Comparison of the effectiveness and obstetric outcomes of various methods of preparing the endometrium for frozen embryo transfer in the natural cycles and against the hormone replacement cycles

Authors

  • V.A. МЦРМ
  • Э.В. Исакова
  • Я.А. Самойлович
  • В.С. Корсак

DOI:

https://doi.org/10.37800/RM.1.2022.44-51

Keywords:

thawed embryo transfer (FET), endometrium, hormone replacement therapy (HRT), natural cycle (NC)

Abstract

Relevance: Increased frequency of using frozen embryo transfer (FET) in assisted reproductive technology (ART) programs makes it relevant to study the effectiveness and analyze the obstetric outcomes of various methods of endometrial preparation in such cycles.

The study aimed to determine the optimal method for preparing the endometrium for FET.

Methods: The effectiveness of endometrial preparation for FET in the natural cycle (Group 1, n=124) and hormone replacement therapy cycles (HRT) (Group 2, n=120) was analyzed in infertile patients aged 22-40 years. The assessed parameters included endometrial thickness on the day of FET, clinical pregnancy rate (CPR), spontaneous miscarriage up to 12 weeks of gestation, threatened miscarriage in the first trimester of pregnancy, gestational diabetes mellitus (GDM), isthmic-cervical insufficiency (ICI), hypertensive disorders in the third trimester of pregnancy, placenta previa, total weight gain, term and method of delivery, birth weight of children, frequency of live births.

Results: The endometrium thickness on FET day in the study groups did not significantly differ (p=0.52). The CPR was higher when using HRT vs. FET in the natural cycle (61.6% and 51.6%, respectively), but the differences were not statistically significant (p=0.057). Spontaneous miscarriage before 12 weeks of pregnancy (p=0.0096) and hypertensive disorders in the third trimester of pregnancy (p=0.0097) were significantly more often recorded in the HRT group.

The groups did not significantly differ in the frequency of threatened miscarriage (p=0.17) and GDM (p=0.26), ICI (p=0.07), placenta previa (p=0.38), total weight gain (p=0.35), term and method of delivery (p=0.35 and 0.27, respectively), birth weight of children (p=0.66 at birth with one child, p= 0.902 at birth with twins), frequency of live births (p=0.942).

Conclusion: This study showed no advantages of any method of preparing the endometrium for FET in terms of CPR. However, HRT was associated with a higher risk of miscarriage and preeclampsia. This requires an individual approach to choosing the most optimal method to prepare the endometrium and ensure high CPR and more favorable outcomes of ART programs.

References

De Geyter C., Wyns C., Calhaz-Jorge C. De Mouzon J., Ferraretti A.P., Kupka M., Anderson A.N., Nygren K.G., Goossens V. 20 years of the European IVF-monitoring Consortium registry: what have we learned? A comparison with registries from two other regions // Hum. Reprod. – 2020. – Vol. 35(12). – P. 2832-2849. https://doi.org/10.1093/humrep/deaa250.

US Dept. of Health and Human Services. Centers for Disease Control and Prevention. National Center for Chronic Disease Prevention and Health Promotion. Division of Reproductive Health. Assisted Reproductive Technology // Fertility Clinic Success Rates Report. – 2018. – 2020. https://www.cdc.gov/art/pdf/2018-report/ART-2018-Clinic-Report-Full.pdf.

Kupka M.S., D’Hooghe T., Ferraretti A.P., De Mouzon J., Erb K., Castilla J.A., Calhaz-Jorge C., De Geyter C., Goossens V. European IVFMC, European Society of Human R, Embryology, Assisted Reproductive Technology in Europe, 2011: Results Generated From European Registers by ESHRE // Hum. Reprod. – 2016. – Vol. 31(2). P. 233-248. https://doi.org/10.1093/humrep/dev319.

