The impact of fetal sex on pregnancy and neonatal outcomes in twin gestation.

PURPOSE: Fetal sex is independently associated with pregnancy complications and impacts neonatal outcomes. Evidence suggests that females have an advantage over males, with a better outcome in the perinatal period. In addition, fetal outcome in twin gestations is also related to the intrauterine position of the fetus, such as the first, the presenting or second twin. It has been demonstrated that the neonatal outcome of the second fetus is worse than that of the first fetus. This study aimed to examine the influence of fetal sex on obstetric outcomes in twin pregnancies based on the location of the fetus in the uterus. METHODS: Retrospective study. Maternal and obstetric outcomes were compared among three groups: male‒male, female‒female, and male‒female groups. Comparisons of neonatal outcomes were performed among the four groups: male A-male B, male A-female B, female A-male B, and female A-female B. RESULTS: A total of 1073 twin gestations were included, comprising 288 male‒male, 288 female‒female, and 497 male‒female gestations. A greater percentage of neonates admitted to the NICU was observed for male fetuses than for female fetuses. Adverse composite neonatal outcome was more common in the male‒male group than in the female‒male group and in the female‒female group. CONCLUSION: Twin gestation with a first twin male tends to have worse neonatal outcomes than does twin gestation with a first twin female. The presence of a male co-twin increases the risk of adverse outcomes.

Unfolding of maternal-infant bonding amidst the COVID-19 pandemic: Social support as a risk and protective factor.

BACKGROUND: Social, familial, and physiological stressors may put maternal-infant bonding at risk. Therefore, it is plausible that the stressful conditions brought on by COVID-19 could influence maternal-infant bonding. This study aimed to elucidate the contribution of COVID-19-related experience to variance in maternal-infant bonding, beyond that of established risk factors and as moderated by social support. METHODS: This longitudinal, multicenter study examined the relationship of demographic and obstetric variables, social support, postpartum depression, as well as COVID-19-related fear, exposure, and subjective difficulty with mother-infant bonding six months following birth. Participants (N = 246) were women who delivered during the pandemics' strict lockdown period and were recruited 10 weeks after a liveborn delivery and followed up six months later. RESULTS: Relationship between fear of COVID-19 and maternal-infant bonding was moderated by social support: Amongst mothers with high levels of social support, fear of COVID-19 negatively predicted bonding. DISCUSSION: Results indicate that social support, while overall a protective factor for mother-infant bonding, may lose its buffering effect when fear of COVID-19 is high. This relationship was maintained even when early bonding experiences such as forced separation and the risk incurred by postpartum depression were accounted for. Implications for providers are discussed.

Maternal fear of COVID-19 and prevalence of postnatal depression symptoms, risk and protective factors.

This is a multicenter prospective observational study, aimed to evaluate the relations between Fear of COVID-19 and postpartum depression (PPD) symptom, that included a cohort of women who delivered during COVID-19 lockdown between 03 and 05/2020. Participants were approached after delivery and asked to complete an online questionnaire. Data was verified with each center's perinatal database. The validated Fear of COVID-19 Scale was in use. PPD was evaluated using the EPDS questionnaire as a categorical (≥13) and as a continuous scale. Pre-existing maternal disability was defined as any prior physiological/psychological chronic health condition. Continuous medical supervision or stress contributing complications at birth included pregnancy and labor related complications. Regression analysis and ROC statistics were utilized to evaluate associations and control for confounders. Overall, 421 women completed the questionnaires. Of them, 53(12.6%) had a high EPDS score. Fear of COVID-19 was positively correlated with PPD symptoms (r = 0.35,p = 0.000), ROC-AUC 0.73, 95% CI 0.65-0.81, p = 0.000. Following adjustment to confounders (maternal age, nulliparity, ethnicity, marital status, financial difficulties, maternal disability, accessibility to medical services, and continuous medical supervision (, the most important factor that correlated with depression symptoms was maternal disability (aOR 4.61,95% CI 1.96-10.82) followed by Fear of COVID-19 (aOR 1.11,95% CI 1.05-1.17). High accessibility to medical services during pregnancy (aOR 0.62, 95%CI 0.45-0.84) was protective for PPD symptoms. To conclude, during the COVID-19 pandemic, maternal disability and Fear of COVID-19 are positively associated with a high EPDS score. High medical accessibility during pregnancy was found as a protective factor for PPD.

Is the Bishop-score significant in predicting the success of labor induction in multiparous women?

