Endometriosis-related spontaneous hemoperitoneum in pregnancy: A case series.

Endometriosis can be associated with adverse pregnancy outcomes. We report six cases of endometriosis-related spontaneous hemoperitoneum diagnosed in pregnant and postpartum women over 13 years. Spontaneous hemoperitoneum in pregnancy mainly occurred in the second half of gestation. All women presented with acute abdominal pain; four of them needed an emergent surgery, two were managed expectantly. The median estimated blood loss was 4250 ml, four women required massive transfusion. Three out of six women had a known history of endometriosis, all of them had histologically confirmed endometriosis after surgery. No maternal or perinatal deaths occurred. In one case, reticence to perform a computed tomography scan led to delayed diagnosis. Since delay can lead to lethal consequences, high levels of suspicion for spontaneous hemoperitoneum should be maintained in cases of severe abdominal pain, even with a woman's negative history of endometriosis. Improved knowledge and regular interdisciplinary meetings are pivotal to ameliorate outcomes.

Fibroids-related complications in pregnancy: a twelve-year long experience at a maternal-fetal medicine referral center.

BACKGROUND: Uterine fibroids are the most frequent female benign tumor, which can cause complications during pregnancy, mainly pain. Differential diagnosis may be challenging and a standardized management approach is lacking. We aim to propose an algorithm for the differential diagnosis of pain during pregnancy and for management of fibroid-related pain. METHODS: A retrospective cohort study of all pregnant women admitted to our center for complications related to fibroids between 2008 and 2019. Data regarding clinical examination, laboratory results, imaging parameters, as well as perinatal outcomes, were collected and assessed (Fisher's Exact Test). RESULTS: Twenty-four pregnant patients were admitted for fibroid-related complications. Six patients were admitted more than one times, for a total of 34 admissions. The main cause of hospital admission was pain (N.=33, 94.1%), which was successfully managed with acetaminophen and/or ketoprofen in 91.2%. In two cases, conservative management failed and a surgical approach was undertaken. Most women (N.=20, 90.9%) delivered at term, with a cesarean delivery and post-partum hemorrhage rate of 22.7%. All newborns had normal APGAR score, umbilical artery pH and birth weight. CONCLUSIONS: Pain is the most common complication of fibroids during pregnancy. Accurate differential diagnosis and adequate management are pivotal to ensure good perinatal outcomes.

Gestational Intraplacental Choriocarcinoma in a Term Pregnancy: A Case Report.

Intraplacental choriocarcinoma (IC) is a rare type of gestational choriocarcinoma (GC) occurring within the placenta, and only a small number of cases have been reported so far. Intraplacental choriocarcinoma is usually asymptomatic or may present with aspecific symptoms, including unexplained vaginal bleeding during pregnancy. Early diagnosis and treatment are pivotal for ensuring optimal outcomes. However, intraplacental choriocarcinoma is rarely suspected due to limited knowledge and awareness of the condition. Here, we report the case of a 34-year-old woman diagnosed with intraplacental choriocarcinoma by placental histological examination performed after delivery due to unexplained vaginal bleeding at 29 gestational weeks, requiring hospital admission. Two lines of chemotherapy and surgery were necessary to achieve complete remission. Since unexplained vaginal bleeding during pregnancy can be a clinical manifestation of intraplacental choriocarcinoma, we propose to consider placental histological examination in all pregnancies with this complication.

Imbalanced Angiogenesis in Pregnancies Complicated by SARS-CoV-2 Infection.

