A New Model Including AMH Cut-off Levels to Predict Post-treatment Ovarian Function in Early Breast Cancer: A Prospective Cohort Study.

BACKGROUND: Breast cancer (BC) treatment decreases fertility capacity, but unnecessary fertility preservation procedures in women who would not be infertile after treatment would be a waste of time and resources and could cause the unwarranted exposure of cancer cells to exogenous sex hormones. It has been largely shown that post-treatment ovarian reserve is directly associated with pre-treatment anti-mullerian hormone levels (AMH0). A threshold for AMH0, or a model including AMH0 and patient characteristics that could distinguish the patients who will be infertile after treatments, still needs to be defined. Accordingly, this study was performed to specifically target this high-priority concern. METHODS: Women≤45 years old with newly diagnosed non-metastatic BC were entered in this multicenter prospective cohort study. AMH0 and two-year post-treatment AMH (AMH2) were measured, and hormonal patient features were recorded as well. Receiver operating characteristic (ROC) curve analysis, decision tree (DT), and random forest analyses were performed to find a cut-off point for AMH0 and define a model involving related features for the prediction of AMH2. RESULTS: The data from 84 patients were analyzed. ROC curve analysis revealed that AMH0>3 ng/mL (Area under the curve=0.69, 95% CI: 0.54‒0.84) was the best indicator for predicting AMH2≥0.7 (sensitivity=79%, specificity=60%). The best model detected by DT and random forest for predicting an AMH2>0.7 with a probability of 93% consisted of a combination of AMH0>3.3, menarche age<14, and age<31. CONCLUSION: This combination model can be used to withhold fertility preservation procedures in BC patients. Performing larger studies is suggested to further test this model.

Outcomes of female reproductive performance with assisted reproductive techniques after recent mild to moderate COVID-19 infections: An observational study.

Objective: The purpose of this study was to evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on clinical outcomes among high-risk patients. Methods: This retrospective study involved 1,368 patients and the same number of cycles, including 520 cycles with PGT-A and 848 cycles without PGT-A. The study participants comprised women of advanced maternal age (AMA) and those affected by recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or severe male factor infertility (SMF). Results: PGT-A was associated with significant improvements in the implantation rate (IR) and the ongoing pregnancy rate/live birth rate (OPR/LBR) per embryo transfer cycle in the AMA (39.3% vs. 16.2% [p<0.001] and 42.0% vs. 21.8% [p<0.001], respectively), RIF (41.7% vs. 22.0% [p<0.001] and 47.0% vs. 28.6% [p<0.001], respectively), and RPL (45.6% vs. 19.5% [p<0.001] and 49.1% vs. 24.2% [p<0.001], respectively) groups, as well as the IR in the SMF group (43.3% vs. 26.5%, p=0.011). Additionally, PGT-A was associated with lower overall incidence rates of pregnancy loss in the AMA (16.7% vs. 34.3%, p=0.001) and RPL (16.7% vs. 50.0%, p<0.001) groups. However, the OPR/LBR per total cycle across all PGT-A groups did not significantly exceed that for the control groups. Conclusion: PGT-A demonstrated beneficial effects in high-risk patients. However, our findings indicate that these benefits are more pronounced in carefully selected candidates than in the entire high-risk patient population.

A higher number of exhausted local PD1+, but not TIM3+, NK cells in advanced endometriosis.

Endometriosis (EMT) is a chronic inflammatory disease characterized by the presence and growth of endometrial-like glandular epithelial and stromal cells outside the uterus. Natural Killer (NK) cell dysfunction/exhaustion has been shown in patients with EMT. In this case-control study, we compared the frequency of exhausted PD-1 or TIM-3 positive NK cells in peripheral blood (PB) and peritoneal fluid (PF) of women with advanced endometriosis to control fertile women. PB and PF were collected from women aged 25-40 who underwent the laparoscopic procedure, including 13 stages III/IV endometriosis and 13 control samples. Multicolor flowcytometry was used to compare the frequency of PD-1 or TIM-3 positive NK (CD3-CD56+) cells in PB and PF of two groups. We demonstrated a higher percentage of PD-1+ NK cells in the peritoneal fluid of patients with endometriosis rather than controls (P-value = 0.039). This significance was related to stage IV of endometriosis (P-value = 0.047). We can not show any significant difference in the number of PD-1 or TIM-3 positive NK cells in peripheral blood. Our results suggest a local exhausted NK cell response in endometriosis that can be a leading factor in the endometriosis pathogenesis.

