Abstract
Purpose: The purpose of this prospective, randomized study was to compare ovarian response and oocyte and embryo yields in women undergoing ovulation induction for IVF/ICSI using recombinant human FSH (rhFSH) alone or in combination with recombinant human LH (rhLH).
Methods: Patients were randomized to receive rhFSH alone (group F; n = 13) or rhFSH + rhLH (group L; n = 15). rhFSH was administered according to a step-down protocol; patients assigned to group L received rhLH at a fixed dose of 75 IU (1 ampoule) throughout the treatment period.
Results: The total dose of rhFSH, number of growing follicles, and serum concentrations of estradiol (E2) on the day of hCG administration were similar in both treatment groups. However, the percentage of metaphase II oocytes and fertilization rate were significantly higher in group F than in group L. The lower fertilization rates associated with rhLH were also seen in a subgroup of patients from group L who had undergone a previous ART cycle stimulated with FSH only and thus acted as their own controls. However, when in vitro fertilization (IVF) and intracytoplasmic sperm injection cycles were considered separately, differences in fertilization rates were statistically significant only for oocytes treated by conventional IVF.
Conclusions: This study shows that the addition of recombinant LH to recombinant FSH in pituitary-suppressed women undergoing ART does not improve the ovarian response and even may have a negative impact on oocyte maturation and fertilization.
Keywords: IVF, LH, oocyte viability, recombinant LH
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REFERENCES
- 1.Filicori M. Gonadotropin-releasing hormone analogs in ovulation induction: currents status and perspectives. J Clin Endocrinol Metab. 1996;81:2413–2416. doi: 10.1210/jcem.81.7.8675552. [DOI] [PubMed] [Google Scholar]
- 2.Lunenfeld B, Lunenfeld E. Gonadotropic preparations-Lessons learned. Fertil Steril. 1997;67:812–814. doi: 10.1016/s0015-0282(97)81389-1. [DOI] [PubMed] [Google Scholar]
- 3.Hull MGR, Armatage RJ, McDermott A. Use of follicle-stimulating hormone alone (urofollitropin*) to stimulate the ovaries for assisted conception after pituitary desensitization. Fertil Steril. 1994;62::997–1003. doi: 10.1016/s0015-0282(16)57064-2. [DOI] [PubMed] [Google Scholar]
- 4.Loumaye E, Engrand P, Howles CM, et al. Assessment of the role of serum luteinizing hormone and estradiol response to follicle-stimulating hormone on in vitro fertilization outcome. Fertil Steril. 1997;67:889–899. doi: 10.1016/s0015-0282(97)81402-1. [DOI] [PubMed] [Google Scholar]
- 5.Daya S. hMGversus FSH: Is there any difference? In: Filicori M, Flamigni C, editors. Ovulation Induction: Update' 98. New York: Parthenon Publishing Group; 1998. pp. 183–192. [Google Scholar]
- 6.Söderström-Anttila V. Clinical outcome of ovulation induction: highly purified FSH versus hMG. In: Filicori M, Flamigni C, editors. Ovulation Induction: Update' 98. New York: Parthenon Publishing Group; 1998. pp. 193–200. [Google Scholar]
- 7.Filicori M. The role of luteinizing hormone in folliculogenis and ovulation induction. Fertil Steril. 1999;71:405–414. doi: 10.1016/s0015-0282(98)00482-8. [DOI] [PubMed] [Google Scholar]
- 8.Chappel SC, Howles C. Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. Hum Reprod. 1991;6:1206–1212. doi: 10.1093/oxfordjournals.humrep.a137513. [DOI] [PubMed] [Google Scholar]
- 9.Fleming R, Chung CC, Yates RWS, et al. Purified urinary follicle stimulating hormone induces different hormone profiles compared with menotrophins, dependent upon the route of administration and endogenous luteinizing hormone activity. Hum Reprod. 1996;11:1854–1858. doi: 10.1093/oxfordjournals.humrep.a019506. [DOI] [PubMed] [Google Scholar]
- 10.Pieters MHEC, Dumoulin JCM, Engelhart CM, et al. Immaturity and aneuploidy in human oocytes after different stimulation protocols. Fertil Steril. 1991;56:306–310. [PubMed] [Google Scholar]
- 11.Balasch J, Fábregues F, Creus M, et al. Pure and highly purified follicle-stimulating hormone alone or in combination with human menopausal gonadotrophin for ovarian stimulation after pituitary suppression in in-vitro fertilization. Hum Reprod. 1996;11:2400–2404. doi: 10.1093/oxfordjournals.humrep.a019123. [DOI] [PubMed] [Google Scholar]
- 12.The European Recombinant Human LH Study Group Recombinant human luteinizing hormone (LH) to support recombinant human follicle-stimulating hormone (FSH)-induced follicular development in LH-and FSH-deficient anovulatory women: a dose-finding study. J Clin Endocrinol Metab. 1998;83:1507–1514. doi: 10.1210/jcem.83.5.4770. [DOI] [PubMed] [Google Scholar]
