Effects of unilateral ovariectomy on female fertility outcome.

PURPOSE: To compare the fertility outcome among women subjected to unilateral ovariectomy and other abdominal or non-gynaecologic pelvic surgery. METHODS: In this retrospective cohort study, 113 fertile women, surgically treated between 1990 and 2001 at Sapienza University of Rome with unilateral ovariectomy (UO), appendectomy (AP) or cholecystectomy (CO) for benign disease, were analysed for fertility outcome. Patients with assessed pre-surgical fertility defects, previous abdominal or pelvic surgeries and post-surgical contraception were not included. RESULTS: Thirty-five women underwent UO, 39 were subjected to AP and 39 were treated with CO. After a minimum 10-year post-surgical interval, the overall number of successful pregnancies was 75. The rate of women who experienced at least one post-operative successful pregnancy was: 48.5 % in UO, 41 % in AP and 53.8 % in CO (UO vs. AP, P = 0.55; UO vs. CO, P = 0.99; AP vs. CO, P = 0.53). One patient (2.8 %) in UO, one patient (2.6 %) in AP and two patients (5.1 %) in CO underwent Assisted Reproductive Technology to become pregnant. The rate of women who reported at least one miscarriage was: 10/35 (28.5 %) in UO, 11/39 (28.2 %) in AP, 12/39 (30.8 %) in CO (UO vs. AP, P = 0.93; UO vs. CO, P = 0.89; AP vs. CO, P = 0.81). One ectopic pregnancy was reported in CO group and one stillbirth occurred in one AP patient. CONCLUSIONS: No statistical difference in terms of post-operative fertility outcome between patients subjected to UO, AP or CO was found, thus allowing to suppose that the removal of one ovary does not significantly worsen the female fertility outcome respect to other abdominal or pelvic procedures.

Dietary Fatty Acids Contribute to Maintaining the Balance between Pro-Inflammatory and Anti-Inflammatory Responses during Pregnancy.

BACKGROUND: During pregnancy, the balance between pro-inflammatory and anti-inflammatory responses is essential for ensuring healthy outcomes. Dietary Fatty acids may modulate inflammation. METHODS: We investigated the association between dietary fatty acids as profiled on red blood cells membranes and a few pro- and anti-inflammatory cytokines, including the adipokines leptin and adiponectin at ~38 weeks in 250 healthy women. RESULTS: We found a number of associations, including, but not limited to those of adiponectin with C22:3/C22:4 (coeff -1.44; p = 0.008), C18:1 c13/c14 (coeff 1.4; p = 0.02); endotoxin with C20:1 (coeff -0.9; p = 0.03), C22:0 (coeff -0.4; p = 0.05); MCP-1 with C16:0 (coeff 0.8; p = 0.04); and ICAM-1 with C14:0 (coeff -86.8; p = 0.045). Several cytokines including leptin were associated with maternal body weight (coeff 0.9; p = 2.31 × 10-5), smoking habits (i.e., ICAM-1 coeff 133.3; p = 0.09), or gestational diabetes (i.e., ICAM-1 coeff 688; p = 0.06). CONCLUSIONS: In a general cohort of pregnant women, the intake of fatty acids influenced the balance between pro- and anti-inflammatory molecules together with weight gain, smoking habits, and gestational diabetes.

Pregnancy in HIV-positive patients: effects on vaginal flora.

A high proportion of HIV-infected pregnant women present pathogenic organisms in their lower genital tract. This has been associated with the development of postpartum morbility, HIV transmission to the partner and offspring, and other gynaecological conditions, such as cervical dysplasia or cancer. Vaginal flora alterations can range from 47% in Western countries to 89% in Africa in pregnant HIV-positive patients, much higher than about 20% of the general population. Pathogen organism retrieval is high. As peripartum complications due to vaginal infections seem higher in HIV-positive patients, accurate investigation and treatment of such infections are strongly mandatory.

The Interplay between CD27dull and CD27bright B Cells Ensures the Flexibility, Stability, and Resilience of Human B Cell Memory.

