Abstract We aim to describe the diagnosis and surgical management of urinary tract endometriosis (UTE). We detail current diagnostic tools including advanced transvaginal ultrasound, magnetic resonance imaging, and surgical diagnostic tools such as cystourethroscopy. While discussing surgical treatment options, we emphasize the importance of an interdisciplinary team, for complex cases that involve the urinary tract. While bladder DE is more straightforward in its surgical treatment, ureteral DE requires a high level of surgical skill. Specialists should be aware of the important entity of UTE due to the serious health implications for women. When UTE exists, it is important to work within a interdisciplinary radiological and surgical team.

Female infertility is a global medical condition that can be caused by various disorders of the reproductive system, including premature ovarian failure (POF), polycystic ovary syndrome (PCOS), endometriosis, Asherman syndrome, and preeclampsia. It affects the quality of life of both patients and couples. Mesenchymal stem cells (MSCs) have received increasing attention as a potential cell-based therapy with several advantages over other cell sources, including greater abundance, fewer ethical considerations, and high capacity for self-renewal and differentiation. Clinical researchers have examined the therapeutic use of MSCs in female infertility. In this review, we discuss recent studies on the use of MSCs in various reproductive disorders that lead to infertility. We also describe the role of microRNAs (miRNAs) and exosomal miRNAs in controlling MSC gene expression and driving MSC therapeutic outcomes. The clinical application of MSCs holds great promise for the treatment of infertility or ovarian insufficiency and to improve reproductive health for a significant number of women worldwide.

Objective: Urinary catheters are known cause of urinary morbidities. The longer the catheter is retained, the greater the risk for contamination and infection. An increasing body of literature suggests routine practice of catheterization and retaining it for 24 hours does not add any procedural advantage. Thus, we sought to study outcomes in relation to early vs. delayed removal of urinary catheters following cesarean section. Methods: We randomly assigned 116 patients into early and delayed removal of urinary catheter groups. In the early group, catheter was removed immediately after the procedure and in the delayed removal group, catheter was removed 24 hours later. Clinical outcomes were measured in terms of significant bacteriuria 72 hours postop, voiding difficulties, urinary retention, mobilization time, length of hospital stay, and patient satisfaction. Results: Study revealed higher incidence of bacteriuria in the delayed removal group (32.8% vs. 15.5%, P = 0.030). Urinary frequency was also higher (34.6% Vs. 8.6%, P=0.001). However, there were no difference between the two groups in other urinary complaints including dysuria and urgency (P = 0.103 & P = 0.087). Urinary retention was more frequent in the early group, but difference was not significant (P = 0.080). Patients with immediate removal of the urinary catheter had early ambulation and early discharge from hospital (P = 0.001 and P = 0.040) and were generally satisfied with the procedure (P= 0.010). Conclusion: Our study showed that immediate removal of urinary catheter was associated with lower urinary complications, shorter length of hospitalization and associated cost.

Identified by the eponym “Edwards’ Syndrome,” trisomy 18 (T18) represents the second most common autosomal trisomy after T21. The pathophysiology underlying the extra chromosome 18 is a nondisjunction error, mainly linked with the advanced maternal age. More frequent in female fetuses, the syndrome portends high mortality, reaching a rate of 80% of miscarriages or stillbirths. The three-step evaluation includes first trimester screening for fetal aneuploidy using a combination of maternal age, fetal nuchal translucency thickness, fetal heart rate and maternal serum free ß-hCG and PAPP-A; followed by the research for fragments of fetal DNA in maternal blood; and, finally, invasive techniques leave to the established diagnosis. Starting with the first trimester scan, selected ultrasound findings should be investigated to define not only the impact of the genetic problem on the fetus, but also to address the prenatal counselling. Previous series underline that T18 is not uniformly lethal. An active dialogue on the choices in the management of infants with T18 has emerged, sustained by the transition from the comfort care to the intervention attitude. Survival rates for individuals with supposedly fatal conditions have increased. In this novel scenario, an ad hoc counselling is pivotal. To support it, a comparative analysis by pictorial assays between ultrasound and autopsy findings could be beneficial. We provide an illustrative tool from a clinical case managed in early second trimester, with the purpose to strive a balanced approach in the hard choice faced by couples of fetuses with T18.

There is accumulating evidence that prenatal exposure to air pollution disturbs fetal growth and development, but little is known about these effects in cold climates or their season-specific or joint effects. Our objective was to assess independent and joint effects of prenatal exposure to specific air pollutants on the risk of low birth weight (LBW). We utilized the 2568 children of the Espoo Cohort Study, born between 1984 and 1990, and living in the City of Espoo. We conducted stratified analyses for births during warm and cold seasons separately. We analyzed the effect estimates using multi-pollutant Poisson regression models with risk ratio (RR) as the measure of effect. The risk of LBW was related to exposure to CO and (adjusted RR 1.44, 95% CI: 1.04-2.00) and exposure to O3 in the spring-summer season (1.82, 1.11-2.96). There was also evidence of synergistic effects between CO and O3 (relative risk due to interaction, RERI, all year 1.08, 95% CI: 0.27-4.94, spring-summer 3.97, 2.17-25.85) and PM2.5 and O3 (all year 0.72, -0.07-3.60, spring-summer 2.80, 1.36-19.88). We present new evidence of both independent and joint effects of prenatal exposure in a cold climate on the risk of LBW at low levels of air pollution.

There is limited data on pregnancy outcomes in Pompe Disease (PD) resulting from deficiency of the lysosomal enzyme acid alpha-glucosidase. Late-onset PD is characterized by progressive proximal muscle weakness and decline of respiratory function secondary to the involvement of the respiratory muscles. In a cohort of twenty-five females, the effects of both PD on the course of pregnancy and the effects of pregnancy on PD were investigated. Reproductive history, course of pregnancy, use of Enzyme replacement therapy (ERT), PD symptoms, and outcomes of each pregnancy were obtained through a questionnaire. Among 20 subjects that reported one or more pregnancies, one subject conceived while on ERT and continued therapy through two normal pregnancies with worsening of weakness during pregnancy and improvement postpartum. While fertility was not affected, pregnancy may worsen symptoms, or cause initial symptoms to arise. Complications with pregnancy or birth were not higher, except for an increase in the rate of stillbirths (3.8% compared to the national average of 0.2-0.7%). Given small sample size and possible bias of respondents being only women who have been pregnant, further data may be needed to better analyze the effects of pregnancy on PD, and the effects of ERT on pregnancy outcomes.

