Pituitary suppression before frozen embryo transfer is beneficial for patients suffering from idiopathic repeated implantation failure

Summary Long-term gonadotropin-releasing hormone agonist (GnRHa) administration before in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in infertile women with endometriosis or adenomyosis significantly enhanced the chances of pregnancy in both fresh and frozen embryo transfer cycles. We hypothesized that long-term GnRHa treatment might also be beneficial for the idiopathic repeated implantation failure (RIF) patients. In the 21 patients receiving GnRHa and hormone replacement therapy (G-HRT) protocols for frozen embryo transfer, their data were compared with those of the 56 of frozen/fresh cycles they had previously undergone (previous protocols). Comparison showed that the finial results were significantly better with G-HRT protocols than with their previous protocols, with pregnancy rate, clinical pregnancy rate, implantation rate and on-going pregnancy rate being 70%, 60%, 40% and 38% respectively with G-HRT protocols, against 17%, 11%, 6.3% and 5% with previous protocols. The results showed that hormonally controlled endometrial preparation with prior GnRHa suppression could be used for patients who had experienced repeated failures of IVF treatment despite having morphologically optimal embryos, and the treatment may help increase the receptivity of the endometrium in these patients. Similar content being viewed by others References Raziel A, Friedler S, Schachter M, et al. Increased frequency of female partner chromosomal abnormalities in patients with high-order implantation failure after in vitro fertilization. Fertil Steril, 2002,78(3):515–519 Rubio C, Gil-Salom M, Simon C, et al. Incidence of sperm chromosomal abnormalities in a risk population: relationship with sperm quality and ICSI outcome. Hum Reprod, 2001,16(10):2084–2092 Voullaire L, Wilton L, McBain J, et al. Chromosome abnormalities identified by comparative genomic hybridization in embryos from women with repeated implantation failure. Mol Hum Reprod, 2002,8(11):1035–1041 Surrey ES. Impact of intramural leiomyomata on in-vitro fertilization-embryo transfer cycle outcome. Curr Opin Obstet Gynecol, 2003,15(3):239–242 Demirol A, Gurgan T. Effect of treatment of intrauterine pathologies with office hysteroscopy in patients with recurrent IVF failure. Reprod Biomed Online, 2004,8(5): 590–594 Costello MF, Lindsay K, McNally G. The effect of adenomyosis on in vitro fertilisation and intra-cytoplasmic sperm injection treatment outcome. Eur J Obstet Gynecol Reprod Biol, 2011,158(2):229–234 Hatasaka H. New perspectives for unexplained infertility. Clin Obstet Gynecol, 2011,54(4):727–733 Isaksson R, Tiitinen A. Present concept of unexplained infertility. Gynecol Endocrinol, 2004,18(5):278–290 Tan BK, Vandekerckhove P, Kennedy R, et al. Investigation and current management of recurrent IVF treatment failure in the UK. BJOG, 2005,112(6):773–780 Coughlan C, Ledger W, Wang Q, et al. Recurrent implantation failure: definition and management. Reprod Biomed Online, 2014,28(1):14–38 Cohen J, DeVane GW, Elsner CW, et al. Cryopreserved zygotes and embryos and endocrinologic factors in the replacement cycle. Fertil Steril, 1988,50(1):61–67 Oehninger S, Mayer J, Muasher S. Impact of different clinical variables on pregnancy outcome following embryo cryopreservation. Mol Cell Endocrinol, 2000,169 (1–2):73–77 de Ziegler D, Cornel C, Bergeron C, et al. Controlled preparation of the endometrium with exogenous estradiol and progesterone in women having functioning ovaries. Fertil Steril, 1991,56(5):851–855 Queenan Jr, Veeck LL, Seltman HJ, et al. Transfer of cryopreserved-thawed pre-embryos in a natural cycle or a programmed cycle with exogenous hormonal replacement yields similar pregnancy results. Fertil Steril, 1994,62(3): 545–550 Lin J, Sun C, Zheng H. Gonadotropin-releasing hormone agonists and laparoscopy in the treatment of adenomyosis with infertility. Chin Med J (Engl), 2000,113(5):442–445 Silva PD, Perkins HE, Schauberger CW. Live birth after treatment of severe adenomyosis with a gonadotropin-releasing hormone agonist. Fertil Steril, 1994,61(1): 171–172 Surrey ES, Silverberg KM, Surrey MW, et al. Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis. Fertil Steril, 2002,78(4): 699–704 Huang FJ, Kung FT, Chang SY, et al. Effects of short-course buserelin therapy on adenomyosis. A report of two cases. J Reprod Med, 1999,44(8):741–744 Devlieger R, D'Hooghe T, Timmerman D. Uterine adenomyosis in the infertility clinic. Hum Reprod Update, 2003,9(2):139–147 Niu Z, Chen Q, Sun Y, et al. Long-term pituitary downregulation before frozen embryo transfer could improve pregnancy outcomes in women with adenomyosis. Gynecol Endocrinol, 2013,29(12):1026–1030 Simon A, Hurwitz A, Zentner BS, et al. Transfer of frozen-thawed embryos in artificially prepared cycles with and without prior gonadotrophin-releasing hormone agonist suppression: a prospective randomized study. Hum Reprod, 1998,13(10):2712–2717 Tremellen K, Russell P. Adenomyosis is a potential cause of recurrent implantation failure during IVF treatment. Aust N Z J Obstet Gynaecol, 2011,51(3):280–283 Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in vitro fertilization. Fertil Steril, 2002,77 (6):1148–1155 Kuivasaari P, Hippelainen M, Anttila M, et al. Effect of endometriosis on IVF/ICSI outcome: stage III/IV endometriosis worsens cumulative pregnancy and live-born rates. Hum Reprod, 2005,20(11):3130–3135 Kyama CM, Debrock S, Mwenda JM, et al. Potential involvement of the immune system in the development of endometriosis. Reprod Biol Endocrinol, 2003,Dec(1):123 Kissler S, Zangos S, Kohl J, et al. Duration of dysmenorrhoea and extent of adenomyosis visualised by magnetic resonance imaging. Eur J Obstet Gynecol Reprod Biol, 2008,137(2):204–209 Sallam HN, Garcia-Velasco JA, Dias S, et al. Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev, 2006:CD004635 Sharpe-Timms KL, Keisler LW, McIntush EW, et al. Tissue inhibitor of metalloproteinase-1 concentrations are attenuated in peritoneal fluid and sera of women with endometriosis and restored in sera by gonadotropin-releasing hormone agonist therapy. Fertil Steril, 1998,69(6): 1128–1134 Ferrero S, Gillott DJ, Remorgida V, et al. Proteomic analysis of peritoneal fluid in fertile and infertile women with endometriosis. J Reprod Med, 2009,54(1):32–40 Ferrero S, Gillott DJ, Remorgida V, et al. GnRH analogue remarkably down-regulates inflammatory proteins in peritoneal fluid proteome of women with endometriosis. J Reprod Med, 2009,54(4):223–231 Wang J, Zhou F, Dong M, et al. Prolonged gonadotropin-releasing hormone agonist therapy reduced expression of nitric oxide synthase in the endometrium of women with endometriosis and infertility. Fertil Steril, 2006,85(4): 1037–1044 Lessey BA. Medical management of endometriosis and infertility. Fertil Steril, 2000,73(6):1089–1096 Ruan HC, Zhu XM, Luo Q, et al. Ovarian stimulation with GnRH agonist, but not GnRH antagonist, partially restores the expression of endometrial integrin beta3 and leukaemia-inhibitory factor and improves uterine receptivity in mice. Hum Reprod, 2006,21(10):2521–2529 Kdous M, Chaker A, Bouyahia M, et al. Increased risk of early pregnancy loss and lower live birth rate with GNRH antagonist vs. long GNRH agonist protocol in PCOS women undergoing controlled ovarian hyperstimulation. Tunis Med, 2009,87(12):834–842 Kwak-Kim JY, Chung-Bang HS, Ng SC, et al. Increased T helper 1 cytokine responses by circulating T cells are present in women with recurrent pregnancy losses and in infertile women with multiple implantation failures after IVF. Hum Reprod, 2003,18(4):767–773 Younis A, Hawkins K, Mahini H, et al. Serum tumor necrosis factor-alpha, interleukin-6, monocyte chemotactic protein-1 and paraoxonase-1 profiles in women with endometriosis, PCOS, or unexplained infertility. J Assist Reprod Genet, 2014,31(11):1445–1451 Ledee-Bataille N, Bonnet-Chea K, Hosny G, et al. Role of the endometrial tripod interleukin-18,-15, and-12 in inadequate uterine receptivity in patients with a history of repeated in vitro fertilization-embryo transfer failure. Fertil Steril, 2005,83(3):598–605 van Gestel I, MM IJ, Hoogland HJ, et al. Endometrial wave-like activity in the non-pregnant uterus. Hum Reprod Update, 2003,9(2):131–138 Urman B, Ata B, Yakin K, et al. Luteal phase empirical low molecular weight heparin administration in patients with failed ICSI embryo transfer cycles: a randomized open-labeled pilot trial. Hum Reprod, 2009,24(7): 1640–1647 Author information Authors and Affiliations Corresponding author Additional information This project was supported by grants from the National Natural Science Foundation of China (No. 81100401 and No. 81470063), Guangdong Natural Science Foundation of China (No. 2014A030313129), and the Doctoral Fund of the Ministry of Education of China (No. 20110171120096). Rights and permissions About this article Cite this article Yang, X., Huang, R., Wang, Yf. et al. Pituitary suppression before frozen embryo transfer is beneficial for patients suffering from idiopathic repeated implantation failure. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 36, 127–131 (2016). https://doi.org/10.1007/s11596-016-1554-2 Received: Revised: Published: Issue date: DOI: https://doi.org/10.1007/s11596-016-1554-2