Lymph node staging in grade 1-2 endometrioid ovarian carcinoma apparently confined to the ovary: Is it worth?

OBJECTIVE: The aim of this study was to assess the disease-free survival (DFS) and overall survival (OS) of patients with grade 1-2 endometrioid ovarian carcinoma apparently confined to the ovary, according to surgical staging. METHODS: Multicenter, retrospective, observational cohort study. Patients with endometrioid ovarian carcinoma, surgical procedure performed between May 1985 and December 2019, stage pT1 N0/N1/Nx, grade 1-2 were included. Patients were stratified according to lymphadenectomy (defined as removal of any lymph node versus no lymph node assessment), and subgroup analyses according to tumor grade were performed. Kaplan-Meier curves and cox regression analyses were used to perform survival analyses. RESULTS: 298 patients were included. 199 (66.8 %) patients underwent lymph node assessment. Of these, 166 (83.4 %) had unilateral/bilateral pelvic and para-aortic/caval lymphadenectomy. Eleven (5.5 %) patients of those who underwent lymph node assessment showed pathologic metastatic lymph nodes (FIGO stage IIIA1). Twenty-seven patients (9.1 %) had synchronous endometrioid endometrial cancer. After a median follow up of 45 months (95 %CI:37.5-52.5), 5-year DFS and OS of the entire cohort were 89.8 % and 96.2 %, respectively. Age ≤ 51 years (HR=0.24, 95 %CI:0.06-0.91; p = 0.036) and performance of lymphadenectomy (HR=0.25, 95 %CI: 0.07-0.82; p = 0.022) represented independent protective factors toward risk of death. Patients undergoing lymphadenectomy had better 5-year DFS and OS compared to those not receiving lymphadenectomy, 92.0 % versus 85.6 % (p = 0.016) and 97.7 % versus 92.8 % (p = 0.013), respectively. This result was confirmed after exclusion of node-positive patients. When stratifying according to tumor grade (node-positive excluded), patients with grade 2 who underwent lymphadenectomy had better 5-year DFS and OS than those without lymphadenectomy (93.0 % versus 83.1 %, p = 0.040 % and 96.5 % versus 90.6 %, p = 0.037, respectively). CONCLUSION: Staging lymphadenectomy in grade 2 endometrioid ovarian carcinoma patients was associated with improved DFS and OS. Grade 1 and grade 2 might be considered as two different entities, which could benefit from different approach in terms of surgical staging. Prospective studies, including molecular profiles are needed to confirm the survival drivers in this rare setting.

Low anterior resection syndrome and its impact on quality of life of ovarian carcinoma patients: A prospective longitudinal study.

OBJECTIVES: Bowel dysfunction is frequently reported in patients with ovarian carcinoma (OC). Our aim was to evaluate the incidence of low anterior resection syndrome (LARS) like symptoms in patients with primary OC and its impact on quality of life (QoL). METHODS: A prospective longitudinal observational cohort study was performed, including patients with newly diagnosed OC treated by primary or interval surgery with residual tumor <1 cm, from 2018 until 2021. Patients with a stoma or recurrence of disease were excluded. Intestinal dysfunction was assessed using the validated LARS score questionnaire pre- and postoperatively. There are 3 subgroups based on the results: no, minor, or major LARS. The impact on QoL was evaluated by an additional question to demonstrate the severity of patient's life impairment. RESULTS: The questionnaire was answered by 78 patients pre- and post-operatively. LARS like symptoms were reported preoperatively in 34.6% (24.4% minor/10.2% major) and significantly increased postoperatively to 47.4% (28.2% minor/19.2% major; p = 0.011). Moderate to severe impairment of QoL correlated with LARS scores pre- (80%) and post-operatively (90%). Patients with two bowel anastomoses (mean score 18.6 pre- and 24.9 post-operatively, p = 0.041) showed a significant increase of the questionnaire score. CONCLUSIONS: Major LARS like symptoms appear in 10% of OC patients preoperatively and significantly increase to almost two-fold postoperatively. Multiple bowel anastomoses had a significant risk for higher postoperative LARS score. QoL impairment correlates linearly with LARS positive scoring, independent on the timing of the complaints.

