Journal of ovarian research · 2026
Beyond metabolic comorbidity: metabolic health stratification reveals BMI-ART associations in tubal factor infertility.
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Wan Xiaoju, Yu Min, Wu Xingwu, Huang Zhihui, Tan Jun
Аннотация
BACKGROUND: The association between body mass index (BMI) and assisted reproductive technology (ART) outcomes remains inconsistent, potentially due to confounding by metabolic comorbidities and underlying infertility etiologies. This study introduced metabolic health stratification to reproductive medicine to examine whether the impact of BMI on ART outcomes differs by metabolic status, independent of ovarian reserve impairment or reproductive endocrinopathies.
METHODS: This retrospective cohort study included 3,770 women with tubal factor infertility and normal ovarian reserve who underwent their first IVF/ICSI cycle between January 2016 and March 2026. The cohort was divided into metabolically healthy (n = 1,849) and metabolically unhealthy (n = 1,921) subgroups based on blood pressure, glucose metabolism, and lipid profiles. Outcomes included oocyte yield (with basal FSH examined as a potential intermediate variable), embryological parameters (MII oocyte rate, 2PN rate, day 3 good-quality embryo rate, good-quality blastocyst formation rate), and clinical outcomes (clinical pregnancy, miscarriage, live birth). Indirect pathway analysis and multivariable logistic regression with power and effect size analyses were performed.
RESULTS: BMI was positively associated with oocyte yield, and the indirect pathway through FSH accounted for 4.7-6.3% of this association-findings that were consistent across both metabolic subgroups (all between-cohort P > 0.05). Overweight/obesity was associated with lower 2PN rate in IVF (- 3.4%) and ICSI (- 3.9%), reduced good-quality blastocyst formation rate in IVF (- 3.5%), and lower MII oocyte rate in ICSI (- 4.1%). Underweight was associated with higher day 3 good-quality embryo rate in ICSI (+ 11.4%). For clinical outcomes, no associations remained significant after multiple comparison correction; however, underweight showed a clinically meaningful reduction in miscarriage rate (- 3.5%), while effect sizes for clinical pregnancy and live birth were small (≤ 2.5% absolute difference). No significant BMI-metabolic status interactions were detected for any outcome.
CONCLUSIONS: The impact of BMI on ART outcomes is independent of metabolic health status. Overweight/obesity exerts consistent detrimental effects on embryological outcomes, while metabolic comorbidities do not modify these associations. Metabolic health stratification suggests that adiposity per se, rather than its associated metabolic abnormalities, may be the primary factor associated with BMI-ART outcomes in tubal factor infertility, although the lack of significant interaction does not exclude metabolic modification.
METHODS: This retrospective cohort study included 3,770 women with tubal factor infertility and normal ovarian reserve who underwent their first IVF/ICSI cycle between January 2016 and March 2026. The cohort was divided into metabolically healthy (n = 1,849) and metabolically unhealthy (n = 1,921) subgroups based on blood pressure, glucose metabolism, and lipid profiles. Outcomes included oocyte yield (with basal FSH examined as a potential intermediate variable), embryological parameters (MII oocyte rate, 2PN rate, day 3 good-quality embryo rate, good-quality blastocyst formation rate), and clinical outcomes (clinical pregnancy, miscarriage, live birth). Indirect pathway analysis and multivariable logistic regression with power and effect size analyses were performed.
RESULTS: BMI was positively associated with oocyte yield, and the indirect pathway through FSH accounted for 4.7-6.3% of this association-findings that were consistent across both metabolic subgroups (all between-cohort P > 0.05). Overweight/obesity was associated with lower 2PN rate in IVF (- 3.4%) and ICSI (- 3.9%), reduced good-quality blastocyst formation rate in IVF (- 3.5%), and lower MII oocyte rate in ICSI (- 4.1%). Underweight was associated with higher day 3 good-quality embryo rate in ICSI (+ 11.4%). For clinical outcomes, no associations remained significant after multiple comparison correction; however, underweight showed a clinically meaningful reduction in miscarriage rate (- 3.5%), while effect sizes for clinical pregnancy and live birth were small (≤ 2.5% absolute difference). No significant BMI-metabolic status interactions were detected for any outcome.
CONCLUSIONS: The impact of BMI on ART outcomes is independent of metabolic health status. Overweight/obesity exerts consistent detrimental effects on embryological outcomes, while metabolic comorbidities do not modify these associations. Metabolic health stratification suggests that adiposity per se, rather than its associated metabolic abnormalities, may be the primary factor associated with BMI-ART outcomes in tubal factor infertility, although the lack of significant interaction does not exclude metabolic modification.