Breastfeeding success and perceived social support in lactating women with a history of COVID 19 infection: a prospective cohort study.

BACKGROUND: Given the limited availability of research on the association between COVID-19 infection and breastfeeding success, the primary objective of this study is to conduct a comprehensive evaluation of this relationship. METHODS: This prospective cohort study included 260 women who were on the postnatal ward of an academic hospital affiliated with Tehran University of Medical Sciences during the COVID-19 pandemic (between March and August 2021). Among these women, 130 had tested positive for COVID-19 in pregnancy, while the remaining 130 were considered healthy. The study aimed to assess various factors, including sociodemographic characteristics and the results of four validated questionnaires: The Bristol Breastfeeding Questionnaire, The Multidimensional of Perceived Social Support (MPSS), The Breastfeeding Self-Efficacy Scale (BSES), and The Postpartum Partner Support Scale (PPSS). These questionnaires were administered to each participant to gather relevant data. After eight weeks, a telephone follow-up was carried out to assess the success of breastfeeding. The evaluation focused on determining if exclusive breastfeeding was maintained or not. Data was collected by questioning mothers about their infants' feeding habits in the past 24 h. Exclusive breastfeeding refers to the exclusive use of breast milk without the introduction of other liquids or solid foods. RESULTS: Women with a previous COVID-19 infection (case group) had a lower mean infant gestational age (P < 0.001) and a higher prevalence of cesarean section (P = 0.001) compared to the control group. The proportion of women who exclusively breastfed was higher in the control group (98.5%) than in women with a history of COVID-19 infection (89.2%) (P = 0.011). Furthermore, the case group reported lower scores in perceived social support and the Breastfeeding Self-Efficacy Scale, in contrast to the control group. Notably, there was a significant correlation between breastfeeding success and women's breastfeeding self-efficacy score. CONCLUSIONS: The findings of this study offer valuable insights for healthcare professionals, enabling them to promote early initiation of breastfeeding in mothers with a history of COVID-19 infection, while ensuring necessary precautions are taken.

Drug repurposing for targeting fibronectin in treatment of endometriosis and cancers.

Increased concentrations of the fibronectin glycoprotein can cause ectopic tissue growth patients with endometriosis and the formation of various cancerous tumors. Furthermore, fibronectin binding to its receptors from the EDA (Extra Domain A) region contributes to promote tumorigenesis, metastasis and vasculogenesis. Thus, the EDA region can be considered a unique target for therapeutic intervention. Therefore, the present study used computational methods to identify the best fibronectin inhibitor(s) among FDA-approved drugs. First, docking-based virtual screening was performed using PyRx 0.8. Next, FDA-approved drugs that obtained favorable results in the docking phase were selected for further studies and analysis using molecular dynamics (MD) simulation. The preliminary findings of the virtual screening showed that 17 FDA-approved drugs (from 2471) had more favorable energy with their binding energy less than -9 kcal/mol. The MD simulation results of these 17 drugs showed that Avapritinib had a lower RMSD value and higher binding energy and hydrogen bonding than the other complexes in the EDA domain. Also, analyses related to the second structure changes displayed that Avapritinib in the EDA domain led to more changes in the second structure. According to the results, the anticancer drug Avapritinib forms a more stable complex with fibronectin than other FDA-approved drugs. Furthermore, this drug leads to more changes in the second EDA structure, which may have more serious potential for inhibiting EDA fibronectin.Communicated by Ramaswamy H. Sarma.

Follicular reconstruction and neo-oogenesis in xenotransplantation of human ovarian isolated cells derived from chemotherapy-induced POF patients.

