The effects of time-restricted eating alone or in combination with probiotic supplementation in comparison with a calorie-restricted diet on endocrine and metabolic profiles in women with polycystic ovary syndrome: A randomized clinical trial.

AIM: To assess the impact of intermittent fasting, with or without probiotic supplementation, versus a calorie-restricted diet on anthropometric measures, metabolic status and gonadal variables in women with polycystic ovary syndrome (PCOS). METHODS: This is a randomized, placebo-controlled, parallel-arm clinical trial. The effects of the 14:10 early time-restricted eating (eTRE) strategy alone or combined with probiotics, on obese women with PCOS, were investigated. Participants were divided into three groups: eTRE plus probiotics (n = 30), eTRE plus placebo (n = 30) and a control group following a standard three-meal-per-day diet with daily calorie restriction (DCR) (n = 30). Over 8 weeks, various anthropometric, metabolic, menstrual and gonadal variables were assessed. RESULTS: A total of 90 individuals were included in the study, with a mean body weight of 81.4 kg, and a mean age of 30 years. Mean (standard deviation) weight loss was not different between the groups at week 8 (TRE + probiotic: -2.2 [1.6] kg vs. TRE + placebo: -2.9 [2.7] kg vs. DCR: -2.5 [1.7] kg). Results revealed that, while all three regimes led to reductions in body weight, body mass index, vascular risk indicators, hirsutism and acne scores, there were no statistically significant differences between the eTRE groups and the control group in terms of weight loss, or improvements in metabolic, menstrual and gonadal variables (P > .05). Additionally, combining probiotics with eTRE did not benefit hormonal and cardiometabolic factors (P > .05). CONCLUSIONS: The eTRE alone or eTRE plus probiotics did not result in significantly greater weight loss or improvements in metabolic, menstrual and gonadal variables compared with the standard three-meal DCR diet.

JAK/STAT3 pathway promotes proliferation of ovarian aggregate-derived stem cells in vitro.

BACKGROUND: The accurate identification and isolation of ovarian stem cells from mammalian ovaries remain a major challenge because of the lack of specific surface markers and suitable in vitro culture systems. Optimized culture conditions for in vitro expansion of ovarian stem cells would allow for identifying requirements of these stem cells for proliferation and differentiation that would pave the way to uncover role of ovarian stem cells in ovarian pathophysiology. Here, we used three-dimensional (3D) aggregate culture system for enrichment of ovarian stem cells and named them aggregate-derived stem cells (ASCs). We hypothesized that mimicking the ovarian microenvironment in vitro by using an aggregate model of the ovary would provide a suitable niche for the isolation of ovarian stem cells from adult mouse and human ovaries and wanted to find out the main cellular pathway governing the proliferation of these stem cells. RESULTS: We showed that ovarian aggregates take an example from ovary microenvironment in terms of expression of ovarian markers, hormone secretion and supporting the viability of the cells. We found that aggregates-derived stem cells proliferate in vitro as long-term while remained expression of germline markers. These ovarian stem cells differentiated to oocyte like cells in vitro spontaneously. Transplantation of these stem cells in to chemotherapy mouse ovary could restore ovarian structure. RNA-sequencing analysis revealed that interleukin6 is upregulated pathway in ovarian aggregate-derived stem cells. Our data showed that JAK/Stat3 signaling pathway which is activated downstream of IL6 is critical for ovarian stem cells proliferation. CONCLUSIONS: We developed a platform that is highly reproducible for in vitro propagation of ovarian stem cells. Our study provides a primary insight into cellular pathway governing the proliferation of ovarian stem cells.

The potential causal effect of the pre-pregnancy dietary phytochemical index on gestational diabetes mellitus: a prospective cohort study.

