Cover
Vol. 11 No. 2 (2021)

Published: October 31, 2021

Pages: 101-116

Research Article

Adding Low Dose hCG to rFSH in GnRH Antagonist ICSI Cycles: A Randomized Controlled Trial

Firas Fadhil Al-Masoody 1 Manal Taha Al-Obaidi
1High Institute of Infertility Diagnosis and Assisted Reproductive Technologies, Al Nahrain University, Baghdad, Iraq.
History
  • Received: November 2, 2020
  • Accepted: August 5, 2021
  • Available Online: November 12, 2021
DOI

https://doi.org/10.28969/IJEIR.v11.i2.r8

Abstract

Inhibition of luteinizing hormone (LH) by gonadotropin releasing hormone (GnRH) antagonist may lead to suboptimal response during ovarian stimulation. In addition, several studies suggest that low level of LH is associated with lowered fertilization and implantation rate and increased early pregnancy loss rate. The aim of this study is to study the effect of adding low dose human chorionic gonadotropin (hCG - 200 IU), as an LH supplement, to recombinant follicle stimulating hormone (rFSH) in a GnRH antagonist cycles in women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. Sixty-three infertile women undergoing IVF were randomly divided into two groups. One group was stimulated with the conventional stimulation protocol (rFSH alone), while the second group received 200 IU hCG in addition to rFSH in the late follicular phase (hCG + rFSH). Both groups' results including pregnancy rate, total dose of rFSH required, duration of stimulation, endometrial thickness, oocytes and embryos characteristic, serum hormone levels (Testosterone, Estradiol, Progesterone, and LH) and level of epidermal growth factor (EGF) were compared. The results show that pregnancy rate among the group of women who received the low dose hCG was higher than those who did not receive hCG. However, this difference did not reach statistical significance. Furthermore, other cycle outcomes and hormonal values were comparable between the two stimulation protocols.

