First Reported Histologically and Molecularly Confirmed Bilateral High-Grade Serous Ovarian Adenocarcinoma Metastasized to Placental Decidua of the Membranes

A 43-year-old female presented with blood loss and persistent abdominal pain at 14 weeks of gestation. Ultrasound examination and subsequent magnetic resonance imaging (MRI) revealed bilateral multicystic uterine adnexa. Exploratory laparotomy was performed at 17 weeks of gestation and bilateral serous ovarian adenocarcinoma FIGO stage IIIC was diagnosed. Complete cytoreductive surgery (CRS) was not feasible at that moment. Nine days after the exploratory laparotomy, immature rupture of membranes and contractions occurred and she delivered a premature boy after 19 weeks of gestation. Pathological examination of the placenta revealed that her ovarian cancer metastasized to the membranes. We describe the first case of ovarian cancer metastasized to the decidua of the placental membranes with histological, immunohistochemical, and molecular confirmation. This case highlights the importance of conscientious evaluation of placenta and membranes in pregnant women with ovarian cancer.</p

Enhancing the Retinopathy Of Prematurity Risk Profile Through Placental Evaluation of Maternal and Fetal Vascular Malperfusion

PURPOSE. To determine the independent effect of uteroplacental malperfusion on the development of retinopathy of prematurity (ROP). METHODS. This cohort study included 591 neonates with a gestational age (GA) ≤ 32 weeks or birthweight (BW) ≤ 1500 g. Clinical data was retrospectively collected and placentas were prospectively examined for maternal vascular malperfusion (e.g., abruption, infarct, distal villous hypoplasia, ischemia, and decidual necrosis) and fetal vascular malperfusion (e.g., thrombosis, fetal hypoxia, and hydrops parenchyma). The primary outcome was ROP. Secondary outcomes were GA, BW, small for gestational age (SGA), mechanical ventilation duration, postnatal corticosteroids, sepsis, and necrotizing enterocolitis. RESULTS. Maternal vascular malperfusion was associated with higher GA, lower BW, and increased SGA rates, except placental abruption, which was associated with lower SGA rates. Fetal vascular malperfusion was associated with lower BW, increased SGA rates and lower duration of mechanical ventilation. Subgroup analysis of placentas without inflammation showed increased rates of distal villous hypoplasia (44% vs. 31%) and hydrops parenchyma (7% vs. 0%) in neonates with ROP. Multivariate regression analyses revealed three placenta factors to be independently associated with ROP: distal villous hypoplasia (OR = 1.7; 95% CI, 1.0–3.0), severe acute histological chorioamnionitis (OR = 2.1; 95% CI, 1.1–3.9) and funisitis (OR = 1.8; 95% CI, 1.0–3.1). CONCLUSIONS. Placental evaluation of distal villous hypoplasia, severe acute chorioamnionitis and funisitis is a novel and valuable addition to the ROP risk profile. Evaluation of these placental risk factors shortly after birth can aid in identifying high-risk infants in an earlier stage than currently possible.</p

Histological analysis of (antral) follicle density in ovarian cortex tissue attached to stripped endometriomas

Purpose: When resecting endometriomas with the stripping technique, in the majority of cases, a thin line of adjacent ovarian cortex is attached to the endometrioma. In this study, we performed histological analysis to determine (antral) follicle density in the ovarian cortex tissue attached to stripped endometriomas and assessed patient- and surgical characteristics that could affect this. Methods: Histological slides of previously removed endometriomas were assessed. Follicles in the attached ovarian tissue were classified according to maturation, and follicular density was determined. Immunofluorescent staining of antral follicles in a subset of endometriomas was also performed. Results: In 90 out of 96 included endometriomas (93.7%), ovarian tissue attached to the cyst wall was observed. One thousand nine hundred forty-four follicles at different maturation stages were identified (3 follicles/mm3). Follicle density was negatively associated with age (p &lt; 0.001). Antral follicles (&lt; 7-mm diameter) were present in the ovarian tissue attached to 35 endometriomas (36.5%) derived from younger patients compared to endometriomas where none were detected (30 versus 35 years, p = 0.003). Antral follicle density was 1 follicle/mm3. Based on immunofluorescence, healthy antral follicles were identified in two out of four examined endometriomas. Conclusions: Ovarian tissue attached to stripped endometriomas holds potential as a non-invasive source for antral follicles. In theory, application of IVM could be an interesting alternative FP option in young patients with endometriomas who undergo cystectomy in order to transform the surgical collateral damage to a potential oocyte source. Our results encourage future research with fresh tissue to further assess the quality and potential of these follicles. Trial registration: Clinical Trials.gov Identifier: B21.055 (METC LDD), date of registration 12–08-2021, retrospectively registered.</p

Histological analysis of (antral) follicle density in ovarian cortex tissue attached to stripped endometriomas

