Performance of plasma kisspeptin as a biomarker for miscarriage improves with gestational age during the first trimester

Objective: To compare the performance of kisspeptin and beta human chorionic gonadotropin (beta hCG), both alone and in combination, as biomarkers for miscarriage throughout the first trimester. Design: Prospective, nested case-control study. Setting: Tertiary Centre, Queen Charlotte Hospital, London, United Kingdom. Patient(s): Adult women who had miscarriages (n = 95, 173 samples) and women with healthy pregnancies (n = 265, 557 samples). Intervention(s): The participants underwent serial ultrasound scans and blood sampling for measurement of plasma kisspeptin and beta hCG levels during the first trimester. Main Outcome Measure(s): The ability of plasma kisspeptin and beta hCG levels to distinguish pregnancies complicated by miscarriage from healthy pregnancies unaffected by miscarriage. Result(s): Gestation-adjusted levels of circulating kisspeptin and beta hCG were lower in samples from women with miscarriages than in women with healthy pregnancies by 79% and 70%, respectively. The area under the receiver-operating characteristic curve for identifying miscarriage during the first trimester was 0.874 (95% confidence interval [CI] 0.844-0.904) for kisspeptin, 0.859 (95% CI 0.820-0.899) for beta hCG, and 0.916 (95% CI 0.886-0.946) for the sum of the two markers. The performance of kisspeptin in identifying miscarriage improved with increasing length of gestation, whereas that of beta hCG worsened. A decision matrix incorporating kisspeptin, beta hCG, and gestational age had 83% to 87% accuracy for the prediction of miscarriage. Conclusion(s): Plasma kisspeptin is a promising biomarker for miscarriage and provides additional value to beta hCG alone, especially during later gestational weeks of the first trimester. (C) 2021 by American Society for Reproductive Medicine.