COVID-19 and preeclampsia (preE) share the ANG-II mediated endothelial dysfunction, resulting from a significant dysregulation of RAS and an imbalanced proportion of anti-angiogenic and pro-angiogenic soluble plasmatic factors. Of note, an increased incidence of preE has been reported among COVID-19-infected mothers compared to the general pregnant population. The two most promising angiogenic markers are the soluble fms-like tyrosine kinase receptor-1 (sFlt-1), the major antiangiogenic factor, and the placental growth factor (PlGF), a powerful angiogenic factor. Since these markers have proven useful in the prediction, diagnosis, and severity of preE, this study aimed to evaluate their maternal serum levels in pregnancies complicated by SARS-CoV-2 infection and to assess their potential use to guide the management of these women. A retrospective analysis of SARS-CoV-2-positive pregnant women was performed. The serum levels of sFlt-1 and PlGF were collected at the diagnosis of SARS-CoV-2 infection at the hospital, before the beginning of steroid/hydroxychloroquine and/or antithrombotic therapy. The sFlt-1/PlGF ratio was stratified using cut-off values clinically utilized in the diagnosis and prediction of preE (low < 38, intermediate 38−85/110* and high >85/110*, * if before or after the 34th week of gestation). A total of 57 women were included, of whom 20 (35%) had signs and symptoms of COVID-19 at hospital presentation and 37 (65%) were asymptomatic. None were vaccinated. The mean gestational age at diagnosis of SARS-CoV-2 infection was 32 weeks in symptomatic patients and 37 weeks and 5 days in asymptomatic ones (p = 0.089). sFlt-1 serum levels were higher in SARS-CoV-2 positive asymptomatic patients compared to women with COVID-19 related symptoms (4899 ± 4357 pg/mL vs. 3187 ± 2426 pg/mL, p = 0.005). sFlt-1/PlGF at admission was <38 in 18 of the 20 symptomatic women (90%) compared to 22 (59%) of the asymptomatic patients (p = 0.018). Of note, two of the three women admitted to the intensive care unit had a very low ratio (<2). In turn, rates of patients with sFlt-1/PlGF at admission > 85/110 were not significantly different between the two groups: 11% in asymptomatic patients (4/37) vs. none of the symptomatic patients (p = 0.286), and all of them presented a placental dysfunction, like preE (n = 1) and FGR (n = 3). Of note, there were no stillbirths or maternal or neonatal deaths among symptomatic patients; also, no cases of preE, FGR, or small for gestational age neonates were diagnosed. In conclusion, our data suggest that SARS-CoV-2 infection during pregnancy could influence the angiogenic balance. A significant pathological alteration of the sFlt-1/PlGF ratio cannot be identified during the symptomatic phase; however, if left untreated, SARS-CoV-2 infection could potentially trigger placental dysfunction.

CD14 positive cells accelerate hematopoietic stem cell engraftment.

The improvement of hematopoietic stem and progenitor cell (HSPC) engraftment remains a high-priority goal when limited cell doses are available, such as in cord blood (CB) transplantation and HSC gene therapy. We observed that monocytes are highly effective at improving the engraftment of both CB-CD34+ and lentivirus-transfected CD34+ cells in a xenogeneic model of HSC transplantation. Moreover, monocytes, in particular the CD14+CD16- classical subset, in co-culture systems increase survival and stemness of CB-CD34+ cells. Both soluble factors and direct-cell contact interactions, such as JAG/NOTCH and COX-2/PGE2 pathways, are critically involved in the HSC-monocyte crosstalk. Our results indicate that the infusion of monocytes improves engraftment when cell dose is a limiting factor.

sFlt-1/PlGF ratio in hypertensive disorders of pregnancy in patients affected by COVID-19.

OBJECTIVES: To analyze soluble Fms-like tyrosine Kinase 1 (sFlt-1) and Placental Growth Factor (PlGF) ratio concentrations in COVID-19 pregnant patients with and without Hypertensive Disorders of Pregnancy (HDP), compared with non COVID-19 pregnant patients with HDP and a control group. STUDY DESIGN: We recruited and obtained a complete follow-up of 19 COVID-19 pregnant patients with HDP and of 24 COVID-19 normotensive pregnant patients. Demographic, clinical and sFlt-1/PlGF ratio findings were compared with a group of 185 non COVID-19 pregnant patients with HDP and 41 non COVID normotensive patients. Findings were based on univariate analysis and on a multivariate adjusted model, and a case by case analysis of COVID-19 pregnant patients with an abnormal sFlt-1/PlGF ratio > 38 at recruitment. MAIN OUTCOME MEASURES: sFlt-1/PlGF ratio. RESULTS: We confirmed a significant higher prevalence of HDP in women affected by COVID-19 compared to control population. sFlt-1/PlGF ratio was found high in HDP patients, with and without of Sars-Cov2 infection. COVID-19 patients with worse evolution of the disease showed greater rates of obesity and other comorbidities. sFlt/PlGF ratio proved not to be helpful in the differential diagnosis of the severity of this infection. CONCLUSIONS: COVID-19 pregnant patients showed a higher prevalence of HDP compared to non COVID-19 controls, as well as higher comorbidity rates. In spite of the possible common endothelial target and damage, between Sars-Cov-2 infection and HDP, the sFlt1/PlGF ratio did not correlate with the severity of this syndrome.

