Luteinizing hormone changes in gonadotropin-releasing hormone antagonist protocol in in vitro fertilization cycles: A cross-sectional study

Abstract

Background: Because of the unexpected and often dramatic inhibition of luteinizing hormone (LH) secretion related with the usage of gonadotropin-releasing hormone (GnRH)-antagonist, there has been a probable need for exogenous LH supplementation. There is a basic and clinical evidences that show late development of follicle needs an LH but there is a threshold for LH requirements during folliculogenesis.
Objective: The purpose of this study was to evaluate the changes in serum LH and the identification of patients who benefit from the addition of LH.
Materials and Methods: Seventy volunteers for antagonist protocol in IVF cycle were enrolled in this prospective cross-sectional study. The study was carried out in Reproductive Health Research Center, University of Medical Sciences between July 2016 and February 2016. Serum LH level was estimated 24 h before and after the first(GnRH) antagonist injection. The primary outcome was the serum level of LH and its change in the three groups and the secondary outcome was Egg and Embryo quality.
Results: LH changes above or below 50% had no effect on the number of follicle, the number of oocyte, Germinal vesicle oocyte, metaphase 1 oocyte, metaphase 2 oocyte, endometrial thickness, and chemical and clinical pregnancy.
Conclusion: We evaluated the changes of serum LH in the patients who were entered in the antagonist protocol. Our study showed no significant difference in LH levels 24h before and after the injection of the antagonist between the three groups, and LH changes did not affect the outcome of pregnancy.

References
[1] Shoham Z. The clinical therapeutic window for luteinizing hormone in controlled ovarian stimulation. Fertil Steril 2002; 77: 1170–1177.

[2] Hillier SG. Gonadotropic control of ovarian follicular growth and development. Mol Cell Endocrinol 2001; 179: 39–46.

[3] Chappel SC, Howles C. Review Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. Hum Reprod 1991; 6: 1206–1212.

[4] Trounson AO, Leeton JF, Wood C, Webb J, Wood J. Pregnancies in humans by fertilization in vitro and embryo transfer in the controlled ovulatory cycle. Science 1981;212: 681–682.

[5] Schally AV, Arimura A, Baba Y, Nair RM, Matsuo H, Redding TW, et al. Isolation and properties of the FSH and LH-releasing hormone. Biochem Biophys Res Commun 1971; 43: 393–399.

[6] Hahn DW, McGuire JL, Vale WW, Rivier J. Reproductive/endocrine and anaphylactoid properties of an LHRHantagonist, ORF 18260 [Ac-DNAL1 (2), 4FDPhe2, D-Trp3, D-Arg6]-GnRH. Life Sci 1985; 37: 505–514.

[7] Fischer R. Understanding the role of LH: myths and facts. Reprod Biomed Online 2007; 15: 468–477.

[8] Fluker MR, Hooper WM, Yuzpe AA. Withholding gonadotropins (“coasting”) to minimize the risk of ovarian hyperstimulation during superovulation and in vitro fertilization-embryo transfer cycles. Fertil Steril 1999; 71: 294–301.

[9] Al-Inany HG, Youssef MA, Aboulghar M, Broekmans F, Sterrenburg M, Smit J, et al. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev 2011; 11: CD001750.

[10] Kolibianakis EM, Collins J, Tarlatzis BC, Devroey P, Diedrich K, Griesinger G. Among patients treated for IVF with gonadotrophins and GnRH analogues, is the probability of live birth dependent on the type of analogue used? Asystematic review and meta-analysis. Hum Reprod Update 2006; 12: 651–671.

[11] Olivennes F, Fanchin R, Bouchard P, de Ziegler D, Taieb J, Selva J, et al. The single or dual administration of the gonadotropin-releasing hormone antagonist Cetrorelix in an in vitro fertilization-embryo transfer program. Fertil Steril 1994; 62: 468–476.

[12] Kol S. Individualized treatment from theory to practice: the private case of adding LH during GnRH antagonist-based stimulation protocol. Clin Med Insights Reprod Health 2014; 8: 59–64.

[13] Ferraretti AP, Gianaroli L. The bologna criteria for the definition of poor ovarian responders: is there a need for revision? Hum Reprod 2014: 29: 1842–1845.

[14] Younis JS, Izhaki I, Ben-Ami M. The effect of LH supplementation to the GnRH antagonist protocol in advanced reproductive aging women: a prospective randomized controlled study. Clin Endocrinol 2016; 84: 99–106.

[15] Hull M, Corrigan E, Piazzi A, Loumaye E. Recombinant human luteinising hormone: an effective new gonadotropin preparation. Lancet 1994; 344: 334–335.

[16] Howles CM. Role of LH and FSH in ovarian function. Mol Cell Endocrinol 2000; 161: 25–30.

[17] Hillier SG. Current concepts of the roles of follicle stimulating hormone and luteinizing hormone in folliculogenesis. Hum Reprod 1994; 9: 188–191.

[18] Balasch J, Fábregues F. Is luteinizing hormone needed for optimal ovulation induction? Curr Opin Obstet Gynecol2002; 14: 265–274.

[19] Al-Inany HG, Youssef MA, Ayeleke RO, Brown J, Lam WS, Broekmans FJ. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev 2016; 4: CD001750.

[20] Huirne JA, van Loenen AC, Schats R, McDonnell J, Hompes PG, Schoemaker J, et al. Dose-finding study of daily GnRH antagonist for the prevention of premature LH surges in IVF/ICSI patients: optimal changes in LH and progesterone for clinical pregnancy. Hum Reprod 2005;20: 359–367.

[21] Loutradis D, Drakakis P, Milingos S, Stefanidis K, Michalas S. Alternative approaches in the management of poor response in controlled ovarian hyperstimulation (COH). Ann NY Acad Sci 2003; 997: 112–119.

[22] Griesinger G, Shapiro DB, Kolibianakis EM, Witjes H, Mannaerts BM. No association between endogenous LH and pregnancy in a GnRH antagonist protocol: part II, recombinant FSH. Reprod Biomed Online 2011; 23: 457–465.

[23] Hill MJ, Levens ED, Levy G, Ryan ME, Csokmay JM, DeCherney AH, et al. The use of recombinant luteinizing hormone in patients undergoing assisted reproductive techniques with advanced reproductive age: a systematic review and meta-analysis. Fertil Steril 2012; 97: 1108–1114.