High ovarian response does not jeopardize ongoing pregnancy rates and increases cumulative pregnancy rates in a GnRH-antagonist protocol

Human M. Fatemi, Kevin Doody, Georg Griesinger, Han Witjes, Bernadette Mannaerts*

*Corresponding author for this work
30 Citations (Scopus)


Study Question Is the ovarian response to controlled ovarian stimulation (COS) related to the ongoing pregnancy rate when taking into account the main covariates affecting the probabilities of pregnancy following fresh embryo transfer? Summary Answer In patients treated with corifollitropin alfa or daily recombinant FSH (rFSH) in a GnRH-antagonist protocol, a high ovarian response did not compromise ongoing pregnancy rates and increased cumulative pregnancy rates following fresh and frozen-thawed embryo transfer.WHAT IS KNOWN AND WHAT THIS PAPER ADDSA strong association between the number of oocytes and pregnancy rates has been described but this is the first comprehensive analysis assessing important confounders that might affect pregnancy rates. Study Design In a large, prospective, double-blind, randomized trial (Engage; n = 1506), patients were treated with either a single dose of 150 μg corifollitropin alfa or daily 200 IU rFSH for the first 7 days of COS in a GnRH-antagonist (ganirelix) protocol. In this retrospective analysis, patients were categorized into five groups according to the number of oocytes retrieved (0-5, 6-9, 10-13, 14-18 and >18 oocytes). The number of good-quality embryos obtained and transferred, as well as the ongoing pregnancy rates, live birth rates and cumulative ongoing pregnancy rates per started cycle by group were evaluated. Univariate analysis was performed to identify factors that predict the chance of ongoing pregnancy. Logistic regression analysis on the dependent variables ongoing pregnancy and cumulative ongoing pregnancy, respectively, including oocyte category as an independent factor in the model, was performed by treatment group (corifollitropin alfa and rFSH) and overall. The likelihood of ongoing pregnancy and cumulative ongoing pregnancy was then evaluated taking into account ovarian response as well as other identified significant predictors of success.PARTICIPANTS AND SETTINGIn total, 1506 patients had been randomized in a ratio of 1:1 to either of the treatment groups. Patients were aged ≤36 years and had a body weight >60 kg. Main Results and the Role of Chance The ongoing pregnancy rates per started cycle increased in the corifollitropin alfa and rFSH groups from 31.9 and 31.3%, respectively, in the lowest response group (0-5 oocytes) to 41.9 and 43.4% in the highest response group (>18 oocytes) with a significant linear trend (P = 0.04). The cumulative pregnancy rates taking frozen-thawed embryo transfers into account increased from 33.0 and 31.3% to 60.8 and 55.9% in the corifollitropin alfa and rFSH groups, respectively. Univariate logistic regression analyses of ongoing pregnancy showed significant effects for the following factors: embryo transfer (double or single, P < 0.01), region of treatment (North America or Europe, P < 0.01), progesterone level on the day of hCG (>1.5 or ≤1.5 ng/ml, P < 0.01), start day of the stimulation (cycle day 2 or 3, P = 0.02) and age (P = 0.04). Logistic regression analysis of ongoing pregnancy using 10-13 oocytes as the reference category, per treatment group and overall revealed estimated odds ratios (OR) close to 1.0 versus the reference, without statistically significant differences with and without adjustment for significant predictive factors affecting pregnancy rates. Unadjusted OR for cumulative pregnancy reflected significantly lower odds of pregnancy for the lowest response group and significantly higher odds of pregnancy for the highest response group in comparison with the reference. When adjusted for the predictive factors, the cumulative ongoing pregnancy OR (95% confidence interval) of the highest response group versus the reference group was 1.87 (1.34-2.59) when the data of both treatment groups were pooled.BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTIONThe number of covariates included in the final model was limited to five major factors and not all other potentially significant predictive factors were available for evaluation.GENERALIZABILITY TO OTHER POPULATIONSThis analysis is limited to IVF patients with a regular menstrual cycle up to 36 years of age and a body weight >60 and ≤90 kg treated with a GnRH-antagonist protocol and cannot be extrapolated to other patient populations or treatment regimens. Study Funding/Competing Interest (S)Financial support for this study was provided by Merck, Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc, Whitehouse Station, NJ, USA. Medical writing and editorial assistance was provided by P. Milner, PhD, of PAREXEL, UK. This assistance was funded by Merck, Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Whitehouse Station, NJ. Author conflicts of interest are as follows: H.F. has received honorarium for expert meeting with MSD, lectures for various companies; K.D. has received consultancy fees for Ferring and TEVA Pharmaceutical, payment for lectures and speaker bureaus for Ferring and Watson Pharmaceutical; G.G. has received honoraria as speaker, and served as advisory board member for Ferring, Merck Serono, MSD and IBSA. He has received travel grants from Merck Serono, MSD and grants from Ferring and Merck Serono; H.W. and B.M. are employees of MSD. Trial Registration Numberntc00696800.

Original languageEnglish
JournalHuman Reproduction
Issue number2
Pages (from-to)442-452
Number of pages11
Publication statusPublished - 01.02.2013


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