BACKGROUND: Phytochemicals are non-nutritive bioactive compounds with beneficial effects on the metabolism of glucose. This study aimed to clarify the possible causal effect of the pre-pregnancy dietary phytochemical index (DPI) on gestational diabetes mellitus (GDM). METHODS: In this prospective cohort study 1,856 pregnant women aged 18-45 years who were in their first trimester, were recruited and followed up until delivery. The dietary intakes of participants were examined using an interviewer-administered validated 168-item semi-quantitative food frequency questionnaire (FFQ). Inverse probability weighting (IPW) of propensity scores (PS), estimated from the generalized boosted model (GBM) were used to obtain a adjusted risk ratio (aRR) for potential confounders. RESULTS: During the follow-up period, 369 (19.88%) women were diagnosed with GDM. DPI scores ranged from 6.09 to 89.45. There was no association between DPI scores and GDM (aRR: 1.01, 95% confidence interval [CI]: 0.92, 1.08; p trend = 0.922). When comparing DPI quartile 4 (most pro-phytochemical content) to quartile 1 (few phytochemical contents), there was no significant difference between them (aRR: 0.97; 95% CI: 0.75, 1.25; p = 0.852). Also, there was no significant difference between DPI quartile 3 and quartile 1 (aRR: 1.04; 95% CI: 0.81, 1.34; p = 0.741) as well as DPI quartile 2 and quartile 1 (aRR: 0.92; 95% CI: 0.71, 1.21; p = 0.593). CONCLUSIONS: Although this data did not support the association between pre-pregnancy DPI scores and GDM, further cohort studies to ascertain the causal association between them are warranted.

Derivation of hormone-responsive human endometrial organoids and stromal cells from cryopreserved biopsies.

The human endometrium is a dynamic tissue that undergoes cyclic changes in response to sex steroid hormones to provide a receptive status for embryo implantation. Disruptions in this behavior may lead to implantation failure and infertility; therefore, it is essential to develop an appropriate in vitro model to study endometrial changes in response to sex hormones. In this regard, the first choice would be human endometrial cells isolated from biopsies that could be used as monolayer cell sheets or to generate endometrial organoids. However, the need for fresh samples and short-time viability of harvested endometrial biopsy limits these approaches. In order to overcome these limitations, we sought to develop an efficient, simple, robust and reproducible method to cryopreserve human endometrial biopsies that could be stored and/or shipped frozen and later thawed to generate endometrial organoids and endometrial stromal cells (EnSCs). These cryopreserved biopsies could be thawed and used to generate simple endometrial organoids or organoids for co-culture with matched stromal cells that are functionally responsive to sex hormones as similar as the organoids generated from fresh biopsy. An optimal endometrial tissue cryopreservation method would allow the possibility for endometrial tissue biobanking to enable future organoid generation from both healthy tissues and pathological conditions, and open new venues for generate endometrial assembloids, consisting of epithelial organoids and primary stromal cells.

Gene expression and demographic analyses in women with the poor ovarian response: a computational approach.

PURPOSE: Poor response to ovarian stimulation (POR) typically is reflected as decreased follicular response and low estradiol (E2) levels following ovarian stimulation by FSH/HMG. Many genes are involved in oocyte maturation, and demographic features and lifestyle can affect the oocyte maturity and developmental competence. The present study was conducted to investigate the magnitude of gene expression and lifestyle habits in POR women as compared to healthy women, using different statistical and computational methods. METHODS: Fifty women in the two groups were studied. The study groups included POR women (n = 25) with 1-9 released oocytes, and the control group (normal women, n = 25) with 9-15 released oocytes. Quantitative PCR was used to estimate the expression of FIGLA, ZAR1, WNT4, LHX8, APC, H1FOO, MOS, and DMC1 genes in granulosa cells. RESULTS: The results showed no significant difference in the magnitude of the studied genes' expression and linear discriminant analysis did not differentiate the studied groups based on all the genes together. Redundancy analysis (RDA) and latent factor mixed model (LFMM) results produce no significant association between the genes' expression magnitude and the geographical variables of the patients' local habitat. Linear discriminant analysis (LDA) of the demographic features differentiated the two groups of women. CONCLUSION: Our results indicate that demographic features may have an effect on sample gene expression levels.

Human uterine fluid lavage-derived extracellular vesicle isolation: a comparative study for minimally invasive endometrial receptivity assessment.

