Definition by FSH, AMH and embryo numbers of good-, intermediate- and poor-prognosis patients suggests previously unknown IVF outcome-determining factor associated with AMH

Abstract

BackgroundThough outcome models have been proposed previously, it is unknown whether cutoffs in clinical pregnancy and live birth rates at all ages are able to classify in vitro fertilization (IVF) patients into good-, intermediate- and poor prognosis.MethodsWe here in 3 infertile patient cohorts, involving 1247, 1514 and 632 women, built logistic regression models based on 3 functional ovarian reserve (FOR) parameters, including (1) number of good quality embryos, (2) follicle stimulating hormone (FSH, mIU/mL) and (3) anti-Müllerian hormone (AMH, ng/mL), determining whether clinical pregnancy and live birth rates can discriminate between good, intermediate and poor prognosis patients.ResultsAll models, indeed, allowed at all ages for separation by prognosis, though cut offs changed with age. In the embryo model, increasing embryo production resulted in linear improvement of IVF outcomes despite transfer of similar embryo numbers; in the FSH model outcomes and FSH levels related inversely, while the association of AMH followed a bell-shaped polynomial pattern, demonstrating “best” outcomes at mid-ranges. All 3 models demonstrated increasingly poor outcomes with advancing ages, though “best” AMH even above age 43 was still associated with unexpectedly good pregnancy and delivery outcomes. Excessively high AMH, in contrast, was at all ages associated with spiking miscarriage rates.ConclusionsAt varying peripheral serum concentrations, AMH, thus, demonstrates hithero unknown and contradictory effects on IVF outcomes, deserving at different concentrations investigation as a potential therapeutic agent, with pregnancy-supporting and pregnancy-interrupting properties.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0924-7) contains supplementary material, which is available to authorized users.

Anti‐Müllerian hormone as a marker of abortion in the first trimester of spontaneous pregnancy

“…Hence, the higher the concentration of AMH, the stronger the inhibition of FSH, which may result in anovulatory cycles, as in PCOS. Women with PCOS show decreased fecundability and increased risk of abortion; similar pregnancy outcomes have also been noted among women with higher AMH levels (>2.5 ng/mL) who do not have PCOS …”

“…Similar to the present study, they identified two thresholds (very low and very high) that, when exceeded in either way, might be perceived as an unfavorable prognosis for pregnancy. In their study, the range of AMH concentrations with an optimal prognosis for pregnancy, assayed in a group of young women (<36 years), was relatively broad (3.5–8.5 ng/mL) …”

“…showed a higher risk of abortion after IVF among women with low AMH (≤1.6 ng/mL), but only for older women (i.e., >34 years) . Moreover, Gleicher et al . reported a range of AMH concentrations reflecting the “best chance for pregnancy,” within which a successful pregnancy course after IVF would be expected.…”

“…Although the above‐mentioned studies also reported a poor pregnancy prognosis for AMH levels higher than 2.5 ng/mL, they included both infertile women and women up to 44 years of age, which might have influenced the low median AMH levels. Gleicher et al . noted that the incidence of abortion was 42.9% for women younger than 36 years with AMH concentrations of 10 ng/mL, but reached 81.8% for women older than 43 years with AMH concentrations of 10 ng/mL.…”

“…For example, Tarasconi et al 10 showed a higher risk of abortion after IVF among women with low AMH (≤1.6 ng/mL), but only for older women (i.e., >34 years). 10 Moreover, Gleicher et al 19 reported a range of AMH concentrations reflecting the "best chance for pregnancy," within which a successful pregnancy course after IVF would be expected. Similar to the present study, they identified two thresholds (very low and very high) that, when exceeded in either way, might be perceived as an unfavorable prognosis for pregnancy.…”