Incidence and Prognostic Impact of Deleterious Germline Mutations in Primary Advanced Ovarian Carcinoma Patients.

Data on deleterious variants in genes other than BRCA1/2 remain limited. A retrospective cohort study was performed, including primary OC cases with TruRisk® germline gene panel testing between 2011 and 2020. Patients with testing after relapse were excluded. The cohort was divided into three groups: (A) no mutations, (B) deleterious BRCA1/2 mutations, and (C) deleterious mutations in other genes. A total of 702 patients met the inclusion criteria. Of these 17.4% (n = 122) showed BRCA1/2 mutations and a further 6.0% (n = 42) in other genes. Three-year overall survival (OS) of the entire cohort was significantly longer in patients with germline mutations (85%/82.8% for cohort B/C vs. 70.2% for cohort A, p < 0.001) and 3-year progression-free survival (PFS) only for cohort B (58.1% vs. 36.9%/41.6% in cohort A/C, p = 0.002). In multivariate analysis for the subgroup of advanced-stages of high-grade serous OC, both cohorts B/C were found to be independent factors for significantly better outcome, cohort C for OS (HR 0.46; 95% CI 0.25-0.84), and cohort B for both OS and PFS (HR 0.40; 95% CI 0.27-0.61 and HR 0.49; 95% CI 0.37-0.66, respectively). Germline mutations were detected in a quarter of OC patients, and a quarter of those in genes other than BRCA1/2. Germline mutations demonstrate in our cohort a prognostic factor and predict better prognosis for OC patients.

Trend and risk Factors for Severe Peripartum Maternal morbidity - a population-based Cohort Study.

OBJECTIVES: While the rates of maternal mortality in developed countries have remained low in recent years, rates of severe maternal morbidity (SMM) are still increasing in high income countries. As a result, SMM is currently used as a measure of maternity care level. The aim of this study was to investigate the prevalence and risk factors of SMM surrounding childbirth. METHODS: A nested case-control study was performed between the years 2013-2018. SMM was defined as peripartum hospitalization involving intensive care unit (ICU). A comparison was conducted between parturient with SMM to those without, randomly matched for delivery mode and date of birth in a 1:1 ratio. Multivariable logistic regression models were used to evaluate the independent association between SMM and different maternal and pregnancy characteristics. RESULTS: During the study period, 96,017 live births took place, of which 144 (1.5 per 1,000 live births-0.15%) involved SMM with ICU admissions. Parturient with SMM were more likely to have a history of 2 or more pregnancy losses (18.2% vs. 8.3%, p = 0.004), deliver preterm (48.9% vs. 8.8%, p < 0.001), and suffer from placenta previa (11.9% vs. 1.5%, p < 0.001), and/or placenta accreta (9.7% vs. 1.5%, p = 0.003). Several significant and independent risk factors for SMM were noted in the multivariable regression models: preterm delivery, history of ≥ 2 pregnancy losses, grand-multiparity, Jewish ethnicity, and abnormal placentation (previa or accreta). CONCLUSIONS FOR PRACTICE: SMM rates in our cohort were lower than reported in developed countries. An independent association exists between peripartum maternal ICU admissions and several demographic and clinical risk factors, including preterm birth and abnormal placentation.

Impact of substage and histologic type in stage I ovarian carcinoma survival: a multicenter retrospective observational study.