BACKGROUND: Developing new strategies to restore fertility in patients with chemotherapy-induced Premature Ovarian Failure (Chemo-POF) is important. We aimed to construct an Artificial Ovary (AO) by seeding Human Ovarian Cortical Cells (HOCCs) into Human ovarian Decellularized Cortical Tissue (DCT). We assessed the AO's ability to produce new ovarian follicles following xenotransplantation to NMRI mice. MATERIAL AND METHODS: The DCTs were prepared, and cell removal was confirmed through DNA content, MTT assay, DAPI and H&E staining. Next, HOCCs were isolated from both Chemo-POF and Trans (as a control group) ovarian patients. The HOCCs were characterized using immunostaining (FRAGILIS, Vimentin, and Inhibin α) and real time PCR (DDX4, STELLA, FRAGILIS, Vimentin, FSH-R, KI67) assays. The HOCCs were then seeded into the DCTs and cultured for one week to construct an AO, which was subsequently xenotransplanted into the mice. The existence of active follicles within the AO was studied with H&E and immunofluorescence (GDF9) staining, Real-time PCR (GDF9, ZP3) and hormone analysis (Estradiol, FSH and AMH). RESULTS: The results of gene expression and immunostaining showed that 85-86% of the isolated cells from both Trans and Chemo-POF groups were positive for vimentin, while 2-5% were granulosa cells and OSCs were less than 3%. After xenotransplantation, histological study confirmed the presence of morphologically healthy reconstructed human ovarian follicles. Additionally, immunofluorescence staining of GDF9 and hormonal assay confirmed the presence of secretory-active follicles on the AO. CONCLUSION: Our findings demonstrate that an artificial ovary produced by seeding HOCCs on DCT can support HOCCs proliferation as well as neo-oogenesis, and enable sex hormone secretion following xenotransplantation.

Fatty acid profiles and Delta9 desaturase (stearoyl-CoA desaturase; SCD 1) expression in adipose tissue surrounding benign and malignant breast tumors.

The progression of tumors occurs through interactions between the tumor and the stroma. Understanding the role of adipose tissue (AT), as the main component of the breast tumor microenvironment (TME) in the development of cancer, is crucial for the early detection of breast cancer (BC). This study compared the FA profiles, desaturase index (DI), and stearoyl CoA desaturase 1 (SCD1) mRNA levels in the AT that surrounds tumors in women with BC and benign breast disease (BBD). Specimens were collected from 40 Iranian women who had undergone breast surgery. These women were age- and BMI-matched and were divided into two groups: BC (n = 20) and BBD (n = 20). Gas chromatography and quantitative real-time PCR were used to analyze the FA profiles and SCD1 mRNA levels, respectively. The DI was calculated by dividing the amounts of monounsaturated FAs by the amount of saturated FA. There were no significant differences in age and BMI between women with BC and BBD. The FA profiles and DI were also similar in both groups. However, mRNA levels of SCD1 were found to be 5 times higher in the breast AT of BC than in the breast AT of BBD (p < 0.0001). We showed that SCD1 was significantly upregulated in the AT surrounding BC tumors, even though the DI and FA profiles were unchanged compared to those in the AT of BBD patients. It is important to note that the breast AT of women with BBD has previously been overlooked and warrants further studies.

The effects of intermittent fasting diet alone or in combination with probiotic supplementation in comparison with calorie-restricted diet on metabolic and hormonal profile in patients with polycystic ovary syndrome: study protocol for a randomized clinical trial.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in females characterized by ovulatory dysfunction, hyperandrogenism, and other metabolic disorders. Both intermittent fasting and specific probiotics have been suggested to help improve patients with PCOS through changes in gut microbial composition, circadian clock, and metabolic regulation. Therefore, the present study aims to investigate the effects of intermittent fasting alone or in combination with probiotic supplementation compared to the calorie-restricted (CR) diet on anthropometric measures, metabolic status, inflammation, and oxidative stress in women with PCOS. METHODS: We will carry out a randomized clinical trial for 8 weeks. Participants will be randomly assigned (1:1:1) to one of the three groups: (1) a 14:10 early time-restricted feeding (TRF) diet with probiotic supplementation (n = 30); (2) a 14:10 early TRF diet with placebo supplementation (n = 30); (3) a CR diet (energy-restricted 25% of required calories) with placebo supplementation as a control group (n = 30). The primary outcomes will be changes in body weight and insulin resistance. However, glycemic control, lipid profile, metabolic parameters, sex hormone-binding globulin, dehydroepiandrosterone, anti-Mullerian hormone, free androgen index, hirsutism, acne, antioxidant and oxidant status, inflammation, anthropometric measures, mental health, sleep quality, appetite, eating behavior, food craving, and blood pressure are secondary outcomes. All outcomes of this study will be evaluated in pre- and post-intervention. DISCUSSION: We hypothesized that 10-h TRE administered alone or in combination with probiotic supplementation to overweight and obese PCOS subjects would lead to weight loss and improved metabolic, hormonal, inflammatory, and antioxidant markers compared to control subjects following a standard 3-meal-per-day CR diet. ETHICAL ASPECTS: The current trial received approval from the Medical Ethics Committee of Tehran University of Medical Sciences, Tehran, Iran (IR.TUMS.MEDICNE.REC.1401.425). TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20121110011421N5. Registered on 3 October 2022.