Endometrial Cancer (EC) is the sixth most commonly occurring cancer in women with 380 000 cases in 2018. Sadly, EC morbidity and mortality are continuously increasing, therefore the medical society have a substantial need for an accurate and inexpensive diagnostic test for EC early detection and a prognostic tool for treatment planning and evaluation. Considering experience with different types of cancers C-reactive protein (CRP) appears to be a promising diagnostic and prognostic factor. Aiming to investigate its potential and in view of EC authors, this paper reviewed the following databases for metanalysis, randomized controlled trials and review articles published up to June 2020: Pubmed, Scopus, Google scholar and ClinicalKey. Studies indicate CRP >3.33 mg/l correlate with EC incidence with HR = 2.29 (p<0.05). Moreover, High-sensitivity CRP assay allows to detect CRP in very low concentrations and distinguish patients with endometriosis, soft tissue sarcomas and possibly EC. Preoperational and postoperational CRP, as well as its dynamic change are independent prognostic factors for EC and are more reliable if analyzed together. However, CRP-to-albumin ratio as well as Glasgow Prognostic Scale have greater prognostic value that CRP alone. Additionally, CRP is possibly a mediator of carcinogenesis and cancer progression through activation of inter alia FcgRs/MAPK/ERK, FcgRs/IL-6/AKT/STAT3 and FcgRs/NF-κB/NLRP3 pathways.

Downregulated microRNA-142-3p signaling contributes to the pathogenesis of endometriosis [1] [2], an invasive disease where the lining of the uterus grows at ectopic locations, by yet incompletely understood mechanisms. Using bioinformatics and in vitro assays, this study identifies cytoskeletal regulation and integrin signaling as two relevant categories of miR-142-3p targets. qPCR revealed that miR-142-3p upregulation in St-T1b cells downregulates ROCK2, CFL2, RAC1, WASL and ITGAV. qPCR and Western-blotting showed miR-142-3p effect on WASL and ITGAV was significant also in primary endometriotic stroma cells. Luciferase reporter assays in ST-T1b cells then confirmed direct regulation of ITGAV and WASL. On the functional side, miR-142-3p upregulation significantly reduced ST-T1b cell size, the size of vinculin plaques, migration through fibronectin-coated transwell filters and the ability of ST-T1b and primary endometriotic stroma cells to contract collagen I gels. These results suggest that miR-142-3p has a strong mechanoregulatory effect on endometrial stroma cells and its external administration reduces the invasive endometrial phenotype. Within the limits of an in vitro investigation, our study provides new mechanistic insights into the pathogenesis of endometriosis and provides a perspective for the development of miR-142-3p based drugs for inhibiting invasive growth of endometriotic cells.

Ovarian hypofunction or primary ovarian insufficiency (POI) is a common cause in the etiology of female infertility. It is a heterogeneous disorder, affecting approximately 1% of women before the age of 40. The characteristics of POI are menstrual disorders, including amenorrhea and delayed menstruation, accompanied by a raised gonadotrophin level and decreased estradiol level. In recent years, electrophysiology (EP) technology has been advancing rapidly in the diagnosis and treatments of numerous diseases. According to studies, bioelectrical stimulation (BES) therapy is an electrophysiology technology that plays significant roles in numerous diseases, including on the thin endometrium in patients with POI. In this review, the overall research progress of this electrophysiological technology has been discussed in relation to the advancement of primary ovarian insufficiency.

Background: Maternal mortality (MM) is a matter of serious concern in low income developing countries (LDCs). Perspective: A great reduction has been observed regarding the maternal deaths globally after huge efforts since 1990 todate. However, the situation continues to be either stagnant or worsening in developing countries, suggesting that the efforts to cope with this issue are either insufficient or not properly implemented. We need to first diagnose the problem areas that are a great hurdle in the road to success towards the reduction of MM. Postpartum haemorrhage and preeclampsia are one of the most common causes of MM. Malnutrition, neurological dysfunction and cancer are among the non-obstetric causes. Trained medical and paramedical staff can be of great help in this regard by increasing awareness among masses at grass root level. Target set by Millennium Development goal has minimized the MM by 44%. But it has not met the target set by Millenium Development Goals 5 and a lot of measures need to be taken in this regard. Conclusions: Majority of the MDs are preventable and can be avoided by adopting appropriate frameworks, linked data sets, surveillance, birth attendants training, preparation for births, etc. Delay in decision to get healthcare, access to healthcare center and receiving these facilities are the main factors in MM.

Anxiety, chronical stress and depression during pregnancy are considered to affect the offspring, presumably through placental dysregulation. We have studied the term placentae of pregnancies clinically monitored with the Beck’s Anxiety Inventory (BAI) and Edinburgh Postnatal Depression Scale (EPDS). A cutoff threshold for BAI/EPDS of 10 classed patients into an Index group (>10, n=23) and a Control group (<10, n=23). Cortisol concentrations in hair (HCC) were periodically monitored throughout pregnancy and delivery. Expression differences of main glucocorticoid pathway genes: i.e. corticotropin-releasing hormone (CRH), 11β-hydroxysteroid dehydrogenase (HSD11B2), glucocorticoid receptor (NR3C1), as well as other key stress biomarkers (Arginine Vasopressin, AVP and O-GlcNAc transferase, OGT) were explored in medial placentae using real-time qPCR and western blotting. Moreover, gene expression changes were considered for their association with HCC, offspring, gender and birthweight. A significant dysregulation of gene expression for CRH, AVP and HSD11B2 genes was seen in the Index group, compared to controls, while OGT and NR3C1 expression remained similar between groups. Placental gene expression of the stress-modulating enzyme 11β-hydroxysteroid dehydrogenase (HSD11B2) was related to both hair cortisol levels (Rho= 0.54; p<0.01) and the sex of the newborn in pregnancies perceived as stressful (Index, p<0.05). Gene expression of CRH correlated with both AVP (Rho= 0.79; p<0.001) and HSD11B2 (Rho= 0.45; p<0.03), and also between AVP with both HSD11B2 (Rho= 0.6; p<0.005) and NR3C1 (Rho= 0.56; p<0.03) in the Control group but not in the Index group; suggesting a possible loss of interaction in the mechanisms of action of these genes under stress circumstances during pregnancy.

