Predictive value of AMH in late reproductive age: a retrospective cohort study.

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Abstract

This study evaluates the predictive value of Anti-Müllerian Hormone (AMH) levels on outcomes in medically assisted reproduction (MAR), with a focus on women of late reproductive age. AMH, produced by granulosa cells in ovarian follicles, serves as an important indicator of ovarian reserve. A retrospective cohort analysis was conducted, encompassing 4891 MAR cycles, to assess the age-specific predictive value of AMH for clinical pregnancy. The results indicate that AMH is significantly correlated with clinical pregnancy outcomes (p < 0.01) and demonstrates potential predictive value in women over 35 years of age, with its predictive capacity increasing notably with age (AUC = 0.62-0.69). However, in younger women, the correlation between AMH levels and MAR outcomes is weaker (AUC = 0.48-0.53). These findings highlight the importance of integrating AMH measurements with age when assessing fertility potential and tailoring MAR treatments, particularly for women approaching the end of their reproductive lifespan.
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Results

Initially, stimulated cycles (n = 4910) performed at a single tertiary center between 2020 and 2024 were included in the analysis. These cycles comprised fresh embryo transfers (ET), cycles canceled prior to oocyte retrieval, and cycles where no embryos were produced. After removing cases with missing data, 4891 cycles were included in the final analysis. Among these, 1187 cycles involved patients aged 40 years or older. The participants’ ages ranged from 20 to 46 years. Additionally, 650 cycles were canceled due to no response or failure to retrieve oocytes. Freeze-all cycles (n = 412) were also included, with the first subsequent ET considered for the analysis. In total, 34.8% of cycles resulted in clinical pregnancy (n = 1703). Women who achieved clinical pregnancy were younger than those who did not (36.4 vs. 33.9 years, p < 0.01). A small but significant difference in BMI was observed (25.3 vs. 25.6, p < 0.01). Early follicular FSH levels were significantly different between the two groups (7.1 vs. 6.4, p < 0.01). Regarding cycle characteristics, the duration of stimulation was shorter in pregnant women (9.66 vs. 9.97 days, p < 0.01). Similarly, the number of retrieved oocytes was significantly higher in women achieving pregnancy (10.2 vs. 7.1, p < 0.01), while the total FSH dosage was higher in the non-pregnant group (1612 IU vs. 1541 IU, p < 0.01). Women who achieved pregnancy also had significantly more cryopreserved embryos (2.9 vs. 1.2, p < 0.01). Table 1 Summary statistics for women by age group and pregnancy status. Younger than 40 40 and above Variable Pregnant (n = 1510) Non-Pregnant (n = 2185) p Pregnant (n = 193) Non-pregnant (n = 994) p AMH ( \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\upmu }$$\end{document} g/L) \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3.71 \pm 3.16$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2.98 \pm 2.82$$\end{document} < 0.001 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2.39 \pm 2.46$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1.48 \pm 1.61$$\end{document} < 0.001 BMI \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$25.43 \pm 23.52$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$25.56 \pm 15.50$$\end{document} 0.85 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$24.13 \pm 5.36$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$25.67 \pm 18.65$$\end{document} 0.03 No. of 2PNs ICSI \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2.84 \pm 4.32$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2.02 \pm 3.45$$\end{document} < 0.001 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1.69 \pm 2.87$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1.11 \pm 1.87$$\end{document} < 0.001 No. of 2PNs IVF \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$4.12 \pm 4.98$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2.48 \pm 4.05$$\end{document} < 0.001 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2.79 \pm 3.73$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1.36 \pm 2.43$$\end{document} < 0.001 No. of vitrified embryos \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3.15 \pm 3.25$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1.61 \pm 2.76$$\end{document} < 0.001 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1.17 \pm 2.15$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$0.42 \pm 1.13$$\end{document} < 0.001 No. of ICSI treated oocytes \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$4.07 \pm 5.88$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3.39 \pm 4.92$$\end{document} < 0.001 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2.45 \pm 3.90$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1.92 \pm 2.82$$\end{document} 0.07 No. of IVF treated oocytes \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$5.76 \pm 6.83$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3.83 \pm 5.71$$\end{document} < 0.001 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3.97 \pm 4.91$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2.16 \pm 3.45$$\end{document} < 0.001 No. of collected oocytes \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$10.62 \pm 6.88$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$8.22 \pm 6.50$$\end{document} < 0.001 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$6.94 \pm 4.81$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$4.55 \pm 3.91$$\end{document} < 0.001 No. of previous cycles \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2.05 \pm 1.65$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2.31 \pm 1.84$$\end{document} < 0.001 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2.68 \pm 2.00$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3.02 \pm 2.10$$\end{document} 0.04 No. of fertilised oocytes \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$7.40 \pm 5.21$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$4.83 \pm 4.77$$\end{document} < 0.001 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$4.87 \pm 3.93$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2.71 \pm 2.85$$\end{document} < 0.001 No. of inseminated oocytes \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$9.83 \pm 6.44$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$7.22 \pm 5.98$$\end{document} < 0.001 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$6.42 \pm 4.61$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$4.07 \pm 3.63$$\end{document} < 0.001 No. of transferred embryos \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1.06 \pm 0.56$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$0.88 \pm 0.65$$\end{document} < 0.001 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1.42 \pm 0.60$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$0.99 \pm 0.75$$\end{document} < 0.001 Duration of stimulation (days) \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$9.65 \pm 1.83$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$9.90 \pm 2.18$$\end{document} < 0.001 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$9.74 \pm 1.98$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$10.13 \pm 2.24$$\end{document} 0.01 Total dosage FSH (IU) \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1543.51 \pm 791.33$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1663.29 \pm 985.72$$\end{document} < 0.001 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1517.65 \pm 1172.25$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1496.52 \pm 1314.80$$\end{document} 0.83 Total dosage hMG (IU) \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$279.08 \pm 861.19$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$398.09 \pm 999.94$$\end{document} < 0.001 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$850.37 \pm 1381.15$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1109.41 \pm 1517.68$$\end{document} < 0.001 Basal FSH (IU/L) \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$6.26 \pm 2.50$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$6.66 \pm 2.84$$\end{document} < 0.001 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$7.35 \pm 3.85$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$8.01 \pm 4.15$$\end{document} 0.03 Basal LH (IU/L) \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$34.52 \pm 1171.39$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$4.34 \pm 2.73$$\end{document} 0.30 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$4.55 \pm 2.96$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$5.15 \pm 12.90$$\end{document} 0.19 Summary statistics for women by age group and pregnancy status. A more detailed age-stratified analysis can be found in Table 1 . Among indications for MAR treatment, idiopathic infertility was the most common (29.6%, n = 1358), followed by diminished ovarian reserve (27.8%, n = 1278), tubal factor (15.2%, n = 699), and endometriosis (10.7%, n = 496). Male factor infertility was present