Lifetime high day 2 FSH and diagnostic accuracy in IVF.

Abstract

Objective: To test diagnostic accuracy of lifetime high day 2 FSH in an unrestricted IVF population. Design: Retrospective analysis of lifetime high day 2 FSH with outcome measure: birth or ongoing pregnancy. Materials/Methods: 2,058 day 2 FSH measurements from 539 women aged 38 ± 4 years (mean ± SD) were studied. FSH standardization was WHO 2nd International Standard (IRP 78/549). Immunoassay was performed using Technicon Immuno 1 (Bayer, Tarrytown NY) (normal follicular phase range less than 9.6 mIU/mL). 730 consecutive IVF stimulations (lifetime IVF cycle 3 ± 2) were begun with flare GnRH-agonist/gonadotropin or clomiphene/gonadotropin/±GnRH-antagonist. All diagnoses were included. Prior to stimulation 80 cycles were deferred on account of elevated FSH (20 ± 7 mIU/mL). 81 cycles were not started on account of functional cysts, persistent luteal function or elevated estradiol. Results: Lifetime high day 2 FSH was greater than 10 mIU/mL in 40% of 730 cycles. Examined in increments of 2 mIU/mL for lifetime high FSH, confidence intervals for crude birth/ongoing pregnancy rates were not different from 4–16 mIU/mL. Receiver operator characteristic curves for cycle and lifetime high FSH had areas of 0.5, indicative of poor test accuracy. FSH greater than 16 mIU/mL gave positive likelihood ratios of 2.6 for cycle FSH (fair test) and 1.9 (poor to fair) for lifetime high FSH. With respect to outcome as the dependent variable, neither cycle FSH, nor lifetime high FSH, nor number of elevated FSHs, nor proportion of FSHs that were elevated were significant independent variables by multiple regression analysis. After starting treatment, 72 cycles (10%) were cancelled for poor response. Lifetime high FSH was greater in cancelled cycles 14.7 ± 8 versus 9.8 ± 4 in cycles completed to oocyte retrieval, (p = 0.001) and risk of cancellation was related to lifetime high FSH, (F = 74, r2 = 0.09, p = 0.001). Conclusions: Mild to moderate elevations of lifetime high day 2 FSH were frequent in an unrestricted IVF population (40%) but did not improve diagnostic accuracy with respect to birth-ongoing pregnancy in the range 4–16 mIU/mL. Using multiple regression, lifetime high day 2 FSH was weakly related to the intermediate endpoint, risk of cancellation. Given the major difficulties diagnosing ovarian reserve and the creative flexibility possible with ovarian stimulation, it may be appropriate to offer determined individuals IVF treatment despite mild to moderate elevations of lifetime high day 2 FSH.