The Iranian Journal of Obstetrics, Gynecology and Infertility

The Iranian Journal of Obstetrics, Gynecology and Infertility

Two Methods of Endometrial Preparation (Hormonal Replacement Therapy and Ovarian Stimulation) in Patients Undergoing Frozen Embryo Transfer Cycle: A Randomized Clinical Trial

Document Type : Original Article

Authors
Samira Azimi 1
Amene Abtahian 1
Tayebeh Esfidani 2
1 Fellowship of Infertility, Nical Research Development Center, Faculty of Medicine, Shahid Beheshti University Medical Science, Tehran, Iran.
2 Assistante Professor, Department of Obstetrics and Gynecology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
10.22038/ijogi.2025.85183.6314
Abstract
Introduction: Currently, there are several protocols for endometrial preparation in patients undergoing frozen embryo transfer, including ovulation induction, natural cycle, hormone therapy, and other methods. Each of these methods has its own advantages and disadvantages. Accordingly, the present study was conducted with aim to evaluate and compare the effect of these two methods on pregnancy outcomes in patients undergoing frozen embryo transfer.
Methods: This single-blind clinical trial study was conducted in 2023-2024 on 208 patients who were treated for infertility at the Mahdieh Hospital Clinic and whose embryos had been frozen, and therefore were candidates for a frozen embryo transfer cycle. Patients were randomly divided into two groups receiving estradiol and letrozole. After the intervention, pregnancy outcomes including clinical and chemical pregnancy, ectopic pregnancy, cycle cancellation, and miscarriage were evaluated. Data analysis was performed using SPSS statistical software (version 26) and Mann-Whitney and Chi-square tests. P<0.05 was considered significant.
Results: The percentage of clinical pregnancy, chemical pregnancy, and stable pregnancy was higher in the hormone replacement therapy group than in the ovarian stimulation group, but this difference was not statistically significant (p>0.05). In contrast, the mean time required for endometrial preparation in the letrozole group was significantly longer than in the estradiol group (p<0.001). Also, a statistically significant difference was observed between the two groups in variables related to ovarian stimulation (including weak, normal and polycystic) (p<0.001).
Conclusion: There was no significant difference in pregnancy outcomes between the two methods of hormone replacement therapy and ovarian stimulation; however, the duration of endometrial preparation was significantly longer in the letrozole group. The choice of treatment protocol can be made based on the individual patient's condition and clinical considerations.
Keywords
Hormone Replacement Therapy
Embryo Transfer
Endometrial Preparation
Ovarian Stimulation
Subjects
  1. Carson SA, Kallen AN. Diagnosis and management of infertility: a review. Jama 2021; 326(1):65-76.
  2. Baruselli PS, Ferreira RM, Vieira LM, Souza AH, Bó GA, Rodrigues CA. Use of embryo transfer to alleviate infertility caused by heat stress. Theriogenology 2020; 155:1-11.
  3. Mo J, Yang Q, Xia L, Niu Z. Embryo location in the uterus during embryo transfer: an in vitro simulation. Plos one 2020; 15(10):e0240142.
  4. Raef B, Maleki M, Ferdousi R. Computational prediction of implantation outcome after embryo transfer. Health informatics journal 2020; 26(3):1810-26.
  5. Roelens C, Blockeel C. Impact of different endometrial preparation protocols before frozen embryo transfer on pregnancy outcomes: a review. Fertility and sterility 2022; 118(5):820-7.
  6. Mohammadi AT, Farnia MR, Mirshekari A, Ghalehno SR, Ahmadipour E, Bazargani Z, et al. Association between oxidative balance score and metabolic syndrome: a systematic review and meta-analysis. Journal of Nephropathology 2025; 14(3):e27622-.
  7. Hu KL, Zhang D, Li R. Endometrium preparation and perinatal outcomes in women undergoing single-blastocyst transfer in frozen cycles. Fertility and Sterility 2021; 115(6):1487-94.
  8. Nezamdoust S, Farzaneh F. Comparison of the effect of trigger of ovulation with HCG and HCG plus oxytocin on the biochemical pregnancy. The Iranian Journal of Obstetrics, Gynecology and Infertility 2020; 22(12):19-23.
  9. Farzaneh F, Ahmadian Shalchi A, Sarhadi S. Relationship between serum progesterone levels at the day before progesterone suppository administration and pregnancy rate in embryo transfer cycles', The Iranian Journal of Obstetrics, Gynecology and Infertility 2021; 23(12):6-12.