in 56% of cases (n = 2745). When considering co-morbidities, 27.8% of women (n = 811) had underlying diagnosed condition regardless of the required treatment. Smoking was present in 15.2% of women (n = 594). Pregnancy rates did not differ significantly based on smoking status (p = 0.1) or comorbidities (p = 0.56). Table 2 Multivariate analysis. Variable Odds ratio (95% CI) p-value Odds ratio (95% CI) p-value (Younger than 40) (40 and above) AMH 1.01 (1.00–1.02) <0.001 1.03 (1.01–1.04) <0.001 Age 0.99 (0.99–0.99) <0.001 0.98 (0.97–1.00) <0.01 Basal FSH 1.00 (0.99–1.01) 0.35 1.00 (0.99–1.01) 0.99 No. of previous cycles 0.99 (0.98–1.00) 0.002 0.99 (0.98–1.00) 0.073 Total Dosage FSH [IU] 1.00 (1.00–1.00) 0.08 1.00 (1.00–1.00) 0.78 No. of fertilized oocytes 1.01 (0.99–1.03) 0.09 1.01 (0.97–1.05) 0.55 Duration of stimulation 1.00 (0.99–1.01) 0.23 0.99 (0.98–1.00) 0.05 No. of transferred 2PN/Emb. 1.20 (1.16–1.23) <0.001 1.10 (1.07–1.14) <0.001 No. of inseminated oocytes 1.01 (1.00–1.02) <0.001 1.00 (0.98–1.03) 0.93 No. of cryopreserved embryos 1.04 (1.03–1.05) <0.001 1.03 (1.00–1.06) 0.02 Multivariate analysis. Fig. 1 No. of collected oocytes stratified by age. Fig. 2 Relationship between AMH concentrations and age. Fig. 3 Significance of correlation between clinical pregnancy and AMH levels, stratified by age. No. of collected oocytes stratified by age. Relationship between AMH concentrations and age. Significance of correlation between clinical pregnancy and AMH levels, stratified by age. AMH was highly correlated with the number of retrieved oocytes (Pearson’s R = 0.526, p < 0.001) (Fig. 1 ). Similar results were observed with age (Pearson’s R = -0.384, p < 0.001) (Fig. 2 ). Regarding pregnancy, AMH levels were significantly higher in women who achieved pregnancy (3.56 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\upmu }$$\end{document} g/L vs. 2.51 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\upmu }$$\end{document} g/L). However, these results were not entirely confirmed when performing subgroup analysis. Stratification of the cohort based on age revealed no significant predictive value of AMH in patients younger than 30 years (Fig. 3 ). AMH became significant in the age group between 30 and 35, with Pearson’s correlation coefficient increasing in later years, indicating a higher degree of correlation (r = 0.07, 0.15, and 0.19 for age cohorts 30–35, 35–40, and > 40, respectively). Results were calculated using Pearson’s correlation coefficient. Additionally, independent predictive value was confirmed through logistic regression, where stratified age group analysis was performed using significant variables from the previous univariate analysis (Table 2 ). Fig. 4 ROC comparison. ROC comparison. The predictive value of AMH varies significantly across different age groups. Several models using logistic regression were developed to evaluate its predictive potential. However, only groups of women aged 30 and above were included due to the significant correlations observed in these age cohorts. Models were assessed using ROC curve analysis. For women aged 30–35, the sensitivity was 0.89 and specificity was 0.21. Predictive value increased with age, with a sensitivity of 0.49 and specificity of 0.72 in women aged 35–40. The highest predictive value was observed in women over 40, where sensitivity reached 0.86 and specificity was 0.44. Additionally, ROC curves were plotted to compare the predictive value of AMH across specific cohorts (Fig. 4 ). The area under the curve (AUC) was 0.48, 0.53, 0.62, and 0.69 for age groups  40, respectively. The effect size, measured by Cohen’s d, ranged from 0.09 to 0.4, indicating a small effect. Considering the sample size and effect size, the study’s power was 0.9 for detecting differences in AMH levels among all included participants. For the age group above 40, the study’s power was slightly lower, at 0.84. Additional attempts were made to analyze AMH differences in one-year age increments; however, due to smaller subgroup sizes, the power was reduced to 0.38. Live birth data were available for 4255 cycles, with 948 live births and 257 failed pregnancies. Key analyses were repeated using live birth rate (LBR) as the outcome instead of clinical pregnancy. The results were consistent, showing a significant correlation between AMH levels and LBR in women of late reproductive age (p = 0.055, 0.378, < 0.05, < 0.05 for age cohorts  40, respectively). However, due to the smaller sample size compared with clinical pregnancy data, the power of the analysis was lower (< 0.5).

