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Background: The intricate molecular pathways and genetic factors that underlie the pathophysiology of cervical insufficiency (CI) remain largely unknown and understudied. Methods: We sequenced exomes from 114 patients in Latvia and Lithuania, diagnosed with a short cervix, CI, or a history of CI in previous pregnancies. To probe the well-known link between CI and connective tissue dysfunction, we introduced a connective tissue dysfunction assessment questionnaire, incorporating Beighton and Brighton scores. The phenotypic data obtained from the questionnaire was correlated with the number of rare damaging variants identified in genes associated with connective tissue disorders (in silico NGS panel). SKAT, SKAT-O, and burden tests were performed to identify genes associated with CI without a priori hypotheses. Pathway enrichment analysis was conducted using both targeted and genome-wide approaches. Results: No patient could be assigned monogenic connective tissue disorder neither genetically, neither clinically upon clinical geneticist evaluation. Expanding our exploration to a genome-wide perspective, pathway enrichment analysis replicated the significance of extracellular matrix-related pathways as important contributors to CI's development. A genome-wide burden analysis unveiled a statistically significant prevalence of rare damaging variants in genes and pathways associated with steroids (p-adj = 5.37E-06). Rare damaging variants, absent in controls (internal database, n = 588), in the progesterone receptor (PGR) (six patients) and glucocorticoid receptor (NR3C1) (two patients) genes were identified within key functional domains, potentially disrupting the receptors' affinity for DNA or ligands. Conclusion: Cervical insufficiency in non-syndromic patients is not attributed to a single connective tissue gene variant in a Mendelian fashion but rather to the cumulative effect of multiple inherited gene variants highlighting the significance of the connective tissue pathway in the multifactorial nature of CI. PGR or NR3C1 variants may contribute to the pathophysiology of CI and/or preterm birth through the impaired progesterone action pathways, opening new perspectives for targeted interventions and enhanced clinical management strategies of this condition. [ABSTRACT FROM AUTHOR]

Objective The practice of induced labour has risen to approximately 33% of all pregnancies. It is essential to know what the outcome will be for patients with higher BMI, as it is a high-risk pregnancy, and this would help avoid surgical interventions and related complications in the future. This study aimed to see how a woman's BMI affects the outcome of induced labour. Methods This retrospective study used data from Riga Maternity Hospital and included 8759 women presenting with induced labour from 2016 to 2022. The data was processed using IBM SPSS Statistics version 28, comparing induction outcomes in two main groups: first-primiparas and second-multiparas. Next, these two groups were divided by BMI and studied separately — Group A or control group with BMI<25; Group B – BMI 25-29; Group C – BMI 30-39; Group D – BMI > 39. Results Primiparas with normal BMI in 23% had a CS, and in 77% had a vaginal birth. Group B primiparas in 31% had a CS, so OR to have a CS is 1.5 (95% CI 1.3-1.8). Group C primiparas in 41% had a CS, so OR is 2.3 (95% CI 1.8-2.8). Group D primiparas in 43% had a CS, so OR to have a CS is 2.6 (95% CI 1.5-4.6). Multiparas with a normal BMI in 7% had a CS, and 93% had a vaginal birth. Group B multiparas in 11% had a CS, so OR is 1.8 (95% Ci 1.4-2.4) Group C multiparas had CS in 13%, so OR is 2.1 (95% CI 1,5-3). Almost all group D multiparas had vaginal birth (95% CI 0.3-2.7). Conclusion Primiparas with obesity have a high CS rate. CS risk increases with the primipara BMI. Multiparas with obesity, despite the BMI, have a high chance of delivering vaginally. Having a normal BMI to deliver the first baby is highly recommended. [ABSTRACT FROM AUTHOR]

Embryo implantation is a complicated process involving mother and conceptus cells differentiation, proliferation and invasion that are essential for successful pregnancy. Almost every cell in the human body is affected by IGF-1 that is one of the most potent natural activators of cell growth and multiplication, and also a potent inhibitor of the programmed cell death. bFGF, acting via its receptor FGFR1, is one of the factors involved in mediating the angiogenesis, proteolysis and apoptosis during the implantation. OBJECTIVE: To establish pregnancy inducted difference of appearance of bFGF, IGF-1 and their receptors in the embryonic, decidual and tubal tissue. STUDY DESIGN: In this study 14 tubal pregnancy and 10 decidual tissue samples were evaluated immunohistochemically in order to define the distribution of bFGF, FGFR1, IGF-1, IGF-1R. RESULTS: The Mann-Whitney U test was used as appropriate for the evaluation of significant differences. FGFR1 appearance dominated on bFGF in the decidual (z=2.539, p=0.01), tubal (z=2.539, p=0.01) and embryonic (z=2.539, p=0.01) tissue. IGF-1 and IGF-1R appearance in the decidual, tubal and embryonic tissue was not statistically different. It was the same as IGF-1 and IGF-1R expression in gravid endometrium, but in the ectopic implantation site IGF-1R was particularly absent (z=1.935, p=0.05), only mesothelium and some epithelial cells stained. CONCLUSION: IGF-1, IGF-1R, bFGF and FGFR1 are widely appearing growth factors in actively developing and differentiating of the human embryonic tissue during the first trimester. Both endometrial and fallopian tube tissues express more FGFR1 than bFGF that testify the stimulation of compensatory adaptation of the organ during pregnancy. IGF-1 and IGF-1R richly appear in gravid endometrium. IGF-1 is widely distributed in both the mother and the embryo tissues but only some of them are IGF-1R marked in a case of ectopic pregnancy. The deficit of IGF-1R in the fallopian tube might be a result of cell growth restriction and the impaired process of trophoblast invasion. [ABSTRACT FROM AUTHOR]