  10. Rad HF, Karimi MS, Behfar M, Nazari A, Hassani N, Hasanvand A, et al. LncRNA Linc00261 sponge's miR-33-regulated PI3-kinase in autism disorder. Gene Reports 2025; 38:102115.
  11. Guo B, Li JJ, Ma YL, Zhao YT, Liu JG. Efficacy and safety of letrozole or anastrozole in the treatment of male infertility with low testosterone‐estradiol ratio: a meta‐analysis and systematic review. Andrology 2022; 10(5):894-909.
  12. Pilehvari S, Yavangi M, Salemi L, Charaghi Z. A comparative study of the effects of two different treatment periods with estradiol in endometrial preparation on the pregnancy outcome of frozen embryos. The Iranian Journal of Obstetrics, Gynecology and Infertility 2023; 26(3):25-32.
  13. Yang AM, Cui N, Sun YF, Hao GM. Letrozole for female infertility. Frontiers in Endocrinology 2021; 12:676133.
  14. Wang X, Li Y, Tan H, Cai S, Ma S, Peng Y, et al. Letrozole-stimulated endometrial preparation protocol is a superior alternative to hormone replacement treatment for frozen embryo transfer in women with polycystic ovary syndrome, a cohort study. Reproductive Biology and Endocrinology 2023; 21(1):101.
  15. Deli T, Orosz M, Jakab A. Hormone replacement therapy in cancer survivors–review of the literature. Pathology & oncology research 2020; 26(1):63-78.
  16. Iwami N, Kawamata M, Ozawa N, Yamamoto T, Watanabe E, Mizuuchi M, et al. New treatment strategy for endometriosis using progestin-primed ovarian stimulation with dienogest: A prospective cohort study, comparison of dienogest versus dydrogesterone. Reproductive Biology 2021; 21(1):100470.
  17. Özdemir AZ, Karli P, Gülümser Ç. Does high estrogen level negatively affect pregnancy success in frozen embryo transfer?. Archives of Medical Science: AMS 2020; 18(3):647.
  18. Hsueh YW, Huang CC, Hung SW, Chang CW, Hsu HC, Yang TC, et al. Finding of the optimal preparation and timing of endometrium in frozen-thawed embryo transfer: a literature review of clinical evidence. Frontiers in Endocrinology 2023; 14:1250847.
  19. Mackens S, Santos-Ribeiro S, Van De Vijver A, Racca A, Van Landuyt L, Tournaye H, et al. Frozen embryo transfer: a review on the optimal endometrial preparation and timing. Human Reproduction 2017; 32(11):2234-42.
  20. Casper RF, Yanushpolsky EH. Optimal endometrial preparation for frozen embryo transfer cycles: window of implantation and progesterone support. Fertility and sterility 2016; 105(4):867-72.
  21. Hosseini-Najarkolaei A, Moini A, Kashani L, Farid Mojtahedi M, Hosseini-Najarkolaee E, Salehi E. The effect of letrozole versus artificial hormonal endometrial preparation on pregnancy outcome after frozen-thawed embryos transfer cycles: a randomized clinical trial. Reproductive Biology and Endocrinology 2020; 18(1):115.
  22. Samsami A, Ghasmpour L, Davoodi S, Alamdarloo SM, Rahmati J, Karimian A, et al. Frozen embryo transfer: Endometrial preparation by letrozole versus hormone replacement cycle: A randomized clinical trial. International Journal of Reproductive Biomedicine 2019; 17(12):915.
  23. Huang PX, Wei JH, Wei LH. Gonadotropin-releasing hormone agonist for oocyte triggering in endometrial preparation of letrozole stimulation protocols does not affect clinical outcome of frozen-thawed embryo transfer. International Journal of Clinical and Experimental Medicine 2015; 8(10):19072.
  24. Sibai H, El Husseiny A, Elgindy E. Letrozole versus artificial hormonal endometrial preparation for vitrified–warmed embryos transfer cycles. Middle East Fertility Society Journal 2016; 21(2):96-100.
  25. Ezoe K, Fukuda J, Takeshima K, Shinohara K, Kato K. Letrozole-induced endometrial preparation improved the pregnancy outcomes after frozen blastocyst transfer compared to the natural cycle: a retrospective cohort study. BMC Pregnancy and Childbirth 2022; 22(1):824.
  26. Shuai J, Chen Q, Wan S, Chen X, Liu W, Ye H, et al. Impact of elevated serum estradiol levels before progesterone administration on pregnancy outcomes in frozen-thawed embryo transfer for hormone replacement therapy. Reproductive Biology and Endocrinology 2024; 22(1):88.
  27. Li SJ, Zhang YJ, Chai XS, Nie MF, Zhou YY, Chen JL, et al. Letrozole ovulation induction: an effective option in endometrial preparation for frozen–thawed embryo transfer. Archives of gynecology and obstetrics 2014; 289(3):687-93.
  28. Hu YJ, Chen YZ, Zhu YM, Huang HF. Letrozole stimulation in endometrial preparation for cryopreserved–thawed embryo transfer in women with polycystic ovarian syndrome: a pilot study. Clinical endocrinology 2014; 80(2):283-9.
The Iranian Journal of Obstetrics, Gynecology and Infertility
Volume 28, Issue 5
July 2025
Pages 29-37