Endometrial preparation for frozen-thawed embryo transfer in an artificial cycle: transdermal versus vaginal estrogen

Romain Corroenne, Hady El Hachem, Caroline Verhaeghe, Guillaume Legendre, Cecile Dreux, Pauline Jeanneteau, Philippe Descamps, Pascale May-Panloup, Pierre-Emmanuel Bouet, Romain Corroenne, Hady El Hachem, Caroline Verhaeghe, Guillaume Legendre, Cecile Dreux, Pauline Jeanneteau, Philippe Descamps, Pascale May-Panloup, Pierre-Emmanuel Bouet

Abstract

The objective was to compare the endometrial thickness (ET) in a frozen embryo transfer (FET) cycle between transdermal and vaginal estrogen. Our secondary objectives were to compare the patient satisfaction and the pregnancy outcomes. Prospective monocentric cohort study between 01/2017 and 12/2017 at a single institution. Choice of administration was left to the patient. 119 cycles had transdermal estrogen (T-group) and 199 had vaginal estrogen (V-group). The ET at 10 ± 1 days of treatment was significantly higher in the T-group compared to the V-group (9.9 vs 9.3 mm, p = 0.03). In the T-group, the mean duration of treatment was shorter (13.6 vs 15.5 days, p < 0.001). The rate of cycle cancelation was comparable between the two groups (12.6% vs 8.5%, p = 0.24). Serum estradiol levels were significantly lower (268 vs 1332 pg/ml, p < 0.001), and serum LH levels were significantly higher (12.1 ± 16.5 vs 5 ± 7.5 mIU/ml, p < 0.001) in the T-group. Patient satisfaction was higher in the T-group (p = 0.04) and 85.7% (36/42) of women who had received both treatments preferred the transdermal over the vaginal route. Live birth rates were comparable between the two groups (18% vs 19%, p = 0.1). Transdermal estrogen in artificial FET cycles was associated with higher ET, shorter treatment duration and better tolerance.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Flow chart of the study.