Memory B cells (MBCs) epitomize the adaptation of the immune system to the environment. We identify two MBC subsets in peripheral blood, CD27dull and CD27bright MBCs, whose frequency changes with age. Heavy chain variable region (VH) usage, somatic mutation frequency replacement-to-silent ratio, and CDR3 property changes, reflecting consecutive selection of highly antigen-specific, low cross-reactive antibody variants, all demonstrate that CD27dull and CD27bright MBCs represent sequential MBC developmental stages, and stringent antigen-driven pressure selects CD27dull into the CD27bright MBC pool. Dynamics of human MBCs are exploited in pregnancy, when 50% of maternal MBCs are lost and CD27dull MBCs transit to the more differentiated CD27bright stage. In the postpartum period, the maternal MBC pool is replenished by the expansion of persistent CD27dull clones. Thus, the stability and flexibility of human B cell memory is ensured by CD27dull MBCs that expand and differentiate in response to change.

Maternal Intake of n-3 Polyunsaturated Fatty Acids During Pregnancy Is Associated With Differential Methylation Profiles in Cord Blood White Cells.

A healthy diet during pregnancy is pivotal for the offspring health at birth and later in life. N-3 polyunsaturated fatty acids (n-3 PUFAs) are not endogenously produced in humans and are exclusively derived from the diet. They are pivotal for the fetus growth and neuronal development and seem beneficial in reducing the risk of cardiometabolic diseases and preventing later allergic disorders in the offspring by modulating the inflammatory immune response. In the present study, we investigated the association between maternal intakes of n-3PUFAs, profiled on maternal erythrocyte membranes at pregnancy term, and offspring DNA methylation on cord blood mononuclear cells in a sample of 118 mother-newborn pairs randomly drawn from the "Feeding fetus' low-grade inflammation and insulin-resistance" study cohort. N-3 PUFA content on erythrocyte membranes is a validated biomarker to measure objectively medium term intake of n-3 PUFAs. Based on distribution of n-3 PUFA in the whole cohort of mothers, we identified mothers with low (n-3 PUFA concentration <25th percentile), medium (n-3 PUFAs between 25th and 75th percentiles), and high n-3 PUFA content (>75th percentile). The HumanMethylation450 BeadChip (Illumina) was used for the epigenome-wide association study using the Infinium Methylation Assay. The overall DNA methylation level was not different between the three groups while there was significant difference in methylation levels at certain sites. Indeed, 8,503 sites had significantly different methylations between low and high n-3 PUFA groups, 12,716 between low and medium n-3 PUFA groups, and 18,148 between high and medium n-3 PUFA groups. We found differentially methylated genes that belong prevalently to pathways of signal transduction, metabolism, downstream signaling of G protein-coupled receptors, and gene expression. Within these pathways, we identified four differentially methylated genes, namely, MSTN, IFNA13, ATP8B3, and GABBR2, that are involved in the onset of insulin resistance and adiposity, innate immune response, phospholipid translocation across cell membranes, and mechanisms of addiction to high fat diet, alcohol, and sweet taste. In conclusion, findings of this preliminary investigation suggest that maternal intake of n-3 PUFAs during pregnancy has potential to influence the offspring DNA methylation. Validation of results in a larger cohort and investigation of biological significance and impact on the phenotype are warranted.

A novel approach in the treatment of neonatal gastroschisis: a review of the literature and a single-center experience.

Gastroschisis is a congenital abdominal wall defect and its management remains an issue. We performed a review of the literature to summarize its evaluation, management and outcome and we describe a new type of surgical reduction performed in our center without anesthesia (GA), immediately after birth, in the delivery room. Between January 2002 and March 2013, we enrolled all live born infants with gastroschisis referred to the third-level Division of Obstetrics and Gynecology "San Camillo" of Rome. Two groups of infants were identified: group 1 in which gastroschis reduction was performed by the traditional technique and group 2 in which reduction was immediately performed after birth in the delivery room without GA. Twelve infants were enrolled in group 1, and seven infants in group 2. Statistical significance was observed between the groups regarding the hospital stay, for the duration of parenteral nutrition and full oral feeds (p = .004). Survival was similar between two groups. The reduction without GA performed immediately after birth in a delivery room encourages the relationship between the mother and her child and appears to be a safe and feasible technique in a selected group of patients with simple gastroschisis defect; for this reason, it could represent a valid alternative to traditional approach.

Association between Maternal and Foetal Erythrocyte Fatty Acid Profiles and Birth Weight.