RESEARCH QUESTION: Does pre-implantation uterine fluid lavage (UFL) of patients undergoing IVF and frozen embryo transfer (FET) affect implantation and clinical pregnancy rates? Which methods among ultracentrifugation, sucrose cushion and qEV column are suitable for isolating UFL extracellular vesicles? DESIGN: First, UFL was collected from 20 patients undergoing IVF and FET 2 days before embryo transfer as the case group. The control group consisted of 20 patients undergoing IVF and FET patients without lavage. All patients were monitored for 6 weeks. In the next step, the UFLs (n = 30) were collected and pooled. The UFL-derived extracellular vesicles were extracted by ultracentrifugation, sucrose cushion and qEV column methods and characterized. RESULTS: Preimplantation uterine lavage sampling did not affect implantation and clinical pregnancy rates. Extracellular vesicles were successfully isolated from UFL by all three methods. Scanning electron microscopy and dynamic light scattering analysis showed that the isolated vesicles were morphologically spherical. The qEV technique showed that they were smaller and homogenized in size. SDS-PAGE of extracellular vesicles showed a weaker albumin band in the qEV column. Western blot analysis indicated that the isolated extracellular vesicles by the qEV column were more immunoreactive for all the common extracellular vesicle markers (CD81, CD9, CD63, and TSG101). Six reference genes were compared by real-time polymerase chain reaction in the isolated extracellular vesicle subpopulations, and lowest cycle threshold value was observed for the 18SrRNA gene. CONCLUSIONS: The isolation of endometrial secretome extracellular vesicles is a minimally invasive procedure for individual assessment of endometrial receptivity and can be carried out during conception cycles along with transvaginal ultrasonography. Molecular analysis of UFL-derived extracellular vesicle components could suggest biomarkers to determine precise extracellular vesicle timing.

Metformin attenuates expression of angiogenic and inflammatory genes in human endometriotic stromal cells.

Endometriosis is a benign gynecological disease that is manifested by the presence and growth of endometrial cells and glands outside the uterine. Active angiogenesis, migration, and invasion of endometrial tissue outside the uterine are critical for the development of endometriosis and lead to the survival and growth of endometriotic lesions. Metformin, as an anti-diabetic agent, represents anti-angiogenic property. Here, we performed a study using human normal endometrial stromal cells (N-ESCs) from healthy endometrial tissue and human eutopic endometrial stromal cells (EU-ESCs) and ectopic endometrial stromal cells (ECT-ESCs) from endometriosis patients. ESCs were cultured and treated with different concentrations of Metformin (0-20 mmol/l) for 72 h to evaluate Metformin effect on cell viability, proliferation, migration was measured by methyl thiazolyl tetrazolium (MTT) assay and scratch test respectively as well as expression of angiogenesis and migration markers. The Metformin reduced cell migration, and proliferation of endometriotic stromal cells in a time and concentration dependently manner. Furthermore, Metformin attenuated the expression of angiogenic and inflammatory genes in human endometriotic stromal cells. The direct anti-proliferative effect on ECT-ESCs combined with the effects of Metformin on inflammatory and angiogenesis-related genes expression supports its therapeutic potential for endometriosis. Metformin could be used as an effective adjuvant in endometriosis treatment.

Evaluation of the association of endometriosis and mammographic breast density, a cross-sectional study.

BACKGROUND: Endometriosis is a common benign but painful gynecologic condition. Studies suggest that the risk of some types of malignancies such as breast cancer is higher in women with endometriosis. Mammographic breast density (MBD) is known as an important predictor for breast cancer. The present study aimed to investigate the potential relationship between endometriosis and MBD. METHODS: This cross-sectional study was conducted on 370 women over 40 years of age. Laparoscopic surgery was carried out for the diagnosis of endometriosis. MBD was classified into four categories according to the ACR BI-RADS classification. Statistical analysis was performed using SPSS software to evaluate the potential association between variables. RESULTS: The mean age of all participants was 47.2 ± 6.4 years, and most participants (76.8%) were premenopausal. Multivariate analysis of the potential predictors of MBD, including age, body mass index, oral contraceptive consumption, progesterone consumption, family history of breast cancer and endometriosis showed that age (P value = 0.002), history of progesterone consumption (P value = 0.004) and endometriosis (P value = 0.006) were independent factors for MBD. CONCLUSION: This study indicated that endometriosis had an inverse association with MBD. Age and history of progesterone use were also independent influential factors for MBD. This finding shows that the positive association between breast cancer and endometriosis is not mediated through MBD.

