Background: Currently, frozen embryo transfers (FET) account for 41% of all embryo transfer cycles. Vaginal progesterone preparations have become the leading choice for luteal phase support due to their convenient application; however, using only vaginal progesterone during FET cycles results in a lower ongoing pregnancy rate.
Objective: This study aimed to investigate whether replacing intramuscular (IM) progesterone with oral dydrogesterone in FET cycles affects pregnancy outcomes or not.
Materials and Methods: In this cross-sectional study, pregnancy outcomes were analyzed in women who underwent cleavage stage FET during an endometrial preparation cycle using hormone replacement therapy at Yazd Reproductive Sciences Institute, Yazd, Iran, between April 2023 and November 2023. The study examined 2 groups based on a luteal phase support regimen: the dydrogesterone group, which received vaginal progesterone and oral dydrogesterone, and the IM progesterone group, which received vaginal progesterone and IM progesterone. Data were extracted from patient files to compare outcomes between the 2 groups.
Results: A total of 960 cycles meeting the inclusion criteria were analyzed, with 292 women in the dydrogesterone group and 668 women in the IM progesterone group, and pregnancy outcomes were compared between the 2 groups. The chemical pregnancy rates (28.4% vs. 29.9%, p = 0.636), clinical pregnancy rates (25.3% vs. 26.9%, p = 0.604), and ongoing pregnancy rates (21.9% vs. 23.8%, p = 0.525) were lower and miscarriage rates (14.7% vs. 11.7%, p = 0.210) were higher in dydrogesterone group compared to IM progesterone group, although this difference was not statistically significant.
Conclusion: Based on the ease of use and similar pregnancy outcomes of oral dydrogesterone, it can potentially replace the daily injections of IM progesterone.
Keywords: Assisted reproductive technology, Luteal phase, Progesterone, Embryo transfer.
[1] de Mouzon J, Chambers GM, Zegers-Hochschild F, Mansour R, Ishihara O, Banker M, et al. International Committee for Monitoring Assisted Reproductive Technologies world report: Assisted reproductive technology 2012. Hum Reprod 2020; 35: 1900–1913.
[2] Duijkers I, Klingmann I, Prinz R, Wargenau M, Hrafnsdottir S, Magnusdottir TB, et al. Effect on endometrial histology and pharmacokinetics of different dose regimens of progesterone vaginal pessaries, in comparison with progesterone vaginal gel and placebo. Hum Reprod 2018; 33: 2131–2140.
[3] Dashti S, Eftekhar M. Luteal-phase support in assisted reproductive technology: An ongoing challenge. Int J Reprod BioMed 2021; 19: 761–772.
[4] Rao KA, Rao VA, Devi R. Principles and practice of assisted reproductive technology: Three volume set. 3rd Ed. New Delhi: Jaypee Brothers Medical Publishers; 2023.
[5] Coombes Z, Plant K, Freire C, Basit AW, Butler P, Conlan RS, et al. Progesterone metabolism by human and rat hepatic and intestinal tissue. Pharmaceutics 2021; 13: 1707.
[6] Piette PC. The pharmacodynamics and safety of progesterone. Best Pract Res Clin Obstet Gynaecol 2020; 69: 13–29.
[7] Di Renzo GC, Tosto V, Tsibizova V. Progesterone: History, facts, and artifacts. Best Pract Res Clin Obstet Gynaecol 2020; 69: 2–12.
[8] Griesinger G, Tournaye H, Macklon N, Petraglia F, Arck P, Blockeel C, et al. Dydrogesterone: Pharmacological profile and mechanism of action as luteal phase support in assisted reproduction. Reprod Biomed Online 2019; 38: 249–259.
[9] Jalaliani S, Davar R, Akbarzadeh F, Emami F, Eftekhar M. Addition of intramuscular to vaginal progesterone for luteal phase support in fresh embryo transfer cycles: A cross-sectional study. Int J Reprod BioMed 2022; 20: 745–752.
