7.CrossRefPubMed
38.
39.
Tournaye H, Sukhikh GT, Kahler E, Griesinger G. 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(5):1019–27.CrossRefPubMedPubMedCentral
40.
Henry A, Santulli P, Bourdon M, Treluyer JM, Chouchana L. O-150 Birth defects reporting and the use of oral dydrogesterone in assisted reproductive technology: a global pharmacovigilance study. Human Reprod. 2023;38(Supplement_1):dead093.177.CrossRef
Metadata
Title
Impact of dydrogesterone use in cycles with low progesterone levels on the day of frozen embryo transfer
Authors
Jose Metello
Claudia Tomás
Pedro Ferreira
Isabel Natário
Samuel Santos-Ribeiro
Publication date
27-04-2024
Publisher
Springer US
Published in
Journal of Assisted Reproduction and Genetics
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-024-03118-5