OBJECTIVE: To determine whether the Bishop-score upon admission effects mode of delivery, maternal or neonatal outcomes of labor induction in multiparous women. STUDY DESIGN: A retrospective study including 600 multiparous women with a singleton pregnancy, 34 gestational weeks and above who underwent labor induction for maternal, fetal or combined indications. Induction was performed with one of three methods- oxytocin, a slow release vaginal prostaglandin E2 insert (10 mg dinoprostone) or a transcervical double balloon catheter. The women were divided into two groups-Bishop-score <6 and Bishop-score ⩾6. We evaluated labor course, maternal complications (postpartum hemorrhage, manual lysis, uterine revision, perineal tear grade 3-4, need for blood transfusions, relaparotomy, prolonged hospitalization) and neonatal outcomes (Apgar score, cord pH, hospitalization in the neonatal intensive care unit, prolonged hospitalization). RESULTS: Both groups had a high rate of vaginal deliveries-93.7% and 94.9%, respectively. There was no difference between the two groups in terms of maternal or neonatal outcomes. CONCLUSION: Labor induction in multiparous women is safe and successful regardless of the initial Bishop-score. In multiparous women the Bishop-score is not a good predictor for the success of labor induction, nor is it a predictor for maternal of neonatal adverse outcomes and complications.

Intracytoplasmic morphologically selected sperm injection and congenital birth defects: a retrospective cohort study.

Our objective was to study the birth defect rates in intracytoplasmic morphologically selected sperm injection (IMSI) pregnancies. A cohort of couples presenting male factor infertility between January 2006 and January 2014 was retrospectively analyzed. Discharge letters and a telephone interview were performed for assessing pregnancy outcome. All clinical data were reviewed by a board certified medical geneticist. Main outcomes were fetal/birth defect and chromosomal abnormality rates. Two thousand two hundred and fifty-eight pregnancies were available for analysis, of them, 1669 (73.9%) resulting from ICSI and 2258 (26.1%) achieved by IMSI. Pregnancy outcome distribution did not show a significant difference. For the fresh embryo transfer cohort, fetal/birth defect rate was 4.5%, chromosomal aberration rate was 1.0%, and structural malformation rate was 3.5%. IMSI vs. ICSI pregnancies were less likely to involve a fetal/birth defect: 3.5% vs. 4.8%, respectively, but did not reach a statistical significance OR 0.71 (95% CI 0.39-1.22). Split by multiplicity, this trend existed only for singleton pregnancies; 1.4% structural malformations rate vs. 3.8%, respectively, OR 0.35 (95% CI 0.11-0.9). The frozen cohort demonstrated a significantly lower birth defect rate (OR 0.25, 95% CI 0.09-0.58). We conclude that IMSI procedure does not involve an increased malformation rate and may offer a reduced anomaly incidence. Further studies are required.

Immediate postpartum ultrasound evaluation for suspected retained placental tissue in patients undergoing manual removal of placenta.

OBJECTIVES: Approximately 1% of term deliveries are complicated by retained products of conception. Untreated, this condition may cause bleeding, infection and intrauterine adhesions. This study assessed whether performing routine bedside uterine ultrasound immediately after manual removal of the placenta reduced the occurrence of undiagnosed, retained products of conception and its associated complications. STUDY DESIGN: A retrospective study was conducted using the records of patients who delivered and underwent manual removal of placenta at a single obstetrics center over a 6-year period. The outcomes of patients who were assessed using immediate bedside ultrasound were compared to a similar group who were treated based on clinical evaluation alone. All patients underwent ultrasound examination prior to discharge. Outcome variables included the rate of additional interventions (medical or surgical), abnormal pre-discharge uterine ultrasound findings, postpartum hemorrhage rate, puerperal fever and length of hospital stay. RESULTS: A total of 399 charts were reviewed. Immediate post-procedural ultrasound was performed in 235 patients. The remaining 164 women did not undergo immediate post-procedural ultrasound. All patients underwent an ultrasound examination prior to discharge. Among the patients who had an immediate post-procedural ultrasound, 12 (5.1%) received immediate re-intervention (2 methergine, 6 curettage and 4 manual uterine revision) vs. no intervention in the second group (p<0.001). No statistically significant difference was found between the group of patients who had immediate post-procedural ultrasound and those who did not, in the rates of postpartum hemorrhage (3.1% vs. 0.7%, p=0.13), abnormal ultrasound findings prior to discharge (14.9% vs. 14.8%, p=0.96) or additional late intervention (7.2% vs. 7.9%, p=0.79), respectively. CONCLUSIONS: Our findings suggest that immediate, bedside uterine ultrasound examination after manual removal of placenta might not change patient outcomes. Furthermore, it might increase unnecessary interventions. Further studies are needed to prospectively assess the benefit of routine uterine ultrasound examination after manual removal of placenta.

Intra-vaginal prostaglandin E2 versus double-balloon catheter for labor induction in term oligohydramnios.