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.

Awareness of Polycystic Ovary Syndrome among Schoolgirls and Their Mothers: A Cross-Sectional Study.

BACKGROUND: One of the most common endocrine disorders of reproductive age women is polycystic ovary syndrome (PCOS). Women with PCOS are at risk for infertility, endometrial cancer, metabolic disorders, and cardiovascular disease. Awareness of the signs and symptoms of PCOS can be effective in diagnosing early stage PCOS and promoting quality of life (QoL). This study assesses the awareness of PCOS in schoolgirls and their mothers. MATERIALS AND METHODS: This cross-sectional study was carried out on 1580 high school girls and 480 of their mothers in Tehran (capital of Iran) in 2017 and 2018. We used the stratified sampling method and divided Tehran into five geographic regions: north, south, east, west, and central. Schools were randomly selected from each of these regions. Students and their mothers separately answered a self-administered questionnaire that pertained to their knowledge of PCOS. Statistical analyses were carried out with SPSS, version 22 (Inc. Chicago, IL, USA) and R version 3.2.1. RESULTS: Students had an average age of 16.97 ± 0.84 years and their mothers' average age was 45.19 ± 5.03 years. The average body mass index (BMI) of the students was 22.01 ± 5.54 kg/m2. The results of this study showed that only 48 students (3.2%) and 148 mothers (27%) had acceptable knowledge about PCOS. The knowledge of students about PCOS was positively related to their mothers' knowledge about PCOS (P<0.001). CONCLUSION: The level of PCOS awareness in Iranian women is insufficient and this may affect their QoL. Therefore, the health authorities should implement educational programs to challenge women's incorrect beliefs about PCOS and increase their awareness of this disease.

Pregnancy outcomes in women with adenomyosis, undergoing artificial endometrial preparation with and without gonadotropin-releasing hormone agonist pretreatment in frozen embryo transfer cycles: An RCT.

Background: Selecting a suitable and preferable method for endometrial preparation in frozen embryo transfer (FET) cycles for women with adenomyosis is still challenging in infertility treatment. Objective: To compare 2 artificial endometrial preparation regimens with and without gonadotropin-releasing hormone agonist (GnRHa) pretreatment in women with adenomyosis undergoing FET cycles. Materials and Methods: This randomized clinical trial study was conducted on 140 adenomyosis cases who underwent FET cycles at Arash Women's hospital, Tehran, Iran from May 2020 to March 2021. Participants were randomly allocated into hormonal replacement therapy (HRT) and HRT+GnRHa pretreatment groups (n = 70/each). Endometrial preparation with 2-6 mg daily estradiol was started in the HRT+GnRHa group, taking after down-regulation with the GnRHa. Within the HRT group, the same dose of estradiol was commenced within the early follicular stage. The main (chemical and clinical pregnancy rates) and auxiliary results (twin pregnancy, miscarriage, and live birth rates) were compared between groups. Results: The demographic characteristics and severity of adenomyosis, endometrial thickness, and pattern at starting progesterone administration were similar in the 2 groups, and triple-line endometrium was found to be the dominant pattern in both groups (p = 0.65). No significant differences were observed in chemical, clinical, and twin pregnancy rates as well as miscarriage and live birth rates between groups (p = 0.71, p = 0.81, p = 0.11, and p = 0.84, respectively). However, the total estrogen dose and duration of estrogen consumption were significantly higher in the pretreatment group (p = 0.001, and p = 0.003). Conclusion: These results indicated that the hormonal endometrial preparation with estrogen and progestin for FET cycles is as efficacious as a protocol involving preceding pituitary suppression with a GnRHa. Further large randomized clinical studies are required to confirm these findings.