Treatment of first trimester miscarriage: a prospective cohort study in a large tertiary care center in Northern Italy.

OBJECTIVE: To assess acceptability, efficacy, and short- and medium-term complications of vaginal misoprostol therapy for the treatment of first trimester miscarriage. STUDY DESIGN: A prospective cohort study including women admitted to the Unit of Obstetrics, MBBM Foundation, San Gerardo Hospital (Monza, Italy) for medical or surgical treatment of first trimester miscarriage between October 2014 and March 2018. As per Institutional protocol, patients in the medical therapy group received 800 µg of misoprostol vaginally. A second dose could be considered 3 days after the first administration if that was ineffective. Surgical treatment consisted of uterine vacuum aspiration. Success of misoprostol treatment was defined as the expulsion of the gestational sac with no need for subsequent surgery. RESULTS: During the study period, 967 patients were diagnosed with first trimester miscarriage and were included in the study. Of these, 514 (53.2%) women were eligible for and consented to medical therapy. Surgical treatment was performed in the remaining 453 (46.8%) patients due to either medical contraindication to misoprostol or patient's choice. Acceptance of misoprostol as first therapeutic choice increased over time, becoming the preferred treatment after approximately 18 months of use in clinical practice. One dose of misoprostol was successful in 69.8% (n = 359) of patients, whereas 20 women required urgent surgery for bleeding (n = 19) or suspected infection (n = 1). Among the remaining 135 patients, 20 (14.8%) refused the second dose of misoprostol and opted for surgery. Expulsion of the gestational sac was obtained in 74 additional cases who completed the medical protocol, for an overall success rate of 87.7% (433/494). The majority of women receiving misoprostol did not experience any short-term complication (92.0%) or side effect (93.8%). Eight (1.6%) cases requiring delayed surgery (hysteroscopy or vacuum aspiration) for retained product of conception were identified at the postmedical treatment follow up, thus leading to an actual success rate of misoprostol of 86.0% (n = 425). CONCLUSIONS: This is the first study assessing the acceptability, efficacy, and complication rate of medical management of first trimester miscarriage in an Italian tertiary care center. Our results confirm that misoprostol alone is an effective as well as a safe therapeutic option for the treatment of first trimester miscarriage.

Letter to the Editor: SFlt-1 and PlGF Levels in Pregnancies Complicated by SARS-CoV-2 Infection.

We read with interest the work by Espino-y-Sosa and colleagues [...].

Preimplantation factor modulates oligodendrocytes by H19-induced demethylation of NCOR2.

Failed or altered gliogenesis is a major characteristic of diffuse white matter injury in survivors of premature birth. The developmentally regulated long noncoding RNA (lncRNA) H19 inhibits S-adenosylhomocysteine hydrolase (SAHH) and contributes to methylation of diverse cellular components, such as DNA, RNA, proteins, lipids, and neurotransmitters. We showed that the pregnancy-derived synthetic PreImplantation Factor (sPIF) induces expression of the nuclear receptor corepressor 2 (NCOR2) via H19/SAHH-mediated DNA demethylation. In turn, NCOR2 affects oligodendrocyte differentiation markers. Accordingly, after hypoxic-ischemic brain injury in rodents, myelin protection and oligodendrocytes' fate are in part modulated by sPIF and H19. Our results revealed an unexpected mechanism of the H19/SAHH axis underlying myelin preservation during brain recovery and its use in treating neurodegenerative diseases can be envisioned.

PreImplantation Factor and Endocrinology of Implantation and Establishment of Early Pregnancy: A Contemporary View.

The earliest stages of pregnancy are marked by countless changes in the maternal environment. A specific coordination of activity is required for a successful pregnancy, starting early in the menstrual cycle. Early establishment of maternal-fetal crosstalk is critical for the progression of pregnancy. Many factors, both maternal and fetal derived, play specific and important roles immediately following fertilization, through implantation and beyond. Here we present a review of some of the key factors involved with a focus on PreImplantation Factor (PIF), a small peptide secreted only by competent embryos, which carries an important role required for pregnancy progression.