Regular foetal development is crucial for assuring good health status in the offspring. The quality and quantity of maternal dietary fatty acids (FAs) can affect growth. The study aimed to: (1) investigate the association of maternal/foetal lipid profiles with birth weight (BW); and (2) compare these profiles in small, appropriate, and large for gestational age (SGA, AGA, and LGA) infants. FAs were measured in erythrocyte membranes using gas chromatography analysis in 607 mother-infant pairs (316 males, 52.1%). In the quantile regression, a significant association between BW and levels of maternal linoleic acid (LA; C18:2, n-6; coefficient: 18.66; p = 0.010), arachidonic acid (AA; C20:4, n-6; coefficient: 11.35; p = 0.007), docosahexaenoic acid (DHA; C22:6, n-3; coefficient: 29.73; p = 0.007), polyunsaturated FAs (coefficient: 8.55; p = 0.001), foetal DHA (coefficient: -22.82; p = 0.037), and saturated FAs (coefficient: -65.41; p = 0.002) was found. Myristic (C14:0) and pentadecanoic acids (C15:0), both maternal (p = 0.000; p = 0.017) and foetal (p = 0.009; p = 0.002), and maternal erucic acid (C22:1, n-9; p = 0.026) were found at higher levels in SGA infants as compared to AGA ones. Conversely, maternal LA, AA, and omega 6 FAs levels were higher in AGA infants (p = 0.037; p = 0.003; p = 0.026, respectively). Maternal and foetal polyunsaturated and omega 6 FAs levels are positively related to BW, while a lipid profile rich in saturated FAs and erucic acid may influence the risk of SGA.

Non-Coding RNAs and Endometrial Cancer.

Non-coding RNAs (ncRNAs) are involved in the regulation of cell metabolism and neoplastic transformation. Recent studies have tried to clarify the significance of these information carriers in the genesis and progression of various cancers and their use as biomarkers for the disease; possible targets for the inhibition of growth and invasion by the neoplastic cells have been suggested. The significance of ncRNAs in lung cancer, bladder cancer, kidney cancer, and melanoma has been amply investigated with important results. Recently, the role of long non-coding RNAs (lncRNAs) has also been included in cancer studies. Studies on the relation between endometrial cancer (EC) and ncRNAs, such as small ncRNAs or micro RNAs (miRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), antisense RNAs (asRNAs), small nuclear RNAs (snRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), competing endogenous RNAs (ceRNAs), lncRNAs, and long intergenic ncRNAs (lincRNAs) have been published. The recent literature produced in the last three years was extracted from PubMed by two independent readers, which was then selected for the possible relation between ncRNAs, oncogenesis in general, and EC in particular.

Influence of Maternal Obesity and Gestational Weight Gain on Maternal and Foetal Lipid Profile.

Fatty acids (FAs) are fundamental for a foetus's growth, serving as an energy source, structural constituents of cellular membranes and precursors of bioactive molecules, as well as being essential for cell signalling. Long-chain polyunsaturated FAs (LC-PUFAs) are pivotal in brain and visual development. It is of interest to investigate whether and how specific pregnancy conditions, which alter fatty acid metabolism (excessive pre-pregnancy body mass index (BMI) or gestational weight gain (GWG)), affect lipid supply to the foetus. For this purpose, we evaluated the erythrocyte FAs of mothers and offspring (cord-blood) at birth, in relation to pre-pregnancy BMI and GWG. A total of 435 mothers and their offspring (237 males, 51%) were included in the study. Distribution of linoleic acid (LA) and α-linolenic acid (ALA), and their metabolites, arachidonic acid, dihomogamma linoleic (DGLA) and ecosapentanoic acid, was significantly different in maternal and foetal erythrocytes. Pre-pregnancy BMI was significantly associated with maternal percentage of MUFAs (Coeff: -0.112; p = 0.021), LA (Coeff: -0.033; p = 0.044) and DHA (Coeff. = 0.055; p = 0.0016); inadequate GWG with DPA (Coeff: 0.637; p = 0.001); excessive GWG with docosaexahenoic acid (DHA) (Coeff. = -0.714; p = 0.004). Moreover, pre-pregnancy BMI was associated with foetus percentage of PUFAs (Coeff: -0.172; p = 0.009), omega 6 (Coeff: -0.098; p = 0.015) and DHA (Coeff: -0.0285; p = 0.036), even after adjusting for maternal lipids. Our findings show that maternal GWG affects maternal but not foetal lipid profile, differently from pre-pregnancy BMI, which influences both.

