The dissertation is devoted to improving the system of early diagnosis of impaired pregnancy in women of reproductive age through a comprehensive assessment of clinical, ultrasound and immunological parameters with determination of the prognostic significance of stress proteins HSP60 and its bacterial homologue GroEL.
Miscarriage in the first trimester remains one of the leading problems of modern obstetrics, forming a significant proportion of early reproductive losses and determining the level of perinatal and maternal morbidity. Despite the use of standard diagnostic approaches, the possibilities of early detection of high-risk pregnancies remain limited, which necessitates the search for new prognostic markers. Of particular scientific interest are the mechanisms of cellular stress, in particular the activity of stress proteins HSP60 and GroEL as potential biomarkers of impaired implantation, however, their clinical significance in the first trimester of pregnancy is still not sufficiently defined.
The aim of the study is to improve the prediction of miscarriage in high-risk women by studying new pathogenetic markers.
Research objectives:
1. To determine the structure of clinical and anamnestic risk factors for miscarriage in the first trimester, dividing them into groups of physiological and complicated gestation.
2. To characterize the ultrasound and Doppler picture of early gestation and determine its association with the subsequent course of pregnancy.
3. To investigate the levels of HSP60 and GroEL in the serum of pregnant women in the first trimester and assess their relationship with clinical, ultrasound indicators and signs of impaired implantation.
4. To determine the diagnostic and prognostic value of HSP60 and GroEL on the basis of ROC analysis and to establish optimal threshold values for early stratification of the risk of miscarriage.
5. To develop an integrated model for predicting the disturbed course of pregnancy in the first trimester, to propose an algorithm for early stratification of the risk of miscarriage and to evaluate its effectiveness.
In accordance with the tasks set, the work was carried out in the format of a prospective cohort study. The study included 94 pregnant women in the first trimester (6–12 weeks), stratified into a group with a physiological course of pregnancy (Norm, n = 33) and a group with signs of impaired implantation or the threat of interruption (Path, n = 61).
A comprehensive examination included an analysis of somatic, reproductive and obstetric anamnesis, assessment of risk factors (age, endocrine disorders, infectious and inflammatory conditions, bad habits), detailed ultrasound examination (localization of the chorion, presence and volume of chorionic hematomas, embryo viability, cardiac activity parameters, cervical length), as well as determination of HSP60 and GroEL levels by ELISA.
Statistical data processing included descriptive statistics, group comparisons, correlation analysis, ROC analysis with calculation of AUC and Youden index, as well as multivariate logistic regression to create an integrated prediction model. The effectiveness of the model was assessed by sensitivity, specificity and prognostic value of the results.
The study design was approved by the Bioethics Commission of the O.O. Bogomolets National Medical University (protocol No. 201 dated December 22, 2025). The study was conducted in compliance with the principles of the Declaration of Helsinki and standards of good clinical practice.
The results of the analysis revealed that women with an unfavorable course of pregnancy more often have a burdened obstetric history, recurrent reproductive losses, endocrine disorders, infectious and inflammatory processes and ultrasound signs of impaired implantation (presence of chorionic hematomas, low or marginal implantation of the chorion, shortening of the cervix). The levels of HSP60 and GroEL in these patients were significantly higher compared to the physiological pregnancy group.
ROC analysis demonstrated the prognostic informativeness of GroEL, as well as HSP60 as part of the integrated prognostic model for the risk of early reproductive losses. Optimal threshold values of HSP60 and GroEL (cut-off) were determined, exceeding which is associated with an increased risk of miscarriage in the first trimester. Based on logistic regression, an integrated prediction model was developed that combines clinical, ultrasound, and immunological data and demonstrates high accuracy in predicting the disturbed course of pregnancy in the first trimester.