Feto-maternal correlation of PTX3, sFlt-1 and PlGF in physiological and pre-eclamptic pregnancies.

OBJECTIVE: PTX3, sFlt-1 and PlGF levels in maternal blood are altered in some obstetric diseases, such as preeclampsia (PE). Nonetheless, only few data on their expression in the fetal compartment have been reported so far. STUDY DESIGN: An observational study was performed by prospectively collecting maternal and fetal serum samples in 51 singleton pregnancies divided into two groups: 22 PE women and 29 healthy controls. The relationships between maternal and fetal marker serum levels were evaluated by Spearman correlation. RESULTS: A feto-maternal correlation was neither identified for PTX3 in either PE or control groups (1.1 versus 3.8 ng/ml, p = 0.17 and 0.9 versus 1.3 ng/ml, p = 0.30, respectively), nor for sFlt-1 and PlGF in healthy pregnancies (158.2 versus 3326.0 pg/ml, p = 0.28 and 11.0 versus 230.9 pg/ml, p = 0.51). In contrast, PE patients showed a significant positive feto-maternal correlation for both sFlt-1 and PlGF (324.1 versus 10 825.0 pg/ml and 7.8 versus 31.6 pg/ml, respectively, p = 0.02 for both markers). CONCLUSION: According to our results, an independent fetal production of the analyzed soluble angiogenic markers can be hypothesized in pregnancies complicated by PE.

Robotic surgical staging for endometrial and cervical cancers in medically ill patients.

OBJECTIVES: Patients with high anesthesiological risk due to old age, obesity and severe co-morbidities alone or in combination are considered as poor candidates for extensive surgical staging procedures, especially if through minimally invasive approach. We aimed to evaluate the feasibility and safety of robotic surgical staging of endometrial and cervical cancers in the medically ill patient. METHODS: Between 07-2007 and 12-2012, consecutive patients scheduled for staging for endometrial or cervical cancer were directed towards robotic staging and divided into two groups according to their starting score in the American Society for Anaesthesiologists (ASA): Group 1 (ASA 1-2) and Group 2 (ASA ≥3). RESULTS: Overall, 169 (71.9%) patients had ASA 1-2 whereas 66 (28.1%) had ASA ≥3. ASA ≥3 were older (p<0.0001) with a greater proportion of co-morbidities (p<0.0001), as well as of Class II (4.7% vs 19.7%; p=0.0007) and Class III obesity (2.4% vs 31.8%; p<0.0001). No differences were found between groups in terms of operative time, blood loss, intra- and post-operative complications, conversion rate and hospitalization. No differences were recorded either in terms of staging procedures performed or in terms of number of pelvic (p=0.72) and para-aortic (p=0.86) lymph nodes retrieved. CONCLUSIONS: Despite theoretical concerns about the performance of robotic surgery in patients with high anesthesiological risk, our experience showed that robotics is a feasible, safe and viable option for the management of endometrial and cervical cancers also in this more vulnerable group of patients.

Identifying the causes of stillbirth: a comparison of four classification systems.

OBJECTIVE: To identify the classification protocol for stillbirth that minimizes the rate of unexplained causes. STUDY DESIGN: All stillbirths at > 22 weeks from 1995-2007 underwent a workup inclusive of fetal ultrasonography, amniocentesis for karyotype and cultures, placental histology, fetal autopsy, skin biopsy, total body X-ray, maternal testing for thrombophilias, TORCH, Parvovirus spp, thyroid function, indirect Coombs, Kleiheuer-Betke test, and genital cultures. To such a cohort, we applied the 4 most commonly used classification protocols. RESULTS: The stillbirth rate during the study period was 0.4% (154/37,958). The RoDeCo classification provided the lowest rate of unexplained stillbirth (14.3%) compared with Wigglesworth (47.4%), de Galan-Roosen (18.2%), and Tulip (16.2%) classifications. Mean gestational age at stillbirth in unexplained vs explained stillbirth was similar in the 4 protocols. CONCLUSION: Adoption of a consistent and appropriate workup protocol can reduce the rate of unexplained stillbirth to 14%.