Establishing Institutional Critical Values of Follicle-Stimulating Hormone Levels to Predict In Vitro Fertilization Success

Military Medicine, Feb 2007 by Joiner, Laura Lee Rihl, Robinson, Randal D, Bates, G Wright, Propst, Anthony M

Elevated follicle-stimulating hormone (FSH) levels during the early follicular phase or in response to the clomiphene citrate challenge test indicate diminished ovarian reserve and poor reproductive potential. We performed a retrospective analysis of 413 infertile women, 23 to 40 years of age, who underwent 523 cycles of in vitro fertilization (IVF) to identify the critical FSH values that would predict a poor likelihood of success in our military IVF program. Each woman underwent a clomiphene citrate challenge test within 1 year of each IVF cycle. The overall live birth and implantation rates were 43% and 24%, respectively. The critical values for day 3 and day 10 FSH levels were 14.1 and 16.9 mIU/mL, respectively, with a 0% live birth rate and a 5% implantation rate above these levels. There were no differences in the live birth/implantation rates when stratified for FSH levels below the critical values. Medical centers offering IVF should determine their critical FSH values, to help identify patients unlikely to benefit from IVF and to ensure appropriate allocation of resources and realistic expectations for infertile couples.

Introduction

To appropriately counsel infertile couples before pursuing infertility treatment, a number of factors that may help in predicting a successful outcome must be considered. Characteristics that are commonly accepted influences on the likelihood of successful infertility treatment include the age of the female patient, the cause of infertility in the couple, and an assessment of ovarian reserve, such as the basal follicle-stimulating hormone (FSH) level or the clomiphene citrate challenge test (CCCT).1,2

The decline in fertility that women experience as they age is well established and has been extensively studied. Pregnancy rates using donor inseminations decrease from 94% in women

Regardless of age, infertile women with diminished ovarian reserve (DOR), based on elevated FSH values using early follicular levels or CCCT results, have been shown to have very low success rates with advanced reproductive treatments, including IVF. Women with DOR who conceive have exceedingly high rates of pregnancy loss and low rates of live birth, regardless of age.5 The CCCT can identify patients with DOR that was not detected with basal FSH measurements.2,6 Stimulated day 10 FSH levels are strongly predictive of decreased IVF success even when day 3 FSH levels are normal.7

An evaluation of ovarian reserve, in combination with infertility diagnosis and age, is important in counseling couples before pursuing assisted reproductive treatment. However, the critical FSH level to identify women with DOR differs because of variations in the FSH assay at each institution. We sought to identify critical levels of FSH that would predict a poor likelihood of success with IVF at our institution.

Methods

A retrospective analysis was performed with all IVF cycles performed at Wilford Hall Medical Center reproductive endocrinology and infertility clinic between 1996 and 2002. A total of 433 infertile women between the ages of 23 and 40 years underwent 548 cycles of IVF during this time period. The study was approved by the Wilford Hall Medical Center institutional review board. All patients enrolled in the IVF treatment program at our clinic undergo an evaluation, which includes a CCCT, within 1 year of initiating ovulation induction for each IW cycle. The CCCT was performed in a standard fashion, as originally described by Navot et al.,4 with FSH and estradiol levels obtained on days 3 and 10 of the menstrual cycle and 100 mg of clomiphene citrate given orally on cycle days 5 to 9. No patient was excluded from IVF on the basis of CCCT results. Twenty subjects with CCCTs completed at outside institutions were excluded from analysis.

Enzyme-linked immunoassays were used to perform all of the assays for FSH, luteinizing hormone, and estradiol (TOSOH Medics, Foster City, California). Each enzyme assay was evaluated for its reliability. FSH concentrations were determined by using a commercially available immunoenzymometric assay. The intraassay and interassay variabilities were 4.0% and 5.9%, respectively. The TOSOH assay was calibrated by using the World Health Organization Second International Reference Preparation for FSH (78/549), with a normal range for premenopausal women in the follicular phase of 0 to 12.0 IU/L. Based on the previous study performed at our institution by Scott et al.,6 a direct comparison between the assays used for the original CCCT (BD radioimmunoassay; BD Biosciences, Orangeburg, New York) and the TOSOH analyzer was completed. To determine the FSH concentration that should be used as the threshold between normal and abnormal for the previous study, both kits were brought into our laboratory and used to assay the same 76 samples. The following equation was used In the regression analysis: y = 1.159x 2.419. The correlation coefficient was 0.986. This comparison revealed that a level of 13.8 IU/L with the TOSOH assay correlated with a value of 10 IU/L with the Becton-Dickinson assay.