Patients

This observational cohort study aimed to evaluate the predictive value of AMH in IVF/ICSI treatment, with clinical pregnancy as the primary outcome and live birth rate (LBR) as the secondary outcome. Based on the study by Dai et al., we focused on different age groups of patients, with an emphasis on older women 15 . Initially, patients were stratified into two groups: those younger than 40 and those aged 40 and above, to determine basic characteristics in relation to pregnancy. Additionally, we created subgroups of women in 5-year increments for a more in-depth analysis. A total of 4,891 MAR cycles, performed in 3,032 couples, were included. Data collection was conducted as part of a broader quality control research program, for which approved by the Medical Ethics Committee of UKC Maribor under approval number UKC-MB-KME-48/24. Informed consent was obtained from all subjects. The study was performed in accordance with the principles outlined in the Declaration of Helsinki. All patient data were processed anonymously. Given the subset nature of the database, this study was exempt from separate ethical approval and informed consent. Patients were treated using either a fixed GnRH antagonist protocol (Cetrotide, Merck Serono) or, less frequently, a GnRH agonist long protocol (Diphereline, Ibsen). Either recombinant FSH (Gonal-F, Merck Serono; Bemfola, Gedeon Richter) or purified human menopausal gonadotropin (Menopur, Ferring) was started on day 2 or 3 of the menstrual cycle. In a few cases, recombinant FSH and LH were used (Pergoveris, Merck). The dosage was adjusted based on the predicted ovarian response or previous stimulations. Cycle monitoring was performed via ultrasonography using a 9 MHz vaginal probe. Ovulation was triggered using 0.25 mg of recombinant HCG (Ovitrelle, Merck) when three or more follicles reached > 17 mm or two follicles > 18 mm. Collected oocytes were inseminated through ICSI or IVF, primarily based on male indication and current sperm analysis. Embryos were cultured until day 3 or day 5, after which one or two embryos were transferred under ultrasound guidance. The decision about single embryo transfer (SET) was individualized, although according to general insurance company rules, SET is performed in women under 36 years undergoing their first or second IVF procedure, transferring a top-grade blastocyst. Micronized progesterone (Crinone, Watson) was supplemented using a vaginal gel once daily until the 10th week of pregnancy. There were several freeze-all cycles, primarily as a result of GnRH agonist triggers in hyper-responder patients at high risk of developing ovarian hyperstimulation syndrome (OHSS). The general rule for using an agonist trigger in short GnRH antagonist protocols was the presence of a high number of follicles during stimulation, with an expected retrieval of 20 or more oocytes, estradiol concentrations > 10 nmol/L, or a history of OHSS. Since such patients are considered to have a good prognosis, and a substantial number of cycles were freeze-all, we included them in the analysis. The first subsequent frozen-thawed embryo transfer was considered in the analysis for pregnancy outcomes. Laboratory hormonal analysis was performed a few months before the first IVF procedure. All female patients provided a blood sample on days 2–3 of their spontaneous menstrual cycle to determine the levels of AMH, LH, and FSH. Serum AMH levels were measured using the AMH Gen II Enzyme-Linked Immunosorbent Assay (ELISA; Beckman Coulter, USA). Samples, controls, and calibrators were prepared using the AMH Gen II Assay Buffer. The reference range for women of reproductive age was 0.35–19.0 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\upmu }$$\end{document} g/L. An AMH level < 0.34 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\upmu }$$\end{document} g/L indicated premature ovarian failure, while levels of 12.6 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\upmu }$$\end{document} g/L or higher were often associated with OHSS or polycystic ovary syndrome (PCOS). FSH levels were assessed in plasma using the Enzyme-Linked Fluorescence Assay (ELFA) on a mini VIDAS analyser (BioMérieux SA, France). The reference range for FSH concentrations during the follicular phase of the menstrual cycle was 4–13 U/L. All calculations were performed using RStudio with R version 4.1.2. For statistical analysis, base R functions were utilized along with non-parametric tests (Kruskal-Wallis and Wilcoxon tests) and the chi-square test to evaluate differences between pregnant and non-pregnant groups. Correlations were calculated using Pearson’s coefficient. Additionally, multivariate analysis was performed using a generalized linear model (GLM) with binary logistic regression to evaluate the independent predictive value of AMH. Since more than one cycle per couple could be included in the analysis, this potential bias was addressed by using the patient’s cycle number as a blocking variable in the regression models to account for repeated cycles. Multivariate analysis was performed using a generalized linear model (GLM) with binary logistic regression to assess the independent predictive value of AMH. As multiple cycles from the same patient could be included, potential bias due to non-independence was mitigated by incorporating the cycle number as a blocking factor in the regression model. This approach aimed to partially account for within-subject variability across repeated cycles. Post-hoc power analysis was conducted using the R “pwr” package. The power of the study was calculated by employing Cohen’s d and subsequent power analysis tests based on the statistical methods used.

