High Gonadotropin Dosage Does Not Affect Euploidy and Pregnancy Rates in IVF PGS Cycles With Single Embryo Transfer

The most effective and reliable method for embryo selection in in vitro fertilization (IVF) cycles is preimplantation genetic screening (PGS). There is a significant decrease in euploidy and blastulation rates with increasing maternal age. To obtain an adequate number of follicles in women of advanced maternal age, the average gonadotropin dosage administered during controlled ovarian stimulation in IVF cycles is significantly increased. However, there are conflicting reports and lack of guidance regarding gonadotropin dosing. Some studies have reported that high gonadotropin dosages have adverse effects on oocyte quality and clinical pregnancy rates, but several recent studies have refuted those findings. Few human gonadotropin doseresponse trials have been performed, and the effect of high gonadotropin doses is still poorly understood. The aim of this retrospective study was to determine whether different dosages of gonadotropins affect euploidy and pregnancy rates in IVF PGS cycles with single embryo transfer. The study was conducted between January 2013 and January 2017. To identify differences in euploidy and clinical pregnancy rates, SNP (single-nucleotide polymorphism) PGS outcome data were obtained from blastocysts biopsied on days 5 or 6. A total of 794 cycles of IVF treatment with PGS followed by 651 single frozen embryo transfers in 506 patients were included in the study. The average maternal age was 37 years. A total of 4034 embryos were analyzed for euploidy rates (5.1 +/- 3.76 per case). After biopsy, all embryos were vitrified, and euploid embryos were subsequently thawed for a hormone replacement frozen embryo transfer cycle. All patient cycles were analyzed by (1) total gonadotropin dosage (< 3000, 3000-5000, and > 5000 IU), (2) number of eggs retrieved (1-5, 5-10, 10-15, and > 15 eggs), and (3) patient's age (< 35, 35-37, 38-40, and = 41 years). Clinical pregnancy was defined by the presence of a fetal heartbeat at 6 to 7 weeks of gestation, and an ongoing pregnancy was defined as a viable pregnancy after 8 weeks' gestation. No significant difference was found in euploidy rates regardless of the total dosage of gonadotropins used or the number of eggs retrieved. In patients younger than 35 years (187 IVF cycles), euploidy rates ranged from 62.3% (when < 3000 IU was used in the IVF cycle) to 67.5% (when > 5000 IU was used in the IVF cycle; odds ratio [OR], 0.862; 95% confidence interval [CI], 0.687-1.082; P = 0.2), and rates ranged from 69.5% (when 1-5 eggs were retrieved) to 60.0% (when > 15 eggs were retrieved) (OR, 0.658; 95% CI, 0.405-1.071; P = 0.09). Similar data were obtained in patients of advanced maternal age (= 41 years of age, 189 IVF cycles). When this age group was analyzed by total dosage of gonadotropins used in the IVF cycle, euploidy rates ranged from 30.7% to 26.4% (OR, 0.811; 95% CI, 0.452-1.454; P = 0.481), and when assessed by the total number of eggs retrieved, rates ranged from 40.0% to 30.7% (OR, 0.531; 95% CI, 0.204-1.384; P = 0.19). Ongoing pregnancy rates were not significantly different within particular age groups and also between different age groups regardless of the total dosage of gonadotropins administered: rates ranged from 63.6% (< 3000 IU, < 35 years of age) to 54.8% (> 5000 IU, = 41 years of age) (OR, 0.696; 95% CI, 0.310-1.565; P = 0.38). Study limitations included the retrospective nature of the study and heterogeneity of patients. These data provide support for the use of relatively high gonadotropin dosage in IVF PGS cycles in order to retrieve an adequate number of oocytes in women of advanced maternal age. The authors believe that the maximum number of follicles recruited in each cycle should be limited only by medical safety concerns and well-being of patients.