The effect of hydroxychloroquine on pregnancy outcomes in patients with unexplained recurrent pregnancy loss: a placebo-controlled study "pilot study".

This double-blind placebo-controlled study investigated the effect of hydroxychloroquine on pregnancy outcomes in people with unexplained recurrent pregnancy loss (URPL). The inclusion criteria included gestational age ≤6 weeks and a history of at least two miscarriages. The exclusion criteria included any known cause for previous abortions or a history of any chronic diseases. Participants were given 200 mg hydroxychloroquine or placebo twice a day until gestational week 20. Twenty-nine women were enrolled. There was no statistically significant difference between the two groups in terms of age, BMI, gravidity, previous abortion, relative married couple, and infertility. Miscarriage occurred in five women including one in the hydroxychloroquine group (7.69%) and four women in the placebo group (28.57%) (OR: 2.36, 95% PL CI:1.07, 8.93). However, after adjusting for potential confounders, there was no significant difference between the two groups (aOR: 2.96, 95%CI: 0.91, 10.02).IMPACT STATEMENTWhat is already known on this subject? Miscarriage, a prevalent concern in the field reproductive medicine, causes psychological and family problems for couples. Unfortunately, no effective treatment has been yet found for URPL. There are some hypotheses about the role of immunological factors in URPL. Hydroxychloroquine (HCQ) has various immunological effects and may theoretically have a role in the treatment of URPL. Although few studies have been registered to investigate the effect of HCQ on URPL, none of them has been published.What do the results of this study add? In our double-blind placebo-controlled trial, the prevalence of abortion in the HCQ group was four times lower than that in the placebo group, however, this difference was not statistically significant, which can be attributed to the small sample size.What are the implications of these findings for clinical practice and/or further research? We hope that HCQ will be of interest to researchers and future research help clarify the role of HCQ in preventing URPL.

Comparing the effect of adjunctive N-acetylcysteine plus low dose contraceptive with low dose contraceptive alone on recurrence of ovarian endometrioma and chronic pelvic pain after conservative laparoscopic surgery: a randomised clinical trial study.

This study aimed to compare the effectiveness of NAC plus low dose contraceptive with low dose contraceptives alone. This was a randomised trial on a sample of women who underwent conservative laparoscopic surgery for ovarian endometrioma. Patients were randomly assigned either to the NAC plus low dose contraceptive group (n = 48) or low dose contraceptive alone (n = 52). To evaluate the recurrence rate transvaginal ultrasound was performed. Pelvic pain was assessed using a visual analogue scale (VAS). All assessments were performed at two points in time: 3 and 6 months post-surgery and compared between the two regimens. The findings indicated that reduction in the recurrence rate of endometrioma and pelvic pain were similar between both groups. The findings showed that adding N-acetylcysteine to low dose contraceptive treatment has a similar effect in reducing the recurrence rate of endometrioma and pelvic pain when compared to low dose contraceptives alone.Impact statementWhat is already known on this subject? Endometriosis is a frequent benign disease-producing inflammatory response with mild to severe symptoms. Although surgical removal of ectopic lesions is the first-line intervention, the recurrence rate of the disease is high. Thus this study aimed to compare the effectiveness of N-acetylcysteine plus low dose contraceptive with low dose contraceptive alone.What do the results of this study add? The findings showed that adding N-acetylcysteine to low dose contraceptive treatment has a similar effect in reducing the recurrence rate of endometrioma and pelvic pain when compared to low dose contraceptives alone.What are the implications of these findings for clinical practice and/or further research? It is recommended to increase the duration of drug administration in future studies.

Evaluation of the predictive value of body mass index (BMI), waist circumference, and visceral fat to differentiate non-alcoholic fatty liver (NAFLD) in women with polycystic ovary syndrome.