Kupka M.S., Ferraretti A.P., De Mouzon J., Erb K., D’Hooghe T., Castilla J.A., Calhaz-Jorge C., De Geyter C., Goossens V., Strohmer H., Strohmer Partnerschaft Goldenes Kreuz-Kinderwunschzentrum, Bogaerts K., Biostat I., Kyurkchiev S., Antonova I., Rezabek K., Markova J., Gissler M., Tiitinen A., Royere D., Buhler K., Uszkoriet M., Loutradis D., Tarlatzis B.C., Kozstolanyi G., Urbencsek J., Bjorgvinsson H., Mocanu E., Scaravelli G., Lokshin V., Valiyev R., Gudleviciene Z., Matkeviciute G., Lazarevski S., Moshin V., Motrenko Simic T., Vukicevic D., Hazekamp J.T., Kursawa R., Laranjeira A.R., Rugescu I., Korsak V., Radunovic N., Tabs N., Tomazevic T., Virant-Klun I., Hernandez J.H., Castilla Alcala J.A., Bergh C., Weder M., De Geyter C., Smeenk J.M.J., Lambalk C., Veselovsky V., Baranowski R. Assisted Reproductive Technology in Europe, 2010: Results Generated from European Registers by ESHRE dagger // Hum. Reprod. – 2014. – Vol. 29(10). – P. 2099–113. https://doi.org/10.1093/humrep/deu175.

Zaat, T., Zagers, M., Mol, F., Goddijn, M., van Wely, M., & Mastenbroek, S. Fresh versus frozen embryo transfers in assisted reproduction // Cochrane Database Syst. Rev. – 2021. – Vol. 2(2). – No. CD011184. https://doi.org/10.1002/14651858.CD011184.pub3.

Корсак В.С., Смирнова А.А., Шурыгина О.В. Регистр ВРТ Российской ассоциации репродукции человека. Отчет за 2019 год // Проблемы репродукции. 2021. – № 27(6). – С. 14-29. [Korsak V.S., Smirnova A.A., Shurygina O.V. Registr VRT Rossijskoj associacii reprodukcii cheloveka. Otchet za 2019 god // Problemy reprodukcii. 2021. – № 27(6). – S. 14-29 (in Russ.)]. https://doi.org/10.17116/repro20212706114.

Wei D., Liu J-Y., Sun Y., Shi Y., Zhang B., Liu J-Q., Tan J., Liang X., Cao Y., Wang Z., Qin Y., Zhao H., Zhou Y., Ren H., Hao G., Ling X., Zhao J., Zhang Y., Qi X., Zhang L. Deng X., Chen X., Zhu Y., Wang X., Tian L-F., Lv Q., Ma X., Zhang H., Legro R.S., Chen Z-J. Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial // Lancet. – 2019. – Vol. 393. – P. 1310-1318. https://doi.org/10.1016/S0140-6736(18)32843-5.

Orvieto R., Kirshenbaum M., Gleicher N. Is Embryo Cryopreservation Causing Macrosomia-and What Else? // Front Endocrinol (Lausanne). – 2020. – Vol. 11. – P. 19. https://doi.org/10.3389/fendo.2020.00019.

Савина В.А., Самойлович Я.А., Исакова Э.В. Опыт применения внутриматочной инфузии плазмы, обогащенной тромбоцитами, при подготовке эндометрия в программах с переносом размороженных эмбрионов у пациенток с неблагоприятным прогнозом результата лечения // Акушерство и Гинекология. – 2020. – №11. – С. 168-173 [Savina V.A., Samojlovich Ya.A., Isakova E'.V. Opyt primeneniya vnutrimatochnoj infuzii plazmy, obogashhennoj trombocitami, pri podgotovke e'ndometriya v programmax s perenosom razmorozhennyx e'mbrionov u pacientok s neblagopriyatnym prognozom rezul'tata lecheniya // Akusherstvo i Ginekologiya. – 2020. – №11. – S. 168-173 (in Russ.)]. https://doi.org/10.18565/aig.2020.11.168-173.

