Role of gestagens in the regulation of kisspeptin-1 levels in patients with sporadic and recurrent pregnancy loss
Authors:   Privolzhsky Research Medical University, Nizhny Novgorod, Russian Federation, Katkova N.Yu. , Bezrukova I.M. ,   Privolzhsky Research Medical University, Nizhny Novgorod, Russian Federation, Kolodkina A.O. ,   Privolzhsky Research Medical University, Nizhny Novgorod, Russian Federation, Pokusaeva K.B. ,   Privolzhsky Research Medical University, Nizhny Novgorod, Russian Federation, Bodrikova O.I. ,   Privolzhsky Research Medical University, Nizhny Novgorod, Russian Federation, Kurtin A.A. ,   Privolzhsky Research Medical University, Nizhny Novgorod, Russian Federation
Published: January 2025

Objective. To study the levels of kisspeptin-1 in patients with recurrent pregnancy loss and the possibility of its correction with
gestagens.
Patients and methods. This prospective comparative study was conducted in two phases. In the first phase, 129 women with registered pregnancy loss (study group 1) were examined and divided into two subgroups: subgroup 1 – 102 patients with sporadic pregnancy loss (SPL), subgroup 2 – 27 patients with recurrent pregnancy loss (RPL). Control group 1 included 80 patients who gave birth to full-term healthy infants. In the second phase of the study, the possibility of correcting kisspeptin-1 levels with gestagens in patients with RPL and
preventing pregnancy loss was determined. In this phase, 72 pregnant women with a history of RPL at 5–9 weeks’ gestation were examined. All women were categorized into two groups based on their levels of kisspeptin-1. The study group comprised of 38 patients with low kisspeptin-1 levels. Depending on the regimen of dydrogesterone therapy for RPL, two patient subgroups were identified: subgroup 1 – 18 pregnant women who received 20 mg of dydrogesterone per day; subgroup 2 – 20 pregnant women with RPL who received 30 mg of dydrogesterone per day. The comparison group included 34 pregnant women with a history of RPL and normal kisspeptin-1 levels, receiving 20 mg of dydrogesterone per day.
Results. Serum kisspeptin-1 levels differed significantly between the study groups. The highest values were registered in the group of women with normal pregnancy – 304.63 ± 70.26 pg/mL. In the SPL subgroup, mean kisspepsin-1 levels were 262.18 ± 51.41 pg/mL (p = 0.014). RPL was accompanied by the lowest levels of kisspepsin-1, one quarter lower than in the control group – 217.91 ± 46.79 pg/mL (p = 0.000). Significant differences in kisspepsin-1 levels were found between the SPL and RPL subgroups: RPL occurred in patients with lower levels of this regulatory peptide (p = 0.007).
Conclusion. A marker of RPL is a decrease in kisspeptin-1 levels. In patients with recurrent miscarriage and normal levels of kisspeptin 1, it is advisable to use dydrogesterone at a dose of 20 mg per day in order to improve pregnancy outcomes. In patients with recurrent miscarriage and reduced levels of kisspepsin 1, it may be advisable to use dydrogesterone at a dose of 30 mg per day. Further research is needed to confirm this theory.
Key words: pregnancy loss, recurrent pregnancy loss, sporadic pregnancy loss, kisspepsin-1, dydrogesterone