Background: Our objective was to determine the overall prevalence of nonalcoholic fatty liver disease (NAFLD) in women with polycystic ovarian syndrome (PCOS) in our sample population. The second aim was to evaluate the predictive value of body mass index (BMI), waist circumference (WC), and visceral fat for the onset of NAFLD in these patients. Materials and Methods: This cross-sectional study was performed on 71 women with PCOS who were referred to Arash Women's Hospital in Tehran. Demographic and clinical information and anthropometric and biomedical indices were collected by a trained nurse. Liver ultrasonography was performed for all participants by a radiologist. Results: NAFLD was identified in 53.5% (n = 38) of subjects and the frequency of mild, moderate, and severe grades were 65.8%, 31.6%, and 2.6%, respectively. BMI and visceral fat of patients with NAFLD were significantly higher than non-NAFLD (P < 0.001). Receiving operating characteristic (ROC) curve analysis revealed that BMI was the best indicator of predicting NAFLD (cutoff = 25.5 kg/m2, sensitivity 75%, and specificity 75%), whereas visceral fat (cutoff = 5.5%, sensitivity 79%, and specificity 67%) and WC (cutoff = 89.5 cm, sensitivity 73%, and specificity 64%) were inferior for predicting NAFLD in PCOS patients. Conclusion: The prevalence of NAFLD in the study population is high. Our findings supported the use of BMI as a simple and practical predictive factor for the NAFLD onset, with a cutoff level of 25.5. The use of this cutoff level will enable physicians to identify PCOS patients at risk for NAFLD.

Disturbed progesterone signalling in an advanced preclinical model of endometriosis.

RESEARCH QUESTION: Do human endometriosis organoids recapitulate aberrant progesterone signalling in the disease to serve as advanced experimental models for uncovering epigenetic mechanisms involved in attenuated progesterone response in endometriosis? DESIGN: Initially, the organoids were established from acquired biopsies (women with and without endometriosis) and characterized by morphological, histological and immunostaining analyses. RESULTS: A panel of endometriosis-related genes showed a pattern of expressions in cytochrome c oxidase subunit II (COX2), matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitor of metalloproteinase-3 (TIMP3), transforming growth factor beta 1 (TGF-ß1), and zinc finger E-box binding homeobox 1 (ZEB1), and a contradictory expression pattern for cadherin (CDH1), POU class 5 homeobox 1 (POU5F1; also known as OCT4), and Nanog homeobox (NANOG) in the endometriosis organoids that is concordant with published research. These endometriosis organoids failed to upregulate 17ß-Hydroxysteroid dehydrogenase 2 (17HSDß2), progestogen associated endometrial protein (PAEP), secreted phosphoprotein 1 (SPP1), and leukaemia inhibitory factor (LIF) in response to progesterone at the level observed in control endometrium organoids. Progesterone receptor B (PRB) gene expression significantly decreased in both eutopic and ectopic organoids compared with control endometrium organoids. DNA hypermethylation, as an epigenetic mechanism for suppression of transcription, was detected at the PRB promoter in the eutopic, but not ectopic, organoids. Therefore, other epigenetic mechanisms, such as histone modifications and microRNAs, may be responsible for PRB downregulation in ectopic organoids. CONCLUSIONS: Endometriosis organoids are powerful preclinical models that can be used to investigate the molecular mechanisms involved in endometriosis-associated progesterone resistance.

Sexual function, mental health, and quality of life under strain of COVID-19 pandemic in Iranian pregnant and lactating women: a comparative cross-sectional study.

