Abstract
BackgroundWomen with diminished ovarian reserve are known to have increased cardiovascular risk, whether there is a continuous association between the ovarian reserve biomarkers; anti-Müllerian hormone (AMH), antral follicle count (AFC) and cardio-metabolic risk factors are unknown.MethodsA cross-sectional study of 398 women intending to undergo IVF with pre-treatment early follicular AMH and AFC measurements. Serum lipids, lipoprotein subclasses and low-molecular-weight metabolites were quantified by NMR spectroscopy (155 metabolic measures). Associations were analysed using multivariable regression.ResultsParticipants were mean 35.5 (SD 4.43) years old and had a median AMH of 16 pmol/l (IQR 8.8, 28.0 pmol/l) and a median AFC of 12 (IQR 7.16). AMH showed positive associations with HDL, omega-6 and polyunsaturated fatty acids and the amino acids isoleucine, leucine and tyrosine, with effects ranging from 0.11 (95%CI 0.004 to 0.21) for total lipids in small HDL to 0.16 (0.06 to 0.26) for isoleucine, for a mean difference of one SD of metabolite per one SD increment in AMH, and negatively with acetate: − 0.31(− 0.22, − 0.004) SD per 1 SD AMH. AFC was positively associated with alanine, glutamine and glycine. Results were consistent, though less precisely estimated, when restricted to those women who were preparing for treatment because of their partner’s infertility.ConclusionsIn women intending to have IVF, AMH and AFC were not associated with traditional lipid measured but were associated with a number of novel cardiovascular risk factors. Prospective studies will be required for replication, determination of causality and confirmation that ovarian reserve is impacting on metabolism rather than variation in metabolism is influencing ovarian reserve.
Highlights
Women with diminished ovarian reserve are known to have increased cardiovascular risk, whether there is a continuous association between the ovarian reserve biomarkers; anti-Müllerian hormone (AMH), antral follicle count (AFC) and cardio-metabolic risk factors are unknown
Several observational studies have investigated the association between these markers of diminished ovarian reserve and cardiovascular risk factors, with several [4,5,6,7,8] but not all studies [9,10,11], suggesting that a diminished ovarian reserve may be associated with an unfavourable circulating cardiometabolic risk profile and cardiovascular events
Serum nuclear magnetic resonance (NMR) metabolomics which enables reproducible quantification of circulating lipids and abundant metabolites [16] has facilitated its use in the assessment of the changes in metabolites with adiposity [17], glycaemia [18], pregnancy [19] and menopausal status [20]
Summary
Women with diminished ovarian reserve are known to have increased cardiovascular risk, whether there is a continuous association between the ovarian reserve biomarkers; anti-Müllerian hormone (AMH), antral follicle count (AFC) and cardio-metabolic risk factors are unknown. Markers of diminished ovarian reserve, such as low anti-Müllerian hormone (AMH) and low antral follicle count (AFC), have been shown to associate with earlier menopause [2, 3]. Serum nuclear magnetic resonance (NMR) metabolomics which enables reproducible quantification of circulating lipids and abundant metabolites [16] has facilitated its use in the assessment of the changes in metabolites with adiposity [17], glycaemia [18], pregnancy [19] and menopausal status [20]
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