Intrafollicular fluid metabolic abnormalities in relation to ovarian hyperstimulation syndrome: Follicular fluid metabolomics via gas chromatography-mass spectrometry

Ovarian hyperstimulation syndrome (OHSS) is the most serious iatrogenic complication of ovulation stimulation during assisted reproductive technology. The main objective of this study was to investigate intrafollicular fluid metabolic change profiles of OHSS in non-ovarian etiologic infertility women (CON) and polycystic ovarian syndrome patients (PCOS). 87 infertile women were divided into four subgroups: CON-Norm (CON with normal ovarian response), CON-OHSS (CON with OHSS), PCOS-Norm (PCOS with normal ovarian response), and PCOS-OHSS (PCOS with OHSS). The intrafollicular fluid metabolic profiles were analyzed with gas chromatography-mass spectrometry. The multivariable-adjusted conditional logistic regression was applied to assess the association of metabolites with OHSS risk. We identified 17 and 3 metabolites that related to OHSS risk in CON and PCOS, respectively. 13 OHSS risk-related metabolites in CON were unsaturated fatty acids, 8 of which were also the significantly altered metabolites between all PCOS and CON-Norm. Our study may shed light on the role of intrafollicular fluid metabolic abnormalities in the pathophysiology of OHSS. The findings suggested that there might be some metabolic heterogeneities underlying the development of OHSS in CON and PCOS women and indicated possible shared etiological factors in the development of PCOS and OHSS.