Ghobara T., Gelbaya T.A., Ayeleke R.O. Cycle regimens for frozen-thawed embryo transfer // Cochrane Database Syst. Rev. – 2017. – Vol. 7. – No. Cd003414. https://doi.org/10.1002/14651858.cd003414.pub3.

Glujovsky D., Pesce R., Fiszbajn G., Sueldo C., Hart R.J., Ciapponi A. Endometrial preparation for women undergoing embryo transfer with frozen embryos or embryos derived from donor oocytes // Cochrane Database Syst. Rev. – 2010. – Vol. (1). – No. CD006359. https://doi.org/10.1002/14651858.CD006359.pub2.

Groenewoud E.R., Cohlen B.J., Al-Oraiby A., Brinkhuis E.A., Broekmans F.J., De Bruin J.P., Van den Dool G., Fleisher K., Friederich J., Goddijn M., Hoek A., Hoozemans D.A., Kaaijk E.M., Koks C.A., Laven J.S., Van der Linden P.J., Manger A.P., Slappendel E., Spinder T., Kollen B.J., Macklon N.S. A randomized controlled, non-inferiority trial of modified natural versus artificial cycle for cryo-thawed embryo transfer // Hum. Reprod. – 2016 Jul. – Vol. 31(7). – P. 1483-1492. https://doi.org/10.1093/humrep/dew120.

Zong L., Liu P., Zhou L., Wei D., Ding L., Qin Y. Increased risk of maternal and neonatal complications in hormone replacement therapy cycles in frozen embryo tranfer // Reprod Biol Endocrinol. – 2020. – Vol. 18(1). – P. 36. https://doi.org/10.1186/s12958-020-00601-3.

Waschkies F., Kroning L., Schill T., Chandra A., Schippert C., Topfer D., Ziert Y., von Versen-Höynck F. Pregnancy Outcomes After Frozen-Thawed Embryo Transfer in the Absence of a Corpus Luteum // Front. Med. (Lausanne). – 2021. – Vol. 8. – No. 727753. https://doi.org/10.3389/fmed.2021.727753.

Gu F., Tan M., Chen Y., Li X., Xu Y. Increased Risk Of Hypertensive Disorders Of Pregnancy In Hormone Replacement Therapy Cycle - A Multicenter Cohort Study In Frozen Blastocyst Transfer In Ovulatory Women // Hum. Reprod. – 2021. – Vol. 36 (Suppl. 1). – No. deab127.084. https://doi.org/10.1093/humrep/deab127.084.

Zheng Y., Li Z., Xiong M., Luo T., Dong X., Huang B., Zhang H., Ai J. Hormonal replacement treatment improves clinical pregnancy in frozen-thawed embryos transfer cycles: a retrospective cohort study // Am. J. Transl. Res. – 2013. – Vol. 6. – P. 85-90. https://pubmed.ncbi.nlm.nih.gov/24349625/.

Кривонос М.И. Патогенетически обоснованная профилактика неблагоприятных исходов экстракорпорального оплодотворения у женщин с наличием антифосфолипидных антител: дис. … канд. мед. наук: 14.01.01. – Санкт-Пебтербург: ФГБНУ «Научно-Исследовательский Институт Акушерства, Гинекологии и Репродуктологии имени Д.О. Отта», 2019. – 172 с. [Krivonos M.I. Patogeneticheski obosnovannaya profilaktika neblagopriyatnyx isxodov e'kstrakorporal'nogo oplodotvoreniya u zhenshhin s nalichiem antifosfolipidnyx antitel: dis. … kand. med. nauk: 14.01.01. – Sankt-Pebterburg: FGBNU «Nauchno-Issledovatel'skij Institut Akusherstva, Ginekologii i Reproduktologii imeni D.O. Otta», 2019. – 172 s. (in Russ.)]. https://www.1spbgmu.ru/images/home/universitet/Struktura/Soveti_i_Komissii/Dissertacii/2018/Кривонос/диссертация_Кривонос_М.И.pdf

Levron J., Yerushalmi G.M., Brengauz M., Gat I., Katorza E. Comparison between two protocols for thawed embryo transfer: natural cycle versus exogenous hormone replacement // Gynecol Endocrinol. – 2014. – Vol. 30(7). – P. 494-497. https://doi.org/10.3109/09513590.2014.900032.

