Biomarkers identification in follicular fluid in relation to live birth in in vitro fertilization of women with polycystic ovary syndrome in different subtypes by using UPLC-MS method

Clin Chim Acta. 2024 Apr 15:557:117860. doi: 10.1016/j.cca.2024.117860. Epub 2024 Mar 18.


Background: Polycystic ovary syndrome (PCOS) is a common infertility disorder which affects reproductive-aged women. However, metabolic change profiles of follicular fluid (FF) in lean and obese women diagnosed with and without PCOS remains unclear.

Methods: 95 infertile women were divided into four subgroups: LC (lean control), OC (overweight control), LP (lean PCOS), and OP (overweight PCOS). The FF samples were collected during oocyte retrieval and assayed by ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) metabolomics.

Results: A total of 236 metabolites were identified by metabolic analysis. The pathway enrichment analysis revealed that the glycerophospholipid metabolism (impact = 0.11182), ether lipid metabolism (impact = 0.14458), and primary bile acid biosynthesis (impact = 0.03267) were related to metabolic pathway between PCOS and control. Correlation analyses showed that epitestosterone sulfate was found positively correlated with fertilization rate in PCOS, while falcarindione, lucidone C. and notoginsenoside I was found to be negatively correlated. The combined four biomarkers including lucidone C, epitestosterone sulfate, falcarindione, and notoginsenoside I was better in predicting live birth rate, with AUC of 0.779.

Conclusion: The follicular fluid of women with PCOS showed unique metabolic characteristics. Our study provides better identification of PCOS follicular fluid metabolic dynamics, which may serve as potential biomarkers of live birth.

Keywords: Biomarker; Follicular fluid; In vitro fertilization; Metabolomics; PCOS.

MeSH terms

  • Adult
  • Biomarkers / analysis
  • Chromatography, Liquid
  • Cyclopentanes*
  • Epitestosterone / analysis
  • Epitestosterone / metabolism
  • Female
  • Fertilization in Vitro
  • Follicular Fluid / metabolism
  • Humans
  • Infertility, Female* / diagnosis
  • Liquid Chromatography-Mass Spectrometry
  • Live Birth
  • Overweight
  • Polycystic Ovary Syndrome* / diagnosis
  • Polycystic Ovary Syndrome* / metabolism
  • Pregnancy
  • Sulfates / analysis
  • Sulfates / metabolism
  • Tandem Mass Spectrometry


  • lucidone
  • Epitestosterone
  • Biomarkers
  • Sulfates
  • Cyclopentanes