OBJECTIVE: Compare mechanical and pharmacological ripening for patients with oligohydramnios at term. STUDY DESIGN: Fifty-two patients with oligohydramnios ⩽ 5 cm and Bishop score ⩽ 6 were randomized for labor induction with a vaginal insert containing 10 mg timed-release dinoprostone (PGE2) or double-balloon catheter. The primary outcome was time from induction to active labor. Time to labor, neonatal outcomes and maternal satisfaction were also compared. RESULT: Baseline characteristics were similar. Time from induction to active labor (13 with PGE2 vs 19.5 h with double-balloon catheter; P = 0.243) was comparable, with no differences in cesarean rates (15.4 vs 7.7%; P = 0.668) or neonatal outcomes. The PGE2 group had higher incidence of early device removal (76.9 vs 26.9%; P = 0.0001), mostly because of active labor or non-reassuring fetal heart rate. Fewer PGE2 patients required oxytocin augmentation for labor induction (53.8 vs 84.6% P = 0.034). Time to delivery was significantly shorter with PGE2 (16 vs 20.5 h; P = 0. 045). CONCLUSION: Intravaginal PGE2 and double-balloon catheter are comparable methods for cervical ripening in term pregnancies with oligohydramnios.

Telomeres are shorter in placentas from pregnancies with uncontrolled diabetes.

INTRODUCTION: The intrauterine environment, including the placenta, is influenced by a variety of factors, among which is diabetes during pregnancy. These factors can affect lifetime morbidity. Senescence is a state of cellular metabolic arrest, known to be correlated with age-related diseases and is usually accompanied by short telomeres. This study evaluated telomere characteristics in placentas and in cord blood from term pregnancies complicated by uncontrolled diabetes mellitus. METHODS: Placental biopsies and cord blood were collected from 16 pregnancies with poorly controlled diabetes and from 16 healthy controls. Senescence-associated heterochromatin foci (SAHF) and senescence-associated ß-galactosidase (SAß-Gal) staining were evaluated. Apoptosis was evaluated using tunel staining. Telomere length and aggregate formation were assessed in placentas and in cord blood using Q-FISH. RESULTS: Increased SAHF (19.28% ± 7.93 vs. 7.78% ± 5.31, P < 0.001) and SAß-Gal (7.1% ± 1.32 vs. 0.8% ± 0.41, P < 0.001), but not apoptosis were present in placentas from diabetic pregnancies compared to controls. Higher percentage of trophoblasts with short telomeres (24.42% ± 12.6 vs. 4.92% ± 6.4, P = 0.013) and noticeably more aggregate formation (2.75% ± 1.14 vs. 0.62% ± 0.87, P < 0.001) were observed in diabetic placentas compared to controls. These differences were not observed in cord blood samples. DISCUSSION: Poorly controlled diabetes is related to increased senescence and shorter telomeres in placentas. Those findings may partially explain increased long-term, related morbidity.

The effect of heat shock protein 27 on extravillous trophoblast differentiation and on eukaryotic translation initiation factor 4E expression.

Heat shock protein (HSP27) is expressed in human placentae. Previously, we showed that HSP27 is expressed in the villous cell column of first trimester placental explants and in extravillous trophoblast (EVT) cells. EVT differentiation is accompanied by increased motility, matrix metalloproteinase (MMP) activity, decreased proliferation and expression of specific markers such as HLAG and CD9. HSP27 regulates cell apoptosis, migration, protein stability and the availability of eukaryotic translation initiation factors, such as eukaryotic translation initiation factor 4E (eIF4E). eIF4E supports trophoblast cell proliferation and survival. We wanted to explore the effect of HSP27 silencing on trophoblast cell phenotype, EVT markers and eIF4E expression and regulators [4E-binding protein (4E-BP1) and MAP kinase-interacting kinase (MNK1)]. This study evaluated the effect of HSP27 siRNA on placental explant and HTR-8/SVneo migration, MMP activity/mRNA, cell death, cell cycle, HLAG/CD9 levels, and eIF4E and its regulators' total and phosphorylated levels. Furthermore, we evaluated HSP27 levels in placentae exposed to ribavirin, which triggers EVT differentiation. We found that HSP27 silencing increased cell death in HTR-8/SVneo and placental explants. Furthermore, it reduced HTR-8/SVneo migration and EVT outgrowth from the explants (P < 0.05), MMP2 activity and expression of EVT markers HLAG and CD9 (in placental explants and HTR-8/SVneo, respectively, P < 0.05). Induction of EVT differentiation by ribavirin elevated HSP27 levels. Finally, HSP27 silencing in both HTR-8/SVneo and placental explants reduced eIF4E levels (33 and 28%, respectively, P < 0.05) and the levels of its regulators 4E-BP1 and MNK1 (37 and 32%, respectively, done on HTR-8/SVneo only), but not their phosphorylated forms. Altogether, our results suggest that HSP27 contributes to EVT cell differentiation.