[10] Mohammed A, Woad KJ, Mann GE, Craigon J, Raine-Fenning N, Robinson RS. Evaluation of progestogen supplementation for luteal phase support in fresh in vitro fertilization cycles. Fertil Steril 2019; 112: 491–502.
[11] Pabuçcu EG, Pabuçcu R, Evliyaoglu Ozdegirmenci O, Bostanci Durmus A, Keskin M. Combined progesterone (IM+V) versus vaginal progesterone for luteal support in cleavage-stage embryo transfer cycles of good prognosis patients. Gynecol Endocrinol 2016; 32: 366–369.
[12] Devine K, Richter KS, Widra EA, McKeeby JL. Vitrified blastocyst transfer cycles with the use of only vaginal progesterone replacement with endometrin have inferior ongoing pregnancy rates: Results from the planned interim analysis of a three-arm randomized controlled noninferiority trial. Fertil Steril 2018; 109: 266–275.
[13] Devine K, Richter KS, Jahandideh S, Widra EA, McKeeby JL. Intramuscular progesterone optimizes live birth from programmed frozen embryo transfer: A randomized clinical trial. Fertil Steril 2021; 116: 633–643.
[14] Homayoon N, Arabian S, Mangoli E, Bayati F, Eftekhar M. Effect of sequential cleavage and blastocyst embryo transfer compared to single cleavage stage embryo transfer on assisted reproductive technology outcome: An RCT. Int J Reprod BioMed 2024; 22: 433–440.
[15] Child T, Leonard SA, Evans JS, Lass A. Systematic review of the clinical efficacy of vaginal progesterone for luteal phase support in assisted reproductive technology cycles. Reprod Biomed Online 2018; 36: 630–645.
[16] Simon V, Robin G, Keller L, Ternynck C, Jonard S, Robin C, et al. Systematic use of long-acting intramuscular progesterone in addition to oral dydrogesterone as luteal phase support for single fresh blastocyst transfer: A pilot study. Front Endocrinol 2022; 13: 1039579.
[17] Ikechebelu JI, Dim CC, Eleje GU, Joe-Ikechebelu N, Okpala BC, Okam PC. A randomised control trial on oral dydrogesterone versus micronized vaginal progesterone pessary for luteal phase support in in vitro fertilization cycles. J Med Life 2023; 16: 62.
[18] Vidal A, Dhakal C, Werth N, Weiss JM, Lehnick D, Kohl Schwartz AS. Supplementary dydrogesterone is beneficial as luteal phase support in artificial frozen-thawed embryo transfer cycles compared to micronized progesterone alone. Front Endocrinol 2023; 14: 1128564.
[19] Salehpour S, Tamimi M, Saharkhiz N. Comparison of oral dydrogesterone with suppository vaginal progesterone for luteal-phase support in in vitro fertilization (IVF): A randomized clinical trial. Iran J Reprod Med 2013; 11: 913–918.
[20] Simon JA, Robinson DE, Andrews MC, Hildebrand III JR, Rocci Jr ML, Blake RE, et al. The absorption of oral micronized progesterone: The effect of food, dose proportionality, and comparison with intramuscular progesterone. Fertil Steril 1993; 60: 26–33.
[21] 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: 1019–1027.
[22] Yang D-Z, Griesinger G, Wang W, Gong F, Liang X, Zhang H, et al. A phase III randomized controlled trial of oral dydrogesterone versus intravaginal progesterone gel for luteal phase support in in vitro fertilization (Lotus II): Results from the Chinese mainland subpopulation. Gynecol Endocrinol 2020; 36: 175–183.
[23] Bachar G, Haskia C, Fainaru O. Comparable outcomes using oral rydrogesterone versus intramuscular progesterone in frozen embryo transfer: A retrospective cohort study. 2023. (Research Square)
[24] Xu H, Zhang X-Q, Zhu X-L, Weng H-N, Xu L-Q, Huang L, et al. Comparison of vaginal progesterone gel combined with oral dydrogesterone versus intramuscular progesterone for luteal support in hormone replacement therapy-frozen embryo transfer cycle. J Gynecol Obstet Hum Reprod 2021; 50: 102110.
留言 (0)