Bio-modulated mice epithelial endometrial organoids by low-level laser therapy serves as an invitro model for endometrial regeneration.

Endometrial regeneration is a dynamic process that is not well understood. The destruction of the endometrium with the formation of intrauterine adhesions is known as Asherman's syndrome. The lesions range from minor to severe adhesions and their impact on pregnancy is well documented. Operative hysteroscopy is the mainstay of diagnosis and treatment of intrauterine adhesions. Nevertheless, the recurrence rates remain high. It was recorded that low-level laser therapy in low doses has a stimulatory effect on different tissues while the high dose produces a suppressive effect. Organoid is a three-dimensional assembly that displays architectures and functionalities similar to in vivo organs that are being developed from human or animal stem cells or organ-specific progenitors through a self-organization process. Our prospective was to study the effect of Low-Level Laser Therapy (LLLT) on mouse epithelial endometrial organoids regarding cell proliferation and endometrial regeneration as a new modality of treatment. An in vitro clinical trial to generate mouse epithelial organoid model and testing LLLT using He:Ne 632.8 nm device on organoids proliferation, function, and their response to ovarian hormones was performed. Trying endometrial regeneration by culturing organoids with decellularized uterine matrix (DUM) and studying the LLLT effect on the regeneration process. LLLT produced a proliferative effect on the epithelial mouse organoids confirmed by Ki67 and PCNA IHC. The organoids could regenerate the epithelial layer of the endometrium in vitro on DUM and LLLT could help in this process. In conclusion, organoids whether control or bio-stimulated proved a new modality to regenerate the endometrium.

Uterine Epithelial Progesterone Receptor Governs Uterine Receptivity Through Epithelial Cell Differentiation.

Progesterone receptor (PGR) is indispensable for pregnancy in mammals. Uterine PGR responds to the heightened levels of ovarian progesterone (P4) after ovulation and regulates uterine gene transcription for successful embryo implantation. Although epithelial and stromal P4-PGR signaling may interact with each other to form appropriate endometrial milieu for uterine receptivity and the subsequent embryo attachment, it remains unclear what the specific roles of epithelial P4-PGR signaling in the adult uterus are. Here we generated mice with epithelial deletion of Pgr in the adult uterus (Pgrfl/flLtfCre/+ mice) by crossing Pgr-floxed and Ltf-Cre mice. Pgrfl/flLtfCre/+ mice are infertile due to the impairment of embryo attachment. Pgrfl/flLtfCre/+ uteri did not exhibit epithelial growth arrest, suggesting compromised uterine receptivity. Both epithelial and stromal expressions of P4-responsive genes decreased in Pgrfl/flLtfCre/+ mice during the peri-implantation period, indicating that epithelial Pgr deletion affects not only epithelial but stromal P4 responsiveness. In addition, uterine LIF, an inducer of embryo attachment, was decreased in Pgrfl/flLtfCre/+ mice. The RNA-seq analysis using luminal epithelial specimens dissected out by laser capture microdissection revealed that the signaling pathways related to extracellular matrix, cell adhesion, and cell proliferation are altered in Pgr fl/flLtf Cre/+ mice. These findings suggest that epithelial PGR controls both epithelial and stromal P4 responsiveness and epithelial cell differentiation, which provides normal uterine receptivity and subsequent embryo attachment.

Strengths of community and health facilities based interventions in improving women and adolescents' care seeking behaviors as approaches for reducing maternal mortality and improving birth outcome among low income communities of Egypt.

BACKGROUND: Provision of emergency obstetric care is considered the key for maternal mortality reduction worldwide. This study evaluated the impact of community- and facility-based educational programs on provision of emergency obstetric care in Egypt. The study focused on evaluating utilization of the available health services and care seeking behaviors of mothers in the childbearing period. METHODS: We implemented a package of community- and facility-focused educational interventions in two of Egypt's lowest income governorates. At facility level, health professionals at rural health units from 21 villages over 5 years were trained. Mass media gathering, individual teaching at health facilities, printed materials and home-based care sessions were provided. Collectively, these interventions were designed to focusing on recognition of the early warning signs during pregnancy, delivery and postpartum period for timely referral to hospitals for 20,494 women and adolescents mothers. RESULTS: The impact of the interventions was highly reflected on the percent of mothers received care during their pregnancy period. Proper antenatal care at governmental or private health facilities was raised dramatically from 0.6 to 59.3% and those who utilized at least one family planning method from 61.4 to 74.4%. Accordingly, the rate of complications significantly reduced during pregnancy (38.1 to 15.1%), during delivery (24.1 to 13.1%) and during postpartum (81.7 to 7.0%). As an impact to the improvement, there was a marked reduction in adolescent pregnancy by 55% and better birth outcome with a reduction in the percent of stillbirth by 11.5%. CONCLUSION: It is important to provide a comprehensive package that works at both improving qualities of care as well as empowering women by knowledge to first aid measures at the community level. The cost-effective way to empower mothers to provide first aid measures as emergency obstetric care is to adopt the outreach approach which could be more influential than mass media campaigns for the at-risk and vulnerable and low-income communities.