The relationship between dietary micronutrients and endometriosis: A case-control study.

Background: Fewer studies were on micronutrient intake in women with endometriosis, and the etiology of endometriosis remains unclear between dietary micronutrients and the risk of endometriosis. Objective: This study aimed to investigate the relationship between dietary micronutrients and the risk of endometriosis. Materials and Methods: This case-control study was conducted on 156 women (18-45 yr) with and without endometriosis in the gynecology clinic of Arash hospital between May 2017 and May 2018 in Tehran, Iran. According to the laparoscopic findings, the participants were divided into 2 groups (n = 78/each), women with pelvic endometriosis as the case group and women without endometriosis pelvic as the control group. Dietary data were collected using a validated 168-item semiquantitative food frequency questionnaire with the standard serving. A logistic regression model was used to determine the association between micronutrients and the risk of endometriosis. Results: Data analysis showed a significant relationship between micronutrients such as: potassium (OR: 0.74; CI: 0.56-0.99; p = 0.01), calcium (OR: 0.70; CI: 0.52-0.94; p = 0.003), and also among the vitamin C (OR: 0.70; CI: 0.52-0.94; p = 0.02), B2 (OR: 0.73; CI: 0.55-0.98; p = 0.01), and B12 (OR: 0.71; CI: 0.53-0.95; p = 0.02) with endometriosis, so those who used fewer micronutrients were at higher risk of endometriosis. Conclusion: The findings showed that the dietary intakes of calcium, potassium, vitamins B12, B2, B6, and C are inversely related to the risk of endometriosis.

Intrauterine administration of autologous peripheral blood mononuclear cells regulates the endometrium estrogen and progesterone receptor expression: An RCT.

Background: Repeated implantation failure (RIF) affects 15% of women of reproductive age. There is a high endometrial expression of both estrogen receptors and progesterone receptors (PRs) during the window of implantation in women with RIF. Objective: To evaluate the effects of intrauterine administration of human peripheral blood mononuclear cells (PBMC) on estrogen receptor α (ERα) and PRs expression in the endometrium of women with RIF during the implantation window. Materials and Methods: This randomized clinical trial study was conducted on 22 women with RIF history from January 2018 to August 2019 in Erfan hospital, Tehran, Iran. Participantswere divided into 2 groups (PBMC-treated group [n = 11] and control group [n = 11]). Endometrial tissue samples were collected at the implantation window time, during the mid-secretory phase (luteinizing hormone surge +7 days) of each menstrual cycle. The quantitative real-time polymerase chain reaction technique was used to measure the mRNA levels of ERα and PRs isoforms (PR-A and PR-B) in endometrial tissues. Furthermore, the protein expression of ERα and PRs was investigated using immunohistochemical staining. Results: PBMC treatment significantly decreased the mRNA expression of endometrial ERα and PRs isoforms at the time of the implantation window (p < 0.001). Moreover, the endometrial ERα and PRs protein localization were significantly lower in PBMC-treated women compared with controls (p = 0.01, and p < 0.001 respectively). Conclusion: The intrauterine administration of PBMC decreased the endometrial ERα and PRs expression during the window of implantation in women with RIF. This local response to PBMC therapy could promote endometrial receptivity and embryo implantation.

Serum and follicular fluid levels of soluble receptor for advanced glycation end-products in women with and without polycystic ovary syndrome.

BACKGROUND: Advanced glycation end products (AGEs) are known to associate with the pathogenesis of several chronic diseases via interaction with their corresponding receptor (RAGE). The soluble forms of RAGE (sRAGE) are considered as anti-inflammatory agents by inhibiting the consequent adverse effects of AGE. We aimed at comparing sRAGE levels in the follicular fluid (FF) and serum of women with or without Polycystic Ovary Syndrome (PCOS) who underwent controlled ovarian stimulation for in vitro fertilisation (IVF). METHODS: A total of forty-five eligible women (26 non-PCOS (control) and 19 patients with PCOS (case)) were included the study. sRAGEs in FF and blood serum were measured using ELISA kit. RESULTS: No statistically significant differences were found in FF and serum sRAGE between case and control groups. Correlation analysis showed a significant and positive relationship between serum levels of sRAGE and FF sRAGE in PCOS (r = 0.639; p = 0.004), in control participants (r = 0.481; p = 0.017), and in total participants (r = 0.552; p = 0.000). Data revealed a statistically significant difference in FF sRAGE concentration among all participants by body mass index (BMI) categories (p = 0.01) and in controls (p = 0.022). Significant differences were found for all the nutrients and AGEs consumption according to Food Frequency Questionnaire in both groups (p = 0.0001). A significant reverse relationship was found between FF levels of sRAGE and AGE in PCOS (r = -0.513; p = 0.025). The concentration of sRAGE in serum and FF is the same in PCOS and control. CONCLUSION: The present study revealed for the first time that there are no statistically significant differences between the concentration of serum sRAGE and FF sRAGE among Iranian women with and without PCOS. However, BMI and dietary intake of AGEs have more significant effects on sRAGE concentration in Iranian women. Future studies in developed and developing countries with larger sample sizes are required to determine the long-term consequences of chronic AGE over consumption and the optimal strategies for minimizing AGE-related pathology, specifically in low income and developing countries.

