Endometrial preparation using gonadotropin-releasing hormone agonist prior to frozen-thawed embryo transfer in women with repeated implantation failure: An RCT

Abstract

Background: Preparation of endometrial thickness in frozen-thawed embryo transfer (FET) is extremely important, particularly in repeated implantation failure (RIF) patients.


Objective: This study aimed to investigate the clinical outcomes of FET cycles among RIF women, based on the effects of administering gonadotropin-releasing hormone (GnRH) agonist prior to estrogen-progesterone preparation of the endometrium.


Materials and Methods: In this randomized clinical trial, 67 infertile women who were candidates for FET were divided into two groups: A) case group (n = 34), treated with GnRH agonist prior to endometrial preparation and B) control group (n = 33), which received the routine protocol. (6 mg daily estradiol started from second day) The clinical outcomes) including chemical and clinical pregnancy, in addition to implantation rates, were compared between the two groups.


Results: The results showed no significant differences in women’s age (p = 0.558), duration (p = 0.540), type (p = 0.562), and cause of infertility (p = 0.699). Regarding pregnancy and implantation rates, there was a trend toward an increase in the case group; however, differences were not statistically significant.


Conclusion: Although our results showed no significant differences between groups. Because there are trends to better results in case group larger sample size may show significant difference.


Key words: Implantation failure, Gonadotropin-releasing hormone, Embryo transfer, Pregnancy, Implantation.

References
[1] Gardner DK, Weissman A, Howles CM, Shoham Z. Textbook of assisted reproductive techniques. 5th Ed. Clinical Perspectives: CRC press; 2017.

[2] Yarali H, Polat M, Mumusoglu S, Yarali I, Bozdag G. Preparation of endometrium for frozen embryo replacement cycle: a systematic review and meta-analysis. J Assist Reprod Genet 2016; 33: 1287–1304.

[3] Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozenthawed embryo transfer in normal responders. Fertility and sterility. 2011 Aug 1;96(2):344–8.

[4] Ming L, Liu P, Qiao J, Lian Y, Zheng X, Ren X, et al. Synchronization between embryo development and endometrium is a contributing factor for rescue ICSI outcome. Reprod Biomed Online 2012; 24: 527–531.

[5] Groenewoud ER, Cantineau AE, Kollen BJ, Macklon NS, Cohlen BJ. What is the optimal means of preparing the endometrium in frozenthawed embryo transfer cycle? A systematic review and meta-analysis. Hum Reprod Updat 2013; 19: 458–470.

[6] Ozgur K, Berkkanoglu M, Bulut H, Humaidan P, Coetzee K. Agonist depot versus OCP programming of frozen embryo transfer: a retrospective analysis of freeze-all cycles. J Assist Reprod Genet 2016; 33: 207–214.

[7] Makrigiannakis A, BenKhalifa M, Vrekoussis T, Mahjub S, Kalantaridou SN, Gurgan T. Repeated implantation failure: a new potential treatment option. Eur J Clin Invest 2015; 45: 380–384.

[8] Roque M, Lattes K, Serra S, Sola I, Geber S, Carreras R, Checa MA. Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis. Fertil Steril 2013; 99: 156–162.

[9] Guo S, Zhang D, Niu Z, Sun Y, FengY. Pregnancy outcomes and neonatal outcomes after pituitary down-regulation in patients with adenomyosis receiving IVF/ICSI and FET. Results of a retrospective cohort study. Int J Clin Exp Med 2016; 9: 14313–14320.

[10] Surrey ES, Silverberg KM, Surrey MW, Schoolcraft WB. Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilizationembryo transfer in patients with endometriosis. Fertil Steril 2002; 78: 699–704.

[11] Niu Z, Chen Q, Sun Y, Feng Y. Long-term pituitary downregulation before frozen embryo transfer could improve pregnancy outcomes in women with adenomyosis. Gynecol Endocrinol 2013; 29: 1026–1030.

[12] Yang X, Dong X, Huang K, Wang L, Xiong T, Ji L, et al. The effect of accompanying dominant follicle development/ovulation on the outcomes of frozen-thawed blastocyst transfer in HRT cycle. Int J Clin Exp Pathol 2013; 6: 718–723.

[13] Hebisha SA, Adel HM. GnRh agonist treatment improves implantation and pregnancy rates of frozen-thawed embryos transfer. J Obstet Gynaecol India 2017; 67: 133–136.

[14] Tsai HW, Wang PH, Lin LT, Chen SN, Tsui KH. Using gonadotropin-releasing hormone agonist before frozen embryo transfer may improve ongoing pregnancy rates in hyperandrogenic polycystic ovary syndrome women. Gynecol Endocinol 2017; 33: 686–689.

[15] Yang X, Huang R, Wang YF, Liang XY. Pituitary suppression before frozen embryo transfer is beneficial for patients suffering from idiopathic repeated implantation failure. J Huazhong Univ Sci Technolog Med Sci 2016; 36: 127–131.

[16] Ferrero S, Gillott DJ, Remorgida V, Anserini P, Ragni N, Grudzinskas JG. Proteomic analysis of peritoneal fluid in fertile and infertile women with endometriosis. J Reprod Med 2009; 54: 32–40.

[17] Ferrero S, Gillott DJ, Remorgida V, Anserini P, Ragni N, Grudzinskas JG. GnRH analogue remarkably down-regulates inflammatory proteins in peritoneal fluid proteome of women with endometriosis. J Reprod Med 2009; 54: 223–231.

[18] Tremellen K, Russell P. Adenomyosis is a potential cause of recurrent implantation failure during IVF treatment. Aust N Z J Obstet Gynaecol 2011; 51: 280–283.

[19] Dal Prato L, Borini A, Cattoli M, Bonu MA, Sciajno R, Flamigni C. Endometrial preparation for frozen-thawed embryo transfer with or without pretreatment with gonadotropin-releasing hormone agonist. Fertil Steril 2002; 77: 956–960.

[20] Davar R, Eftekhar M, Tayebi N. Transfer of cryopreserved-thawed embryos in a cycle using exogenous steroids with or without prior gonadotropihin-releasing hormone agonist. J Med Sci 2007; 7: 880–883.