Abstract
Background: Few studies have been published on the role of support of luteal phase of natural frozen embryo transfers (FET).
Methods: This was a retrospective study comparing 893 frozen warmed frozen embryo transfer (FET) natural cycle protocol using 364 dydrogesterone (DYD) and human chorionic gonadotrophin (hCG) cycles for support of the luteal phase versus 529 cycles of artificial protocol over 6 years (2014 to 2019) in a single in vitro fertilization centre (IVF).
Results: There was no difference in live birth rate amongst the protocols of luteal support in the natural cycle FET. DYD was given with hCG as luteal support. Mean age of natural cycle FET protocol was higher than the artificial cycle group (36.5 versus 35.2 years) but the successful outcomes were similar. Overall successful outcomes in total, day 3 and day 5 transfers were not significant except for natural cycle FET multiple pregnancy results being significantly higher in day 5 FETs. Successful implantation rate (baby per embryo) and multiple pregnancy rate per embryo were significantly higher in the natural FET protocol for day 5 transfers, likely due to significantly more embryos being transferred and the presence of embryos with better implantation potential in the day 5 natural cycle FET. The older mean age at transfer at day 5 did not seem to affect multiple pregnancy rates.
Conclusion: DYD with hCG support of natural cycle FET yielded similar success compared to artificial cycles. There was significantly higher implantation rate with day 5 natural cycle FET despite an older age cohort.
References
Queisser-Luft. Dydrogesterone use during pregnancy: overview of birth defects reported since 1977. Early Hum Dev. 2009;85(6):375-377.
Mirza FG, Patki A, Pexman-Fieth C. Dydrogesterone use in early pregnancy. Gynecol Endocrinol. 2016;32(2):97-106.
Schindler AE, Campagnoli C, Druckmann R, et al. Classification and pharmacology of progestins. Maturitas 2008;61(1-2):171–180.
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. Human Reprod. 2017;32(10):2152.
Griesinger G, Blockeel C, Sukhikh GT, et al. Oral dydrogesterone versus intravaginal micronized progesterone gel for luteal phase support in IVF. Hum Reprod. 2018;33(12):2212-2221.
Rashidi BH, Ghazizadeh M, Tehrani Nejad ES, Bagheri M, Gorginzadeh M. Oral dydrogesterone for luteal support in frozen-thawed embryo transfer artificial cycles: A pilot randomized controlled trial.Asian Pacific J Reprod. 2016;5(6):490–494. Available at: https://www.sciencedirect.com/science/article/pii/S2305050016302433
Ozer G, Yuksel B, Yucel Cicek OS, Kahraman S. Oral dydrogesterone vs. micronized vaginal progesterone gel for luteal phase support in frozen-thawed single blastocyst transfer in good prognosis patients. J Gynecol Obstet Hum Reprod. 2021;50(5):102030. 10.1016/j.jogoh.2020.102030.
Atzmon Y, Aslih N, Estrada D, Bilgory A, Ellenbogen A, Shalom-Paz E. Comparable Outcomes Using Oral Dydrogesterone Vs. Micronized Vaginal Progesterone in Frozen Embryo Transfer: a Retrospective Cohort Study. Reprod Sci. 2021;28(7):1874-1881.
Guo W, Chen X, Ye D, et al. [Effects of oral dydrogesterone on clinical outcomes of frozen-thawed embryo transfer cycles]. Nan Fang Yi Ke Da Xue Xue Bao. 2013;33(6):861-865.
Yang R, Chi H, Chen L, Li R, Liu P, Qiao J. [Impact of different luteal support methods on clinical outcomes of frozen-thawed embryo transfer cycles]. Zhonghua Yi Xue Za Zhi. 2014;94(41):3256-3258.
Jiang Y, Wang L, Shen H, et al. The effect of progesterone supplementation for luteal phase support in natural cycle frozen embryo transfer: a systematic review and meta-analysis based on randomized controlled trials. Fertil Steril. 2023;119(4):597-605.
Tu BK. Effect of HCG on human corpus lutrum of menstruation and early gestation. Endocrinol Jpn. 1978;25(6):569-574.
Mizrachi Y, Horowitz E, Ganer Herman H, Farhi J, Raziel A, Weissman A. Should women receive luteal support following natural cycle frozen embryo transfer? A systematic review and meta-analysis. Hum Reprod Update. 2021;27(4):643-650.
Wen W, Li N, Shi J, Zhou H, Fan L. Use of hCG for luteal support in natural frozen-thawed blastocyst transfer cycles: a cohort study. Front Endocrinol (Lausanne). 2024;15:1391902.
Zarei A, Sohail P, Parsanezhad ME, Alborzi S, Samsami A, Azizi M. Comparison of four protocols for luteal phase support in frozen-thawed embryo transfer cycles: a randomized clinical trial.Arch Gynecol Obstet. 2017;295(1):239–246.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2025 Yu Su-Ling, Rajesh Hemashree, Lim Whui-Whui, Yong Tze-Tein