External genital endometriosis in the pathogenesis of recurrent miscarriage
AbstractBackground. The elucidation of the mechanisms underlying recurrent pregnancy loss (RPL) in endometriosis, as well as the role of immune cells and the receptor apparatus in the disruption of immune tolerance of the mother-fetus interface, appears to be a tool for prediction and effective interventions to overcome reproductive losses.
The aim of the study was to expand the understanding of the role of external genital endometriosis in the pathogenesis of recurrent pregnancy loss (RPL).
Material and methods. An open prospective observational study was conducted from 2020 to 2023 at the Center for Reproduction and Genetics “Nova Clinic”. The study cohort included 176 patients of reproductive age (average age – 35.8±4.6 years) with RPL (with the anamnesis ≥2 pregnancy losses), divided into groups: the first (n=57) – with a verified diagnosis of external genital endometriosis (EGE), the second (n=60) – without EGE. The comparison group (n=59) consisted of women with realized fertility. For pathomorphological and immunohistochemical studies [estrogen receptors (ER); progesterone receptors (PR); CD138+, CD56+ markers], endometrial sampling using pipell biopsy on days 20–22 of the menstrual cycle was carried out in 100 patients. Groups were randomly formed from the total sample: the first (n=38) – with RPL and EGE, the second (n=34) – with RPL, the third (morphological control) (n=28) – women with realized fertility.
Results. After an immunohistochemical study, taking into account obtained pathomorphological conclusions, a violation of the secretory transformation of the endometrium was revealed in the group with EGE, which was manifested in a significantly greater decrease in the PR expression in the glandular compartment of the endometrium compared with patients with RPL only (p<0.05) and the comparison group (p<0.05); and also a decrease in the ER expression in the stromal compartment of the endometrium of patients with RPL in contrast to the morphological control group (p<0.05). The pathogenetic role of a persistent inflammatory process in the RPL genesis is confirmed by an increase in the expression of CD138+ and CD56+ markers, more pronounced in women with EGE.
Conclusion. The basis of the RPL pathogenesis is a violation of the secretory transformation of the endometrium and a shift of the implantation window due to a decrease in the PR expression in the glandular compartment, which is significantly greater in case of EGE, along with a comparably low ER expression in the stromal compartment.
The molecular determinants of defects in the mechanisms of decidualization of the stroma and the secretory potential of the endometrial glands in women with RPL on the EGE background are caused by an excessive pro-inflammatory immune microenvironment and persistent inflammation of the basal-endometrial complex (increased expression of CD138+ and CD56+).
Keywords: recurrent miscarriage; external genital endometriosis; reproductive losses; implantation window; pathogenesis
Funding. The study had no sponsor support.
Conflict of interest. The authors declare no conflict of interest.
For citation: Mikhalev S.A., Kurtser M.A., Masalimova D.N., Mikhaleva L.M. External genital endometriosis in the pathogenesis of recurrent miscarriage. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie [Obstetrics and Gynecology: News, Opinions, Training]. 2024; 12 (3): 102–8. DOI: https://doi.org/10.33029/2303-9698-2024-12-3-102-108 (in Russian)
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