BACKGROUND Krukenberg tumor is a rare metastatic tumor of the ovary with characteristic histopathological features known as signet-ring cells. It usually presents in women around 45 years of age, however, we present an uncommon case in a 38-year-old pregnant woman. We report this case because of the unusual findings, the uncommon presentation in this younger age bracket, its diagnostic challenge, and poor prognosis. CASE PRESENTATION We describe an unusual case of a young woman with a history of painful vaginal bleeding at 13 weeks of pregnancy and treated for abruptio placentae. In her routine prenatal visit at week 20 of pregnancy, she was found to have a uterine fundus greater than her gestational age and referred to the hospital to discard polyhydramnios. At her admission a pelvic ultrasound was performed with normal findings of a 25 weeks pregnancy, also showing bilateral enlarged ovaries with heterogeneous echogenicity. The MRI showed a left tumoral lesion with dimensions of 22.1 x 13.6 x 16.3 cm, with lobulated regular contours with displacement of peripheral structures and mild compression of the bladder, the left ureter, and the inferior vena cava. The lesion was heterogeneous with irregular borders. The patient was programmed for a cesarean section; during the operation, the abdominal cavity showed bilateral tumors compatible with MRI findings, the ovarian tumors were sent to pathology and the results showed poorly differentiated mucinous adenocarcinoma (WHO III) with extensive signet-ring cells, an indicative of Krukenberg tumor. CONCLUSION: The case presented is rare due to its presentation in a pregnant woman without identifiable risk factors for gastric cancer. The incidental finding suggests the pregnancy masked the clinical presentation of gastric cancer, and the rapid deterioration of the patient is consistent with the aggressiveness described in the literature. The limited descriptions of this neoplasm in our country and the torpid evolution of this case highlight the importance of further studies of this cancer in Mexico.

Pregnancy-induced hypertension and preeclampsia are associated with significant maternal and fetal mortality. A better understanding of those diseases, delineation of molecular pathomechanism, and efficient treatment development are some of the most urgent tasks in obstetrics and gynecology. Recent findings indicate a crucial role of inflammation in the development of hypertension and preeclampsia. Although the mechanism is very complex and needs further explanation, it appears that high levels of cholesterol, urate, and glucose activates NLRP3 inflammasome, which produces IL-1β, IL-18 and gasdermin D. Production of these proinflammatory chemokines is a beginning of local and general inflammation, what results in sympathetic outflow, angiotensin II production, proteinuria, hemolysis, liver damage, immunothrombosis, and coagulopathy. NLRP3 inflammasome is a critical complex in the mediation of inflammatory response, which makes it crucial for the development of pregnancy-induced hypertension and preeclampsia, as well as its complications, such as placental abruption and HELLP syndrome. Herein presented the article delineate molecular mechanisms of those processes, indicating directions of future advance.

Abnormalities in male fertility constitute about 50% of all infertility causes. According to some data, the quality of human semen has deteriorated by 50-60 % over the last 40 years. A high-fat diet and obesity, the development of which is encouraged by the western lifestyle, affects the structure of spermatozoa, but also the development of the offspring and their health in later stages of life. In obese individuals, disorders on the hypothalamic-pituitary-gonadal axis are observed, as well as elevated oestrogen levels with simultaneous decrease of testosterone, LH and FSH hormone levels. Healthy dietary models clearly correlate with better sperm quality and a smaller risk of abnormalities in parameters, such as sperm count, sperm concentration and motility, as well as lower sperm DNA fragmentation. Apart from mineral components such as zinc and selenium, the role of omega-3 fatty acids and antioxidant vitamins should be emphasized, since their action will be based primarily on the minimization of oxidative stress and inflammation process. Additionally, the incorporation of carnitine supplements and coenzyme Q10 in therapeutic intervention seems also promising. Therefore, it is advisable to have a varied and balanced diet based on vegetables and fruit, fish and seafood, nuts, seeds, whole-grain products, poultry and low-fat dairy products.

The potential for transmission of the SARS-CoV-2 virus during minimally invasive gynaecological procedures, such as hysteroscopy or laparoscopy, on the reproductive tract of patients with COVID-19 is not known. We examined existing data for prevalence of virus in the reproductive tract and other bodily fluids.

The potential for transmission of the SARS-CoV-2 virus during minimally invasive gynaecological procedures, such as hysteroscopy or laparoscopy, on the reproductive tract of patients with COVID-19 is not known. We examined existing data for prevalence of virus in the reproductive tract and other bodily fluids.

In this study, we wanted to discuss the acute coronary syndromes in the pregnant womens which are very important for life ofthe fetus. Spontaneous coronary artery dissection and management, which is the most common cause of acute coronary syndrome in pregnant women is also discussed. About 300 articles were examined and 35 articles which published in high quality journals with high level of evidence were chosen and this review was prepared.

Cervical cancer screening systems aim to detect established HPV infections early. However, if there are no high-grade lesions, the intervention choice is basically limited to observational follow-up with recommendations on life habits like diet, to favor infection control. Therefore, it is important to establish specific feeding guidelines that provide clear evidence about the benefit they may bring against HPV infections. The present study evaluates the benefits of nutritional supplementation with a casein hydrolysate-based formula in patients with HR-HPV infection, compared with a non-supplemented control group. A total of 118 patients completed 6 months of follow-up. Significant differences between supplemented and control groups were observed for total or partial HR-HPV clearance at 6 months (74.6% vs 35.6%). Supplemented patients also suffered a lower occurrence of new intracervical lesions (0% vs 28.6%), a significantly greater resolution (67.4% vs 41.9%) and less progression of pre-existing lesions (4.7% vs 9.7%) at 6 months. An increase in the effectors of cellular immunity that could be responsible for their effect was also observed in supplemented patients. We conclude that nutritional supplementation with this casein hydrolysate-based formula could improve the outcomes of observational management of HPV infection.

