Clinical and immunological characteristics of women with infertility and/or a history of recurrent pregnancy loss

Aim: to conduct a comprehensive analysis of clinical, anamnestic and immunological characteristics of women with infertility and/or a history of recurrent pregnancy loss.

Materials and Methods. A cross-sectional study included 302 women of reproductive age with a history of infertility and/or recurrent pregnancy loss by enrolling those who was planning pregnancy and directed for preconceptional councelling in 2023–2024. Patients were divided into 3 groups depending on whether they had experienced infertility (n = 108), recurrent pregnancy loss (n = 141), infertility and recurrent pregnancy loss (n = 53). The study flowchart included the collection of gynecological and obstetric histories, as well as ultrasound examination of the pelvic organs in follicular phase. Expression of innate immunity gene mRNAs was carried out: interleukins (IL) IL-1β, IL-10, IL-18, tumor necrosis factor-alpha (TNF-α), Toll-like receptor 4 (TLR4), GATA-binding protein 3 (GATA3), cluster of differentiation 68 (CD68), β₂-microglobulin. Based on the mRNA expression profiles of the studied genes, the integral inflammation index (II) was calculated automatically using binary logistic regression software. A local inflammatory reaction in the cervical mucosal scraping was recorded when the II value exceeded 60 %. Statistical analysis was performed using R v 4.4.3. In hypothesis testing, differences were considered statistically significant at p < 0.05.

Results. The prevalence of inflammatory endometrial pathology (chronic endometritis diagnosed by ultrasound) was comparable among groups 1, 2, 3 (16.7; 19.9; 18.9 %; p > 0,05). A greater incidence of ultrasound detected intrauterine adhesions was found in group 2 with combined infertility and recurrent pregnancy loss (17,0 %) compared to infertility group 1 (4.6 %; p = 0,022) and comparable to recurrent pregnancy loss group 3 (14.9 %; p > 0,05). Uterine septal removal was performed more often in group 2 (17.0 %) than in group 1 (1.9 %; p = 0,003). Endometriosis was diagnosed more often in group 2 (24,5 %) than in group 3 (7.8 %; p = 0,009). Reproductive history in combined pathology group 2 compared to infertility group 1 showed higher number of pregnancies (4.0 [3.0; 4.0] vs. 1.0 [0.0; 1.0]; p < 0.001), proportion of spontaneous miscarriages (50.9 % vs. 5.6 %; p < 0.001), prevalence of secondary infertility (24.5 % vs. 11.1 %; p < 0,001) and in vitro fertilization attempts (1.0 [0.0; 3.0] vs. 0.0 [0.0; 2.0]; p = 0.002). We found the difference in IL-1β gene expression in group 1 and group 3 (4.6 [3.5; 5.3]) vs. 4.9 [4.1; 5.8]; p = 0,044). This may suggest different mechanisms underlying endometrialembryonic dialogue disorders with common inflammatory background: the general index of local inflammation was high in all groups (more than 60 %).

Conclusion. Prevalence of ultrasound chronic endometritis signs in groups 1, 2, 3 was up to 20 %. Patients with infertility and/or recurrent pregnancy loss, with chronic endometritis, concomitant dysbiotic disorders and activated local immunity need to correct vaginal microbiocenosis before pregnancy in order to prevent infectious and inflammatory complications. It is necessary to develop a screening program based on the characteristics of gynecological, obstetric, reproductive history, morbidity and local inflammatory gene expression levels. Our data confirm the importance of an integrated approach in assessing a role of infectious factor in origin of reproductive disorders.

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