Total Testosterone Measured by Liquid Chromatograph‐Tandem Mass Spectrometry Refines Diagnosis of Biochemical Hyperandrogenism and Better Identifies Subgroup at Genuine Risk of Adverse Fertility Outcomes in Women With Polycystic Ovary Syndrome

ABSTRACT Purpose To compare total testosterone (TT) measured by liquid chromatograph‐tandem mass spectrometry (LC–MS/MS) with electro‐chemiluminescent immunoassay (ECLIA) in the diagnosis and management of infertile women with polycystic ovary syndrome (PCOS). Methods Baseline TT was measured by LC–MS/MS and ECLIA in 906 infertile women with PCOS. The associations of TT from both methods with clinical phenotypes and fertility outcomes were estimated; relative risk (RR) and 95% confidence intervals (CIs) were computed. Subgroup analysis was conducted according to the TT levels. Results The average TT levels measured by ECLIA were higher than those measured by LC–MS/MS (mean percentage difference 23.8%, 95% limits of agreement −44.2% to 91.9%). When biochemical hyperandrogenism (HA) defined as TT ≥ 1.7 nmol/L by LC–MS/MS method, a higher proportion of patients were identified having biochemical HA using ECLIA (44.0% vs. 24.0%, p < 0.001) than LC–MS/MS. Only those with TT levels ≥ 1.7 nmol/L measured by LC–MS/MS had an increased risk of adverse fertility outcomes compared to patients with normal TT levels, including ovulation, preterm labor, and neonatal intensive care unit. Conclusion Our findings indicated that LC–MS/MS refined the diagnosis of biochemical hyperandrogenism and better identified the subgroup at genuine risk of adverse fertility outcomes in infertile women with PCOS. Trial Registration The NIH Clinical Trial Registry number: NCT01573858 and Chinese Clinical Trial. Registry number: ChiCTR‐TRC‐12002081