Integrative Processes Between Various Endocrine Subsystems and Some Paracrine Regulation Parameters in Pregnant Women With Isthmic-Cervical Insufficiency Depending on Fetal Sex and Their Clinical Significance

BACKGROUND: Infectious and inflammatory diseases of the cervix and congenital undifferentiated connective tissue dysplasia are known to be the main causes of functional isthmic-cervical insufficiency. Some patients who meet these criteria do not always develop isthmic-cervical insufficiency, and in their absence, on the contrary, they can do, which necessitates the search for additional prognostic factors. Of great importance in the pathogenesis of isthmic-cervical insufficiency is the hormonal arrangement and paracrine regulation that ensure gestational processes, which will differ due to varying fetal-maternal signaling modulated by fetal sex.

AIM: The aim of this study was to evaluate the clinical significance of the integration of various links in the hormonal profile and some paracrine regulation indices in women with isthmic-cervical insufficiency and normal pregnancy depending on fetal sex.

METHODS: The prospective part of this study included 1,629 women, who were divided into Group I (458 patients with functional isthmic-cervical insufficiency manifestation) and Group II (1,171 patients with normal pregnancy). The sex of the fetus was determined using genetic analysis (in the first trimester) and ultrasound examination (in the second and third trimesters). The levels of some steroid, placental and stress hormones, as well as melatonin metabolites, were measured using enzyme immunoassay. The incidence of isthmic-cervical insufficiency, other pregnancy complications and birth outcomes depending on fetal sex was studied based on 41,564 electronic outpatient cards of primiparous women with singleton pregnancies.

RESULTS: On average, over the entire gestation period, isthmic-cervical insufficiency was 4.5 times more common in pregnant women with a male fetus compared to those with a female fetus. Absolute levels of 6-sulfatoxymelatonin, cortisol, and placental lactogen were higher in women with female fetuses, while progesterone levels were higher in women with male fetuses in both normal pregnancy and isthmic-cervical insufficiency. Free estriol levels in normal pregnancy were higher in women with female fetuses, while in isthmic-cervical insufficiency, they were higher in women with male fetuses. We found differences in the structure of correlation matrices in patients with isthmic-cervical insufficiency and patients with normal pregnancy, which were characterized by maximal information, differences in the strength of relationships and the structure of correlation pairs, as well as in the magnitude of correlation weights depending on fetal sex.

CONCLUSION: The data obtained expand our understanding of the pathogenetic mechanisms of developing isthmic-cervical insufficiency and establish the male sex of the fetus as an additional factor in the formation of risk groups for this pathology. This may be aimed at further development of individualized approaches to gestational support, prognosis and prevention of isthmic-cervical insufficiency and preterm birth.