Abstract
Purpose
To assess the effect of supplementation with recombinant human luteinizing hormone (rhLH) for patients treated either with recombinant follicle stimulating hormone (rFSH) plus rhLH or with rFSH plus human menopausal gonadotrophin (HMG) in a long gonadotrophin-releasing hormone (GnRH) agonist-stimulation protocol.
Methods
A single-centre, retrospective analysis of patients with hypo responsiveness to a long GnRH agonist protocol (n = 174), with consecutive in-vitro fertilization or intracytoplasmic sperm injection cycles, compared the outcomes of long luteal GnRH agonist ovarian stimulation using rFSH combined with HMG (n = 100) versus rFSH combined with rhLH (n = 74). The endpoints included clinical pregnancy, number of oocytes retrieved, and total gonadotrophin dose.
Results
Significantly more clinical pregnancies were achieved after stimulation with rFSH and rhLH than after stimulation with rFSH and HMG (35.1 vs. 19%, p < 0.01). More oocytes were recovered (13.1 vs. 11.3, p = 0.024) with less FSH utilized in the rFSH and rhLH group than in the rFSH and HMG group (2706.4 vs. 4134.2 U, p < 0.001).
Conclusions
Use of rFSH combined with rhLH in long GnRH agonist assisted reproductive technology (ART) cycles was associated with more clinical pregnancies, recovery of more oocytes, and reduction in gonadotrophin use, suggesting that the superior purity and consistency of rFSH and rhLH may result in better clinical outcomes.
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References
Humaidan P, Bungum L, Bungam M, Andersen C. Ovarian response and pregnancy outcome related to midfollicular LH levels in women undergoing assisted reproduction with GnRH agonist down-regulation and recombinant FSH stimulation. Hum Reprod. 2002;17:2016–21.
Lahoud R, Al-Jefout M, 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. Hum Reprod. 2006;21:2645–9.
Nakagawa K, Ohgi S, Nakashima A, Horikawa T, Sugiyama R, Saito H. The ratio of late-follicular to midfollicular phase LH concentrations efficiently predicts ART outcomes in women undergoing ART treatment with GnRH-agonist long protocol and stimulation with recombinant FSH. J Assist Reprod Genet. 2008;25:359–64.
Lisi F, Rinaldi L, Fishel S, Lisi R, Pepe G, Picconeri MG. Use of recombinant follicle-stimulating hormone (Gonal F) and recombinant luteinizing hormone (Luveris) for multiple follicular stimulation in patients with a suboptimal response to in vitro fertilization. Fertil Steril. 2003;79:1037–8.
Mochtar MH, van der Veen F, Ziech M, van Wely M Musters A. Recombinant luteinizing hormone (rLH) for controlled ovarian hyperstimulation in assisted reproductive cycles. Cochrane Database Syst Rev. 2007;18:CD005070.
Ferraretti AP, Gianaroli L, Magli MC, D’angelo A, Fafalli V, Montanaro N. Exogenous luteinizing hormone in controlled ovarian hyperstimulation for assisted reproduction techniques. Fertil Steril. 2004;82:1521–6.
Veeck L. Atlas of the human oocytes and early conceptus. Baltimore: Williams and Wilkins; 1991. p. 46.
Hugues JN, Bstandig B, Bry-Gauillard H, Uzan M, Cedrin-Durnerin I. Comparison of the effectiveness of recombinant and urinary FSH preparations in the achievement of follicular selection in chronic anovulation. Reprod Biomed Online. 2001;3:195–8.
Bergh C, Howles CM, Borg K, Hamberger L, Josefsson B, Nilsson L, Wikland M. Recombinant human follicle stimulating hormone (r-hFSH; Gonal-F®) versus highly purified urinary FSH (Metrodin HP®): results of a randomized comparative study in women undergoing assisted reproductive techniques. Hum Reprod. 1997;12:2133–9.
Hillier SG. Paracrine support of ovarian stimulation. Mol Hum Reprod. 2009;15:843–50.
Carone D, Vizziello G, Vitti A, Chiappetta R. Clinical outcomes of ovulation induction in WHO Group I anovulatory women using r-hFSH + r-hLH in a 2:1 ratio compared to hMG. Hum Reprod. 2010;25:i285–321.
Thornton K, Alper MM, Ryley D, Ezcurra D. Outcomes of GnRH antagonist IVF cycles using LH supplementation for COH: FSH/rhLH vs. FSH/hMG. Fertil Steril. 2006;86:S411.
Shoham Z. The clinical therapeutic window for luteinizing hormone in controlled ovarian stimulation. Fertil Steril. 2002;77:1170–7.
Weghofer A, Munne S, Brannath W, Chen S, Barad D, Cohen J, Gleicher N. The impact of LH-containing gonadotropin stimulation on euploidy rates in preimplantation embryos: antagonist cycles. Fertil Steril. 2009;92:937–42.
Grondahl ML, Borup R, Lee YB, Myrhoj V, Meinertz H, Sorensen S. Differences in gene expression of granulosa cells from women undergoing controlled ovarian hyperstimulation with either recombinant follicle-stimulating hormone or highly purified human menopausal gonadotropin. Fertil Steril. 2009;91:1820–30.
Pezzuto A, Ferrari B, Coppola F, Nardelli GB. LH supplementation in down-regulated women undergoing assisted reproduction with baseline low serum LH levels. Gynecol Endocrinol. 2010;26:118–24.
Acknowledgments
We would like to thank Dr K. Murali Krishna for his help in the preparation of this manuscript.
Conflict of interest
G.A. Ramaraju, Kavitha, Kavitha Lakshmi and Ravikrishna have no conflicts of interest to declare. S.C Teng is an employee of Merck Pte Ltd.
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Raju, G.A.R., Teng, S.C., Kavitha, P. et al. Combination of recombinant follicle stimulating hormone with human menopausal gonadotrophin or recombinant luteinizing hormone in a long gonadotrophin-releasing hormone agonist protocol: a retrospective study. Reprod Med Biol 11, 129–133 (2012). https://doi.org/10.1007/s12522-012-0120-2
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DOI: https://doi.org/10.1007/s12522-012-0120-2