Background: Effectiveness of Anastrozole and levonorgestrel-releasing intrauterine device (LNG-IUD, Mirena®) in the treatment of endometriosis. Methods: Randomized clinical trial. Elegibility criteria: Endometriomas >3×4 cm, CA-125>35 U/mL and symptoms suggestive of endometriosis. Thirty-one women were randomized to anastrozole+Mirena®+Conservative Surgery(CS) (n=8), anastrozole+Mirena®+transvaginal ultrasound-guided puncture-aspiration(TUGPA) (n=7), Mirena®+CS (n=9), or Mirena®+TUGPA (n=7). Interventions: Anastrozole 1 mg/day and/or only Mirena® for 6 months. CS or TUGPA one month after starting medical treatment. Results: A significant improvement in symptoms during the treatment (difference of 43%, 95% CI 29.9-56.2) occurred, which was maintained at 1 and 2 years. It was more significant in patients treated with anastrozole. For CA-125, the most significant decrease was observed without anastrozole. After CS for endometriosis, a reduction of findings of endometriomas and long-term recurrences occurred, with or without anastrozole, although anastrozole seems to delay recurrences. At 4,2±1,7 years, 88% of the patients who underwent CS were asymptomatic, compared to only 21% if TUGPA was performed, with or without anastrozole (p=0.019). Conclusion: Dosing anastrozole for 6 months, starting one month before CS of endometriosis, reduces more significantly the painful symptoms and delays recurrences, but has no other significant advantages over the single insertion of LNG-IUD (Mirena®) during the same time.

This paper questions the potential shift of reproduction towards assisted reproductive technologies due to benefits provided by genetic manipulation of embryos. In order to examine the viability of such a shift and its implications from a regulatory perspective, we relied on two panels of experts from Israel and Spain, using the Delphi method and a series of in-depth interviews. We anticipate, at a first stage, a continuous-steady growth in the use of IVF, supplemented by preimplantation genetic diagnosis and the introduction of CRISPR/Cas. At a second stage, attracting a growing share of fertile people would require developments in genomics. While it is unclear whether these developments will fully materialize, they could be replaced by technoscientific imaginaries generating perceived benefits. We conclude that the regulation of reproductive genetics is becoming more critical and complex. The aim should be to ensure good practices and equity, while providing more information to the public. A broad and inclusive societal debate may overcome the difficulty of drawing a clear line between medical uses and non-medical uses of genetic selection and engineering and may contribute to finding the right balance between allowing autonomous decisions of patients and protecting the public interest.

Preeclampsia (PE) is characterized by a series of clinical features such as hypertension and proteinuria associated with endothelial dysfunction and the impairment of placenta vascular endothelial integrity. This study aimed to investigate the effect of serum copper (Cu) level on some angiogenesis-related factors including vascular endothelial growth factor-A (VEGF-A), soluble Fms-like tyrosine kinase-1 (sVEGF-R1), soluble endoglin (sEng) and cerruloplasmin (Cp) in Iraqi women with preeclampsia (PE) and control pregnant women. Therefore, 60 women with PE in addition to 30 healthy pregnant women were enrolled in the study. Serum concentration of sEng, VEGF-A, sVEGF-R1, and Cu in PE group significantly increased (p<0.05) in the PE group compared with that in the control group. Increased production of antiangiogenic factors, soluble VEGF-A and sEng contribute to the pathophysiology of PE, indicating the involvement of these parameters in the angiogenic balance in patients with PE. Tests for between-subject effects showed that the circulating angiogenesis factors and Cu were significantly associated with the presence of PE. Serum Cu level was significantly correlated with VEGF- A and VEGF-R1 levels but not with sEng. Multiple regression analysis revealed that only Cp and BP can significantly predict the complications in women with PE. In conclusion, serum Cu has a role in the angiogenesis in women with PE and may be a new drug target in the prevention or treatment of PE.

The focus of the presented work was to isolate and characterize circulating endometrial cells (CECs) enriched from peripheral blood (PB) of patients with diagnosed endometriosis to support endometriosis diagnosis and treatment. Material and Methods Blood samples (n=423) were tested for CECs presence. Subsequently, gene expression analysis (GEA) was carried out for CECs. In parallel, the presence and character of CECs was tested during phases of menstrual cycle (MC) (n= 11). CECs were isolated by size-based separation from 2x 8ml PB. Results CECs were detected in 78.4% of blood samples. In line with the revised American Fertility Society (rAFS) classification CECs presence was confirmed in all the acknowledged endometriosis stages: minimal, mild, moderate and severe. Surprisingly, the highest CEC negativity rate was reported for severe disease (21.1%). The highest CEC numbers were detected in the mid-secretory periods of MC, which corresponds with uterine lining decidualization. The cytomorphology of CECs captured during MC is changing between the epithelial, stromal and stem cell-like. CECs captured in mid-secretory period expressed KRT18, NANOG and VIM in higher amounts when compared to the genes in the proliferative phase of MC when KRT19 and ESR1 were mostly observed. GEA of the super-positive CECs samples (1000 CECs/8mL PB) revealed high expression of KRT18, VIM, NANOG and FLT1. The expression of these genes was elevated in the endometriosis tissue samples and endometrioma, too. Conclusion The panel of the identified CECs - genes could be tested in a prospective manner to confirm the predictive value of CECs in endometriosis diagnostics.

Plasma microRNAs are considered to be potential diagnostic biomarkers for endometriosis. Increasing evidence has shown that a huge amount of miRNAs are abnormally expressed in endometriosis plasma and play irreplaceable roles in diagnosis. The aim of the our study was to identify the differential expression of circular miRNA by reviewing the PubMed, ScienceDirect, and Cochrane databases between normal women and women with endometriosis and analyzing the miRNA data downloaded from the GEO database. Because of the differential miRNA expression in this review, we evaluated the diagnostic values of the differentially expressed miRNAs, particularly during the menstrual phases. According to the cut-off criteria with |log 2 FC|>1.0 and P < 0.05, 36 differentially expressed miRNAs were identified, including 13 upregulated miRNAs and 23 downregulated miRNAs. We developed miR-155, miR-574, miR-23a, and miR-520d via a Venn diagram. Functional enrichment analysis considered that the target miRNAs might be involved in various pathways related to endometriosis, including neurotrophin, Hippo, oocyte meiosis, ubiquitin mediated proteolysis, HTLV-Infection, FoxO, and Rap1 signaling pathways. CTNNB1, MYC, and ES R1 of transcription factors were related to the differentially expressed miRNAs. In summary, our study suggested that a four-miRNA could be included as a prognostic marker in endometriosis.