OBJECTIVE: This international study aimed to investigate the impact of substage, histological type and other prognostic factors on long-term survival for stage I ovarian carcinoma. METHODS: Our study was a retrospective multicenter cohort study that included patients with the International Federation of Gynecology and Obstetrics (FIGO) stage I (IA-IC3) ovarian carcinoma treated at four European referral centers in Germany and Italy. Using Kaplan-Meier survival curves we compared overall and disease-free survival between the different stage I groups. RESULTS: A total of 1115 patients were included. Of these, 48.4% (n=540) were in stage IA, 6.6% (n=73) stage IB, and 45% (n=502) stage IC, of the latter substage IC1, 54% (n=271), substage IC2, 31.5% (n=158), and substage IC3, 14.5% (n=73). Five-year overall and disease-free survival rates for the entire cohort were 94% and 86%, respectively, with no difference between stage IA and IB. However, there was a significantly better overall and disease-free survival for stage IA as compared with stage IC (p=0.007 and p<0.001, respectively). Multivariate analysis revealed incomplete/fertility-sparing staging (HR 1.95; 95% CI 1.27 to 2.99, and HR 3.54; 95% CI 1.83 to 6.86, respectively), and stage IC (HR 2.47; 95% CI 1.63 to 3.75) as independent risk factors for inferior disease-free survival, while low-grade endometrioid (HR 0.42; 95% CI 0.25 to 0.72) and low-grade mucinous (HR 0.17; 95% CI 0.06 to 0.44) histology had superior disease-free survival. Considering overall survival, stage IC (HR 2.41; 95% CI 1.45 to 4.01) and older age (HR 2.41; 95% CI 1.46 to 3.95) were independent risk factors. CONCLUSION: Although stage I ovarian carcinoma exhibited excellent outcomes, the prognosis of patients with stage IA differs significantly compared with stage IC. Sub-optimal staging as an indicator for quality of care, and tumor biology defined by histology (low-grade endometrioid/mucinous) independently impact disease-free survival.

Cord Blood Cell-Free DNA Concentration: A Novel Marker for Neonatal Wellbeing.

OBJECTIVE: Cord gas values and Apgar scores, currently used as markers for newborn wellbeing and postpartum complications, provide rough estimates, and their use remains elusive. Circulating cell-free DNA (cfDNA) may better represent newborn status at birth and the effect of parturition on the fetus. This pilot study investigates the association between cord blood (CB) cfDNA and neonatal outcomes. STUDY DESIGN: In a prospective cohort study, cfDNA concentration was measured in immediately following delivery collected CB sera of newborns using our rapid fluorescent assay. RESULTS: During the study period, blood samples from umbilical cords of 100 newborns were collected. Vaginal delivery was associated with a higher median CB cfDNA than cesarean delivery (277 [95% confidence interval [CI] 199-377] vs. 100 [95% CI 43-265] ng/mL, p < 0.01). cfDNA levels were significantly associated with gestational age at delivery (rho = 0.308, p = 0.002) and CB base deficit (BD, r = 0.252, p = 0.017). According to maternal and fetal complications, CB cfDNA was elevated in fetuses with category II of heart rate tracing (p < 0.05), with maternal positive vaginal culture (p < 0.01), and with premature rupture of membranes (PROM, p < 0.001). Logistic regression models of CB cfDNA fourth quartiles demostrate a double odds ratio for elevated BD (>3mmol/L) and for worse heart rate tracing category. CONCLUSION: Serum CB cfDNA concentration reflects the newborn's status and hazards with an excellent association with CB BD, fetal heart rate category, and maternal risk factors for infection (positive vaginal culture and PROM). This preliminary observation suggests that cfDNA can serve as a point of care biomarker for newborn status at the time of delivery. KEY POINTS: · CB cfDNA levels correlated with newborn's BD.. · CB cfDNA levels reflect parturition stress and inflammation.. · cfDNA serve as a diagnostic and prediction tool for the identification of newborns at risk for morbidity..

Antepartum vaginal Candida colonization and the risk for obstetrical tears.

OBJECTIVE: Vaginal Candida colonization is very common during pregnancy. An association between Candida colonization and obstetrical tears has not yet been investigated. We investigated whether vaginal Candida colonization during pregnancy is associated with an increased risk for obstetrical tears. STUDY DESIGN: A prospective cohort study was undertaken between the years 2014-2016, comparing pregnancy and delivery characteristics of women with and without Candida colonization during pregnancy. Clinical characteristics of Candida positive women and those with normal vaginal flora were collected. To test the statistical significance of the categorical variables, the chi-square test or Fisher's exact test were used, where appropriate. For continuous variables, the Student's t-test was used. RESULTS: During the study period, 102 women with vaginal Candida during pregnancy (of whom 70% had Candida albicans species) and 102 controls with normal vaginal flora were included in the analysis. No significant differences were observed between Candida positive women and those with normal vaginal flora. Pregnancy and delivery outcomes were comparable and no increased risk of obstetrical tears was found in the Candida group. CONCLUSIONS: Vaginal colonization with Candida species during pregnancy was not found to be associated with an increased risk of obstetrical tears.