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.

Evaluation of the relationship between ovarian reserve with congenital anomalies and intramural uterine leiomyoma among infertile women: a cross-sectional study.

BACKGROUND: Ovarian reserve is a crucial indicator of a woman's fertility potential, which is determined by the quality and quantity of antral follicles and oocytes. However, certain factors such as endometriosis, pelvic inflammatory disease, myoma, and the natural process of aging can lead to a poor ovarian response to stimulation, reducing a woman's chances of conceiving. OBJECTIVE: To evaluate the effect of uterus congenital anomalies and uterine leiomyoma are associated on ovarian reserve. METHODS: The present cross-sectional study was performed on 321 infertile women in three groups consisted of 97 infertile women with intramural uterine leiomyoma and 81 infertile women with uterine anomalies and 143 infertile women without uterine anomalies and uterine leiomyoma during 2017-2019 in Royan Center. Sampling method was continuous and available. Data collection tool in this study was a questionnaire which was in two parts of individual variables and the second part was related to ultrasound results (number of antral follicles and ovarian volume) and laboratory tests (Anti-Mullerian Hormone (AMH) and Follicle-stimulating Hormone (FSH)). Ovarian reserve parameters were measured in three groups on the third day of the cycle in both groups. Data analysis was performed using SPSS software version 21. Quantitative variables were analyzed using t-test, qualitative variables were analyzed using chi-square test. RESULTS: The results of in laboratory parameters showed that there was no statistically significant difference between the three groups in FSH (2.35 ± 1.55, 2.07 ± 1.81, 2.31 ± 1.93) and AMH (6.84 ± 2.75,7.52 ± 3.14,6.93 ± 3.04), respectively (P > 0.05). The results of sonographic variables also showed that the variables include number of antral follicles in right ovarian, number of antral follicles in left ovarian have statistically significant between the three groups (5.73 ± 2.69,4.84 ± 3.14,6.66 ± 3.13), respectively (P < 0.05). CONCLUSION: The results of the present study showed that uterine abnormalities and uterine leiomyoma with different mechanisms such as reduce of antral follicle numbers and the effect on uterine and ovarian blood flow lead to a decrease in ovarian reserve and infertility. Therefore, treatment and surgery can reduce these effects and improve the fertility of the affected women.

In-vivo oogenesis of oogonial and mesenchymal stem cells seeded in transplanted ovarian extracellular matrix.

OBJECTIVE (S): One way to overcome the recurrence of cancer cells following ovarian tissue transplantation is to use decellularized tissues as a scaffold that does not have any cellular components. These cell-free scaffolds can be seeded with different type of stem cells for ovarian restoration. MATERIALS AND METHODS: OSCs, PMSCs and BMSCs (oogonial, peritoneal and bone marrow mesenchymal stem cells, respectively) were seeded into human decellularized ovarian tissue as 4 groups: Scaffold + OSCs (SO), Scaffold + OSC + PMSCs (SOP), Scaffold + OSC + BMSCs (SOB) and Scaffold + OSC + PMSCs + BMSCs (SOPB). The produced grafts were transplanted into the sub-peritoneal space of ovariectomized NMRI mice as artificial ovary (AO). The expression of Vegf, CD34, Gdf9, Zp3, Ddx4, Amh and Lhr genes in AOs were measured by qRT-PCR. Also, histotechniques were considered to detect the anti GFP, PCNA, VEGF, GDF9, ZP3 and AMH proteins. RESULTS: H & E staining showed follicle-like structures in all groups; the number of these structures, in the SOP and SOB groups, were the highest. In SO group, differentiation ability to oocyte and granulosa cells was observed. Endothelial, oocyte, germ, and granulosa cell-like cells were specially seen in SOP and angiogenesis capability was more in SOB group. However, angiogenesis ability and differentiation to theca cell-like cells were more often in SOPB group. While none of the groups showed a significant difference in AMH level, estradiol levels were significantly higher in SOPB group. CONCLUSION: Integration of OSCs + PMSCs and those OSCs + BMSCs were more conducive to oogenesis.