This study aimed to evaluate the impact of selected pregnancy pathologies statistically depending on overweight/obesity and excessive maternal weight gain during pregnancy on women who gave birth in the years 2013–2015 at the Second Department of Gynecology and Obstetrics at the University Hospital in Bratislava, Slovakia. In a retrospective study, we analyzed data gathered from the sample, which consisted of 7,122 women. Our results indicate a positive statistical dependency of the groups of women with overweight and obesity and gestational hypertension (adjusted odds ratio [AOR]=15.3; 95% CI 9.0−25.8 for obesity), preeclampsia (AOR=3.4; 95% CI 1.9−6.0 for overweight and AOR=13.2; 95% CI 7.7−22.5 for obesity), and gestational diabetes mellitus (AOR=1.9; 95% CI 1.2−2.9 for overweight and AOR=2.4; 95% CI 1.4−4.0 for obesity). A higher incidence of pregnancies terminated by cesarean section was observed in the group of obese women. Gestational weight gain above the IOM (the Institute of Medicine) recommendations was associated with a higher risk of pregnancy terminated by C-section (AOR=1.2; 95% CI 1.0−1.3), gestational hypertension (AOR=1.7; 95% CI 1.0−2.7), and infant macrosomia (AOR=1.7; 95% CI 1.3−2.1). Overweight and obesity during pregnancy significantly contribute to the development of pregnancy pathologies and increased incidence of cesarean section. Systematic efforts to reduce weight before pregnancy through pre-pregnancy dietary counseling, regular physical activity, and healthy lifestyle should be the primary goal.

Growing body of evidence endorse the hypothesis of a protective role played by the in-utero environment on a suitable fetal programming, mainly sustained by fitting maternal diet. Our purpose was to assess the linkage between maternal food intake and poor obstetric results, with a special focus on typical Italian food. A cross sectional study including delivering women was designed. A self-reported questionnaire about socio-demographic data, obstetric history, and food frequency intake during pregnancy was administrated. A composite of adverse perinatal outcomes (APO) was constructed. Statistically significant differences were found between APO and control group in smoking habit (9.7 vs. 3.2%, p=0.045) and BMI at delivery (27.9±4.9 vs. 26.9±3.9, p=0.003). Women complicated by any or more APOs reported increased rates of pasta (5.3± 3.6 vs.4.4±1.9 times per week, p<0.001) and pizza (1.9±3.4 vs. 1.1±0.6, p<0.001) intake, with lower consumption of vegetables (5.4±3.9 vs. 7.1±2.9, p<0.001). By logistic regression analysis and after adjustments for maternal age, ethnicity, SES, maternal BMI at delivery, excessive ingestion of pizza (aOR 1.676, 95%CI 1.199-2.343, p=0.033), but not pasta (aOR 1.077, 95%CI 0.950-1.211, p=0.244), was found associated with APO. Vegetable consumption showed a protective role in reducing APOs (aOR 0.897, 95%CI 0.818-0.985, p=0.022). Nutrition in pregnancy should minimalize pizza intakes.

In last decades, growing migration flows have modified the obstetric clinical care, requiring specific attention by health care systems. The aim was to describe the phenomenon focusing on miscarriage (pregnancy loss at <20 weeks). Patients admitted for care at miscarriage in a six-year period (2012-17) were revised. Miscarriage rates in all ethnic groups, dichotomized in early (within the first 12 weeks of gestation) and late (at <20 weeks) pregnancy loss. Associations between women's characteristics (age, parity, inter-pregnancy interval (IPI)) were explored to elucidate any differences. A total of 1,940 patients were included, segregated in early (n = 1769, 91.2%) and late (n = 171, 8.8%) pregnancy losses. Caucasian ethnicity was the most common (87.9%), leaving the minority groups to 12.1%. Maternal age was higher among Caucasians women than other subgroups, in contrast to Asiatic patients. Nulliparity was observed in 1045 (53.9%) patient, more widespread among Caucasian and Maghrebins. A positive obstetric history counting at least one miscarriage was frequent, ranging from 22.2% to 75%, in particular among Asiatic women, while the recurrence in Caucasians. In Afro-Carribeans the most relevant rate of late miscarriage was found. By multiple regression modelling, maternal age, nulliparity and Afro-Carribean were identified as determinants. Maternal ethnicity should be considered in the management of pregnancy losses in combination with already well-defined risk factors, including age at miscarriare and nulliparity.

Hyperandrogenism and insulin resistance are co-pathologies of polycystic ovary syndrome (PCOS). Recent evidence has suggested that elevated local cortisol levels are associated with ovarian and endometrial insulin resistance in hyperandrogenic PCOS patients, but the molecular mechanisms underlying these clinical findings remain unclear. We and others have used chronic treatment with human chorionic gonadotropin (hCG) and insulin to create an in vivo rodent model for the onset and development of PCOS-like phenotypes. Here, we aimed to determine whether the molecular mechanisms of glucocorticoid receptor (GR) signaling, mitochondrial function, and local inflammation in the ovary and uterus are intrinsically different in PCOS-like rats compared to controls. In both the ovary and the uterus, decreased expression of two GR protein isoforms was concurrent with increased expression of Fkbp51 but not Fkbp52 mRNA in PCOS-like rats compared to controls. However, PCOS-like rats exhibited an opposite regulation of Hsd11b1 or Hsd11b2 mRNAs in the two tissues. Further, the expression of several oxidative phosphorylation-related protein components was decreased in the PCOS-like ovary and uterus, but surprisingly the expression of many genes involved in mitochondrial function and homeostasis was increased in the same tissues and animals. Additionally, PCOS-like rats showed the increased expression of ovarian and uterine NFκB signaling proteins and Tnfaip3 mRNA. In PCOS-like rats, while similar decreased expression of Il1b, Il6, and Mmp2 mRNAs was seen in the ovary and uterus, the opposite regulation of Tnfa, Ccl2, Ccl5, and Mmp3 mRNA expression was observed in the two tissues. Both ovaries and uteri from PCOS-like animals showed increased collagen deposition compared to controls. Collectively, our observations suggest that hyperandrogenism and insulin resistance disrupt ovarian and uterine GR activation and trigger compensatory or adaptive effects for mitochondrial homeostasis, allowing tissue-level maintenance of mitochondrial function in order to limit ovarian and uterine dysfunction. Our study also suggests that hyperandrogenism and insulin resistance-induced activation of NFκB signaling resulting in aberrant regulation of inflammation-related gene expression might be tissue specific in female reproductive tissues.

