Metabolic risk factors and fertility disorders: A narrative review of the female perspective Original paper

What was reviewed?

This narrative review comprehensively examined the associations between metabolic risk factors and female fertility disorders, focusing on obesity, the female athlete triad (low energy intake, menstrual dysfunction, decreased bone density), and oxidative stress as potential contributors to infertility. The authors aimed to clarify how these metabolic conditions, alongside major infertility-related disorders such as polycystic ovary syndrome (PCOS) and endometriosis, impact women’s reproductive health. The review synthesized evidence from 50 selected studies published between 2006 and 2020, integrating pathophysiological, genetic, lifestyle, and epidemiological perspectives. It also highlighted the prevalence, mechanisms, and clinical consequences of metabolic risks with female infertility and discussed gaps in current knowledge, especially regarding idiopathic infertility and the need for robust molecular markers.

Who was reviewed?

The review focused on studies involving women of reproductive age experiencing infertility. It included populations affected by PCOS, endometriosis, obesity, and those displaying characteristics of the female athlete triad. The selected studies varied in design but excluded animal research and clinical trials of pharmaceutical treatments. The review encompassed diverse geographic regions and considered women with both known and idiopathic infertility, as well as those undergoing assisted reproductive technology (ART). The aim was to gather data relevant to women at risk for or experiencing infertility due to metabolic and lifestyle factors.

Most important findings

The review established a clear and direct association between obesity and increased risk of female infertility, with obese women exhibiting up to a three-fold higher risk compared to those with normal body mass index (BMI). Obesity was linked to anovulation, reduced ART success rates, and increased miscarriage risk. Mechanistically, excess body fat disrupts ovarian steroidogenesis, induces hyperandrogenism, and promotes chronic low-grade inflammation, all of which impair reproductive function. PCOS was highlighted as a central metabolic-endocrine disorder, often comorbid with obesity, insulin resistance, and increased cardiovascular risk. Endometriosis risk showed a more complex relationship with BMI, with evidence suggesting both inverse and direct associations, possibly due to genetic and hormonal influences. The female athlete triad, though less well-studied in this context, was associated with hypothalamic suppression, menstrual dysfunction, and reduced fertility, primarily through chronic energy deficiency and altered estrogen signaling. Oxidative stress, driven by lifestyle factors (e.g., smoking, alcohol, drug use), was identified as a pervasive mediator, damaging DNA and germ cells, increasing risks for PCOS and endometriosis, and contributing to idiopathic infertility. The review emphasized a lack of large-scale population studies and molecular biomarker research linking metabolic status and infertility.

Key implications

For clinicians, the review underscores the necessity of assessing metabolic risk factors, especially obesity and undernutrition, when addressing female infertility. Interventions targeting weight management, healthy nutrition, and lifestyle modification may improve hormonal balance and reproductive outcomes, particularly in women with PCOS. The review also calls for interdisciplinary collaboration to integrate molecular, metabolic, and psychosocial approaches to infertility. Given the anticipated rise in obesity prevalence among women, proactive metabolic assessment and the development of diagnostic molecular signatures are critical for improving ART outcomes and reducing unexplained infertility. Further, the establishment of consensus definitions and large-scale biobank studies will be pivotal for advancing personalized infertility care.