Purpose: When resecting endometriomas with the stripping technique, in the majority of cases, a thin line of adjacent ovarian cortex is attached to the endometrioma. In this study, we performed histological analysis to determine (antral) follicle density in the ovarian cortex tissue attached to stripped endometriomas and assessed patient- and surgical characteristics that could affect this. Methods: Histological slides of previously removed endometriomas were assessed. Follicles in the attached ovarian tissue were classified according to maturation, and follicular density was determined. Immunofluorescent staining of antral follicles in a subset of endometriomas was also performed. Results: In 90 out of 96 included endometriomas (93.7%), ovarian tissue attached to the cyst wall was observed. One thousand nine hundred forty-four follicles at different maturation stages were identified (3 follicles/mm3). Follicle density was negatively associated with age (p &lt; 0.001). Antral follicles (&lt; 7-mm diameter) were present in the ovarian tissue attached to 35 endometriomas (36.5%) derived from younger patients compared to endometriomas where none were detected (30 versus 35 years, p = 0.003). Antral follicle density was 1 follicle/mm3. Based on immunofluorescence, healthy antral follicles were identified in two out of four examined endometriomas. Conclusions: Ovarian tissue attached to stripped endometriomas holds potential as a non-invasive source for antral follicles. In theory, application of IVM could be an interesting alternative FP option in young patients with endometriomas who undergo cystectomy in order to transform the surgical collateral damage to a potential oocyte source. Our results encourage future research with fresh tissue to further assess the quality and potential of these follicles. Trial registration: Clinical Trials.gov Identifier: B21.055 (METC LDD), date of registration 12–08-2021, retrospectively registered.</p

Identification of a unique intervillous cellular signature in chronic histiocytic intervillositis

Introduction: Chronic histiocytic intervillositis (CHI) is a rare histopathological lesion in the placenta characterized by an infiltrate of CD68+ cells in the intervillous space. CHI is associated with adverse pregnancy outcomes such as miscarriage, fetal growth restriction, and (late) intrauterine fetal death. The adverse pregnancy outcomes and a variable recurrence rate of 25–100% underline its clinical relevance. The pathophysiologic mechanism of CHI is unclear, but it appears to be immunologically driven. The aim of this study was to obtain a better understanding of the phenotype of the cellular infiltrate in CHI. Method: We used imaging mass cytometry to achieve in-depth visualization of the intervillous maternal immune cells and investigated their spatial orientation in situ in relation to the fetal syncytiotrophoblast. Results: We found three phenotypically distinct CD68+HLA-DR+CD38+ cell clusters that were unique for CHI. Additionally, syncytiotrophoblast cells in the vicinity of these CD68+HLA-DR+CD38+ cells showed decreased expression of the immunosuppressive enzyme CD39. Discussion: The current results provide novel insight into the phenotype of CD68+ cells in CHI. The identification of unique CD68+ cell clusters will allow more detailed analysis of their function and could result in novel therapeutic targets for CHI

Identification of a unique intervillous cellular signature in chronic histiocytic intervillositis

Introduction: Chronic histiocytic intervillositis (CHI) is a rare histopathological lesion in the placenta characterized by an infiltrate of CD68+ cells in the intervillous space. CHI is associated with adverse pregnancy outcomes such as miscarriage, fetal growth restriction, and (late) intrauterine fetal death. The adverse pregnancy outcomes and a variable recurrence rate of 25-100% underline its clinical relevance. The pathophysiologic mechanism of CHI is unclear, but it appears to be immunologically driven. The aim of this study was to obtain a better understanding of the phenotype of the cellular infiltrate in CHI.Method: We used imaging mass cytometry to achieve in-depth visualization of the intervillous maternal immune cells and investigated their spatial orientation in situ in relation to the fetal syncytiotrophoblast.Results: We found three phenotypically distinct CD68+HLA-DR+CD38+ cell clusters that were unique for CHI. Additionally, syncytiotrophoblast cells in the vicinity of these CD68+HLA-DR+CD38+ cells showed decreased expression of the immunosuppressive enzyme CD39.Discussion: The current results provide novel insight into the phenotype of CD68+ cells in CHI. The identification of unique CD68+ cell clusters will allow more detailed analysis of their function and could result in novel therapeutic targets for CHI.Research into fetal development and medicin

Enhancing the Retinopathy Of Prematurity Risk Profile Through Placental Evaluation of Maternal and Fetal Vascular Malperfusion

PURPOSE. To determine the independent effect of uteroplacental malperfusion on the development of retinopathy of prematurity (ROP). METHODS. This cohort study included 591 neonates with a gestational age (GA) ≤ 32 weeks or birthweight (BW) ≤ 1500 g. Clinical data was retrospectively collected and placentas were prospectively examined for maternal vascular malperfusion (e.g., abruption, infarct, distal villous hypoplasia, ischemia, and decidual necrosis) and fetal vascular malperfusion (e.g., thrombosis, fetal hypoxia, and hydrops parenchyma). The primary outcome was ROP. Secondary outcomes were GA, BW, small for gestational age (SGA), mechanical ventilation duration, postnatal corticosteroids, sepsis, and necrotizing enterocolitis. RESULTS. Maternal vascular malperfusion was associated with higher GA, lower BW, and increased SGA rates, except placental abruption, which was associated with lower SGA rates. Fetal vascular malperfusion was associated with lower BW, increased SGA rates and lower duration of mechanical ventilation. Subgroup analysis of placentas without inflammation showed increased rates of distal villous hypoplasia (44% vs. 31%) and hydrops parenchyma (7% vs. 0%) in neonates with ROP. Multivariate regression analyses revealed three placenta factors to be independently associated with ROP: distal villous hypoplasia (OR = 1.7; 95% CI, 1.0–3.0), severe acute histological chorioamnionitis (OR = 2.1; 95% CI, 1.1–3.9) and funisitis (OR = 1.8; 95% CI, 1.0–3.1). CONCLUSIONS. Placental evaluation of distal villous hypoplasia, severe acute chorioamnionitis and funisitis is a novel and valuable addition to the ROP risk profile. Evaluation of these placental risk factors shortly after birth can aid in identifying high-risk infants in an earlier stage than currently possible