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

Plasma kisspeptin provides additional predictive value for identification of miscarriage compared with beta human chorionic gonadotropin alone, and its performance improves during later gestational weeks of the first trimester.

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VOLUME 116, ISSUE 3, P809-819


Ali Abbara, Ph.D., Maya Al-Memar, Ph.D., Maria Phylactou, Ph.D., Christopher Kyriacou, M.B.B.S., Pei Chia Eng, Ph.D., Rans Nadir, B.Sc., Chioma Izzi-Engbeaya, Ph.D., Sophie A. Clarke, Ph.D., Edouard G. Mills, M.B.B.S., Elisabeth Daniels, B.Sc., Lechun Huo, M.Res., Ewa Pacuszka, Pg.Dip., Lisa Yang, Ph.D., Bijal Patel, M.B.B.S., Tricia Tan, Ph.D., Paul Bech, Ph.D., Alexander N. Comninos, Ph.D., Hanine Fourie, Ph.D., Tom W. Kelsey, Ph.D., Tom Bourne, Ph.D., Waljit S. Dhillo, Ph.D. 



To compare the performance of kisspeptin and beta human chorionic gonadotropin (βhCG), both alone and in combination, as biomarkers for miscarriage throughout the first trimester.


Prospective, nested case-control study.


Tertiary Centre, Queen Charlotte Hospital, London, United Kingdom.


Adult women who had miscarriages (n = 95, 173 samples) and women with healthy pregnancies (n = 265, 557 samples).


The participants underwent serial ultrasound scans and blood sampling for measurement of plasma kisspeptin and βhCG levels during the first trimester.

Main Outcome Measure(s)

The ability of plasma kisspeptin and βhCG levels to distinguish pregnancies complicated by miscarriage from healthy pregnancies unaffected by miscarriage.


Gestation-adjusted levels of circulating kisspeptin and βhCG 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 βhCG, 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 βhCG worsened. A decision matrix incorporating kisspeptin, βhCG, and gestational age had 83% to 87% accuracy for the prediction of miscarriage.


Plasma kisspeptin is a promising biomarker for miscarriage and provides additional value to βhCG alone, especially during later gestational weeks of the first trimester.

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.