Defining ?ovarian age? and its impact on the selection of a stimulation protocol

Abstract

Female fertility declines with advancing maternal age and leads to decreased fecundity. The concept of ovarian reserve is hardly novel, but its application by physicians is, for the most part, kept for the unmistakably sub-fertile patient who has failed previous ovulation induction. An increased basal FSH or an inadequate response to gonadotrophin stimulation may recognize diminished ovarian function. Unlike early concepts that suggested maternal age in combination with basal FSH concentrations had predictive values for ART outcome, the goal of this study is to develop the concept of “ovarian age” as an extrapolative tool to help physicians define an appropriate stimulation protocol for all IVF patient populations. We tested the hypothesis that unlike chronological age, a progressive definition of ovarian age (i.e., function or reserve) which takes into account various clinically relevant factors can serve as a dynamic measure for the clinician for all IVF candidates. This report describes the initial 13 normal women who were randomized to either a “low” rFSH (150IU/150IU rFSH; Follistim®, Organon Pharmaceuticals USA,) or a “high” rFSH protocol (300 IU/300IU rFSH). The high-dosage group had a slightly elevated BMI compared to the low-dosage group (26 vs. 21) and median day3 FSH levels were elevated (12IU/ml vs. 5.3IU/ml). Similar total ovarian volumes were measured (580mm2 vs. 669mm2). Day 3 mean E2 levels were higher in the low dosage group (42.3pg/ml.vs. 28.3pg/ml) as was the mean follicle number (11 vs. 8.5) and the historical use of OCP (85 % vs 50%). Correspondingly the total number of oocytes recovered, number of mature oocytes, number of oocytes fertilized, total embryo number, and number of embryos transferred were all elevated in the “low-dosage” group. More pregnancies were seen in the “low-dosage” group as well (4/7 vs 2/6). These data are preliminary and the differences noted between the group’s BMI and d3FSH cannot be overlooked, but should normalize themselves by study completion. Data appear to support the hypothesis that chronological age does not predicate the responsiveness to rFSH therapy. Thus far, the low-dosage group has achieved superior clinical results. Ultimately, a dynamic approach of analysis and synthesis of these data is expected to yield a clinically effective tool (equation or schema) for the development of tailored stimulation regimens for women undergoing IVF. Female fertility declines with advancing maternal age and leads to decreased fecundity. The concept of ovarian reserve is hardly novel, but its application by physicians is, for the most part, kept for the unmistakably sub-fertile patient who has failed previous ovulation induction. An increased basal FSH or an inadequate response to gonadotrophin stimulation may recognize diminished ovarian function. Unlike early concepts that suggested maternal age in combination with basal FSH concentrations had predictive values for ART outcome, the goal of this study is to develop the concept of “ovarian age” as an extrapolative tool to help physicians define an appropriate stimulation protocol for all IVF patient populations. We tested the hypothesis that unlike chronological age, a progressive definition of ovarian age (i.e., function or reserve) which takes into account various clinically relevant factors can serve as a dynamic measure for the clinician for all IVF candidates. This report describes the initial 13 normal women who were randomized to either a “low” rFSH (150IU/150IU rFSH; Follistim®, Organon Pharmaceuticals USA,) or a “high” rFSH protocol (300 IU/300IU rFSH). The high-dosage group had a slightly elevated BMI compared to the low-dosage group (26 vs. 21) and median day3 FSH levels were elevated (12IU/ml vs. 5.3IU/ml). Similar total ovarian volumes were measured (580mm2 vs. 669mm2). Day 3 mean E2 levels were higher in the low dosage group (42.3pg/ml.vs. 28.3pg/ml) as was the mean follicle number (11 vs. 8.5) and the historical use of OCP (85 % vs 50%). Correspondingly the total number of oocytes recovered, number of mature oocytes, number of oocytes fertilized, total embryo number, and number of embryos transferred were all elevated in the “low-dosage” group. More pregnancies were seen in the “low-dosage” group as well (4/7 vs 2/6). These data are preliminary and the differences noted between the group’s BMI and d3FSH cannot be overlooked, but should normalize themselves by study completion. Data appear to support the hypothesis that chronological age does not predicate the responsiveness to rFSH therapy. Thus far, the low-dosage group has achieved superior clinical results. Ultimately, a dynamic approach of analysis and synthesis of these data is expected to yield a clinically effective tool (equation or schema) for the development of tailored stimulation regimens for women undergoing IVF.