References

    1. CDC. American Society for Reproductive Medicine; Society for Assisted Reproductive Technology. 2016 assisted reproductive technology national summary report. Atlanta, GA: US Department of Health and Human Services, CDC. (2018).
    1. McLernon DJ, et al. Clinical effectiveness of elective single versus double embryo transfer: meta-analysis of individual patient data from randomised trials. BMJ. 2010;341:c6945. doi: 10.1136/bmj.c6945.
    1. Agence de la Biomédecine. Activité d’Assistance Médicale à la Procréation - Rapport de l’Agence de la biomédecine. (2015).
    1. Shapiro BS, et al. Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozen-thawed embryo transfers in high responders. Fertility and Sterility. 2011;96:516–518. doi: 10.1016/j.fertnstert.2011.02.059.
    1. 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;33:1287–1304. doi: 10.1007/s10815-016-0787-0.
    1. Mackens S, et al. Frozen embryo transfer: a review on the optimal endometrial preparation and timing. Hum. Reprod. 2017;32:2234–2242. doi: 10.1093/humrep/dex285.
    1. Wright KP, et al. Artificial versus stimulated cycles for endometrial preparation prior to frozen-thawed embryo transfer. Reprod. Biomed. Online. 2006;13:321–325. doi: 10.1016/S1472-6483(10)61434-4.
    1. Groenewoud ER, et al. A randomized controlled, non-inferiority trial of modified natural versus artificial cycle for cryo-thawed embryo transfer. Hum. Reprod. 2016;31:1483–1492. doi: 10.1093/humrep/dew120.
    1. Ziegler WF, Russell JB. High success with gestational carriers and oocyte donors using synchronized cycles. J. Assist. Reprod. Genet. 1995;12:297–300. doi: 10.1007/BF02213707.
    1. Abu-Musa A, Hannoun A, Khalil A, Masaad Z, Karam K. Artificial endometrial preparation for oocyte donation using synthetic estrogen and progestogen. Clin Exp Obstet Gynecol. 1998;25:83–85.
    1. Devroey P, Pados G. Preparation of endometrium for egg donation. Hum. Reprod. Update. 1998;4:856–861. doi: 10.1093/humupd/4.6.856.
    1. Paulson RJ. Hormonal induction of endometrial receptivity. Fertil. Steril. 2011;96:530–535. doi: 10.1016/j.fertnstert.2011.07.1097.
    1. Li TC, et al. Endometrial responses in artificial cycles: a prospective study comparing four different oestrogen dosages. Br J Obstet Gynaecol. 1992;99:751–756. doi: 10.1111/j.1471-0528.1992.tb13878.x.
    1. Krasnow JS, et al. Comparison of transdermal versus oral estradiol on endometrial receptivity. Fertil. Steril. 1996;65:332–336. doi: 10.1016/S0015-0282(16)58094-7.
    1. Weissman A, Leong M, Sauer MV, Shoham Z. Characterizing the practice of oocyte donation: a web-based international survey. Reprod. Biomed. Online. 2014;28:443–450. doi: 10.1016/j.rbmo.2013.12.004.
    1. Kuhl H. Pharmacokinetics of oestrogens and progestogens. Maturitas. 1990;12:171–197. doi: 10.1016/0378-5122(90)90003-O.
    1. Jiménez, P. T., Schon, S. B., Odem, R. R., Ratts, V. S. & Jungheim, E. S. A retrospective cross-sectional study: fresh cycle endometrial thickness is a sensitive predictor of inadequate endometrial thickness in frozen embryo transfer cycles. in Reproductive biology and endocrinology: RB&E, 10.1186/1477-7827-11-35 (2013).
    1. El-Toukhy T, et al. The relationship between endometrial thickness and outcome of medicated frozen embryo replacement cycles. Fertil. Steril. 2008;89:832–839. doi: 10.1016/j.fertnstert.2007.04.031.
    1. Bu Z, Wang K, Dai W, Sun Y. Endometrial thickness significantly affects clinical pregnancy and live birth rates in frozen-thawed embryo transfer cycles. Gynecol. Endocrinol. 2016;32:524–528. doi: 10.3109/09513590.2015.1136616.
    1. Liu KE, Hartman M, Hartman A, Luo Z-C, Mahutte N. The impact of a thin endometrial lining on fresh and frozen-thaw IVF outcomes: an analysis of over 40 000 embryo transfers. Hum. Reprod. 2018;33:1883–1888. doi: 10.1093/humrep/dey281.
    1. Ferrer-Molina P, et al. Oral versus transdermal oestrogen delivery for endometrial preparation before embryo transfer: a prospective, comparative, randomized clinical trial. Reprod. Biomed. Online. 2018;37:693–702. doi: 10.1016/j.rbmo.2018.09.003.
    1. Davar R, Janati S, Mohseni F, Khabazkhoob M, Asgari S. A Comparison of the Effects of Transdermal Estradiol and Estradiol Valerate on Endometrial Receptivity in Frozen-thawed Embryo Transfer Cycles: A Randomized Clinical Trial. J Reprod Infertil. 2016;17:97–103.
    1. Kahraman S, Çetinkaya CP, Sahin Y, Oner G. Transdermal versus oral estrogen: clinical outcomes in patients undergoing frozen-thawed single blastocyst transfer cycles without GnRHa suppression, a prospective randomized clinical trial. J. Assist. Reprod. Genet. 2019;36:453–459. doi: 10.1007/s10815-018-1380-5.
    1. Tourgeman DE, Gentzchein E, Stanczyk FZ, Paulson RJ. Serum and tissue hormone levels of vaginally and orally administered estradiol. Am. J. Obstet. Gynecol. 1999;180:1480–1483. doi: 10.1016/S0002-9378(99)70042-6.
    1. Bilsel AS, Onaran N, Moini H, Emerk K. Long-term effect of 17beta-estradiol and thrombin on tissue factor pathway inhibitor release from HUVEC. Thromb. Res. 2000;99:173–178. doi: 10.1016/S0049-3848(00)00228-0.
    1. Richardson MA, et al. 17beta-estradiol, but not raloxifene, decreases thrombomodulin in the antithrombotic protein C pathway. Endocrinology. 2000;141:3908–3911. doi: 10.1210/endo.141.10.7798.
    1. Farhi J, et al. High serum oestradiol concentrations in IVF cycles increase the risk of pregnancy complications related to abnormal placentation. Reprod. Biomed. Online. 2010;21:331–337. doi: 10.1016/j.rbmo.2010.04.022.
    1. Imudia AN, et al. Peak serum estradiol level during controlled ovarian hyperstimulation is associated with increased risk of small for gestational age and preeclampsia in singleton pregnancies after in vitro fertilization. Fertil. Steril. 2012;97:1374–1379. doi: 10.1016/j.fertnstert.2012.03.028.
    1. Hu X-L, et al. High maternal serum estradiol environment in the first trimester is associated with the increased risk of small-for-gestational-age birth. J. Clin. Endocrinol. Metab. 2014;99:2217–2224. doi: 10.1210/jc.2013-3362.
    1. Treeck O, Diepolder E, Skrzypczak M, Schüler-Toprak S, Ortmann O. Knockdown of estrogen receptor β increases proliferation and affects the transcriptome of endometrial adenocarcinoma cells. BMC Cancer. 2019;19:745. doi: 10.1186/s12885-019-5928-2.
    1. Bouskine A, et al. Estrogens promote human testicular germ cell cancer through a membrane-mediated activation of extracellular regulated kinase and protein kinase A. Endocrinology. 2008;149:565–573. doi: 10.1210/en.2007-1318.
    1. Hartman J, et al. Estrogen receptor beta inhibits angiogenesis and growth of T47D breast cancer xenografts. Cancer Res. 2006;66:11207–11213. doi: 10.1158/0008-5472.CAN-06-0017.
    1. Dal Prato L, et al. Endometrial preparation for frozen-thawed embryo transfer with or without pretreatment with gonadotropin-releasing hormone agonist. Fertil. Steril. 2002;77:956–960. doi: 10.1016/S0015-0282(02)02960-6.
    1. Glujovsky, D. et al. Endometrial preparation for women undergoing embryo transfer with frozen embryos or embryos derived from donor oocytes. Cochrane Database Syst Rev CD006359, 10.1002/14651858.CD006359.pub2 (2010)
    1. Agence de la Biomédecine. Evaluation des résultats des centres d’assistance médicale à la procréation pratiquant la fécondation in vitro en France. Agence de le Biomedecine. Rapport national des résultats. (2014).
    1. De Geyter C, et al. ART in Europe, 2014: results generated from European registries by ESHRE: The European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE) Hum. Reprod. 2018;33:1586–1601. doi: 10.1093/humrep/dey242.
    1. Madero S, Rodriguez A, Vassena R, Vernaeve V. Endometrial preparation: effect of estrogen dose and administration route on reproductive outcomes in oocyte donation cycles with fresh embryo transfer. Hum. Reprod. 2016;31:1755–1764. doi: 10.1093/humrep/dew099.
    1. Gardner D, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Blastocyst score affects implantation and pregnancy outcome: Towards a single blastocyst transfer. Fertility and sterility. 2000;73:1155–8. doi: 10.1016/S0015-0282(00)00518-5.

Source: PubMed

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