Optimal delivery timing for dizygotic twins - the short- and long-term perspective.

Major obstetrics and gynecology societies offer inconsistent recommendation regarding optimal delivery timing in uncomplicated dizygotic twins. We sought to investigate the impact of delivery timing within term gestation, in dizygotic twins, on the short- and long-term offspring morbidity. A prospectively analyzed cohort of dizygotic twin deliveries was conducted. All women delivered at a regional tertiary medical center, at term (≥37 0/7), between the years 1991 and 2014, were included. The primary exposure was delivery at 37 0/7-37 + 6/7 weeks, while delivery at ≥38 0/7 weeks' gestation was considered the reference. Neonatal short- and long-term outcomes according to hospitalizations of offspring up to 18 years of age due to cardiac, respiratory, hematological, neurological, and infectious morbidity were compared. Kaplan-Meier survival curves were used to compare cumulative incidences per each major-system hospitalization. Cox regression models were used to estimate the adjusted hazard ratios, while adjusting for variables with clinical importance. During the study period, 612 dizygotic twin deliveries met the inclusion criteria. Of them, 200 (31.3%) occurred at 37-37 6/7 weeks, and 412 (68.7%) occurred at ≥38 0/7 weeks' gestation. In the long-term analysis, rates of hospitalizations involving several major morbidity categories exhibited comparable rates in both groups. The Cox regression models did not demonstrate an independent association between gestational age within term and later major pediatric morbidity in offspring (total long-term morbidity: adjusted hazard ratio 1.33, 95% confidence interval 0.77-2.29). Dizygotic twin deliveries occurring at different gestational ages within term do not appear to significantly impact on major short- and long-term outcomes.

Inter-pregnancy interval and later pediatric cardiovascular health of the offspring - a population-based cohort study.

Recent evidence suggests that a long inter-pregnancy interval (IPI: time interval between live birth and estimated time of conception of subsequent pregnancy) poses a risk for adverse short-term perinatal outcome. We aimed to study the effect of short (<6 months) and long (>60 months) IPI on long-term cardiovascular morbidity of the offspring. A population-based cohort study was performed in which all singleton live births in parturients with at least one previous birth were included. Hospitalizations of the offspring up to the age of 18 years involving cardiovascular diseases and according to IPI length were evaluated. Intermediate interval, between 6 and 60 months, was considered the reference. Kaplan-Meier survival curves were used to compare the cumulative morbidity incidence between the groups. Cox proportional hazards model was used to control for confounders. During the study period, 161,793 deliveries met the inclusion criteria. Of them, 14.1% (n = 22,851) occurred in parturient following a short IPI, 78.6% (n = 127,146) following an intermediate IPI, and 7.3% (n = 11,796) following a long IPI. Total hospitalizations of the offspring, involving cardiovascular morbidity, were comparable between the groups. The Kaplan-Meier survival curves demonstrated similar cumulative incidences of cardiovascular morbidity in all groups. In a Cox proportional hazards model, short and long IPI did not appear as independent risk factors for later pediatric cardiovascular morbidity of the offspring (adjusted HR 0.97, 95% CI 0.80-1.18; adjusted HR 1.01, 95% CI 0.83-1.37, for short and long IPI, respectively). In our population, extreme IPIs do not appear to impact long-term cardiovascular hospitalizations of offspring.

Maternal Chronic Hypertension Elevates the Risk for Long-Term Selected Endocrine and Metabolic Morbidity in the Offspring, Particularly Childhood Obesity.

