Research Progress of GnRHa Down-Regulation Protocols in Frozen-Thawed Embryo Transfer

Abstract

Abstract: The frozen-thawed embryo transfer (FET) has been a widely used technique in the past decades, in which two key factors of a successful pregnancy are the well-potential embryo the well-prepared endometrium. The protocols of endometrial preparation include natural cycle (NC), hormone replacement treatment cycle (HRT), controlled ovarian stimulation cycle (COS), and down-regulation plus HRT cycle. The down-regulation plus HRT cycle, also known as down-regulation artificial cycle, is a protocol of the endometrial preparation by adding exogenous estrogen after the pituitary down-regulation by using gonadotropin-releasing hormone agonist (GnRHa). GnRHa can regulate the pituitary gland by inhibiting the hypothalamic-pituitary-ovarian axis, avoid the uncontrolled follicular development and the elevated serum LH, and improve endometrial receptivity through energy metabolism and immune response. GnRHa can improve the pregnancy outcomes in people with endometriosis and adenomyosis, polycystic ovary syndrome, recurrent implantation failure, elevated progesterone in follicular phase, and thin endometrium.

Key words: Embryo transfer；, Cryopreservation；, Gonadotropin-releasing hormone；, Down-regulation；, Endometrium

CLC Number:

XING Ya-chun，LING Xiu-feng，SU Yan，ZHAO Chun，ZHANG Jun-qiang. Research Progress of GnRHa Down-Regulation Protocols in Frozen-Thawed Embryo Transfer[J]. Journal of International Reproductive Health/Family Planning, 2020, 39(3): 233-237.

