A systematic review of tests predicting ovarian reserve and IVF outcome

Abstract

The age-related decline of the success in IVF is largely attributable to a progressive decline of ovarian oocyte quality and quantity. Over the past two decades, a number of so-called ovarian reserve tests (ORTs) have been designed to determine oocyte reserve and quality and have been evaluated for their ability to predict the outcome of IVF in terms of oocyte yield and occurrence of pregnancy. Many of these tests have become part of the routine diagnostic procedure for infertility patients who undergo assisted reproductive techniques. The unifying goals are traditionally to find out how a patient will respond to stimulation and what are their chances of pregnancy. Evidence-based medicine has progressively developed as the standard approach for many diagnostic procedures and treatment options in the field of reproductive medicine. We here provide the first comprehensive systematic literature review, including an a priori protocolized information retrieval on all currently available and applied tests, namely early-follicular-phase blood values of FSH, estradiol, inhibin B and anti-Müllerian hormone (AMH), the antral follicle count (AFC), the ovarian volume (OVVOL) and the ovarian blood flow, and furthermore the Clomiphene Citrate Challenge Test (CCCT), the exogenous FSH ORT (EFORT) and the gonadotrophin agonist stimulation test (GAST), all as measures to predict ovarian response and chance of pregnancy. We provide, where possible, an integrated receiver operating characteristic (ROC) analysis and curve of all individual evaluated published papers of each test, as well as a formal judgement upon the clinical value. Our analysis shows that the ORTs known to date have only modest-to-poor predictive properties and are therefore far from suitable for relevant clinical use. Accuracy of testing for the occurrence of poor ovarian response to hyperstimulation appears to be modest. Whether the a priori identification of actual poor responders in the first IVF cycle has any prognostic value for their chances of conception in the course of a series of IVF cycles remains to be established. The accuracy of predicting the occurrence of pregnancy is very limited. If a high threshold is used, to prevent couples from wrongly being refused IVF, a very small minority of IVF-indicated cases (approximately 3%) are identified as having unfavourable prospects in an IVF treatment cycle. Although mostly inexpensive and not very demanding, the use of any ORT for outcome prediction cannot be supported. As poor ovarian response will provide some information on OR status, especially if the stimulation is maximal, entering the first cycle of IVF without any prior testing seems to be the preferable strategy.

Use of anti-mullerian hormone for testing ovarian reserve: a survey of 796 infertility clinics worldwide

“…However, when ovarian reserve testing is applied broadly, especially to young women, the potential for a false positive result identifying low ovarian reserve increases and lowers the predictive power of the test, and may be misleading [1,15]. In a recent ASRM committee opinion, the authors concluded that evidence of decreased ovarian reserve does not necessarily equate with inability to conceive, which has a significant amount of literature to support it [15][16][17]. However, the ASRM committee opinion does not discourage the broad use of AMH as there is likely benefit and conclude by stating Bthere is insufficient evidence to recommend that any ovarian reserve test now available should be used as a sole criterion for the use of assisted reproductive technologies^ [1].…”

“…Within the literature, multiple analyses comparing the various ovarian reserve tests have been completed investigating outcomes. Again, no clear consensus was reached [16,18]; however, AMH and AFC appear to be favored within the literature [18][19][20]. Prior researchers have attempted to address the precision, accuracy, and predictive value of AMH in addressing those outcomes, comparing AMH both individually and in combination with other tests.…”

What is the best treatment option for infertile women aged 40 and over?

“…Basal FSH levels are easy and cheap to obtain and the results require little skill to interpret which makes it an accessible test. However, only extremely elevated results are useful in predicting poor response to ovarian stimulation and non pregnancy [20].…”

“…Thus AMH is emerging as an indirect approximation of age-related NGF populations and rates of recruitment. As such it provides moderate value in prediction of ovarian response in in-vitro fertilization (IVF), however may not be a good predictor of pregnancy [20]. Recently, Bhide et al set out to establish whether there was a link between basal AMH and clinical pregnancy rates in women undergoing IVF/ICSI treatment and attempted to determine a cut off point, below which there are no pregnancies.…”

The value of human chorionic gonadotropin stimulation test in predicting ovarian response during in-vitro fertilization

“…Theca cell function is necessary for normal folliculogenesis and a minimal threshold level of LH is needed for theca cell stimulation and production of androgens to improve folliculogenesis, as was demonstrated in hypogonadotropic hypogonadism patients [31]. Several tests that examine granulosa cell function were developed to evaluate ovarian reserve before ART: day 3 FSH, day 3 estradiol, inhibin B, CCCT, EFORT, and GAST [32]. Most of these tests have shown only a modest predictive value and consequently, have not gained wide clinical acceptance and application.…”