Recent policy and service provision recommends a woman-centered approach to maternity care and encourages the development of personalized models of clinical assistance. As ethnicity has been recognized as determinant in the risk calculation of some obstetric complication, our aim was to assess costs for birth assistance according to the maternal ethnicities. In a five-year period (2012-16) all women admitted for delivery at the Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario ‘A. Gemelli’ IRCCS, Rome, Italy were investigated. Economic evaluations were performed by using the ‘diagnosis-related group’ (DRG) approach. Cost analysis was completed by including maternal ethnicity, delivery mode and perinatal complications. A total of 18,093 patients were involved in the analysis. An overall care expense of €42.663.481 was calculated. Caucasian was the main ethnicity (90.7%), leaving the minority groups to 9.3%. Vaginal delivery (VD) was the most common mode of delivery in all ethnic clusters, with a global rate of 59.6%. Not including Asiatic women, increased CS rates were recorded in all minority ethnic groups (Maghreb (51.5%) and Afro-Caribbean (47.8%)). A double incidence of complicated VD was observed in the minority groups, primarily among Afro-Caribbean (69.9%), followed by Asiatic (64.1%), Maghreb (63.2%) and Latin-America (62.7%) patients. By logistic regression, Afro-Caribbean delivering women had a significant increased risk of complicated CS among all subgroups. Minority groups (Afro-Caribbean, in particular) increase the health care cost for birth assistance due to higher incidence of adverse perinatal outcomes.

Current prenatal genetic evaluation showed a significantly increase in non-invasive screening and the reduction of invasive diagnostic procedures. To evaluate the diagnostic efficacy on detecting common aneuploidies, structural chromosomal rearrangements and pathogenic copy number variants (pCNV), we performed a retrospective analysis on a case series initially analyzed by aneuvysion fluorescence in situ hybridization (FISH) and karyotyping then followed by array comparative genomic hybridization (aCGH). Of the 386 cases retrieved from the past decade, common aneuploidies were detected in 137 cases (35.5%), other chromosomal structural rearrangements were detected in four cases (1%), and pCNV were detected in five cases (1.3%). The relative frequencies for common aneuploidies suggested a under detection of sex chromosome aneuploidies. Approximately 9.5% of cases with common aneuploidies showed a mosaic pattern. Inconsistent results between FISH and karyotyping were noted in cases with pseudo-mosaicism introduced by culture artifact or variable cellular proliferation from cells with mosaic karyotypic complements under in vitro cell culture. Based on findings from this case series, cell-based FISH and karyotyping should be performed to detect common aneuploidies, structural chromosomal abnormalities, and mosaic pattern. DNA-based aCGH and reflex FISH should be performed to detect and confirm genomic imbalances and pCNV. Practice points to ensure the diagnostic accuracy and efficacy were summarized.

Beginning with the discovery of the BRCA ovarian cancer susceptibility genes and subsequent detailed examination of risk reduction salpingo-oophorectomy (RRSO) specimens, a new paradigm of ovarian carcinogenesis has unfolded with attention to the distal fallopian tube. The primary focus has been an early cancer in the fallopian tube which is seen in virtually all incidentally discovered high-grade serous cancers in asymptomatic women. This high-frequency of tubal involvement in early serous cancer - serous tubal intraepithelial carcinoma or STIC - has galvanized attention to this organ as a primary source of this disease. However, an enduring mystery has been the relatively low frequency of STIC in fallopian tubes of women with advanced malignancy. This paradox, a high-frequency of tubal involvement early and a low-frequency late in the disease process has spurred interest in other potential sources, such as the ovarian surface or secondary Mullerian system. However, because essentially all high-grade serous carcinomas are linked by TP53 mutations, and because fallopian tubes frequently contain early serous proliferations (ESPs) with these mutations, attention has turned to the possibility that nonmalignant but TP53 mutated tubal epithelium could be responsible for an eventual malignancy. Recent data have shown evidence of lineage continuity between ESPs and concurrent serous carcinomas prompting the concept of "precursor escape". This creates a 2nd component of the paradigm by which cells from early lesions can escape the fallopian tube and undergo future malignant transformation later, emerging suddenly as widespread malignancy. This dualistic model thus explains the paradox and opens new questions pertaining to the challenge of both early detection and prevention of this lethal malignancy.

Beginning with the discovery of the BRCA ovarian cancer susceptibility genes and subsequent detailed examination of risk reduction salpingo-oophorectomy (RRSO) specimens, a new paradigm of ovarian carcinogenesis has unfolded with attention to the distal fallopian tube. The primary focus has been an early cancer in the fallopian tube which is seen in virtually all incidentally discovered high-grade serous cancers in asymptomatic women. This high-frequency of tubal involvement in early serous cancer - serous tubal intraepithelial carcinoma or STIC - has galvanized attention to this organ as a primary source of this disease. However, an enduring mystery has been the relatively low frequency of STIC in fallopian tubes of women with advanced malignancy. This paradox, a high-frequency of tubal involvement early and a low-frequency late in the disease process has spurred interest in other potential sources, such as the ovarian surface or secondary Mullerian system. However, because essentially all high-grade serous carcinomas are linked by TP53 mutations, and because fallopian tubes frequently contain early serous proliferations (ESPs) with these mutations, attention has turned to the possibility that nonmalignant but TP53 mutated tubal epithelium could be responsible for an eventual malignancy. Recent data have shown evidence of lineage continuity between ESPs and concurrent serous carcinomas prompting the concept of "precursor escape". This creates a 2nd component of the paradigm by which cells from early lesions can escape the fallopian tube and undergo future malignant transformation later, emerging suddenly as widespread malignancy. This dualistic model thus explains the paradox and opens new questions pertaining to the challenge of both early detection and prevention of this lethal malignancy.

The current clinical model for genetic-testing is based on clinical-criteria/family-history(FH) and a pre-defined mutation probability threshold. It requires people to develop cancer before identifying unaffected individuals in the family to target prevention. This process is inefficient, resource intense and misses >50% of individuals/mutation carriers at risk. Population genetic-testing can overcome these limitations. It is technically feasible to test populations on a large scale; genetic-testing costs are falling and the acceptability/awareness is rising. MEDLINE/EMBASE/Pubmed/CINAHL/PsychINFO databases were searched using a free-text and MeSH terms; reference lists of publications retrieved screened; additionally web-based platforms, Google, and clinical-trial registries were searched. Quality of studies were evaluated using appropriate check-lists. A number of studies have evaluated population-based BRCA-testing in the Jewish-population. This has been found to be acceptable, feasible, clinically-effective, safe, associated with high satisfaction rates and extremely cost-effective. Data support change in guidelines to population-based BRCA-testing in the Jewish-population. Population panel-testing for BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 gene mutations is the most cost-effective genetic-testing strategy in general-population women and can prevent thousands more breast/ovarian cancers than current clinical-criteria based approaches. A few ongoing studies are evaluating population-based genetic-testing for multiple cancer susceptibility genes in the general-population but more implementation studies are needed. A future population-testing programme could also target other chronic diseases.

