P-718: Effects of low ovarian reserve versus maternal age on ovarian responsiveness, preembryo quality and clinical outcome in assisted reproduction

Abstract

Decreased ovarian reserve is associated with a decline in oocyte number and quality, higher Day 3 (D3) serum Follicle Stimulating Hormone (FSH) levels, an increase in chromosome abnormalities and potentially lower pregnancy rates. However, it is not clear whether the association between decreased ovarian reserve and preembryo quality is causal. In addition, the relative importance of chronological versus biological age in declining fertility rates is controversial. The objectives of the present study were to determine 1) the effect of basal D3 FSH (a marker of ovarian reserve) on preembryo quality in ART patients, and 2) the relative importance of maternal age and D3 FSH on declining pregnancy rates. A retrospective analysis of 1381 ART patients attending the Weill-Cornell Center for Reproductive Medicine and Infertility from 2002 to 2005 was performed. Patients were grouped in two ways: 1) according to female age (< 34 yrs, 34-36 yrs, 37-39 yrs, and ≥40 yrs) and 2) based on their D3 FSH values (<5 mIU/mL, 5-9 mIU/mL, and ≥10 mIU/mL). Outcome variables included the number of oocytes harvested, fertilization rate, preembryo grade, clinical pregnancy rate (CP), ongoing/delivered pregnancy rate (OP), and implantation rate (IR). The percentage of mature eggs was determined in a subset of patients who underwent ICSI, using the same subgroups as above. Serum FSH was measured on Day 2 or Day 3 of a patient’s cycle prior to their IVF treatment using the Immulite FSH assay (Diagnostic Products Corporation, Los Angeles, CA). Oocyte harvest occurred 35 hr post-hCG administration and fertilization was assessed 15-18 hr post-insemination or ICSI. Embryo transfer was performed on Day 3 post-harvest. Preembryos were selected for transfer based on morphology and rate of development. An Embryo Grade was assigned to the best quality preembryo being transferred based on these criteria [on a scale of 1 (highest quality) to 5 (extremely poor quality)]. Logistic regression and two-way analysis of variance were used for the analysis of binary and continuous outcomes, respectively. High D3 FSH levels and advanced maternal age both significantly reduced the number of oocytes retrieved per patient, but no effects were observed on either the percentage of mature eggs retrieved or the rate of fertilization. There was a significant difference in the distribution of preembryo grades between the various age groups (p=0.003), arising primarily from a shift of Grade 1 prembryos to Grade 2 prembryos in older patients. In contrast, no significant differences in grade distribution between FSH patient groups were observed. Maternal age was strongly associated with implantation and pregnancy outcome. Both CP and OP were significantly reduced in patients 37 years of age and older. There was a marginally significant decline in CP in the middle FSH group (5-9 mIU/ml)as compared to the lowest FSH group. However, no effect of D3 FSH on OP or IR was seen. Interactions between age and FSH in the study population were not significant. The successful outcome of a patient’s cycle was much more dependent on maternal age than ovarian status, at least when using D3 FSH as a marker of ovarian status in an IVF Program where higher FSH values result in cycle cancellations. Based on these data, maternal age should be considered more strongly than D3 FSH when counseling patients regarding their chances of achieving pregnancy.