Conclusion

AMH shows potential as a predictor of MAR success, with its predictive value showing a tendency to increase with age. This emphasizes the critical role of age in fertility treatments and highlights the necessity of individualized treatment planning based on comprehensive ovarian reserve assessments. Further research involving a broader population and utilizing LBR as the primary outcome is essential to explore the combined predictive value of AMH alongside other markers, thereby improving the accuracy of MAR outcome predictions across different age groups.

Discussion

This study demonstrates that AMH provides statistically significant predictive value for clinical pregnancy outcomes following MAR cycles in women of late reproductive age. Our findings align with previous studies, which highlight AMH as a reliable marker of ovarian reserve and a predictor of the number of retrieved oocytes, thereby reinforcing its value as a tool in reproductive medicine 7 , 16 – 18 . The association between AMH and clinical pregnancy outcomes varies significantly with age, becoming more pronounced in women aged 35 and older, while demonstrating weaker associations in younger cohorts. The stronger correlation of AMH with pregnancy rates in older women suggests that, with advancing age, AMH becomes a more critical factor in predicting MAR success. This may be due to the declining ovarian reserve and increased variability in response to ovarian stimulation in older women, highlighting AMH as an important marker for assessing fertility potential 15 , 19 , 20 . While AMH levels are positively associated with MAR outcomes, it is important to acknowledge that AMH alone is not a definitive predictor of fertility potential 21 , 22 . Other factors, such as age, body mass index (BMI), and baseline FSH levels, also play crucial roles in determining MAR outcomes 13 , 18 , 23 , 24 . This is underscored by our multivariate analysis, which demonstrates that although AMH remains a significant predictor, the odds ratios indicate that its predictive value increases only modestly with advancing age. The inconsistent results in previous studies regarding the relationship between AMH and MAR outcomes are noteworthy. While some studies have reported a positive association between AMH and cumulative live birth rates (CLBR) in women with good prognoses, even after adjusting for age 25 – 27 , others suggest that AMH has limited predictive value for natural pregnancy and live birth rates once a euploid embryo is identified 15 . Our findings consistently support the notion that AMH’s predictive value is highly context-dependent, becoming more pronounced in assisted reproduction settings, particularly in women over 35 28 . While AMH is primarily recognized as a marker of ovarian reserve and oocyte quantity 4 , 5 , its relationship with oocyte quality remains less clearly defined. Some studies suggest that higher AMH levels may be associated with improved oocyte competence and embryo developmental potential, particularly in women of advanced reproductive age 14 , 15 . However, AMH does not directly reflect oocyte chromosomal integrity or morphological quality 29 . Nevertheless, other studies have confirmed that AMH can serve as a valuable predictor of successful oocyte retrievals in donor populations when specific threshold values are applied 30 . The ROC analysis further supports the conclusion that AMH becomes a significant predictor in older age cohorts, with AUC values demonstrating improved predictive accuracy as age increases. This suggests that while AMH testing is beneficial for all age groups, particularly for evaluating ovarian stimulation response, its utility is notably enhanced in women over 35, while still remaining moderate. In this demographic, AMH provides significant insights into the likelihood of MAR success, supporting individualized patient counseling and informed treatment planning. These findings align with studies indicating that AMH levels are more strongly associated with MAR outcomes in older women, where ovarian reserve is more variable and generally lower 17 , 23 , 28 . These results have important clinical implications. In younger women, AMH may serve as a component of ovarian reserve assessment; however, clinicians should not rely solely on AMH levels. In contrast, for older women, AMH testing can provide valuable insights for MAR treatment planning, including predicting ovarian response to stimulation and potential pregnancy outcomes 14 . Accurately predicting MAR success in older women is particularly critical, given the limited timeframe for conception and the necessity for efficient and effective treatment strategies. Live birth rates (LBR) are considered a superior variable for measuring MAR outcomes due to their broader applicability 15 , 25 . Our LBR results support our findings, demonstrating a similar correlation between AMH and LBR in late reproductive age as observed with clinical pregnancy outcomes. However, due to the smaller sample size, the power of the analysis was reduced, rendering it inappropriate to use LBR as the primary outcome. In addition to AMH, other confounding factors such as BMI, FSH levels, and the ovarian stimulation may influence MAR outcomes and should be considered when interpreting predictive models. Higher BMI has been associated with altered hormonal dynamics and reduced ovarian response 31 , while elevated baseline FSH may indicate diminished ovarian reserve independent of AMH levels 32 . Moreover, variability in stimulation protocols–including differences can impact oocyte yield and embryo quality, potentially modifying the relationship between AMH and clinical outcomes. Although these variables were included in multivariate models, residual confounding cannot be fully excluded. This study has several limitations, the most significant being its single-center design and retrospective nature. Although it can be considered representative of real-world data, the potential for selection bias cannot be reliably excluded. These factors may limit the generalizability of the findings to other settings with different clinical protocols or patient populations. Since more than one cycle per couple could be included in the analysis, this potential bias was addressed by using the patient’s cycle number as a blocking variable in the regression models to account for repeated cycles. Although not a full mixed-effects model, this approach allowed partial control for within-subject variability; however, future multicentric studies on different populations may benefit from using random-effects or hierarchical modeling for more robust adjustment.

