Integral comparison of static and dynamic ovarian reserve tests; a prospective study and a systematic review

Summary Summary In the introduction (chapter 1) of this thesis static and dynamic ovarian function tests are reviewed, which supposedly can predict ovarian reserve leading to a prognosis of the reproductive potential of a woman. Ovarian reserve is currently defined as the number and quality of the follicles left at any moment in the ovary. The aim of the studies described in this thesis was to find an answer to the following questions: a. Which ovarian reserve test or a certain combination can predict the cohort size of small antral follicles in the early follicular phase. b. Which ovarian reserve test or combination of ovarian reserve tests gives the best prognostic information on the probability of poor and hyper ovarian response in an IVF population. c. Which ovarian reserve test or combination of ovarian reserve tests gives the best prognostic information on the probability of pregnancy in an IVF population. We approached this questions in two ways. 1. A prospective study was conducted that compared in an integral way all currently available static ovarian reserve tests: early follicular phase blood values of follicle stimulating hormone (FSH), oestradiol (E2), inhibin B and anti-mullerian hormone (AMH), the dynamic ovarian reserve tests: the exogenous FSH ovarian reserve test (EFORT), the Clomiphene Citrate Challenge Test (CCCT), the ultrasound tests: antral follicle count (AFC), basal ovarian volume (BOV) and the intercycle variability of test results with regard to the prediction of the ovarian response after ovarian hyperstimulation in an IVF treatment. The results of this study are reported in chapters 2, 3, 4, 5 and 6. 2. A systematic review of the literature was provided including an a priori protocolised information retrieval on all currently available and applied tests, namely early follicular phase blood values of follicle stimulating hormone (FSH), oestradiol, inhibin B and anti-mullerian hormone (AMH), the antral follicle count (AFC), the ovarian volume and the ovarian blood flow and furthermore the clomiphene citrate challenge test (CCCT), the exogenous FSH ovarian reserve test (EFORT) and the gonadotropin releasing hormone agonist stimulation test (GAST) as measures to determine ovarian reserve and their capability to predict ovarian response and chance of pregnancy. This systematic review is reported in chapter 7. Chapter 2 presents the comparison between the endocrine tests, Clomiphene citrate Challenge Test (CCCT), Exogenous FSH Ovarian Reserve Test (EFORT) and basal FSH, basal E2, basal Inhibin B as an integral part of all CCCT’s and EFORT’s, with respect to their ability to estimate the stimulable cohort of follicles in the ovaries (ovarian reserve) and analysis which test or combination of tests would give the best prediction of ovarian reserve. One hundred and ten regularly menstruating patients, aged 18-39 years, participated in this prospective study, randomized, by a computer designed 4-blocks system study into two groups. Fifty six patients underwent a CCCT, and 54 patients underwent an EFORT. In all patients, the test was followed by an IVF treatment. The result of ovarian hyperstimulation during IVF treatment, expressed by the total number of follicles, was used as gold standard. We showed that the best prediction of ovarian reserve was seen, when E2-increment and Inhibin B-increment were used simultaneously in a stepforward multiple regression prediction model. The CCCT could not be used in a prediction model.This findings indicates that the EFORT is the endocrine test which gives the best prediction of ovarian reserve in a linear way. Chapter 3 reports the results of a comparison between the Clomiphene Citrate Challenge Test (CCCT) versus the Exogenous Follicle stimulation hormone Ovarian Reserve Test (EFORT) as single test for identification of poor and hyper responders to in vitro fertilization (IVF). We defined a ‘poor’ ovarian response as less than 6 oocytes after ovarian hyperstimulation in an IVF treatment and a ‘hyper’ response as more than 20 oocytes after such an IVF treatment. We showed that the best predictor for poor response is the CCCT.