Background: Maternal hypertensive disorders during pregnancy are known to be associated with high rates of perinatal complications for both mother and child. We aimed at determining whether maternal chronic hypertension impacts long-term pediatric endocrine and metabolic morbidity. Methods: A population-based, retrospective cohort study was performed. Exposure was defined as the presence of maternal chronic hypertension. Hospitalizations of the offspring up to the age of 18 years involving endocrine and metabolic morbidity were evaluated. A Kaplan-Meier survival curve was employed to compare the cumulative morbidity incidence between both groups (exposed and unexposed offspring). Cox proportional hazards models were used to control for confounders. Results: During the study period, 232,841 singleton deliveries met the inclusion criteria. Of them, 1.1% (n = 2655) were exposed to maternal chronic hypertension during pregnancy. Total hospitalization rate involving endocrine-metabolic morbidities was doubled in the hypertensive group (1% vs. 0.5% in the normotensive group, p < 0.001). Specifically, childhood obesity was significantly more common in offspring of mothers with chronic hypertension (0.7% vs. 0.2%, respectively, p < 0.001). The survival curve demonstrated significantly higher cumulative incidence of total endocrine and metabolic morbidity in the exposed group (log rank p = 0.002). In a Cox regression model, maternal chronic hypertension exhibited an independent association with long-term childhood endocrine or metabolic morbidity (adjusted hazard ratio = 1.5, 95% confidence interval 1.01-2.2, p = 0.045). Conclusions: Maternal chronic hypertension appears to be an independent and a significant risk factor for long-term pediatric endocrine and metabolic morbidity, and specifically for childhood obesity, in the offspring.

Preterm prelabor rupture of membranes prior to early preterm delivery elevates the risk of later respiratory-related hospitalizations in the offspring.

OBJECTIVE: Preterm prelabor rupture of membranes (PPROM) precedes 30%-40% of all preterm births. Early preterm delivery (<34 gestation weeks) is a well-established risk factor for short- and long-term respiratory morbidity in the offspring. We aimed to ascertain whether the presence of PPROM, before early preterm delivery, independently impacts long-term respiratory hospitalizations in the offspring. STUDY DESIGN: A population-based retrospective cohort analysis was performed including all singleton early preterm deliveries. Exposure was defined as the presence of PPROM. Hospitalizations of the offspring up to the age of 18 years involving respiratory-related morbidity were evaluated. A Kaplan-Meier survival curve and multivariable Cox regression model were used to assess the association. RESULTS: During the study period, 3309 early preterm deliveries met the inclusion criteria. In 22.4% of cases (n = 742), PPROM was documented. Rates of respiratory-related hospitalizations of the offspring up to the age of 18 years were significantly higher in the exposed group (12.5% vs 9.4% in the unexposed group, P = .023). The survival curve demonstrated significantly higher cumulative incidence of respiratory hospitalizations in the exposed group (logrank P = .018). In the Cox regression model controlled for gestational age, and other clinically relevant confounders - PPROM before early preterm deliveries was independently associated with an increased risk for long-term childhood respiratory-related hospitalizations in the offspring (adjusted hazard ratio 1.40, 95% confidence interval, 1.05-1.87, P = .021). CONCLUSION: Fetal exposure to PPROM before early preterm delivery was associated with an increased risk for long-term respiratory hospitalizations in the offspring.

Fertility treatments and the risk of pediatric obstructive sleep apnea in the offspring-Results from a population-based cohort study.

OBJECTIVE: While the impact of fertility treatments on the perinatal outcome is well established, the long-term effects on offspring are yet to be determined. The current study aimed to investigate the risk of long-term obstructive sleep apnea (OSA) among children born following in vitro fertilization (IVF) and ovulation induction (OI) as compared with spontaneously conceived pregnancies. STUDY DESIGN: A retrospective population-based cohort study was performed. Exposure was defined as delivery following pregnancies conceived by IVF or OI. Incidence of OSA related hospitalizations of the offspring, up to the age of 18 years, was evaluated. A Kaplan-Meier survival curve and multivariable Cox regression models were used to assess the association. RESULTS: During the study period, 242 187 singleton deliveries met the inclusion criteria; 1.1% were conceived following IVF (n = 2603), and 0.7% following OI (n = 1721). Offspring hospitalization rates, involving OSA (n = 1607), were higher among children conceived following IVF and OI pregnancies as compared with the rate in children conceived spontaneously (1.4% vs 1.2% vs 0.7%, respectively; P < .001). The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of OSA related hospitalizations following IVF and OI (log-rank P < .001). Using multiple Cox regression models, controlled for gestational age, maternal age, maternal smoking, maternal obesity, birthweight, offspring gender and obesity, IVF as well as OI exhibited a significant and independent association with pediatric OSA in all models with adjusted hazard ratios of 2.25, (95% confidence interval [CI] = 1.6-3.1) and 1.63 (95% CI = 1.1-2.5), respectively. CONCLUSION: Both IVF and OI treatments appear to be independently associated with OSA in the offspring.