BACKGROUND: The impact of COVID-19 pandemic on mental health of pregnant and lactating women is unclear. This study aimed to assess the impact of COVID-19 on psychological health, sexual function, and quality of life (QoL) in Iranian pregnant and lactating women and compare the results with non-pregnant/non-lactating women. METHOD: This comparative cross-sectional study was carried out on pregnant and lactating women, with non-pregnant/non-lactating women from May to Jun 2020. Patients were asked to complete three questionnaires: Hospital Anxiety and Depression Scale (HADS), Female Sexual Function Index (FSFI), and Short-Form Health Survey (SF-12). One-way ANOVA was used to reveal the statistical differences between the three groups. RESULT: The mean age of patients was 20.81 ± 5.92 years old. The mean (SD) score of HADS in pregnant, lactating and non-pregnant / non-lactating women were 12.11 (6.72), 11.98 (8.44) and 9.38 (6.2) respectively, and the results showed that the scores in pregnant, lactating women were higher than non-pregnant / non-lactating women (P < 0.001). Also the mean (SD) score of QOL and FSFI was 68.29 (9.47), 74.18 (12.65), 79.03 (10.48) and 22.71 (8.16), 22.72 (8.16), 26.19 (3.93) in three groups and the scores in pregnant, lactating women were lower than non-pregnant/non-lactating women (P < 0.001). CONCLUSION: The COVID-19 epidemic increases the risk of depression, anxiety, FSD, and lowers QoL in pregnant and lactating women, with the general population. This suggests the urgent need for psychological intervention in the maternal population during the epidemic.

Differences in expression of genes related to steroidgenesis in abdominal subcutaneous adipose tissue of pregnant women with and without PCOS; a case control study.

BACKGROUND: It was reported that steroid-related gene expressions in the adipose tissue (AT) of women differ between women affected with polycystic ovary syndrome (PCOS) and non-PCOS. Although association between PCOS in mother and offspring's health is a crucial issue, there are few studies focusing on AT of pregnant women suffering from PCOS. Our objectives were to determine the differences between mRNA expression levels of key steroid-converting enzymes in abdominal subcutaneous AT of pregnant women afflicted with PCOS and non-PCOS. METHODS: Twelve pregnant women with PCOS (case) and thirty six non-PCOS pregnant women (control) (1:3 ratio; age- and BMI-matched) undergoing cesarean section were enrolled for the present study. Expressions of fifteen genes related to steriodogenesis in abdominal subcutaneous AT were investigated using quantitative real-time PCR. RESULTS: No significant differences were detected with respect to age, BMI (prior pregnancy and at delivery day), gestational period and parity among pregnant women with PCOS and non-PCOS. Most of the sex steroid-converting genes except 17ß-Hydroxysteroid dehydrogenases2 (17BHSD2), were highly expressed on the day of delivery in subcutaneous AT. Women with PCOS showed significantly higher mRNA levels of steroidgenic acute regulator (STAR; P < 0.001), cytochrome P450 monooxygenase (CYP11A1; P < 0.05), 17α-hydroxylase (CYP17A1; P < 0.05), and 11ß-Hydroxysteroid dehydrogenase (11BHSD1 and 11BHSD2; P < 0.05). The expression of steroid 21-hydroxylase (CYP21) in non-PCOS was fourfold higher than those of women with PCOS (P < 0.001). There were no significant differences between relative expression of aromatase cytochrome P450 (CYP19A1), 3ß-hydroxysteroid dehydrogenase (3BHSD1 and 3BHSD2), and 17BHSD family (1, 3, 5, 7, and 12) between the two groups. CONCLUSION: The expression levels of genes related to sex steroids metabolism were similar to age-matched and BMI- matched pregnant non-PCOS and pregnant women with PCOS at delivery day. However, the alterations in gene expressions involved in glucocorticoids and mineralocorticoids metabolism were shown. It is necessary to point out that further studies regarding functional activity are required. More attention should be given to AT of pregnant women with PCOS that was previously ignored.

