Volume 108, Issue 1 , Pages 69-70, January 2010
Higher leuprolide dose does not diminish the ovarian response to gonadotropins in a protocol using pre-treatment with oral contraceptives
Article Outline
Keywords: Gonadotropin-releasing hormone agonist, Infertility, In vitro fertilization, Leuprolide, Ovarian follicle
The optimal leuprolide dose for in vitro fertilization (IVF) protocols using oral contraceptives has not been determined. The aim of the present study was to investigate whether higher leuprolide doses altered ovarian stimulation, cycle cancellation rates, IVF outcomes, or baseline ovarian cysts compared with lower doses.
A retrospective study of 393 consecutive oral contraceptive/leuprolide IVF cycles from 2000 to 2005 was approved by Institutional Review Board. Three physicians each primarily used a different dose of leuprolide for downregulation and stimulation: 1.0/0.5
mg; 1.0/0.25mg; or 0.5/0.25mg. Other aspects of the treatment were the same in each group, such as: indications for IVF; pre-cycle desogestrel 0.15mg and ethinylestradiol 30µg for 14–21days; use of mixed gonadotropins (starting dose, 300IU/day; maximal dose, 450IU/day); oocyte retrieval; and embryo transfer. Patients with diminished ovarian reserve were excluded.
The statistical methods used were χ2, Fisher's exact, Wilcoxon rank-sum, and t tests. A generalized estimating equation was used to correct for the intra-class correlation in the data.
The 1.0/0.5-mg group had the lowest total gonadotropin requirement, and the largest number of oocytes and embryos was obtained in this group (P<0.05) (Table 1). The demographic data were similar for all groups and there were no differences in the initial gonadotropin dose, incidence of baseline ovarian cysts, cycle cancellation rate, or pregnancy rate.
Table 1. Clinical outcomes with different leuprolide doses.
| Leuprolide dose, mg | Gonadotropin dose, units a | Cycles cancelled, % | Mean No. of oocytes retrieved a, b | Mean No. of embryos a, b | Pregnancy rate, % |
|---|---|---|---|---|---|
| 1.0/0.5 | 3127 | 2.6 | 18.6 | 11.8 | 61 |
| 1.0/0.25 | 3405 | 8.9 | 16.2 | 11.0 | 61 |
| 0.5/0.25 | 3587 | 7.1 | 14.4 | 9.2 | 58 |
aComparison of leuprolide doses 1.0/0.5 and 0.5/0.25 |
bComparison of leuprolide doses 1.0/0.25 and 0.5/0.25 |
The results from the present study were not as expected. Gonadotropin response was not enhanced by low-dose leuprolide compared with higher doses, as would be expected if leuprolide had a direct effect on the ovaries [1], [2]. Furthermore, the incidence of baseline ovarian cysts and premature ovulation was similar with all doses of leuprolide, which was inconsistent with a more complete suppression of endogenous follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by higher doses.
Oral contraceptives were used before leuprolide was initiated in all of the cycles [3], and it is possible that—as occurs with long-term use of gonadotropin-releasing hormone (GnRH) agonists—this minimized the incidence of baseline ovarian cysts and provided comparable endogenous LH and FSH suppression among the 3 groups [4].
The results of the present study must be interpreted with caution. In any retrospective study, there is potential for bias between the groups. Furthermore, the results are not applicable to cycles in which oral contraceptives are not used or to GnRH antagonist protocols. Nevertheless, they indicate that higher leuprolide doses do not diminish the ovarian response or impair fertilization in a stimulation protocol using pre-treatment with oral contraceptives.
Conflict of interest
The authors have no conflicts of interest.
References
- . Management of the poor responder: the role of GnRH agonists and antagonists. J Assist Reprod Genet. 2007;24(12):613–619
- . Leuprolide acetate reduces both in vivo and in vitro ovarian steroidogenesis in infertile women undergoing assisted reproduction. Steroids. 2008;73(14):1475–1484
- . A randomized prospective trial comparing gonadotropin-releasing hormone (GnRH) antagonist/recombinant follicle-stimulating hormone (rFSH) versus GnRH-agonist/rFSH in women pretreated with oral contraceptives before in vitro fertilization. Fertil Steril. 2005;83(2):321–330
- . Effect of halving the daily dose of triptorelin at the start of ovarian stimulation on hormone serum levels and the outcome of in vitro fertilization. Fertil Steril. 2005;83(3):785–788
PII: S0020-7292(09)00507-4
doi:10.1016/j.ijgo.2009.08.026
© 2009 Published by Elsevier Inc.
Volume 108, Issue 1 , Pages 69-70, January 2010
