STUDY QUESTION
Is serum anti-Müllerian hormone (AMH) level predictive of cumulative live birth (CLB) rate after ART or in women trying to conceive naturally?


SUMMARY ANSWER
Serum AMH level is linked to CLB after IVF/ICSI but data are lacking after IUI or in women trying to conceive without ART.


WHAT IS KNOWN ALREADY
Serum AMH level is a marker of ovarian reserve and a good predictor of ovarian response after controlled ovarian stimulation. It is unclear whether AMH measurement can predict CLB in spontaneous or assisted conception.


STUDY DESIGN, SIZE, DURATION
A systematic review and meta-analysis was undertaken to assess whether serum AMH level may predict chances of CLB in infertile women undergoing IVF/ICSI or IUI and/or chances of live birth in women having conceived naturally.


PARTICIPANTS/MATERIALS, SETTING, METHODS
A systematic review and meta-analysis was performed using the following keywords: 'AMH', 'anti-mullerian hormone', 'live-birth', 'cumulative live birth'. Searches were conducted from January 2004 to April 2021 on PubMed and Embase. Two independent reviewers carried out study selection, quality, and risk of bias assessment as well as data extraction. Odds ratios were estimated using a random-effect model. Pre-specified sensitivity analyses and subgroup analyses were performed. The primary outcome was CLB.


MAIN RESULTS AND THE ROLE OF CHANCE
A total of 32 studies were included in the meta-analysis. Overall, 27 articles were included in the meta-analysis of the relation between AMH and CLB or AMH and LB after IVF/ICSI. A non-linear positive relation was found in both cases. A polynomial fraction was the best model to describe it but no discriminant AMH threshold was shown, especially no serum AMH level threshold below which live birth could not be achieved after IVF/ICSI. After IVF-ICSI, only four studies reported CLB rate according to AMH level. No statistically significant differences in mean serum AMH levels were shown between patients with and without CLB, but with a high heterogeneity. After exclusion of two studies with high risks of bias, there was no more heterogeneity [I2 = 0%] and the mean AMH level was statistically significantly higher in women with CLB. There were not enough articles/data to assess the ability of AMH to predict CLB rate or find an AMH threshold after IUI or in women without history of infertility trying to conceive without ART.


LIMITATIONS, REASONS FOR CAUTION
The systematic review and meta-analysis had some limitations owing to the limits and bias of the studies included. In the present meta-analysis, heterogeneity may have been caused by different baseline characteristics in study participants, different stimulating protocols for ART, different serum AMH level thresholds used and the use of various assays for serum AMH. This could explain, in part, the absence of a discriminating AMH threshold found in this analysis.


WIDER IMPLICATIONS OF THE FINDINGS
Serum AMH level is linked to CLB rate after IVF/ICSI but no discriminating threshold can be established, therefore low serum AMH level should not be used as the sole criterion for rejecting IVF treatment, especially in young patients. Data are lacking concerning its predictive value after IUI or in women trying to conceive without ART. Our findings may be helpful to counsel candidate couples to IVF-ICSI.


STUDY FUNDING/COMPETING INTERESTS
No external funding was obtained for this study. There are no conflicts of interest.


REGISTRATION NUMBER
PROSPERO CRD42021269332.

Using serum anti-Müllerian hormone levels to predict the chance of live birth after spontaneous or assisted conception: a systematic review and meta-analysis.

Objective The aim of this study was to assess the correlation of oocyte number with serum anti-Müllerian hormone (AMH) levels measured by two automated methods (Access or Elecsys) in fresh stimulated in vitro fertilization (IVF) cycles. Methods In this retrospective study at a university hospital, data were collected from 243 fresh stimulated IVF cycles performed from August 2016 to December 2020. The serum AMH level was measured by Access in 120 cycles and by Elecsys in 123 cycles. The cut-off of serum AMH for prediction of poor responders (three or fewer oocytes) or high responders (15 or more oocytes) was calculated by the receiver operating characteristic curve analysis. Results For the two automated methods, the following equations were derived: total oocyte number=2.378+1.418×(Access-AMH) (r=0.645, p<0.001) and total oocyte number=2.417+2.163×(Elecsys-AMH) (r=0.686, p<0.001). The following combined equation could be derived: (Access-AMH)=0.028+1.525×(Elecsys-AMH). To predict poor responders, the cut-off of Access-AMH was 1.215 ng/mL (area under the curve [AUC], 0.807; 95% confidence interval [CI], 0.730–0.884; p<0.001), and the cut-off of Elecsys-AMH was 1.095 ng/mL (AUC, 0.848; 95% CI, 0.773–0.923; p<0.001). To predict high responders, the cut-off of Access-AMH was 3.450 ng/mL (AUC, 0.922; 95% CI, 0.862–0.981; p<0.001), and the cut-off of Elecsys-AMH was 2.500 ng/mL (AUC, 0.884; 95% CI, 0.778–0.991; p<0.001). Conclusion Both automated methods for serum AMH measurement showed a good correlation with oocyte number and good performance for predicting poor and high responders in fresh stimulated IVF cycles. The Access method usually yielded higher measured serum AMH levels than the Elecsys method.