Fatty Acids in Subcutaneous Adipose Tissue of Pregnant Women with and without Polycystic Ovary Syndrome Are Associated with Genes Related to Steroidogenesis: A Case-Control Study.

BACKGROUND: The qualitative analysis of adipose tissue (AT) is an exciting area for research and clinical applications in several diseases and it is emerging along with the quantitative approach to research on overweight and obese people. While the importance of steroid metabolism in women with polycystic ovary syndrome (PCOS) has been reported, limited data exists on the effective roles of AT in pregnant women suffering from PCOS. The aim of this study was to determine association of fatty acid (FA) profiles with expression of 14 steroid genes in abdominal subcutaneous AT of PCOS vs. non-PCOS pregnant women. MATERIALS AND METHODS: In this case-control study, the AT samples of 36 non-PCOS pregnant women and 12 pregnant women with PCOS (3:1 ratio control: case) who underwent cesarean section were collected. Relationship of expressing gene targets and different features were performed using Pearson correlation analysis on the R 3.6.2 software. The ggplot2 package in R tool was used to draw the plots. RESULTS: Age (31.4 and 31.5 years, P=0.99), body mass index (BMI) (prior pregnancy 26 and 26.5 kg.m-2, P=0.62) and at delivery day (30.1 and 31, P=0.94), gestational period (264 and 267 days, P=0.70) and parity (1.4 and 1.4, P=0.42) of non-PCOS and PCOS pregnant women were similar. Expression of steroidogenic acute regulator (STAR) and 11ß-Hydroxysteroid dehydrogenase (11BHSD2) in non-PCOS pregnant women showed the highest association with eicosapentaenoic acid (EPA, C20:5 n-3, r=0.59, P=0.001) and (r=0.66, P=0.001), respectively. In the all participants, STAR mRNA level showed the greatest association with the EPA fatty acid concentration (P=0.001, r=0.51). CONCLUSION: Our results showed a link between the genes involved in steroid metabolism and fatty acids in AT of pregnant women, especially for omega-3 FA and the gene involved in the first step of steroidogenesis in subcutaneous AT. These findings warrant further studies.

Infertility Does Not Increase the Rate of Breast Fibroadenoma.

Background: Fibroadenoma (FA) and infertility can share common risk factors and probably common underlying pathophysiology, but yet there is no study evaluating the prevalence of FA in infertile women. Therefore, the aim of in the present study, the purpose was evaluating the association of FA and infertility for the first time. Methods: This short communication is a secondary analysis of a primary study that was performed in Arash Women's Hospital, Tehran, Iran. Participants were selected among reproductive-aged women with a history of infertility as the case and women without infertility as the control group. The criteria for diagnosis of FA were histopathologic assessment for lumps 1 cm in size or larger, and a typical ultrasound image for smaller lumps. Assisted reproductive technology (ART) was defined as any previous history of undergoing ovulation stimulation, intrauterine insemination, intracytoplasmic sperm injection, or in vitro fertilization. Results: Overall, 155 cases with a mean age of 39.2±6.9, and 167 controls with a mean age of 43.08±8.3 were included (p=0.0001). Interestingly, the incidence of FA was lower in the case group (18.7% vs. 25.7%), however, the difference was not statistically significant (p=0.13). Also, logistic regression analysis showed that the chance for an infertile woman who undergoes ART to get FA is 1.7 times higher in comparison to non-ART group, although the difference was not significant (p=0.21). Conclusion: Infertility and ART were not associated with increased risk of FA; however, larger prospective studies should be conducted in the future in order to achieve conclusive results.