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

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.HighlightsEndometriosis 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.

Leprosy epidemics during history increased protective allele frequency of PARK2/PACRG genes in the population of the Mljet Island, Croatia.

INTRODUCTION: Two regulatory polymorphisms (rs1040079 and rs9356058) shared by PARK2 and PACRG genes were identified as major risk variants for leprosy susceptibility. The aim of this study was to investigate if allele frequencies of these polymorphisms in the isolated population of the island of Mljet, which served as a quarantine for leprosy patients during past centuries, were different to allele frequencies in two control populations with no history of leprosy. SUBJECTS AND METHODS: This study included 88 unrelated Caucasian individuals from the island of Mljet while two control groups included 93 individuals from the island of Rab and 160 individuals from the region of Split. Genotyping for rs1040079 and rs9356058 was performed by "real-time" PCR analysis. We also compared the allele frequency of the rs9356058 polymorphism from the population of Mljet with allele frequencies derived from the existing genome wide association scans in two additional island populations, Vis (924 subjects) and Korcula (909 subjects). RESULTS: We found a significant increase in the frequency of rs9356058 allele C in the population of Mljet when compared to both control groups. We also observed a significant increase in the frequency of rs1040079 allele A in the population of Mljet when compared with the population of Rab, however this increase was not significant when compared with the population of Split. Allele frequencies of both examined polymorphisms did not differ between the two control populations. Protective haplotype rs9356058-rs1040079 CA was also more frequent in the population of Mljet compared with the Rab and Split populations. In addition, an increase of frequency of rs9356058 allele C was also observed in the population of Mljet when compared with the frequency in the Korcula population. CONCLUSION: The results of our study show the association of polymorphisms rs9356058 and rs1040079 in gene PARK2/PACRG with leprosy. The results of our study indicate that exposure to leprosy and mortality in the population caused by leprosy on Mljet resulted in the selection of rs9356058 "protective" C allele in the PARK2 gene, while this was not observed in the two control groups. This is the first study to assess the genetic susceptibility to leprosy in a European population.