References

[1] Ch.DeGeyter，C.Calhaz-Jorge，M.S.Kupka，et al. ART in Europe,2014: results generated from European registries by ESHRE. [J]. Human Reproduction, Vol 33, No.9 pp. 1586–1601, 2018. [2]Mackens S , Santos-Ribeiro S , Van d V A , et al. Frozen embryo transfer: a review on the optimal endometrial preparation and timing[J]. Human Reproduction, 2017, 32(11):2234-2242. [3]El-Toukhy T , Taylor A , Khalaf Y , et al. Pituitary suppression in ultrasound-monitored frozen embryo replacement cycles. A randomized study[J]. Human Reproduction, 2004, 19(4):874-879. [4]Qian Chen，Feng Yu，Yan Li，et al. Comparative proteomics reveal negative effects of gonadotropin-releasing hormone agonist and antagonist on human endometrium. Drug Design， Development and Therapy 2019:13 1855–1863. [5] 张少娣, 耿嘉瑄, 路锦, et al. 促性腺激素释放激素激动剂降调节方案对子宫内膜容受性的研究进展[J]. 中华生殖与避孕杂志, 2017(8). [6] Rackow B W , Kliman H J , Taylor H S . GnRH antagonists may affect endometrial receptivity[J]. Fertility & Sterility, 2008, 89(5):0-1239. [7] Daftary G S , Troy P J , Bagot C N , et al. Direct regulation of beta3-integrin subunit gene expression by HOXA10 in endometrial cells.[J]. Molecular Endocrinology, 2002, 16(3):571. [8] Mabuchi Y , Yamoto M , Minami S , et al. Immunohistochemical localization of inhibin and activin subunits, activin receptors and Smads in ovarian endometriosis[J]. International Journal of Molecular Medicine, 2010, 25(1):17-23. [9] Beshay V E , Carr B R . Hypothalamic-Pituitary-Ovarian Axis and Control of the Menstrual Cycle[M]// Clinical Reproductive Medicine and Surgery. Springer New York, 2013. [10] Fukui A , Kwak-Kim J , Ntrivalas E , et al. Intracellular cytokine expression of peripheral blood natural killer cell subsets in women with recurrent spontaneous abortions and implantation failures[J]. Fertility & Sterility, 2008, 89(1):0-165. [11]周卫琴，江雅丽，汤海波，et al. 促性腺激素释放激素激动剂对子宫内膜胞饮突的影响中华妇产科杂志 2017 Aug 25;52(8):539-544. [12] Song G , Zhichao L , Li Y , et al. GnRH agonist improves pregnancy outcome in mice with induced adenomyosis by restoring endometrial receptivity[J]. Drug Design, Development and Therapy, 2018, Volume 12:1621-1631. [13] 郝丽, 黄元华, 黄海溶. GnRH激动剂应用于子宫内膜准备对冻胚移植后妊娠结局影响的meta分析[J]. 生殖医学杂志, 2018. [14]Nekoo E A , Chamani M , Tehrani E S , et al. Artificial Endometrial Preparation for Frozen-Thawed Embryo Transfer with or without Pretreatment with Depot Gonadotropin Releasing Hormone Agonist in Women with Regular Menses[J]. Journal of Family & Reproductive Health, 2015, 9(1):1-4. [15] Samsami A, Chitsazi Z, Namazi G. Frozen thawed embryo transfer cycles; A comparison of pregnancy outcomes with and without prior pituitary suppression by GnRH agonists: An RCT. Int J Reprod Biomed (Yazd). 2018 Sep;16(9):587-594. [16] Jieun K , Jisun P , Dawn C , et al. Comparison of the clinical outcome of frozen-thawed embryo transfer with and without pretreatment with a gonadotropin-releasing hormone agonist[J]. Obstetrics & Gynecology Science, 2018, 61(4):489-. [17] 韩笑，陈圆辉，张少娣，et al. GnRH-a降调节方案用于冻融胚胎移植内膜准备的适宜人群[J]. 生殖医学杂志, 2016(25):918. [18] Irusta G , Parborell F , Peluffo M , et al. Steroidogenic acute regulatory protein in ovarian follicles of gonadotropin-stimulated rats is regulated by a gonadotropin-releasing hormone agonist.[J]. Biology of Reproduction, 2003, 68(5):1577-83. [19] Rahmawati E, Yang WV, Lei YP, et al. Decreased Level of Neurotrophic Factor Neuritin 1 in Women with Ovarian Endometriosis after Receiving Gonadotropin-Releasing Hormone Agonist Treatment. Int J Mol Sci. 2019;20(18):4352. [20] Woo P C , Hye C M , Moon Y K , et al. Pregnancy rate in women with adenomyosis undergoing fresh or frozen embryo transfer cycles following gonadotropin-releasing hormone agonist treatment[J]. Clinical and Experimental Reproductive Medicine, 2016, 43(3):169-. [21] Niu Z , Chen Q , Sun Y , et al. Long-term pituitary downregulation before frozen embryo transfer could improve pregnancy outcomes in women with adenomyosis[J]. Gynecological Endocrinology, 2013, 29(12):1026-1030. [22] Woo P C , Hye C M , Moon Y K , et al. Pregnancy rate in women with adenomyosis undergoing fresh or frozen embryo transfer cycles following gonadotropin-releasing hormone agonist treatment[J]. Clinical and Experimental Reproductive Medicine, 2016, 43(3):169-. [23]张群芳, 陈国勇, 刘芸. 