Phylogenetic and Metabolic Tracking of Gut Microbiota during Perinatal Development.

The colonization and development of gut microbiota immediately after birth is highly variable and depends on several factors, such as delivery mode and modality of feeding during the first months of life. A cohort of 31 mother and neonate pairs, including 25 at-term caesarean (CS) and 6 vaginally (V) delivered neonates (DNs), were included in this study and 121 meconium/faecal samples were collected at days 1 through 30 following birth. Operational taxonomic units (OTUs) were assessed in 69 stool samples by phylogenetic microarray HITChip and inter- and intra-individual distributions were established by inter-OTUs correlation matrices and OTUs co-occurrence or co-exclusion networks. 1H-NMR metabolites were determined in 70 stool samples, PCA analysis was performed on 55 CS DNs samples, and metabolome/OTUs co-correlations were assessed in 45 CS samples, providing an integrated map of the early microbiota OTUs-metabolome. A microbiota "core" of OTUs was identified that was independent of delivery mode and lactation stage, suggesting highly specialized communities that act as seminal colonizers of microbial networks. Correlations among OTUs, metabolites, and OTUs-metabolites revealed metabolic profiles associated with early microbial ecological dynamics, maturation of milk components, and host physiology.

Antiretroviral therapeutic drug monitoring in HIV-infected pregnant women: maternal immunovirological outcome at delivery and during the 18 month follow-up period.

No data are available on the long-term immunovirological outcome of HIV-positive pregnant women experiencing sub-therapeutic antiretroviral drug (ARV) concentrations during pregnancy. The objective of our study was to assess the long-term virological outcome in pregnant women treated with HAART. A prospective, multi-center study enrolled 60 HIV-infected pregnant women stratified into 3 groups according to the response to HAART. Group A, women successfully treated with HAART; Group B, women with confirmed virological failure during HAART; Group C, women successfully treated with HAART during pregnancy for prevention of vertical transmission only. Smoking, alcohol use, low adherence to therapy, and increased viral load at delivery were significantly associated to virological failure at univariate analysis. At multivariate regression analysis, only adherence to therapy was reported as an independent variable related to the virological response (p < 0.001). Virological failure during follow-up was reported in 2 (25.0%) of the 8 women with sub therapeutic Ctrough and in 4 of the 33 (12.1%) women with therapeutic Ctrough (p=0.33). In group C, the viro-immunological set points during follow-up did not differ from those observed before HAART initiation. No significantly increased rate of virological failure after delivery was reported in women with sub-therapeutic ARV concentrations during pregnancy and long-term follow-up. The long-term virological outcome was independently associated to reduced adherence to therapy. Evaluation of the clinical impact of the low plasma ARV concentrations during pregnancy on the long-term virological outcome deserves further larger studies.

Transplacental transfer of antiretroviral drugs and newborn birth weight in HIV-infected pregnant women.

Although it is well known that antiretroviral drugs (ARVs) across the placenta in different extents, few data are available concerning the impact of the transplacental passage of ARVs on newborn outcome. The aim of this study is to evaluate the transplacental diffusion of ARVs and the clinical assessment of the newborn. Mother and cord lopinavir, nelfinavir, atazanavir and nevirapine plasma levels were determined by high-performance liquid chromatography. Newborn gestational age, weight, and Apgar score were recorded. Cord-to-mother ratio (C:M) was calculated to estimate the placental passage of ARVs. Preterm birth was defined as delivery at <37 weeks of gestation and low birth weight was defined as a birth weight of <2500g. Twenty-six HIV-infected pregnant women were enrolled. Nevirapine presented the highest C:M ratio (0.60 +/- 0.19), the C:M ratio of nelfinavir and atazanavir was 0.37 +/- 0.38 and 0.20 +/- 0.14, respectively. The lopinavir level in the cord was undetectable. The observed prevalence rate of neonatal low birth weight and preterm delivery was 19,2% (n = 5) and 15.4% (n = 4), respectively. A significant linear regression analysis was reported between the C:M ratio and newborn birth weight (p = 0.01). Although the role of highly active antiretroviral therapy (HAART) in preventing mother-to-child transmission is indisputable, these data indicate a pharmacological rationale to the association between birth weight and highly active antiretroviral therapy during pregnancy.