Anti-Müllerian hormone-based prediction model for a live birth in assisted reproduction

Abstract

Prediction of assisted reproduction treatment outcome has been the focus of clinical research for many years, with a variety of prognostic models describing the probability of an ongoing pregnancy or a live birth. This study assessed whether serum anti-Müllerian hormone (AMH) concentrations may be incorporated into a model to enhance the prediction of a live birth in women undergoing their first IVF cycle, by analysing a database containing clinical and laboratory information on IVF cycles carried out between 2005 and 2008 at the Mother–Infant Department of University Hospital, Modena. Logistic regression was used to examine the association of live birth with baseline patient characteristics. Only AMH and age were demonstrated in regression analysis to predict live birth, so a model solely based on these two criteria was generated. The model permitted the identification of live birth with a sensitivity of 79.2% and a specificity of only 44.2%. In the prediction of a live birth following IVF, a distinction, however moderate, can be made between couples with a good and a poor prognosis. The success of IVF was found to mainly depend on maternal age and serum AMH concentrations, one of the most relevant and valuable markers of ovarian reserve.

The prediction of assisted reproduction treatment outcome has been the focus of clinical research for many years, with a variety of prognostic models describing the probability of an ongoing pregnancy or a live birth. The present study assessed whether serum anti-Müllerian hormone (AMH) concentrations may be incorporated into a prediction model to enhance the prediction of a live birth in women undergoing their first IVF. Statistical analysis was used to examine the association of live birth with baseline patient characteristics, in particular age, AMH, body mass index, and type, duration and aetiology of infertility. Given that only AMH and age were demonstrated to predict live birth, a model solely based on these two criteria was generated. At the best cut-off, the model permitted the identification of live birth with a sensitivity of 79.2% and specificity of 44.2%. The present study demonstrates that in the prediction of a live birth following IVF a distinction, however moderate, can be made between couples with a good and a poor prognosis. The success of IVF was found to mainly depend on maternal age and serum AMH concentrations, one of the most relevant and valuable markers of ovarian reserve.

Introduction

The prediction of assisted reproduction treatment outcome has been the focus of clinical research for many years, with a variety of prognostic models describing the probability of an ongoing pregnancy or a live birth following treatment. To date, models have predominantly been established using patient baseline characteristics and although these models have been heterogeneous in their performance they consistently demonstrate that certain patient characteristics are associated with IVF/intracytoplasmic sperm injection (ICSI) success, including female age (Bancsi et al., 2000, Bouckaert et al., 1994, Carrera-Rotllan et al., 2007, Commenges-Ducos et al., 1998, Hughes et al., 1998, Hunault et al., 2002, Hull et al., 1996, Lee et al., 2009, Lintsen et al., 2005, Minaretzis et al., 1998, Ottosen et al., 2007, Stolwijk et al., 1996, Stolwijk et al., 2000, Templeton et al., 1996, van Weert et al., 2008, Younis et al., 2009), duration of infertility (Haan et al., 1991, Lintsen et al., 2007, Younis et al., 2009), pregnancy history (Lintsen et al., 2007, Stolwijk et al., 2000, Templeton et al., 1996, van Weert et al., 2008), diagnostic category (Bancsi et al., 2000, Lintsen et al., 2007, van Weert et al., 2008) and body mass index (BMI; Ferlitsch et al., 2004, Verberg et al., 2008).

Alternative models have incorporated the characteristics of the intermediate results of the first treatment cycle thereby improving the accuracy of probability estimates for future cycles. The variables used in these models include the number of retrieved oocytes (Bouckaert et al., 1994, Hunault et al., 2002, Verberg et al., 2007), the fertilization rate and embryo number and quality (Hunault et al., 2002, Minaretzis et al., 1998, Ottosen et al., 2007, Verberg et al., 2007). Moreover it has been clearly demonstrated that in models predicting pregnancy based on intermediate results (at embryo transfer), the number of retrieved and fertilized oocytes have the highest prognostic value (Ferlitsch et al., 2004, Verberg et al., 2007). This suggests that any marker which can predict the number of retrieved oocytes prior to ovarian stimulation may be of value in initial baseline prognostic models (Bancsi et al., 2000, Carrera-Rotllan et al., 2007, Ferlitsch et al., 2004, Lee et al., 2009, Ottosen et al., 2007, Younis et al., 2009).

Recent studies have indicated that anti-Müllerian hormone (AMH) may constitute an important novel measure of ovarian reserve, with the current literature indicating that AMH is a superior marker for predicting ovarian response over either age of the patient, day-3 FSH, oestradiol or inhibin B levels, whereas the vast majority of studies have found AMH and antral follicle count to have similar predictive value (for review, see La Marca et al., 2009). Consistent with AMH being a strong correlate of oocyte yield, AMH has recently been proposed as a useful clinical marker for the prediction of both poor- and hyperresponses to ovarian stimulation (La Marca et al., 2009). In addition to reflecting the quantitative ovarian response, several authors have found a significant positive correlation between AMH concentrations and oocyte quality (Cupisti et al., 2007, Ebner et al., 2006, Hazout et al., 2004, Silberstein et al., 2006), fertilization rate (Lekamge, 2007) and embryo morphology (Silberstein et al., 2006). However, this relationship has not been confirmed by others (Lie Fong et al., 2008, Smeenk et al., 2007). Hence the possible prediction of qualitative aspects of assisted reproduction programmes by AMH measurement is largely controversial.

In one large study, AMH was shown to be associated with live birth independent of age after treatment (Nelson et al., 2007). More recently a further large cohort study demonstrated that serum AMH concentrations may predict live birth in women older than 34 (Lee et al., 2009). The aim of the present study was to assess whether serum AMH concentrations may be incorporated into a prediction model to enhance the prediction of a live birth in women undergoing their first IVF. In particular, the objective was to develop a simple multivariate score based on basal patients characteristics which was capable of predicting the outcome of the treatment cycle and to express this in a clean format which could be easily adopted into daily clinical practice.