Building Oncofertility Core Competency in Developing Countries: Experience From Egypt, Tunisia, Brazil, Peru, and Panama.

Purpose: Little is known about oncofertility practice in developing countries that usually suffer from a shortage of health services, especially those related to cancer care. Materials and Methods: To learn more about oncofertility practice in developing countries, we generated a survey to explore the barriers and opportunities associated with oncofertility practice in five developing countries from Africa and Latin America within our Oncofertility Consortium Global Partners Network. Responses from Egypt, Tunisia, Brazil, Peru, and Panama were collected, reviewed, and discussed. Results: Common barriers were identified by each country, including financial barriers (lack of insurance coverage and high out-of-pocket costs for patients), lack of awareness among providers and patients, cultural and religious constraints, and lack of funding to help to support oncofertility programs. Conclusion: Despite barriers to care, many opportunities exist to grow the field of oncofertility in these five developing countries. It is important to continue to engage stakeholders in developing countries and use powerful networks in the United States and other developed countries to aid in the acceptance of oncofertility on a global level.

Building Oncofertility Core Competency in Developing Countries: Experience From Egypt, Tunisia, Brazil, Peru, and Panama.

PURPOSE: Little is known about oncofertility practice in developing countries that usually suffer from a shortage of health services, especially those related to cancer care. MATERIALS AND METHODS: To learn more about oncofertility practice in developing countries, we generated a survey to explore the barriers and opportunities associated with oncofertility practice in five developing countries from Africa and Latin America within our Oncofertility Consortium Global Partners Network. Responses from Egypt, Tunisia, Brazil, Peru, and Panama were collected, reviewed, and discussed. RESULTS: Common barriers were identified by each country, including financial barriers (lack of insurance coverage and high out-of-pocket costs for patients), lack of awareness among providers and patients, cultural and religious constraints, and lack of funding to help to support oncofertility programs. CONCLUSION: Despite barriers to care, many opportunities exist to grow the field of oncofertility in these five developing countries. It is important to continue to engage stakeholders in developing countries and use powerful networks in the United States and other developed countries to aid in the acceptance of oncofertility on a global level.

Enhancing the value of women's reproductive rights through community based interventions in upper Egypt governorates: a randomized interventional study.

BACKGROUND: In 2012, the WHO described the quality of health care as the route to equity and dignity for women and children. AIM OF THE WORK: To provide community based support and empowerment to women in childbearing period to seek optimal prenatal, natal and postnatal healthcare. Achieving this is anticipated to decrease maternal morbidity and mortality in Egypt. SUBJECTS AND METHODS: An interventional study was conducted among women in childbearing period in the poorest two governorates of Upper Egypt. The study passed through three stages over three and a half years; pre-interventional assessment of awareness (n = 1000), educational interventions targeting the health providers and all women in childbearing period in their communities (n = 20,494), and post-intervention evaluation of change in awareness of their rights for prenatal, natal and postnatal care (no = 1150). RESULTS: The studied indicators relating to receiving care in pregnancy, labor, and puerperium have changed dramatically as a result of the study interventions. Results of the study showed that before interventions, the surveyed women had inaccurate knowledge regarding most of the items related to their rights. The percentages of women aware of their right to have pregnancy card increased and those who possessed a pregnancy card were doubled with a significant percent change of more than 25%. Some indicators showed more than 75% improvement, including; percent of surveyed women who knew that it's their right to follow up their pregnancy and to deliver with a specialized doctor, a trained nurse or at an equipped health facility, and those who knew their right to have at least two home preparations necessary for safe delivery at home. CONCLUSION AND RECOMMENDATIONS: More work is needed in order to achieve the targeted reduction of maternal mortality. This could be achieved by ensuring accessible and high quality care provided by the governmental health facilities together with increasing the awareness of women regarding their rights in receiving such care.