Keywords

References

  1. Efstratios M, Kolibianakis JK, Tarlatzis BC. Gonadotropin-releasing hormone antagonists in ovarian stimulation for in vitro fertilization. In Gardner DK, Weissman A, Howles CM, Shoham Z (Eds.), Textbook of Assisted Reproductive Techniques volume 2: Clinical Perspectives, 5th ed., CRC Press, 2018:533–561. [Online article link]
  2. Tarlatzis BC, Fauser BC, Kolibianakis EM, Diedrich K, Devroey P. GnRH antagonists in ovarian stimulation for IVF. Human Reproduction Update. Oxford University Press (OUP); 2006 Mar 24;12(4):333–40. [Online article link]
  3. Griesinger G. Ovarian Hyperstimulation Syndrome Prevention Strategies: Use of Gonadotropin-Releasing Hormone Antagonists. Seminars in Reproductive Medicine. Georg Thieme Verlag KG; 2010 Nov;28(06):493–9. [Online article link]
  4. Khalaf OI, Al-Obaidi MT, Al-Anbari LA. Role of Low-Dose Human Chorionic Gonadotropin Following Clomiphene Citrate in Folliculogenesis and Ovulation in Infertile Women. Iraqi Journal of Embryos and Infertility Researches, 2018;8(1):29-37. [Online article link]
  5. Griesinger G, Dawson A, Schultze-Mosgau A, Finas D, Diedrich K, Felberbaum R. Assessment of luteinizing hormone level in the gonadotropin-releasing hormone antagonist protocol. Fertility and Sterility. Elsevier BV; 2006 Mar;85(3):791–3. [Online article link]
  6. Gardner DK, Weissman A, Howles CM, Shoham Z. (Eds.). Textbook of Assisted Reproductive Techniques Volume 2: Clinical Perspectives, 5th ed., CRC Press, 2018. [Online article link]
  7. Barbieri RL. The Endocrinology of the Menstrual Cycle. Human Fertility. Springer Al-Masoody and Al-Obaidi. http://doi.org/10.28969/IJEIR.v11.i2.r8 112 New York; 2014;145–69. [Online article link]
  8. Hillier SG, Whitelaw PF, Smyth CD. Follicular oestrogen synthesis: the “two- cell, two-gonadotrophin” model revisited. Molecular and Cellular Endocrinology. Elsevier BV; 1994 Apr;100(1-2):51–4. [Online article link]
  9. Propst AM, Hill MJ, Bates GW, Palumbo M, Van Horne AK, Retzloff MG. Low-dose human chorionic gonadotropin may improve in vitro fertilization cycle outcomes in patients with low luteinizing hormone levels after gonadotropin-releasing hormone antagonist administration. Fertility and Sterility. Elsevier BV; 2011 Oct;96(4):898– 904. [Online article link]
  10. Urman B, Ata B, Yarali H. Endocrine characteristics of assisted reproduction technology cycles. In Gardner DK, Weissman A, Howles CM, Shoham Z. Textbook of Assisted Reproductive Techniques. Volume 2: Clinical Perspectives, 5th ed., CRC Press, 2018:533– 542. [Online article link]
  11. Acevedo B, Sanchez M, Gomez JL, Cuadros J, Ricciarelli E, Hernández ER. Luteinizing hormone supplementation increases pregnancy rates in gonadotropin- releasing hormone antagonist donor cycles. Fertility and Sterility. Elsevier BV; 2004 Aug;82(2):343–7. [Online article link]
  12. Alviggi C, Clarizia R, Mollo A, Ranieri A, De Placido G. Who needs LH in ovarian stimulation? Reproductive BioMedicine Online. Elsevier BV; 2011 Feb;22:S33– S41. [Online article link]
  13. Van Horne AK, Bates GW, Robinson RD, Arthur NJ, Propst AM. Recombinant follicle-stimulating hormone (rFSH) supplemented with low-dose human chorionic gonadotropin compared with rFSH alone for ovarian stimulation for in vitro fertilization. Fertility and Sterility. Elsevier BV; 2007 Oct;88(4):1010–3. [Online article link]
  14. Filicori M, Cognigni GE, Gamberini E, Parmegiani L, Troilo E, Roset B. Efficacy of low-dose human chorionic gonadotropin alone to complete controlled ovarian stimulation. Fertility and Sterility. Elsevier Al-Masoody and Al-Obaidi. http://doi.org/10.28969/IJEIR.v11.i2.r8 113 BV; 2005 Aug;84(2):394–401. [Online article link]
  15. Serafini P, Yadid I, Motta E, Alegretti J, Fioravanti J, Coslovsky M. Ovarian stimulation with daily late follicular phase administration of low-dose human chorionic gonadotropin for in vitro fertilization: a prospective, randomized trial. Fertility and Sterility. Elsevier BV; 2006 Oct;86(4):830– 8. [Online article link]
  16. Ferraretti AP, La Marca A, Fauser BCJM, Tarlatzis B, Nargund G, Gianaroli L. ESHRE consensus on the definition of ’poor response to ovarian stimulation for in vitro fertilization: The Bologna criteria. Human Reproduction, Oxford University Press (OUP); 2011;26(7):1616–1624. [Online article link]
  17. Bosch E, Ezcurra D. Individualised controlled ovarian stimulation (iCOS): maximising success rates for assisted reproductive technology patients. Reproductive Biology and Endocrinology. Springer Science and Business Media LLC; 2011;9(1):82. [Online article link]
  18. Mochtar MH, Danhof NA, Ayeleke RO, Van der Veen F, van Wely M. Recombinant luteinizing hormone (rLH) and recombinant follicle stimulating hormone (rFSH) for ovarian stimulation in IVF/ICSI cycles. Cochrane Database of Systematic Reviews. Wiley; 2017 May 24;2017(5). [Online article link]
  19. Kolibianakis EM, Kalogeropoulou L, Griesinger G, Papanikolaou EG, Papadimas J, Bontis J, et al. Among patients treated with FSH and GnRH analogues for in vitro fertilization, is the addition of recombinant LH associated with the probability of live birth? A systematic review and meta- analysis. Human Reproduction Update. Oxford University Press (OUP); 2007 Jun 23;13(5):445–52. [Online article link]
  20. Cole LA. Biological functions of hCG and hCG-related molecules. Reproductive Biology and Endocrinology. Springer Science and Business Media LLC; 2010;8(1):102. [Online article link]
  21. Aghahosseini M, Aleyasin A, Yekehtaz H, Kashani L. Low-dose human chorionic gonadotropin adjunct to an antagonist Al-Masoody and Al-Obaidi. http://doi.org/10.28969/IJEIR.v11.i2.r8 114 protocol in assisted reproductive technology: a randomized trial study. Acta Med Iran. 2014;52(6):430-7. PMID: 25130149. [Online article link]
  22. Humaidan P, Bungum M, Bungum L, Yding Andersen C. Effects of recombinant LH supplementation in women undergoing assisted reproduction with GnRH agonist down-regulation and stimulation with recombinant FSH: an opening study. Reproductive BioMedicine Online. Elsevier BV; 2004 Jan;8(6):635–43. [Online article link]
  23. Filicori M, Cognigni GE, Taraborrelli S, Spettoli D, Ciampaglia W, Tabarelli de Fatis C. Low-dose human chorionic gonadotropin therapy can improve sensitivity to exogenous follicle-stimulating hormone in patients with secondary amenorrhea. Fertility and Sterility. Elsevier BV; 1999 Dec;72(6):1118–20. [Online article link]
  24. Gomaa H, Casper RF, Esfandiari N, Chang P, Bentov Y. Addition of low dose hCG to rFSh benefits older women during ovarian stimulation for IVF. Reproductive Biology and Endocrinology. Springer Science and Business Media LLC; 2012 Aug 6;10(1). [Online article link]
  25. Levi-Setti PE, Cavagna M, Bulletti C. Recombinant gonadotrophins associated with GnRH antagonist (cetrorelix) in ovarian stimulation for ICSI: Comparison of r-FSH alone and in combination with r-LH. European Journal of Obstetrics & Gynecology and Reproductive Biology. Elsevier BV; 2006 Jun;126(2):212–6. [Online article link]
  26. Tarlatzis B, Tavmergen E, Szamatowicz M, Barash A, Amit A, Levitas E, et al. The use of recombinant human LH (lutropin alfa) in the late stimulation phase of assisted reproduction cycles: a double- blind, randomized, prospective study. Human Reproduction. Oxford University Press (OUP); 2005 Sep 19;21(1):90–4. [Online article link]
  27. Lahoud R, Jefout MA-, Tyler J, Ryan J, Driscoll G. A relative reduction in mid- follicular LH concentrations during GnRH agonist IVF/ICSI cycles leads to lower live birth rates. Human Reproduction. Oxford Al-Masoody and Al-Obaidi. http://doi.org/10.28969/IJEIR.v11.i2.r8 115 University Press (OUP); 2006 Jun 19;21(10):2645–9. [Online article link]
  28. O’Dea L, O’Brien F, Currie K, Hemsey G. Follicular development induced by recombinant luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in anovulatory women with LH and FSH deficiency: evidence of a threshold effect. Current Medical Research and Opinion. Informa Healthcare; 2008 Aug 25;24(10):2785–93. [Online article link]
  29. Tesarik J, Hazout A, Mendoza C. Luteinizing hormone affects uterine receptivity independently of ovarian function. Reproductive BioMedicine Online. Elsevier BV; 2003 Jan;7(1):59–64. [Online article link]