Abstract / Summary
Kisspeptin is a key reproductive neuropeptide whose actions extend beyond hypothalamic gonadotropin-releasing hormone stimulation to the ovary, endometrium, and placenta. Increasing translational and clinical evidence links dysregulated kisspeptin signaling with infertility phenotypes, assisted reproduction outcomes, and early pregnancy failure. This narrative review synthesizes human clinical and translational evidence published between 2015 and 2025 regarding kisspeptin and its receptor in assisted reproduction, implantation biology, and early pregnancy outcomes. PubMed/MEDLINE (primary), Embase, and Web of Science were searched using Medical Subject Headings (MeSH) and free-text terms. Included studies comprised meta-analyses, systematic reviews, randomized controlled trials, observational studies, and clinically informative tissue-based investigations; findings were qualitatively summarized due to heterogeneity. Clinical trials indicate that kisspeptin-54 can trigger oocyte maturation in women at high risk of ovarian hyperstimulation syndrome, based on endocrine profiles that may limit excessive luteinization relative to conventional triggers. Observational in vitro fertilization studies associate circulating or follicular fluid kisspeptin levels with oocyte maturity and treatment outcomes, although heterogeneity persists in assay methods and sampling timing. Mechanistic studies support roles for uterine and placental kisspeptin in decidualization and signaling at the maternal–fetal interface. In early pregnancy, low circulating kisspeptin levels are consistently associated with nonviable pregnancies and miscarriage. The diagnostic performance of kisspeptin in distinguishing viable pregnancies from early pregnancy failure appears to improve with gestational age in the first trimester. Kisspeptin occupies a clinically actionable role linking endocrine regulation, implantation biology, and early pregnancy maintenance. The field is transitioning from proof of concept to risk-stratified use in assisted reproduction and biomarker-informed monitoring in threatened pregnancy. Priorities for clinical translation include standardized assays, prospective validation cohorts, and adequately powered trials evaluating kisspeptin-guided strategies.