Effects of sequential and fixed-dose estradiol valerate administration on premature progesterone rise in frozen-thawed embryo transfer cycles

Abstract

Aim: This study investigated the risk of premature progesterone (P4) rise in the fixed and sequential estradiol valerate (EV) administration for frozen embryo transfer (FET) cycles.
Material and Method: In this cross-sectional case-control study, 1272 cycles of FET were analyzed retrospectively from computer records between January 2015 to August 2020. EV was administrated in 795 patients with a fixed dose and in 477 patients with a sequential dose. P4 values were measured on the day when the endometrial thickness reached 8 mm in the patients.
Results: There were 795 patients in the fixed EV administration group with a mean age of 30.75±3.39 and 477 patients in the sequential EV administration with a mean age of 30.75±3.39. P4 of the sequential-dose group (1.05±0.31) was significantly higher than the fixed-dose group (1.01±0.33). The Pairwise Z-Tests found that the abort rate was significantly higher in the sequential-dose group (p=0.04).
Conclusion: Our results showed a higher P4 and abortion rate in the sequential-dose group. These findings show that premature P4 rise can be considered a risk factor.

Keywords

• Estradiol valerate
• progesterone
• FET

References

1. Dokuzeylul Gungor N,Gurbuz T. Prediction of the number of oocytes based on AMH and FSH levels in IVF candidates. J Surg Med 2020; 4: 733-7.
2. 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: 633-43.
3. Gaggiotti-Marre S, Martinez F, Coll L, et al. 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: 439-42.
4. Ghaffari F, Chekini Z, Vesali S. Duration of estradiol supplementation in luteal phase support for frozen embryo transfer in hormone replacement treatment cycles: a randomized, controlled phase III trial. Arch Gynecol Obstet 2022; 305: 767-75.
5. Healy MW, Patounakis G, Connell MT, et al. Does a frozen embryo transfer ameliorate the effect of elevated progesterone seen in fresh transfer cycles? Fertil Steril 2016; 105: 93-9.
6. Hussein RS, Elnashar I, Amin AF, et al. Effect of metformin on premature luteinization and pregnancy outcomes in intracytoplasmic sperm injection-fresh embryo transfer cycles: a randomized double-blind controlled trial. Int J Fertil Steril 2021; 15: 108-14.
7. Ji M, Zhang L, Fu X, Xie W, Wu X, Shu J. The outcomes of sequential embryo transfer in patients undergoing in vitro fertilization with frozen-thawed embryos: a retrospective study. J Obstet Gynaecol Res 2022; 48: 2563-70.
8. Kumari J, Nayar KD, Gupta S, Sanan S, Mehra P. A prospective randomized comparative study between transdermal estradiol gel and oral estradiol valerate tablets for successful clinical outcome in frozen-thawed embryo transfer cycles. IFS 2021; 8: 83.

9. Labarta E, Mariani G, Paolelli S, et al. 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: 683-92.
10. Le TMC, Duong KT, Nguyen QA, et al. Effectiveness of progesterone supplementation in women presenting low progesterone levels on the day of frozen embryo transfer: a randomised controlled trial. BMJ Open 2022; 12: e057353.
11. Levi Setti PE, Cirillo F, De Cesare R, et al. Seven years of vitrified blastocyst transfers: comparison of 3 preparation protocols at a single ART center. Front Endocrinol (Lausanne) 2020; 11: 346.
12. Li R, Wu H-C, Xiang S, Jia Z-C, Lian F, Guo Y. Does adding vaginal oestradiol after oral oestradiol facilitate artificial autologous freeze-thaw embryo transfer cycles? a retrospective cohort study. Res Squa 2022.
13. Liu X, Bai H, Shi W, Shi J. Frozen-thawed embryo transfer is better than fresh embryo transfer in GnRH antagonist cycle in women with 3-10 oocytes retrieved: a retrospective cohort study. Arch Gynecol Obstet 2019; 300: 1791-6.
14. Liu Y, Wu Y. Progesterone Intramuscularly or vaginally administration may not change live birth rate or neonatal outcomes in artificial frozen-thawed embryo transfer cycles. Frontiers in Endocrinology 2020; 11: 539427.
15. Orief YI, Mahmoud TH, abdelwahed HS. Comparison between the effect of fixed and ascending dose of estrogen during endometrial preparation for frozen embryo transfer. Alexmed Eposters 2022; 4: 28-9.
16. Pabuccu E, Pabuccu R, Demirel C. Very high serum progesterone levels on the day of embryo transfer do not have an impact on outcomes in artificially prepared frozen embryo transfer cycles. Fertility and Sterility 2022; 118: e162.
17. Pais F, Mackens S, Roelens C, et al. P-640 Impact of adding oral dydrogesterone (OD) in patients with low serum progesterone (P) levels in artificially prepared frozen embryo transfer cycles (FET-HRT). Human Reprod 2022; 37; 589.
18. Pan P, Zheng L, Chen X, Huang J, Yang D, Li Y. Successful live birth in a Chinese woman with P450 oxidoreductase deficiency through frozen-thawed embryo transfer: a case report with review of the literature. J Ovarian Res 2021; 14: 22.
19. Seshadri S, Odia R, Ozturk O, et al. A Comparative analysis of outcomes between two different intramuscular progesterone preparations in women undergoing frozen embryo transfer cycles. J Reprod Infertil 2022; 23: 46-53.
20. Shen L. Effects of pelvic floor muscle massage on the pregnancy outcome of frozen embryo transfer in patients with thin endometrium. Comput Math Methods Med 2022; 2022: 2803363.
21. Shen L, Liu C. The influence of the pelvic floor muscle massage on pregnancy outcome in patients treated with frozen-thawed embryo transfer. Tobacco Regulatory Sci 2021; 7: 1842-52.
22. Wu H, Wei F, Tan W, et al. Administration of depot GnRH agonist prior to programmed frozen-thawed embryo transfer does not improve the live birth rate in ovulatory women: A large, multi-center retrospective study. Med 2022; 101: e30991.
23. Xu H, Zhang XQ, Zhu XL, 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.
24. Ying Y, Wu Y, Liu S, Huang Q, Liu H. The timing for initiating estrogen stimulation in artificial cycle for frozen-thawed embryo transfer can be flexible. Reprod Health 2021; 18: 181.