Induction of labor in cases of late preterm isolated oligohydramnios: is it justified?

OBJECTIVES: To analyze in a retrospective cohort study the outcomes of pregnancies with isolated oligohydramnios at the late preterm period (34-36.6 weeks of gestation). STUDY DESIGN: This retrospective cohort study included three groups of women: (1) Women with isolated oligohydramnios whose pregnancy was managed conservatively (n = 33 births); (2) women with isolated oligohydramnios who were managed actively (i.e. induction of labor) (n = 111 births); and (3) a control group including women with normal amount of amniotic fluid who had a spontaneous late preterm delivery (n = 10,445 births). Maternal and fetal characteristics and obstetrics outcomes were collected from a computerized database of all deliveries at Soroka University Medical Center during the study period. RESULTS: Our cohort included 10,589 births. The rate of inducing labor was higher in the oligohydramnios groups compared to the controls (p < .001). There was an increase in the rate of cesarean section (CS) in the conservative treatment group (p < .001), compared with the other groups. Conservative management was associated with higher rates of maternal infection (p = .026), chorioamnionitis (p = .01), and transitory tachypnea of the newborn (p = .02). After controlling for confounding factors, mal presentation (OR = 19.9), and a prior CS (OR = 2.4) were independently associated with an increased risk for CS, while induction of labor was associated with a reduced risk for CS (OR = 0.28). CONCLUSIONS: Women with late preterm isolated oligohydramnios had a higher rate of induction of labor than women with a normal amount of amniotic fluid. Induction of labor seems to be beneficial to both the neonate and the mother as seen by a lower rate of CS conducted in this group, as well as lower maternal and neonatal morbidity in comparison to the conservative group. Therefore, women with oligohydramnios at late preterm may benefit from induction of labor.

The association between gestational age and otitis media during childhood: a population-based cohort analysis.

Otitis media (OM) carries a tremendous global health burden and potentially severe long-term consequences. The objective of this study was to determine the impact of birth at different gestational ages on the incidence of childhood OM.A population-based cohort analysis was conducted. All singleton deliveries occurring between 1991 and 2014 at a regional tertiary medical center were included. Gestational age on delivery was divided into six subgroups: early (<34 weeks gestation; 0 out of 7) and late (34 weeks gestation; 0 out of 7 to 36 weeks gestation; 6 out of 7) preterm, and early (37 weeks gestation; 0 out of 7 to 38 weeks gestation; 6 out of 7), full (39 weeks gestation; 0 out of 7 to 40 weeks gestation; 6 out of 7), late (41 weeks gestation; 0 out of 7 to 41 weeks gestation; 6 out of 7) and post (⩾42 weeks 0 out of 7) term deliveries. Rates of OM-related hospitalizations up to 18 years of age were assessed. Weibull parametric hazards model was used to study the association between gestational age at birth and the risk for OM-related hospitalizations while controlling for potential confounders.During the study period, 238,622 deliveries met the inclusion criteria. OM-related hospitalizations of the offspring (n=4724) were significantly more common in the preterm (early 3.6%, late 2.4%) and early-term born children (2.2%) and decreased gradually across the full (1.9%), late (1.7%) and post (1.6%) term groups (χ2-test for trends P<0.001). In the Weibull regression model, early preterm, as well as early-term deliveries exhibited an independent association with pediatric OM (adjusted hazard ratios: 1.67 and 1.09, respectively, P<0.02).Deliveries occurring at preterm and early term are associated with higher rates of pediatric OM-related hospitalizations, which decrease gradually as gestational age advances.