Purpose: Expanded carrier screening (ECS) informs couples of their risk of having offspring affected by certain genetic conditions. Limited data exists assessing the actions and reproductive outcomes of at-risk couples (ARCs). We describe the impact of ECS on planned and actual pregnancy management in the largest sample of ARCs studied to date. Methods: Couples who elected ECS and were found to be at high risk of having a pregnancy affected by at least one of 176 genetic conditions were invited to complete a survey about their actions and pregnancy management. Results: Three hundred ninety-one ARCs completed the survey. Among those screened before becoming pregnant, 77% planned or pursued actions to avoid having affected offspring. Among those screened during pregnancy, 37% elected prenatal diagnostic testing (PNDx) for that pregnancy. In subsequent pregnancies that occurred in both the preconception and prenatal screening groups, PNDx was pursued in 29%. The decision to decline PNDx was most frequently based on the fear of procedure-related miscarriage, as well as the belief that termination would not be pursued in the event of a positive diagnosis. Conclusions: ECS results impacted couples’ reproductive decision-making and led to altered pregnancy management that effectively eliminates the risk of having affected offspring.

Consumption of coffee by women early in their pregnancy has been viewed as potentially increasing the risk of miscarriage, low birth weight, and childhood leukemias. Many of these reports of epidemiologic studies have not acknowledged the potential biases inherent in studying the relationship between early-pregnancy-coffee consumption and subsequent events. I discuss five of these biases, recall bias, misclassification, residual confounding, reverse causation, and publication bias. Each might account for claims that attribute adversities to early-pregnancy-coffee consumption. To what extent these biases can be avoided remains to be determined. At a minimum, they need to be acknowledged wherever they might account for what is reported.

Background: As noninvasive prenatal screening usage grows in the general obstetrics setting, proper patient education on the screen’s benefits and limitations is needed. Objective: Describe the use of a technology platform designed for large-scale dissemination of noninvasive prenatal screening information and results. Study Design: The technology platform functioned as follows: Patients were emailed a link to an noninvasive prenatal screening general-education video upon laboratory receipt of a test requisition. Providers were then notified upon availability of patients’ results. If noninvasive prenatal screening results were negative, the patient was sent an automated email with instructions to access results through a secure portal where she could watch tailored informational videos, request “on-demand” or scheduled genetic counseling, or decline any further services. If genetic counseling was elected, a summary of the session was sent to the ordering provider and patient upon completion. If noninvasive prenatal screening results were positive, either the ordering provider or a board-certified genetic counselor contacted the patient directly to communicate test results and provide counseling. The number and type of results issued through the platform, the number and type of genetic counseling consultations completed, and factors associated with requesting laboratory-delivered genetic counseling were tracked and analyzed for a 39-month period. Results: Over the study period, 67,122 noninvasive prenatal screening results were issued through the platform, and 4,673 patients elected genetic counseling consultations; 95.2% (n=4,450) of consultations were for patients receiving negative results. Over 70% (n= 3,370) of consultations were on-demand rather than scheduled. Median consultation time was 14 minutes for positive results and six minutes for negative results. A positive screen, advanced maternal age, family history, previous history of a pregnancy with a chromosomal abnormality, and other high-risk pregnancy were associated with the greatest odds of electing laboratory-delivered genetic counseling. Conclusions: By combining web education, automated notifications, and genetic counseling, we implemented a service that effectively facilitates results disclosure for ordering providers. These data demonstrate the capability to deliver noninvasive prenatal screening results, education, and counseling—congruent with management guidelines—to a large population, which is imperative to quality care as uptake increases.

Metformin use in pregnancy is increasing worldwide as randomised controlled trial (RCT) evidence is emerging demonstrating its safety and efficacy. The Metformin in Gestational Diabetes (MiG) RCT changed practice in many countries demonstrating that metformin had similar pregnancy outcomes to insulin therapy with less maternal weight gain and a high degree of patient acceptability. A multicentre RCT is currently assessing the addition of metformin to insulin in pregnant women with type 2 diabetes. RCT evidence is also available for the use of metformin for women with Polycystic Ovarian Syndrome and for non-diabetic women with obesity. No evidence of an increase in congenital malformations or miscarriages has been observed even when metformin is started before pregnancy and continued to term. Body composition and metabolic outcomes at two, seven and nine years have now been reported for the offspring of mothers treated in the MiG study. In this review, we will briefly discuss the action of metformin and then consider the evidence from the key clinical trials.

Background: The endocannabinoid system (ECS) is a very heterogeneous array consisting of many proteins like ligands, enzymes and receptors synthetized in various tissues and immunity cells. The main endogenous ligands are unsaturated fatty acid derivatives like anandamide(AEA), 2-arachidonoylglycerol(2-AG), but many others are under study. Endocannabinoids are involved in both physiological and pathological conditions. ECS plays an important role in the regulation of main processes which lead to cancer and also in sex steroid hormone-related cancers. Methods: With focus on gynaecological cancers, main papers and review articles, up to April 2018, on the role of the ECS, were acquired by PubMed searches using the search terms: ‘cancer’, ‘cannabinoid’, ‘endocannabinoid’, ‘gynaecology’ and ‘malignancy’. Results: The review of recent literature data showed the involvement of the endocannabinoid system in numerous physiological and pathological conditions of the female genital tract up to the development of gynaecological malignancy as cervical, endometrial and ovarian cancer. Conclusions: The endocannabinoid system has an important role in antitumor actions involving different signalling receptor and receptor-independent pathways. It represents an exciting challenge to researchers for its potential use in diagnosis and treatment of all gynaecological malignancies

