Novel polycystic ovary syndrome clusters identified by endocrine-metabolic clustering: impact on reproductive outcomes after fertility treatment.

OBJECTIVE

To identify novel polycystic ovary syndrome (PCOS) clusters using endocrine and metabolic clustering and to investigate the impact of these clusters on reproductive and pregnancy outcomes after fertility treatment.

DESIGN

Prospective study.

SUBJECTS: Women diagnosed with PCOS according to the Rotterdam criteria, undergoing fertility treatment.

EXPOSURE: Comprehensive assessment of 27 endocrine and metabolic parameters followed by unsupervised clustering analysis to identify distinct phenotypes; participants subsequently underwent fertility treatment.

MAIN OUTCOME MEASURES: Identification of novel PCOS clusters; comparison of live birth rates and the incidence of major pregnancy complications (gestational diabetes mellitus and hypertension) across the identified clusters.

RESULTS

A total of 1,149 Vietnamese women diagnosed with PCOS were included in this study. Three distinct PCOS clusters were identified: metabolic-disturbance PCOS (MD-PCOS; n = 453), metabolic-sparing PCOS (MS-PCOS; n = 334), and neuro-reproductive PCOS (NR-PCOS; n = 362). The MD-PCOS cluster had severe metabolic dysfunction, whereas the NR-PCOS cluster had the most pronounced neuroendocrine dysregulation. Reproductive outcomes differed significantly, with the MD-PCOS cluster having the lowest live birth rate (44.8% vs. 59.3% in MS-PCOS and 51.4% in NR-PCOS). Rates of pregnancy complications were significantly higher in the MD-PCOS cluster compared with the MS-PCOS and NR-PCOS clusters, respectively, for gestational diabetes mellitus (33% vs. 19% vs. 15%) and hypertension in pregnancy (10% vs. 1% vs. 5%).

CONCLUSION

Endocrine and metabolic clustering identified three novel PCOS phenotypes with distinct clinical profiles and reproductive prognoses. The MD-PCOS cluster represents a high-risk group for adverse pregnancy outcomes, highlighting the clinical utility of this classification for preconception risk stratification.