Impact of Body Mass Index on female fertility and ART outcomes.

As the global mean Body Mass Index (BMI) is on the rise, the importance of understanding exactly how female fertility is impacted by once outlier BMI values, becomes ever more important. Studies have implicated abnormal BMI on the female reproductive system by contributing to anovulation, irregular menses, adverse oocyte quality, endometrial alterations, and hormonal imbalances. These well ultimately result in female infertility, which could complicate natural conception efforts and request considering assisted reproductive technology (ART) in such couples. With an increase in the demand for ART, it is crucial to understand what factors can be altered by the female BMI in order to maximize the opportunity for successful pregnancy. The current manuscript aimed to review the information about the effect of BMI on the female fertility and ART outcomes. The complex nature of the female reproductive system leaves space for multiple factors to adversely affect its processes. Imbalances in the hypothalamus-pituitary-ovarian axis can impede efforts for couples to conceive. Leptin and estrogen are two hormones that have been implicated in regulating BMI as well as reproductive physiology. Lifestyle modifications prior to, and during ART have shown promise in enhancing fecundity. The intricacies in female reproductive system leaves much to the unknown, and often with conflicting results. Further research is required to fully elucidate what aspects of female fertility are influenced by BMI, and how the healthcare provider can facilitate successful outcomes. The current review will enable a better consultation and treatment.

Maternal total cell-free DNA in preeclampsia and fetal growth restriction: Evidence of differences in maternal response to abnormal implantation.

OBJECTIVES: Preeclampsia and fetal growth restriction are obstetrical syndromes associated with abnormal placental implantation and changes in the activation status of maternal leukocytes. This study is aimed to determine by a simple, rapid fluorescent assay the changes in maternal serum total cell-free DNA (t-cfDNA) concentrations in women with preeclampsia and those with fetal growth restriction (FGR). STUDY DESIGN: A cross-sectional study was conducted measuring maternal serum t-cfDNA concentrations. Women were classified into the following groups: 1) patients with preeclampsia (n = 21); 2) FGR-estimated fetal weight below the 10thpercentile (n = 28); and 3) normal pregnancy (n = 39). Serum samples were directly assayed for t-cfDNA using a rapid fluorescent SYBR Gold assay. Elevated maternal serum t-cfDNA concentrations were defined as a cutoff>850ng/ml. Nonparametric statistics were used for analysis. RESULTS: Women with preeclampsia had a higher median maternal serum concentration (802 ng/ml, 400-2272 ng/ml) than women with a normal pregnancy (499 ng/ml, 0-1892 ng/ml, p = 0.004) and those with FGR (484 ng/ml, 72-2187 ng/ml, p = 0.012). Moreover, even patients with FGR <5th percentile and abnormal Doppler had a lower median maternal serum t-cfDNA than those with preeclampsia (median 487 ng/ml, 144-1971 ng/ml, p = 0.022). The median concentration of t-cfDNA did not differ between women with a normal pregnancy and those with FGR (p = 0.54), as well as those with fetuses <5th percentile and abnormal Doppler (p = 0.7). Women with preeclampsia had a higher proportion of elevated t-cfDNA than those with a normal pregnancy (p = 0.015) and patients with FGR (p = 0.025). CONCLUSIONS: Preeclampsia is associated with higher maternal serum t-cfDNA concentration than normal pregnancy or FGR. This observation may reflect an increased systemic activation of the maternal inflammation, rather than placental; this assumption is supported by the fact that we did not observe a significant change in the maternal serum t-cfDNA in patients with placental-mediated FGR.

Advanced maternal age during pregnancy and the risk for malignant morbidity in the childhood.