不同内膜准备方案在子宫内膜异位症患者冻融囊胚移植中的疗效观察[J]. 生殖医学杂志, 2019(6). [24] Schulte M M B , Tsai J H , Moley K H . Obesity and PCOS: The Effect of Metabolic Derangements on Endometrial Receptivity at the Time of Implantation[J]. Reproductive Sciences, 2015, 22(1):6-14. [25] Paprocki E, Barral RL, Vanden Brink H, et al. GnRH Agonist Improves Hyperandrogenism in an Adolescent Girl With an Insulin Receptor Gene Mutation. J Endocr Soc. 2019;3(6):1196–1200. [26] Wei D , Shi Y , Li J , et al. Effect of pretreatment with oral contraceptives and progestins on IVF outcomes in women with polycystic ovary syndrome[J]. Human Reproduction, 2016, 32(2):354. [27]季晓媛，王佳怡，赵纯，et al. 不同内膜准备方案对多囊卵巢综合征患者冻融胚胎移植周期临床结局的影响[J]. 国际生殖健康/计划生育杂志，2019，38(01):18-21. [28]苏雁. 降调节联合激素替代方案在冻融胚胎移植中的临床应用价值[J]. 中国妇幼保健(17):4027-4030. [29] Coughlan C, Ledger W, Wang Q, et al. Recurrent implantation failure: definition and management. Reprod Biomed Online 2014;28:14-38. [30] Kim SM, Kim JS. A review of mechanisms of implantation. Dev Reprod 2017;21:351-9. [31] Bashiri A, Halper KI, Orvieto R. Recurrent implantation failure-update overview on etiology, diagnosis, treatment and future directions. Reprod Biol Endocrinol 2018;16:121. [32] Huang C, Liang P, Diao L, et al. Thyroid autoimmunity is associated with decreased cytotoxicity T cells in women with repeated implantation failure. Int J Environ Res Public Health 2015;12:10352-61. [33] Di Rosa R, Ferrero S, Cifani N, et al. In vitro fertilization and autoimmunity: evidence from an observational study. Eur J Obstet Gynecol Reprod Biol 2019;234:137-42. [34] Gaynor L M , Francesco C . Uterine Natural Killer Cells: Functional Distinctions and Influence on Pregnancy in Humans and Mice[J]. Frontiers in Immunology, 2017, 8:467-. [35]郝翊, 徐野, 李建华, et al. 黄体期降调节联合人工周期方案在冻融胚胎反复移植失败患者中的应用[J]. 生殖医学杂志, 2018, v.27(07):26-30. [36] Reda S. Hussein，Ihab Elnashar，Ahmed F. Amin，et al. Revisiting debates of premature luteinization and its effect on assisted reproductive technology outcome. [J] Assist Reprod Genet (2019). [37] Haouzi D，Bissonnette L，Gala A，et al. Endometrial Receptivity Profile in Patients with Premature Progesterone Elevation on the Day of hCG Administration[J]. BioMed Research International，2014，2014:1-10. [38] Huang B, Ren X, Wu L, et al. Elevated progesterone levels on the day of oocyte maturation may affect top quality embryo IVF cycles. PLoS One 2016;11. [39] Vanni V S , Somigliana E , Reschini M , et al. Top quality blastocyst formation rates in relation to progesterone levels on the day of oocyte maturation in GnRH antagonist IVF/ICSI cycles[J]. Plos One, 2017, 12(5):e0176482. [40] Xiong Y, Wang J, Liu L, et al. Effects of high progesterone level on the day of human chorionic gonadotrophin administration in in vitro fertilization cycles on epigenetic modification of endometrium in the peri-implantation period. [J] Assist Reprod Genet Fertil Steril. 2017;108(2):269–76.e1. [41] Liu L, Huang J, Li TC, et al. The effect of elevated progesterone levels before oocyte retrieval in women undergoing ovarian stimulation for IVF treatment on the genomic profile of peri-implantation endometrium. [J] Reprod Immunol. 2017;121:17–25. [42] Racca A , Santos-Ribeiro S , De Munck N , et al. Impact of Late-Follicular Phase Elevated Serum Progesterone on Cumulative Live Birth Rates:, Is There a Deleterious Effect on Embryo Quality?[J]. Obstetrical & Gynecological Survey, 2018, 73. [43] Jingjie Li, Yue Gao, Lihuan Guan, et al. Lipid Profiling of Peri-implantation Endometrium in Patients With Premature Progesterone Rise in the Late Follicular Phase. [J] Clin Endocrinol Metab. 2019 Nov 1;104(11):5555-5565. [44] Kasius A, Smit JG, Torrance HL, et al. Endometrial thickness and pregnancy rates after IVF: a systematic review and meta-analysis. Hum Reprod Update. 2014;20(4):1-12. [45] Song J , Sun X , Qian K . Endometrial but not Ovarian Response is Associated With Clinical Outcomes and can be Improved by Prolonged Pituitary Downregulation in Patients With Thin and Medium Endometrium[J]. Reproductive Sciences, 2018. [46] Qublan H，Amarin Z，Al-Quda M，et al. Luteal phase support with GnRH-a improves implantation and pregnancy rates in IVF cycles with endometrium of ≤7 mm on day of egg retrieval[J]. Human Fertility，2008，11(1):43-47.