Morozov V., Ruman J., Kenigsberg D., Moodie G., Brenner S. Natural cycle cryo-thaw transfer may improve pregnancy outcome // J. Assist Reprod. Genet. – 2007. – Vol. 24(4). – P. 119-123. https://doi.org/10.1007/s10815-006-9100-y.

Gelbaya T.A., Nardo L.G., Hunter H.R., Fitzgerald C.T., Horne G., Pease E.E., Brison D.R., Lieberman B.A. Cryopreserved-thawed embryo transfer in natural or down-regulated hormonally controlled cycles: a retrospective study // Fertil. Steril. – 2006. – Vol. 85. – P. 603-609. https://doi.org/10.1016/j.fertnstert.2005.09.015.

Mounce G., McVeigh E., Turner K., Child T.J. Randomized, controlled pilot trial of natural versus hormone replacement therapy cycles in frozen embryo replacement in vitro fertilization // Fertil Steril. – 2015. – Vol. 104. – P. 915.e1–920.e1. https://doi.org/10.1016/j.fertnstert.2015.07.1131.

Kalem Z., Kalem M.N., Bakirarar B., Kent E., Gurgan T. Natural cycle versus hormone replacement therapy cycle in frozen-thawed embryo transfer // Saudi Med J. – 2018. – Vol. 39(11). – P. 1102–1108. https://doi.org/10.15537/smj.2018.11.23299.

Pijnenborg R., Bland J.M., Robertson W.B., Brosens I. Uteroplacental arterial changes related to interstitial Trophoblast migration in early human pregnancy // Placenta. 1983. – Vol. 4. – P. 397-414. https://doi.org/10.1016/s0143-4004(83)80043-5.

Pijnenborg R., Vercruysse L., Hanssens M. The uterine spiral arteries in human pregnancy: facts and controversies // Placenta. – 2006. – Vol. 27. – P. 939-958. https://doi.org/10.1016/j.placenta.2005.12.006.

Albrecht E.D., Bonagura T.W., Burleigh D.W., Enders A.C., Aberdeen G.W., Pepe G.J. Suppression of extravillous trophoblast invasion of uterine spiral arteries by estrogen during early baboon pregnancy // Placenta. – 2006. – Vol. 27. – P. 483-490. https://doi.org/10.1016/j.placenta.2005.04.005.

Babischkin J.S., Burleigh D.W., Mayhew T.M., Pepe G.J., Albrecht E.D. Developmental regulation of morphological differentiation of placental villous trophoblast in the baboon // Placenta. – 2001. – Vol. 22. – P. 276-283. https://doi.org/10.1053/plac.2000.0621.

Bonagura T.W., Pepe G.J., Enders A.C., Albrecht E.D. Suppression of extravillous trophoblast vascular endothelial growth factor expression and uterine spiral artery invasion by estrogen during early baboon pregnancy // Endocrine. – 2008. – Vol. 149. – P. 5078-5087. https://dx.doi.org/10.1210%2Fen.2008-0116.

Veleva Z., Tiitinen A., Vilska S., Hydén-Granskog C., Tomás C., Martikainen H., Tapanainen J.S. High and low BMI increase the risk of miscarriage after IVF/ICSI and FET // Hum. Reprod. – 2008 Apr. – Vol. 23(4). – P. 878-84. https://doi.org/10.1093/humrep/den017.