Introduction

Anti-Müllerian Hormone (AMH) is a protein secreted by granulosa cells in small primordial follicles within the ovaries. It plays a key role in regulating ovarian function and maintaining the follicle pool by modulating stimulatory growth factors required for the cyclic recruitment of primordial follicles 1 – 3 . In recent years, AMH has emerged as one of the most reliable markers of ovarian reserve and MAR treatment outcomes 4 , 5 . It is frequently used in assisted reproduction due to its stable expression, which is independent of the menstrual cycle 6 . AMH correlates with oocyte yield and clinical pregnancy, particularly in women of late reproductive age 6 – 10 . However, most of AMH’s predictive value is likely related to ovarian reserve and the number of retrieved oocytes 11 , 12 . In MAR treatment, women with lower AMH levels may require higher doses of fertility drugs, have a reduced likelihood of successful fertilization, and face challenges in producing enough oocytes for a successful cycle 12 . Older women, who typically have lower AMH levels, may also experience a higher risk of miscarriage and a reduced chance of live birth 13 . The underlying mechanisms of AMH’s role are not yet fully understood, though some evidence suggests a relationship between oocyte quality and AMH 14 , 15 . There is an increasing need to develop accurate predictive models for MAR treatment, especially for women of late reproductive age. To enhance our understanding of AMH’s role as a predictor of IVF/ICSI success and to explore its interaction with age, we conducted an retrospective observational cohort study. This study aimed to evaluate AMH’s ability to predict clinical pregnancy outcomes across different age groups and quantify its predictive potential.

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