A high ovarian response does not compromise the chance of pregnancy

Introduction: Recently it has been suggested that the use of traditional controlled ovarian stimulation (COS) regimens may negatively affect embryo quality and implantation rates and further studies would be required to assess the impact of mild vs conventional stimulation in relation to oocyte/embryo chromosomal competence as well as endometrial receptivity.1 One aspect of this complex question may be analyzed by comparing the clinical outcome of low, normal, and high responders to a fixed treatment protocol of either corifollitropin alfa or recombinant follicle-stimulating hormone (rFSH), in a gonadotropin-releasing hormone (GnRH) antagonist protocol. The current subset analysis evaluates the relationship between the ovarian response to COS and ongoing pregnancy rates. Material and Methods: In a large, prospective, double-blind, randomized trial (Engage; N = 1506), patients aged 18-36 years with a body weight of > 60 kg were treated with either a single dose of 150 ?g corifollitropinalfa (Elonva, N.V, Organon) (n = 756) or daily 200 IU rFSH (follitropin beta, Puregon Pen, N.V. Organon) (n = 750) for the first 7 days of COS in a GnRH antagonist (ganirelix, Orgalutran, N.V. Organon) protocol. In this analysis, patients were categorized into 5 groups according to the number of oocytes retrieved (0-5, 6-9, 10-13, 14-18, and > 18 oocytes) and the number of good-quality embryos obtained and transferred, and the ongoing pregnancy rates by group were evaluated. Per treatment group, the results of a logistic regression model of the ongoing pregnancy rate, including covariates oocyte group, age, region (North America or Europe), and embryo transfer (single or double) in patients with embryo transfer were evaluated. Results: The distribution of patients in oocyte retrieval groups 0-5, 6-9, 10- 13, 14-18, and > 18 oocytes was 12.6%, 18.2%, 22.6%, 21.8%, and 24.9%, respectively, in the corifollitropin alfa arm, and 12.9%, 22.9%, 25.2%, 20.9%, and 18.2%, respectively, in the rFSH arm. Across the range from low to high responders, differences in patient demographic and fertility characteristics were similar in the corifollitropin alfa and rFSH arms: high responders were younger, and on stimulation day 1 had lower FSH levels and a higher antral follicle count. The mean (SD) number of good-quality embryos obtained increased with the ovarian response from 1.2 (1.2) in the lowest response group to 8.0 (5.8) in the highest response group in the corifollitropin alfa arm, and from 1.1 (1.2) in the lowest response group to 8.0 (5.5) in the highest response groups in the rFSH arm. From the lowest to highest ovarian response groups, a mean of 0.2-4.9 and 0.2-4.2 embryos were cryopreserved in the corifollitropin alfa and rFSH arms, respectively. A mean of 0.9-1.4 and 0.9-1.5 good-quality embryos were transferred in the corifollitropin alfa and rFSH arms, respectively. The ongoing pregnancy rates in patients with embryo transfer ranged in the corifollitropin alfa arm from 40.9%-48.4%, and in the rFSH arm from 38.0%- 45.0%: the difference between the lowest and highest response group was not statistically significant (P = 0.20 (corifollitropin alfa) and 0.32 (rFSH). Compared with patients with 10-13 oocytes (odds ratio [OR] = 1), the adjusted ORs (95% confidence interval [CI]) of ongoing pregnancy for patients with embryo transfer in the 0-5, 6-9,14-18, and > 18 oocytes groups, were respectively 1.10 (0.62-1.98), 0.99 (0.61-1.60), 0.92 (0.59-1.45), and 1.15 (0.74-1.80) in the corifollitropin alfa arm, and 1.06 (0.61-1.87), 1.13 (0.72-1.76), 1.03 (0.65-1.63), and 1.03 (0.64-1.67), respectively, in the rFSH arm. Conclusions: In patients treated with corifollitropin alfa or daily rFSH in a GnRH antagonist regimen the ongoing pregnancy rate was independent of the ovarian response. A higher ovarian response does not compromise the chance of pregnancy. Reference: 1 Fauser BC et al. Hum Reprod. 2010;25:2678-2684. Support: Financial support for this study was provided by Merck.