Metabolic parameters in cord blood of neonate of mothers with obese and non-obese PCOS and controls: retrospective cohort study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by reproductive disorder and increased risk of metabolic syndrome. This study aimed to assess the metabolic parameters in the cord blood of neonate of mothers with obese PCOS and comparison with non-obese PCOS and controls. METHODS: This retrospective cohort study was conducted in Arash and Kamali Hospital in 2017-2018. The biochemical test was conducted on 78 neonates from obese PCOS mothers, 78 neonates from non-obese PCOS mothers, and 78 neonates from healthy mothers. Finally, cord blood lipid profile and insulin and blood sugar were determined by specific kits. Correlations between variables were compared with chi-square, Mann-Whitney's U, Kruskal-Wallis H tests and regression model by SPSS 23 and P < 0.05 was considered significant. RESULTS: Triglycerides (TG) and high-density lipoprotein cholesterol (HDL) were higher in cord blood of newborn of obese PCOS women than non-obese PCOS and controls (P = 0.02, P < 0.001, respectively). Also, the mean insulin was higher in cord blood of neonate of non-obese PCOS women than in obese PCOS and controls (12.26 ± 12.79 vs. 11.11 ± 16.51 vs. 6.21 ± 10.66, P = 0.01). But in the study, there was no significant difference between the mean of umbilical cord low-density lipoprotein cholesterol (LDL), total cholesterol and blood sugar in three groups. The logistic regression model showed that metabolic parameters were related to PCOS. CONCLUSIONS: In the present study, there was a significant difference between the mean of umbilical cord HDL, cholesterol, and the insulin level in the three groups. But, there was no significant association between the mean of blood sugar, LDL, and TG in the groups. The metabolic disorder in PCOS might affect cord blood lipid and insulin and adulthood health.

Mothers and their children's health (MATCH): a study protocol for a population-based longitudinal cohort.

BACKGROUND: The quality of prenatal care is critical for the prevention of adverse pregnancy outcomes. However, according to the World Health Organization (WHO), only 64 % of women worldwide have access to over four sessions of prenatal care throughout their pregnancy. Thus, studies that address factors affecting maternal and child health status before and after pregnancy are of immense importance. The primary aim of the mothers and their children's health (MATCH) cohort study is to evaluate the effect of nutrition, sleep quality, and lifestyle on maternal and neonatal outcomes. METHODS: A prospective cohort of > 2500 pregnant women in the first trimester (before 12 weeks' gestation) will be recruited at Arash Women's Hospital in Tehran, Iran between February 2020 and August 2021. All eligible pregnant women will be followed from their first trimester of pregnancy until delivery at four time points and assessed through a series of in-person visits with interviewer-administered questionnaires and telephone interviews. Detailed data will be collected on maternal demographics, lifestyle, medical history, reproductive history, obstetric history, dietary intake, sleep pattern, blood specimens, and anthropometric measurements, alongside paternal demographics, lifestyle, and family history. The outcomes will include antenatal, peripartum, and postnatal maternal complications and infant growth and neurodevelopment. DISCUSSION: The results of the MATCH cohort study will support the development of contextual interventions that can enhance antenatal, peripartum, and postnatal status, neonatal outcomes, and longevity mother and child.

Notch signaling pathway in cumulus cells reflecting zygote and embryo quality in polycystic ovary syndrome.

PURPOSE: The present study aimed to explore the associations between the expression pattern of molecules in the Notch pathway in the cumulus cells of polycystic ovary syndrome (PCOS) patients and the quality of zygotes and embryos. METHODS: A total of 200 cumulus complexes surrounding mature oocytes were obtained from 40 patients with and without PCOS undergoing intracytoplasmic sperm injection (ICSI). The expressions of Notch-1, Notch-2, and Notch-3 genes were examined by Reverse Transcription Q-PCR assay. Moreover, immunocytochemistry was performed for the expressions of Jagged-1 and Jagged-2 proteins. The correlations between the Notch receptors and their ligand expressions and the qualities of the zygote and embryo were investigated. RESULTS: The expression levels of Notch-2, Notch-3, Jagged-1, and Jagged-2 were significantly lower in patients with PCOS than in normal women (p < 0.05), while Notch-1 showed no meaningful difference between the groups. A positive correlation was found between Notch-1 and embryo quality. Furthermore, only Notch-2 and Jagged-2 marginally correlated with zygote quality. CONCLUSION: The data of the present study indicated that evaluating the molecules in the Notch pathway in PCOS patients' cumulus cells provides a novel approach to predict the zygote and embryo quality. However, further studies on a larger population are needed to validate this finding.

Residency training amid the COVID-19 pandemic: exploring the impact on mental health and training, a lesson from Iran.

