Association of Serum Kisspeptin Levels and Pregnancy Outcomes in Assisted Reproductive Technology
Abstract
Kisspeptin, a neuropeptide produced by syncytiotrophoblast cells, has been hypothesized to regulate successful placental formation. Several studies have shown a positive correlation between maternal serum kisspeptin levels and successful pregnancy outcomes in second and third-trimester pregnancy, but trends in early pregnancy have not been well-established. In this prospective case-control study, we examine whether kisspeptin levels correlate with serum beta-human chorionic gonadotropin (bhCG), progesterone, or pregnancy outcomes at the time of pregnancy testing in cis-gendered females (n= undergoing assisted reproductive technology. Pregnancy testing occurred at an average of 33 days after the last menstrual period for non-IVF protocols and an average of 12 days after blastocyst transfer for IVF protocols. Outcome groups included: viable first-trimester pregnancy (n=18), early miscarriage (n=12), ectopic pregnancy (n=5), biochemical pregnancy (n=16), and not pregnant (n=12). Descriptive statistics including Chi-squared or Fisher’s Exact, ANOVA and Pearson’s correlation coefficient were utilized. Kisspeptin values did not show a significant difference between outcome groups. A weak positive correlation was demonstrated between kisspeptin and bhcg in biochemical and viable pregnancy but not for other outcomes. In contrast, a significant correlation between kisspeptin and measured progesterone value or exogenous progesterone, regardless of administration route, was not observed. In this study population, a single serum measurement of kisspeptin very early in pregnancy was not significantly different between pregnancy outcomes. The utility of kisspeptin as a pregnancy biomarker in the first trimester remains unclear. Additional studies are needed to further investigate the relationship between viable intrauterine pregnancy and serum kisspeptin concentration in the early first trimester and the current findings suggest that it may prove useful in combination with bHCG.
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References
Pervention CfDCa. 2019 Assisted Repoductive Technology Fertility Clinic and National Summary Report 2019.
Horne AW, McBride R, Denison FC. Normally rising hCG does not predict live birth in women presenting with pain and bleeding in early pregnancy. European Journal of Obstetrics and Gynecology and Reproductive Biology. 2011;156(1):120-1.
Doubilet PM, Benson CB, Bourne T, et al. Diagnostic criteria for nonviable pregnancy early in the first trimester. New England Journal of Medicine. 2013;369(15):1443-51.
Millar RP, Babwah AV. KISS1R: Hallmarks of an Effective Regulator of the Neuroendocrine Axis. Neuroendocrinology. 2015;101(3):193-210.
Kotani M, Detheux M, Vandenbogaerde A, et al. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. Journal of Biological Chemistry 2001;276(37):34631-6.
Roseweir AK, Katz AA, Millar RP. Kisspeptin-10 inhibits cell migration in vitro via a receptor-GSK3 beta-FAK feedback loop in HTR8SVneo cells. Placenta. 2012;33(5):408-15.
Bilban M, Ghaffari-Tabrizi N, Hintermann E, et al. Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts. Journal of Cell Science. 2004;117(8):1319-28.
Hiden U, Bilban M, Knöfler M, et al. Kisspeptins and the placenta: regulation of trophoblast invasion. Reviews in Endocrine and Metabolic Disorders. 2007;8(1):31-9.
Francis VA, Abera AB, Matjila M, et al. Kisspeptin regulation of genes involved in cell invasion and angiogenesis in first trimester human trophoblast cells. PLoS One. 2014;9(6):e99680.
Horikoshi Y, Matsumoto H, Takatsu Y, et al. Dramatic elevation of plasma metastin concentrations in human pregnancy: metastin as a novel placenta-derived hormone in humans. Journal of Clinical Endocrinology and Metabolism. 2003;88(2):914-9.
Hu KL, Chen Z, Deng W, et al. Diagnostic Value of Kisspeptin Levels on Early Pregnancy Outcome: a Systematic Review and Meta-analysis. Reproductive Sciences. 2022;29(12):3365-72.
Yu H, Liu J, Guo H, et al. Prognostic value of repeated serum kisspeptin measurements in early first trimester pregnancy: a preliminary study. Reproductive Biomed Online. 2019;38(3):465-71.
Hu KL, Zhang Y, Yang Z, et al. Predictive value of serum kisspeptin concentration at 14 and 21 days after frozen-thawed embryo transfer. Reproductive Biology and Endocrinology. 2019;39(1):161-7.
Romero-Ruiz A, Avendaño MS, Dominguez F, et al. Deregulation of miR-324/KISS1/kisspeptin in early ectopic pregnancy: mechanistic findings with clinical and diagnostic implications. American Journal of Obstetrics and Gynecology. 2019;220(5):480.e1-.e17.
Yuksel S, Ketenci Gencer F. Serum kisspeptin, to discriminate between ectopic pregnancy, miscarriage and first trimester pregnancy. J Obstet Gynaecol. 2022;42(6):2095-9.
Abbara A, Al-Memar M, Phylactou M, et al. Performance of plasma kisspeptin as a biomarker for miscarriage improves with gestational age during the first trimester. Fertility and Sterility. 2021;116(3):809-19.
Calder M, Chan YM, Raj R, et al. Implantation failure in female Kiss1-/- mice is independent of their hypogonadic state and can be partially rescued by leukemia inhibitory factor. Endocrinology. 2014;155(8):3065-78.
Zhang P, Tang M, Zhong T, et al. Expression and function of kisspeptin during mouse decidualization. PLoS One. 2014;9(5):e97647.
Wu HM, Huang HY, Soong YK, et al. Kisspeptin regulation of human decidual stromal cells motility via FAK-Src intracellular tyrosine kinases. Human Reproduction. 2019;34(7):1291-301.
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