- 13.Veeck LL. Atlas of the Human Oocyte and Early Conceptus. Baltimore: Williams & Wilkins; 1986. [Google Scholar]
- 14.Jacobson A, Marshall JR. Ovulatory response rate with human menopausal gonadotropins of varying FSH-LH ratios. Fertil Steril. 1969;20:171–175. doi: 10.1016/s0015-0282(16)36915-1. [DOI] [PubMed] [Google Scholar]
- 15.Louwerens B. The clinical significance of the FSH/LH ratio in gonadotropin preparations of human origin. A review. Acta Obstet Gynecol Scand. 1969;48(Suppl1):31–40. doi: 10.3109/00016346909156676. [DOI] [PubMed] [Google Scholar]
- 16.Balasch J, Miró F, Burzaco I, et al. The role of luteinizing hormone in human follicle development and oocyte fertility: Evidence from in-vitro fertilization in a woman with long-standing hypogonadotrophic hypogonadism and using recombinant human follicle stimulating hormone. Hum Reprod. 1995;10:1678–1683. doi: 10.1093/oxfordjournals.humrep.a136154. [DOI] [PubMed] [Google Scholar]
- 17.Fox R, Ekeroma A, Wardle P. Ovarian response to purified FSH in infertile women with long-standing hypogonadotropic hypogonadism. Aust NZ J Obstet Gynaecol. 1997;37:92–94. doi: 10.1111/j.1479-828x.1997.tb02226.x. [DOI] [PubMed] [Google Scholar]
- 18.Cortvrindt R, Hu Y, Smitz J. Recombinant luteinizing hormone as a survival and differentiation factor increases oocyte maturation in recombinant follicle stimulating hormone-supplemented mouse preantral follicle culture. Hum Reprod. 1998;13:1292–1302. doi: 10.1093/humrep/13.5.1292. [DOI] [PubMed] [Google Scholar]
- 19.Hillier SG. Current concepts of the roles of follicle stimulating hormone and luteinizing hormone in folliculogenesis. Hum Reprod. 1994;9:188–191. doi: 10.1093/oxfordjournals.humrep.a138480. [DOI] [PubMed] [Google Scholar]
- 20.Zelinski-Wooten MB, Hutchinson JS, Hess DL, et al. Follicle stimulating hormone alone supports follicle growth and oocyte development in gonadotrophin-releasing hormone antagonist-treated monkeys. Hum Reprod. 1995;10:1658–1666. doi: 10.1093/oxfordjournals.humrep.a136151. [DOI] [PubMed] [Google Scholar]
- 21.Weston AM, Zelinski-Wooten MB, Hutchinson JS, et al. Developmental potential of embryos produced by invitro fertilization from gonadotrophin-releasing hormone antagonist-treated macaques stimulated with recombinant human follicle stimulating hormone alone or in combination with luteinizing hormone. Hum Reprod. 1996;11:608–613. doi: 10.1093/humrep/11.3.608. [DOI] [PubMed] [Google Scholar]
- 22.Kelly EE, Nebiolo L. Recombinant FSH therapy alone versus combination therapy with recombinant LH therapy in patients down-regulated with a low-dose luteal GnRH agonist protocol: Preliminary results. In: Jansen R, Mortimer D, editors. Towards Reproductive Certainty: Fertility & Genetics Beyond 1999. New York: Parthenon Publishing Group; 1999. pp. 200–204. [Google Scholar]
- 23.Sills ES, Levy DP, Moomjy M, et al. A prospective, randomized comparison of ovulation induction using highly purified follicle-stimulating hormone alone and with recombinant human luteinizing hormone in in-vitro fertilization. Hum Reprod. 1999;14:2230–2235. doi: 10.1093/humrep/14.9.2230. [DOI] [PubMed] [Google Scholar]
- 24.Bukovsky A, Chen TT, Wimalasena J, et al. Cellular localization of luteinizing hormone receptor immunoreactivity in the ovaries of immature, gonadotropin-primed and normal cycling rates. Biol Reprod. 1993;48:1367–1382. doi: 10.1095/biolreprod48.6.1367. [DOI] [PubMed] [Google Scholar]
- 25.Schreiber JR, Reed R, Ross GT. A receptor-like testosterone-binding protein in ovaries from estrogen-stimulated hypophysectomized immature female rats. Endocrinology. 1976;98:1206–1213. doi: 10.1210/endo-98-5-1206. [DOI] [PubMed] [Google Scholar]
- 26.Erickson GF, Magoffin DA, Dyer CA, et al. The ovarian androgen producing cells: A review of structure/function relationships. Endocrin Rev. 1985;6:371–399. doi: 10.1210/edrv-6-3-371. [DOI] [PubMed] [Google Scholar]
- 27.Rodgers M, McLoughlin J, Peers N, et al. Accumulation of human chorionic gonadotrophin in the serum of patients during in-vitro fertilization treatment cycles with Pergonal. Hum Reprod. 1994;9:638–642. doi: 10.1093/oxfordjournals.humrep.a138562. [DOI] [PubMed] [Google Scholar]
- 28.Eshkol A. Recombinant gonadotrophins: An introduction. Hum Reprod. 1996;11(Suppl1):89–94. doi: 10.1093/humrep/11.suppl_5.89. [DOI] [PubMed] [Google Scholar]
- 29.Siebold B. Physicochemical characterization of recombinant human follicle stimulating hormone. Hum Reprod. 1996;11(Suppl1):109–115. doi: 10.1093/humrep/11.suppl_5.109. [DOI] [PubMed] [Google Scholar]