Lin J., Zhao J., Hao G., Tan J., Pan Y., Wang Z., Juang Q., Xu N., Shi Y. Maternal and Neonatal Complications After Natural vs. Hormone Replacement Therapy Cycle Regimen for Frozen Single Blastocyst Transfer // Front. Med. (Lausanne). – 2020. – Vol. 7. – No. 338. https://doi.org/10.3389/fmed.2020.00338.

Ginström Ernstad E., Wennerholm U.B., Khatibi A., Petzold M., Bergh C. Neonatal and maternal outcome after frozen embryo transfer: Increased risks in programmed cycles // Am J Obstet Gynecol. – 2019. – Vol. 221. – P. 126.e1–126.e18. https://doi.org/10.1016/j.ajog.2019.03.010.

Khong T.Y., De Wolf F., Robertson W.B., Brosens I. Inadequate maternal vascular response to placentation in pregnancies complicated by preeclampsia and by small for-gestational-age infants // BJOG. – 1986. – Vol. 93. – P. 1049-1056. https://doi.org/10.1111/j.1471-0528.1986.tb07830.x.

Labarrere C.A., Althabe O.H. Inadequate maternal vascular response to placentation in pregnancies complicated by preeclampsia and by small for-gestational-age infants // BJOG. – 1987. – Vol. 94. – P. 1113-1115. https://doi.org/10.1111/j.1471-0528.1987.tb02302.x.

Pljnenborg R.A.J., Davey D.A., Rees A., Tiltman A., Vercruysse L., Assche A. Placental bed spiral arteries in the hypertensive disorders of pregnancy // BJOG. – 1991. –Vol. 98. – P. 648-655. https://doi.org/10.1111/j.1471-0528.1991.tb13450.x.

Von Versen-Höynck F., Narasimhan P., Selamet Tierney E.S., Martinez N., Conrad K.P., Baker V.L., Winn V.D. Absent or excessive corpus luteum number is associated with altered maternal vascular health in early pregnancy // Hypertension. – 2019. – Vol. 73(3). – P. 680-690. https://doi.org/10.1161/hypertensionaha.118.12046.

Hisaw F.L. Experimental relaxation of the pubic ligament of the guinea pig // Proc. Soc. Exp. Biol. Med. – 1926. – Vol. 23. – P. 661-663. https://doi.org/10.3181%2F00379727-23-3107.

De Vries M.J., Dekker G.A., Schoemaker J. Higher risk of preeclampsia in the polycystic ovary syndrome: A case control study // Eur. J. Obstet. Gynecol. Reprod. Biol. – 1998. – Vol. 76(1). – P. 91-95. https://doi.org/10.1016/s0301-2115(97)00164-4.

Naver K.V., Grinsted J., Larsen S.O., Hedley P.L., Jorgensen F.S., Christiansen M., Nilas L. Increased risk of preterm delivery and pre-eclampsia in women with polycystic ovary syndrome and hyperandrogenaemia // BJOG. – 2014. – Vol. 121(5). – P. 575-581. https://doi.org/10.1111/1471-0528.12558.

Преэклампсия. Эклампсия. Отеки, протеинурия и гипертензивные расстройства во время беременности, в родах и послеродовом периоде // Клинические рекомендации МЗ РФ. – 2021. [Pree'klampsiya. E'klampsiya. Oteki, proteinuriya i gipertenzivnye rasstrojstva vo vremya beremennosti, v rodax i poslerodovom periode // Klinicheskie rekomendacii MZ RF. – 2021 (in Russ.)]. https://cr.minzdrav.gov.ru/schema/637_1#doc_b. 01.02.2022.

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2022-04-01

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[1]
В.А., Исакова, Э., Самойлович, Я. and Корсак, В. 2022. Comparison of the effectiveness and obstetric outcomes of various methods of preparing the endometrium for frozen embryo transfer in the natural cycles and against the hormone replacement cycles. Reproductive Medicine (Central Asia). 1(50) (Apr. 2022), 44–51. DOI:https://doi.org/10.37800/RM.1.2022.44-51.

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No. 1(50) (2022): Reproductive medicine

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