/pdf/correlation-of-oocyte-number-with-serum-anti-mullerian-3je9abpl.pdf

Correlation of oocyte number with serum anti-Müllerian hormone levels measured by either Access or Elecsys in fresh in vitro fertilization cycles

Anti-Müllerian hormone (AMH) is a peptide belonging to the transforming growth factor beta superfamily and acts exclusively through its receptor type 2 (AMHR2). From the 8 th week of pregnancy, AMH is produced by Sertoli cells, and from the 23 rd week of gestation, it is produced by granulosa cells of the ovary. AMH plays a critical role in regulating gonadotropin secretion, ovarian tissue responsiveness to pituitary hormones, and the pathogenesis of polycystic ovarian syndrome. It inhibits the transition from primordial to primary follicles and is considered the best marker of ovarian reserve. Therefore, measuring AMH concentration of the hormone is valuable in managing assisted reproductive technologies. AMH was initially discovered through its role in the degeneration of Müllerian ducts in male fetuses. However, due to its ability to inhibit the cell cycle and induce apoptosis, it has also garnered interest in oncology. For example, antibodies targeting AMHR2 are being investigated for their potential in diagnosing and treating various cancers. Additionally, AMH is present in motor neurons and functions as a protective and growth factor. Consequently, it is involved in learning and memory processes and may support the treatment of Alzheimer’s disease. This review aims to provide a comprehensive overview of the biology of AMH and its role in both endocrinology and oncology. 

Anti-Müllerian hormone: biology and role in endocrinology and cancers

Objective and Methods: All women seen at the Homerton Fertility Center, London (Site 1, n = 1787) and Hewitt Fertility Center, Liverpool (Site 2, n = 1258) in 15 months had serum AMH measured using...

Automated anti-Mullerian hormone measurement: data review to provide insights and interpretation.

In women, the majority of anti-Mullerian hormone (AMH) measured in serum originate from small antral follicles measuring 2–10 mm. In gonadotrophin-stimulated cycles prior to assisted reproductive t...

Contribution of recruitable follicles to circulating anti-Müllerian hormone levels following maximal gonadotrophin stimulation in patients with limited ovarian reserve

In assisted reproductive technology, prediction of treatment failure remains a great challenge. The development of more sensitive assays for measuring anti-Mullerian hormone (AMH) has allowed for the possibility to investigate if a lower threshold of AMH can be established predicting very limited or no response to maximal ovarian stimulation. A prospective observational multicenter study of 107 women, < 40 years of age with regular menstrual cycle and serum AMH levels ≤ 12 pmol/L, treated with 300 IU/day of HP-hMG in a GnRH-antagonist protocol. AMH was measured before treatment start using the Elecsys® AMH assay by Roche Diagnostics. The ability of AMH to predict follicular development and ovarian response was assessed by receiver operating characteristics (ROC). Furthermore, the relationship between AMH at start of stimulation and cycle outcome was investigated using multivariate logistic regression analysis. Five out of 107 cycles (4.7%) were cancelled due to lack of follicular development and 60/107 (56%) women did not reach the classical hCG criteria for ovulation induction (≥ 3 follicles of ≥17 mm). An AMH threshold of 4 pmol/L predicted failure to reach the classical hCG criteria with 89% specificity and 53% sensitivity and an area under the curve (AUC) of 0.76 (95% CI 0.66–0.85). AMH predicted cycle cancellation due to lack of follicular development, using a cut-off value of 1.5 pmol/L, with a specificity of 96% and sensitivity of 80% (AUC = 0.92, 95% CI 0.79–1.00). A single-unit increase in AMH was associated with a 29% decrease in odds of failure to reach the classical hCG criteria (OR 0.71 95% CI 0.59–0.85, p < 0.01). The lowest AMH value compatible with a live birth was 1.3 pmol/L. Among women with a limited ovarian reserve, pre-treatment serum AMH levels significantly predicted failure to reach the classical hCG triggering criteria and predicted lack of follicular development using a new sensitive assay, but AMH was not suitable for withholding fertility treatment, as even very low levels were associated with live births. Not relevant

/pdf/prediction-of-the-lower-serum-anti-mullerian-hormone-by2jbklh15.pdf

Prediction of the lower serum anti-Müllerian hormone threshold for ovarian stimulation prior to in-vitro fertilization using the Elecsys® AMH assay: a prospective observational study.

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Prediction of the lower serum anti-Müllerian hormone threshold for ovarian stimulation prior to in-vitro fertilization using the Elecsys® AMH assay: a prospective observational study.