Histopathologic characteristics of term placentas in singleton pregnancies in women with endometriosis-related infertility after ART treatment: case-control study

Abstract

Objectives Endometriosis is one of the leading causes of infertility, due to negative impact on ovarian folliculogenesis and endometrial receptivity. Literature show that endometriosis could be associated with perinatal complications such as preterm birth (PTB) and preeclampsia (PE). Authors hypothesized that women with endometriosis-related infertility conceived by assisted reproductive technology (ART) treatment have higher frequency of placental disorders. Main outcome is the occurrence of histopathologic alterations of term placentas in singleton pregnancies of women with endometriosis conceived by ART treatment, compared to healthy women with infertility due to male factor (MF) conceived by ART and to healthy women with spontaneous pregnancies. Secondary outcome include the occurrence of perinatal complications and the relationship of endometriosis and placental histopathologic characteristics. Methods Single-center, case-control study of term placentas that were collected within Department of Obstetrics and Gynecology of University Hospital Center (UHC) Split and analyzed in the Pathology department of the same hospital, by one senior perinatal pathologist. Histopathologic analysis was reported using Amsterdam Placental Workshop Group Consensus. All the noted placental lesions were divided into following categories: anatomic, inflammatory, villous maturation and vascular malperfusion disorders. Required sample size was 80 placentas, and study results were reported with descriptives, and analyzed with chi-squared, Fisher’s exact test and Kruskal-Wallis ANOVA. Multivariate regression analysis was carried with adjustment for confounding factors. Ethics approval: Class n. 520-03/24-01/83. Results Study included term placentas of 107 women, of which 36 were women with endometriosis conceived by ART, 31 were healthy women with MF infertility conceived by ART and 40 healthy women with spontaneous pregnancies. Endometriosis women were predominantly primiparas, with longer infertility duration. Endometriosis group had higher occurrence of early pregnancy bleeding and imminent preterm labor. Endometriosis and MF groups had higher occurrence of Cesarian delivery (CS), while endometriosis group had newborns with lowest birthweight. Endometriosis group had shorter placental cords (PC), higher rates of increased syncytial knotting and vascular malperfusion disorders (subchorionic and perivillous fibrin, intervillous thrombosis, high grade fetal vascular malperfusion). Finally, endometriosis is showed to be associated with increased syncytial knots’ formation and PC hypercoiling, after adjustment for confounding factors in the multivariate regression analysis. Conclusions Despite low rates of perinatal complications, we report endometriosis to have higher occurrence of increased syncytial knotting and vascular malperfusion placental disorders, compared to control groups. Endometriosis is also associated with increased syncytial knotting and PC hypercoiling. Further studies are needed to elucidate the endometriosis impact on endometrial receptivity and immunopathogenesis in placental disorders and perinatal complications. Highlights Endometriosis women were predominantly primiparas, with longer infertility duration. Endometriosis group had higher occurrence of early pregnancy bleeding and imminent preterm labor. Moreover, endometriosis and MF groups had higher occurrence of Cesarian delivery, while endometriosis group had newborns with lowest birthweight. Endometriosis group had shorter placental cords, higher rates of increased syncytial knotting and vascular malperfusion lesions. Endometriosis is showed to be associated with increased syncytial knots formation and hypercoiling of placental cord, after adjustment for confounding factor.