Background: Maternal near-miss refers to a situation where a woman who nearly died but survived from severe life-threatening obstetric complications that occurred during pregnancy, childbirth or within 42 days of termination of pregnancy. It has been estimated that up to 9 million women survive obstetric complications every year. According to studies done around the world most mothers suffer from Near Miss due to the factors which includes, low socioeconomic status, patient related, health provider related, and health related and health institution related issues. Objectives: The objective of the study was to determine the proportion of maternal near misses and its associated factors in Selected Public Health Institutions of Keffa, Bench-Maji and Sheka Zones of South Nations Nationalities and Peoples Regional state, South West Ethiopia, 2017. Methodology: Hospital based cross-sectional study design was employed and simple random sampling techniques (Lottery Method) was used to select the study institution and Systematic sampling technique was used to select 845 study participants every 5^th interval. Information was collected by using pre-tested and structured interviewer administered questioner. Using SPSS version 21 software, descriptive statistics and bivariate logistic regression analysis was done and variables with p-value <0.2 were transferred to multivariate analysis and during Multivariate logistic regression analysis Variables with P-value < 0.05 were considered as statistically significant and AOR with 95% CI were used to control for possible confounders and to interpret the result. The results were summarized by tables, graphs and charts. Result: There were 5530 Live Births, 227 Sever Acute Maternal Morbidity cases of this 210 were Maternal Near-Misses cases and 17 were maternal deaths, 364 Maternal Near-Misses Events. The overall Maternal Near-Misses Proportion is 24.85%. The maternal Near-Misses outcome ratio was 41 cases/1,000 live births (LB); mortality ratio was 12.35cases/1 maternal death and 74.8/1000LB of mortality index. Parity, residence, distance of living place from hospital, ANC Follow up, duration of labor, and administrative related problems were found to have statistically significant associations. Conclusion: The proportion of Maternal Near-Misses is relatively high when compared to other regional studies and efforts should be done to lower the near-misses.

Fetal weight estimation before delivery is important in obstetrics, which assists doctors diagnose abnormal or diseased cases. Linear regression based on ultrasound measures such as bi-parietal diameter (bpd), head circumference (hc), abdominal circumference (ac), and fetal length (fl) is common statistical method for weight estimation but the regression model requires that time points of collecting such measures must not be too far from last ultrasound scans. Therefore this research proposes a method of early weight estimation based on expectation maximization (EM) algorithm so that ultrasound measures can be taken at any time points in gestational period. In other words, gestational sample can lack some or many fetus weights, which gives facilities to practitioners because practitioners need not concern fetus weights when taking ultrasound examinations. The proposed method is called dual regression expectation maximization (DREM) algorithm. Experimental results indicate that accuracy of DREM decreases insignificantly when completion of ultrasound sample decreases significantly. So it is proved that DREM withstands missing values in incomplete sample or sparse sample.

Persistent cervical infection with high-risk Human papillomaviruses (hrHPVs) is a necessary, but not sufficient, condition for the development of cervical cancer. Therefore, there are other co-factors facilitating the hrHPV carcinogenic process, one of which is smoking. In order to assess the effect of smoking on high-risk (hr) HPV DNA positivity and on the expression of HPV E7 oncoprotein, as a surrogate of persistent hrHPV infection, we used data from women recruited for the PIPAVIR project, which examined the role of E7 protein detection in cervical cancer screening. Women were tested for hrHPV DNA, using Multiplex Genotyping and E7 protein, using a novel sandwich ELISA method, and gave information on their smoking habits. Among 1473 women, hrHPV prevalence was 19.1%. The odds ratio (OR) for hrHPV positivity of smokers compared to non-smokers was 1.785 (95%CI: 1.365-2.332, p<0.001). The ORs for E7 positivity, concerning hrHPV positive women, ranged from 0.720 to 1.360 depending on the E7 detection assay used, but this was not statistically significant. Smoking increases the probability of hrHPV infection, and smoking intensity is positively associated to this increase. Smoking is not related to an increased probability of E7 protein positivity for hrHPV positive women.

The traditional herbal medicine, Hochu-ekki-to, has been shown to have preventive effects on viral infection and stress. This study aimed to evaluate the clinical effects of Hochu-ekki-to on two stress-related rat models of polycystic ovarian syndrome. Female Sprague-Dawley rats were divided into control and treatment groups, the latter of which were subjected to stress induced by exposure to adrenocorticotropic hormone (ACTH) or cold temperatures. After these stress inductions, rats were orally treated with dissolved Hochu-ekki-to once per day for 7 days. Rats subjected to the two different stressors exhibited upregulation of steroid hormone receptors (in ovaries) and reproductive hormones (in blood), and consequent stimulation of abnormal follicle development accompanied by elevation of Hsp 90 expression (in ovaries). Treatment with Hochu-ekki-to for 7 days after stress induction increased immune functions, reduced the stress-induced activation of Hsp 90, and normalized the levels of the tested steroid hormone receptors and reproductive hormones. Our findings suggest that stress stimulations may promote the activation of Hsp 90 via the dysregulation of steroid hormone receptors and reproductive hormones, but that post-stress treatment with Hochu-ekki-to improves reproductive and immune functions in the ovaries of stressed rats.

Oxidative and nitrosative stress are a common problem when manipulating gametes in vitro. In vitro development in mammalian embryos is highly affected by culture conditions, especially by reactive oxygen species (ROS) and reactive nitrogen species (RNS), because its absence or over production causes embryo arrest and changes in gene expression. Melatonin in gamete co-incubation during IVF has deleterious or positive effects depending on the concentration used in culture medium, demonstrating the delicate balance that must exist between antioxidant and pro-oxidant activity. Further research is needed to better understand the possible impact of melatonin on the different IVP steps in domestic animals, especially in seasonal breeds where this neuro-hormone system highly regulates its reproduction physiology.

Long-term safety of a nutraceutical combination based on agnus castus and magnolia extracts combined with soy isoflavones (SI) and lactobacilli, and effectiveness on vasomotor symptoms and sleep disorders in postmenopausal women, were assessed. A controlled study was carried-out in menopausal women comparing this nutraceutical combination (ESP group) with formulation containing isoflavones alone (C group), at the dosage recommended. Kuppermann index, PSQI, and SF-36 were determined at baseline, 3, 6 and 12 months. Endometrial thickness, mammary density and liver function were evaluated at baseline and after 12 months. 180 women (100 in ESP group and 80 in C group, mean age 55.5 years, in menopause for about 36 months) were enrolled in the study. At the treatment end, mammary density, endometrial thickness, and hepatic function did not show substantial differences between groups. Kuppermann index, and particularly hot flushes, were progressively and significantly decreased in frequency and severity during ESP versus C treatment. No adverse events were observed. Agnus castus and magnolia, combined with SI + lactobacilli, can effectively and safely be used in symptomatic postmenopausal women, mainly when quality of sleep is the most disturbing complaint. Endometrium, mammary glands and liver function, were unaffected after 12 months treatment.