In the past several decades, rates of delayed childbearing have increased, and as a result, maternal age has advanced. Our objective was to evaluate whether advanced maternal age is independently associated with an increased risk of childhood cancers in the offspring. A retrospective cohort study of women who delivered between the years 1991 and 2014 was conducted. Elderly parturients (≥ 35 years) were divided into two sub-categories: 35-39 and 40-50 years. The comparison group consisted of parturients aged 20-34 years. All hospitalizations of offspring up to the age of 18 years involving malignant morbidity were compared between the groups. A Kaplan-Meier survival curve was used to compare cumulative malignant morbidity incidence of the offspring. A Weibull regression model was used to control for confounders. During the study period, 201,738 deliveries met the inclusion criteria. Of them, 16.3% (n = 32,804) occurred in mothers aged 35 years or more (35-39 years old n = 26,145, 79.7%; 40-50 years old n = 6659, 20.3%). In the Weibull regression model, advanced maternal age exhibited no association with general malignant morbidity in the offspring up to 18 years of age (mothers aged 35-39: adjusted HR 1.06, 95% CI 0.76-1.48, p = 0.727; mothers aged 40-50: adjusted HR 0.73, 95% CI 0.36-1.46, p = 0.373). For leukemia, the regression model exhibited an independent association in maternal ages of 35-39 (adjusted HR 2.23, 95% CI 1.34-3.69, p = 0.002). CONCLUSION: Advanced maternal age does not appear to raise the risk for future malignancy in the offspring up to the age 18 years. The specific nature of the association between maternal age and leukemia of the offspring necessitates further investigation. What is Known: • Advanced maternal age is associated with a marked elevation in the risk of different pregnancy complications and adverse pregnancy outcomes. What is New: • Advanced maternal age does not appear to raise the risk for future malignancy in the offspring up to the age 18 years. • Leukemia of the offspring may be associated with advanced maternal age although the specific nature of the association necessitates further investigation.

Postpartum uterine artery blood flow impedance following cesarean section or vaginal delivery.

PURPOSE: To compare uterine arteries (UtA) blood flow after cesarean section (CS) or vaginal delivery (VD). METHODS: We performed a prospective case-control study comparing UtA blood flow impedance in patients who delivered by CS or VD. The UtA pulsatility index (PI) was measured with Doppler ultrasound during post partum using a transabdominal convex probe. Maternal and gestational age, parity, gravidity, and delay between delivery and Doppler measurement were noted. RESULTS: We examined 106 postnatal patients, of whom 35 had CS delivery and 71 had VD. The median delay from delivery to Doppler measurement was 35 hours for the CS group and 32 hours for the VD group. The mean PI following CS and VD was 1.62 ± 0.45 and 1.42 ± 0.47, respectively. Using a linear model, the regression coefficients for mean, right, and left PI were not significantly different depending on the mode of delivery. There was no difference between emergency and elective CS. CONCLUSIONS: Early postpartum UtA blood flow impedance is not significantly different after CS or VD. © 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:278-283, 2016.

[TRIAL OF LABOR AFTER CESAREAN IN TWIN GESTATIONS: DOES IT INCREASE MATERNAL OR NEONATAL COMPLICATIONS?]

OBJECTIVES: To investigate the rate, success and pregnancy outcome following a trial of labor after cesarean (TOLAC) in twin gestations. Study design: A retrospective study including all twin pregnancies with a single prior cesarean delivery between the years 2006 to 2011 was performed. Women with medical indications for cesarean delivery (CD) were excluded. Maternal and neonatal outcomes were compared between women who delivered by CD to those who underwent TOLAC. Stratified analysis using a multiple logistic regression model was performed to control for confounders. RESULTS: During the years 2006-2011, 110 women met the inclusion criteria. Of these, 20% (n=22) underwent a TOLAC. The success rate of vaginal birth after cesarean was 77.2% (n=17). No cases of uterine rupture or dehiscence were noted. No significant difference was documented in neonatal outcome (including pH and Apgar scores) between the TOLAC and the CD group. Fertility treatment was noted as a risk factor for repeated CD (35.2 vs. 4.5%, OR=8.6, 95% CI 1.21-61.3, P=0.005). Using a multivariable analysis, with repeated CD as the outcome variable, controlling for confounders such as maternal age, and gestational age, fertility treatment was an independent risk factor for repeated CD (adjusted OR=5.2, 95% CI 0.01-0.70; P=0.02). CONCLUSIONS: A TOLAC in twin gestation seems to be a safe option for the mother and newborn. Fertility treatment is an independent risk factor for repeated CD in twins.