Telomeres in trisomy 21 amniocytes.

Individuals with trisomy 21 have an increased risk of developing leukemia and premature dementia. They also have a higher rate of telomere loss. The aim of the study was to compare telomere length and the hTERC gene copy number, which encodes the telomerase RNA subunit, in amniocytes of trisomy 21 conceptions and normal pregnancies. A quantitative fluorescence-in-situ protocol (Q-FISH) was used to compare telomere length in amniocytes cultured from 11 trisomy 21 conceptions and from 14 normal pregnancies. Quantification was conducted using novel computer software. Fluorescence in situ hybridization (FISH) was used to assess the percentage of cells with additional copies of hTERC. We found that the immunofluorescence intensity, which represents telomere length, was significantly lower in amniocytes from trisomy 21 conceptions compared to the control group. The trisomy 21 group had a higher number of cells with additional copies of hTERC. This observation could be one of the cytogenetic parameters that represent a state of genetic instability and might play a role in the pathomechanism of typical features of Down syndrome, such as dementia and malignancy.

Hypoxia enhances the expression of follistatin-like 3 in term human trophoblasts.

Hypoxic injury hinders placental differentiation and alters trophoblast gene expression. We tested the hypothesis that the expression of follistatin-like 3 (FSTL3), a member of the follistatin family of proteins, is modulated by hypoxia in primary human trophoblast (PHT). Using immunofluorescence of human term placental villi we detected the expression of FSTL3 protein in placental villi, primarily in trophoblasts. We verified this finding in cultured term PHT cells. Basal expression of FSTL3 transcript in cultured PHT cells, determined using quantitative PCR, was stable over the culture period. Importantly, when compared to culture in FiO(2)=20% or FiO(2)=8%, PHT cells cultured in FiO(2) <1% exhibited a 4-6 fold increase in FSTL3 mRNA expression as early as 4h in hypoxia. Whereas cellular FSTL3 protein was unchanged in hypoxia, we found that hypoxia increased the level of FSTL3 in the medium. Lastly, the exposure of PHT cells to either the hypoxia-mimetic cobalt chloride or the proline hydroxylase inhibitor dimethyloxaloylglycine upregulated the expression of FSTL3 transcript. Our data indicate that hypoxia enhances the expression of FSTL3 and its release from PHT cells. Our finding that hypoxia-mimetic agents enhance FSTL3 expression implicates HIF1alpha in this process.

High incidence of BRCA1-2 germline mutations, previous breast cancer and familial cancer history in Jewish patients with uterine serous papillary carcinoma.

OBJECTIVE: To test the carrier status of the three germline founder mutations in Jewish patients with uterine serous papillary carcinoma (USPC) and to evaluate its association to their personal and familial cancer records. METHODS: Retrospective analysis of histologically confirmed USPC Jewish patients diagnosed between April 1, 1997 and December 31, 2003. All cases were genetically tested for the three BRCA1-2 founder germline mutations (185delAG and 5382insC in BRCA1 and 6174delT in BRCA2). The analysis was performed on genomic DNA extracted from whole blood or paraffin embedded normal tissue of these patients, employing PCR amplification of target sequences and differential digestion with restriction enzymes. The carrier frequency was compared to the known population frequency of these mutations. RESULTS: The study group comprised 22 Jewish patients with USPC diagnosed within this timeframe. The mean age was 71.8 years (range 56-79). FIGO surgical stage distribution revealed 59% at stages III-IV. Seven USPC patients (32%) with a previous diagnosis of breast cancer were identified. Familial cancer history was recorded in 23% of the patients (four with breast cancer and one with ovarian cancer). DNA analysis revealed six BRCA1-2 germline mutation carriers (27%) as follows: three with BRCA2-6174delT, two with BRCA1-185delAG, and one with BRCA1-5382insC mutation. Three of the carriers had a previous diagnosis of breast cancer. Four carriers had familial cancer history in first-degree relative (three with breast cancer and one with ovarian cancer). CONCLUSIONS: The high rate of BRCA germline mutations in USPC patients observed in the present study, coupled with the strong personal and familial cancer history as well as the histological and clinical resemblance to the ovarian cancer, may indicate that USPC is a part or an expression of the hereditary breast-ovarian cancer syndrome. This option may have implications in our clinical recommendations for non-affected BRCA1-2 carriers.

Primary peritoneal borderline tumor. A case report and review of the literature.

A case report and review of the literature of a primary peritoneal borderline tumor is presented. A patient with primary peritoneal borderline tumor diagnosed by elevated of serum CA-125 and asymptomatic pelvic cysts, two years after laparotomy due to mullerian cysts, is discussed.