BACKGROUND: COVID-19 has affected the training programs and the clinical schedules of surgical wards in many countries, including Iran. Also, the continuous involvement with COVID-19 patients has caused stress in health care workers; among them, residents are on the frontlines of care delivery. Therefore, we designed a study to assess the mental effects of these circumstances, and the effects on General Surgery and Obstetrics & Gynecology residency training in the busiest surgical departments of our university. METHODS: Participants of this cross-sectional study were residents of General Surgery and Obstetrics & Gynecology of Tehran University of Medical Sciences, and the conventional sampling method was used. We used a questionnaire consisting of 47 questions (mostly using multiple choice questions and answers on the Likert scale) about personal, familial, and demographic characteristics; training activities, and mental effects of COVID-19. RESULTS: The response rate was 63.5%. (127 filled questionnaires). Around 96% of the residents had emotional problems, 85.9% were highly stressed about contracting COVID-19, 81.3% were worried about transferring it to their families; and 78% believed that their residency training had been impaired. CONCLUSION: Overall, our study shows the negative impact of COVID-19 on mental health and the training of residents. We propose that appropriate emotional support and suitable planning for compensation of training deficits is provided for residents.

Evaluating hematological parameters in women with endometriosis.

In the present study, we aimed to evaluate the relationship between the level of hematological parameters and the presence and stage of endometriosis. We included medical records of patients diagnosed with endometriosis (endometriosis group) and patients diagnosed with benign non-endometriotic ovarian masses (control group), who were eligible based on inclusion and exclusion criteria and compared the preoperative level of hematological parameters between the two groups. According to our findings, neutrophil and WBC counts, mean platelet volume, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were significantly higher, and the haemoglobin concentration, platelet count, and absolute lymphocyte count were lower in women diagnosed with endometriosis compared to the control group. There was no significant difference in hematological parameters of patients with endometriosis stages III and IV. Finally, we found that the preoperative level of hematological parameters lacked sufficient power for the diagnosis of endometriosis. Also, our results indicate that endometriosis is associated with an inflammatory processes.IMPACT STATEMENTWhat is already known on this subject? Inflammatory factors are believed to be involved in the pathogenesis of endometriosis; however, there are inconsistent reports on the association between blood inflammatory markers and endometriosis.What do the results of this study add? The results of this study indicate that endometriosis is associated with inflammatory processes that lead to changes in hematological parameters; however, preoperative measurement of these parameters has not sufficient power for the diagnosis of endometriosis.What are the implications of these findings for clinical practice and/or further research? The preoperative level of hematological parameters lacks sufficient power for the diagnosis of endometriosis, but they may help doctors make a diagnosis in the clinical setting as auxiliary findings.

Mutation in ALOX12B likely cause of POI and also ichthyosis in a large Iranian pedigree.

Premature ovarian insufficiency (POI) is a clinically and etiologically heterogeneous disorder characterized by menstrual irregularities and elevated levels of FSH before age of 40 years. Genetic anomalies are among the recognized causes of POI. Here, we aimed to identify the genetic cause of POI in an inbred pedigree with nine POI and two ichthyosis-affected members. Inheritance of POI and ichthyosis were, respectively, dominant and recessive. Reproduction-related information and measurements of relevant hormones were obtained. Genetic studies included homozygosity mapping, linkage analysis, exome sequencing, and screening of candidate variants. A mutation within ALOX12B, which is a known ichthyosis causing gene, was identified as cause of ichthyosis. ALOX12B encodes a protein involved in steroidogenesis and lipid metabolism. Considering the importance of steroidogenesis in reproduction functions, the possibility that the ALOX12B mutation is also cause of POI was considered. Screenings showed that the mutation segregated with POI status. Linkage analysis with respect to POI identified a single strongly linked locus (LOD > 3) that includes ALOX12B. Exome sequencing on POI-affected females identified the mutation in ALOX12B and also a sequence variation in SPNS2 within the linked locus. A possible contribution of the SPNS2 variation to POI was not strictly ruled out, but various data presented in the text including reported association of variations in related gene ALOX12 with menopause-age and role of ALOX12B in atretic bovine follicle formation argue in favor of ALOX12B. It is, therefore, concluded that the mutation in ALOX12B is the likely cause of POI in the pedigree.