Fetal Biometric Charts and Reference Equations for Pregnant Women Living in Port Said and Ismailia Governorates in Egypt.

AIM: To construct new fetal biometric charts and equations for some fetal biometric parameters for women between 12th and 41st weeks living in Ismailia and Port Said Governorates in Egypt. MATERIAL AND METHODS: This cross-sectional study was carried out on 656 Egyptian women (from Ismailia and Port Said governorates) with an uncomplicated pregnancy, and all were sure of their dates. The selected group was between the 12th and 41st weeks of gestation, recruited from the district general hospital in Ismailia and Port Said to measure ultrasonographically biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL), then for each measurement separate regression models were fitted to estimate both the mean and the Standard deviation at each gestational age. RESULTS: New Egyptian charts were reported for BPD, HC, AC, and FL. Reference equations for the dating of pregnancy were presented. The mean of the previous measurements at 12th and 41st weeks were as follows: (23.37, 98.72), (83.05, 336.12), (67.85, 332.57) and (12.50, 74.92) respectively. CONCLUSION: New fetal biometric charts and regression equations for pregnant women living in Port Said & Ismailia governorates in Egypt.

Differentially expressed genes: OCT-4, SOX2, STAT3, CDH1 and CDH2, in cultured mesenchymal stem cells challenged with serum of women with endometriosis.

Endometriosis is a common chronic gynecological disorder defined as the presence of ectopic functional endometrial tissues, outside uterine cavity, primarily on the pelvic peritoneum and the ovaries. Several studies revealed a correlation between aberrant stem-cell activity in the endometrium and endometriosis. Yet the molecular and cellular behaviors of mesnchymal stem cells in development of endometriosis are hampered by lack of invitro experiments. Our aim was to explore morphological and molecular changes associated with mesenchymal stem cells (MSCs) exposition to serum derived from women with severe endometriosis. Two cell cultures of MSCs isolated from endometrial tissues of two endometriosis-free women. Each cell culture was treated individually with the serum of women with endometriosis (experimental group/n = 7), and serum of women without endometriosis (control group/ n = 4) for 14 days. Quantitative Real-Time PCR was performed later to reveal expression of OCT-4, CDH1 and CDH2, STAT3 and SOX2 genes. Morphologically, cells showed no significant changes. However from molecular point of view, we found increased expression in OCT-4, CDH1 and CDH2. For STAT3 and SOX2 we did not find a significant difference. This study shows that endometriosis serum induced molecular changes in human endometrial MSCs (EnMSCs) that might be related to altered cell behavior which may be a step in differentiation that may be completed invivo by other factors to complete the process of transition. Further researches are needed for optimization to reach differentiation.

Effect of laser-assisted zona thinning, during assisted reproduction, on pregnancy outcome in women with endometriosis: randomized controlled trial.

OBJECTIVE: To compare the ICSI-ET outcomes in patients with endometriosis with or without laser-assisted zona pellucida thinning. DESIGN: Randomized controlled trial. SETTING: The study was conducted in the Obstetrics & Gynecology Department, Cairo University hospital, and two private IVF centers in Cairo & Beni-Suif from July 2015 to January 2017 upon infertile and known endometriosis patients who planned to do ICSI-ET. INTERVENTIONS: Before randomization, all patients received the same ovarian stimulation preparation, oocyte retrieval procedures, and the same intracytoplasmic sperm injection procedures. After randomization, laser-assisted hatching was performed only for embryos of 158 patients, while the other group (n = 150) no laser-assisted hatching was made. The verification of pregnancy was achieved by the serum hCG concentration 14 days after the embryo transfer, and the clinical pregnancy was confirmed 2 weeks later by the presence of gestational sac with pulsating fetal pole on vaginal ultrasonography. MEASUREMENTS: The main outcome measures were the clinical pregnancy rate and the clinical implantation rate. MAIN RESULTS: Both groups were comparable with regard their baseline characteristics, baseline hormonal profile, the ovarian stimulation characteristics, and the ovulation characteristics. The mean number of embryos developed per patient and the mean transferred number of embryos per patient were comparable between groups (p value > 0.05). The implantation rate was significantly higher (p value 0.002) in the study group than the control group with an odds ratio of 1.86 (CI 95% 1.24-2.80) and NNT 13.81 (CI 95% 8.35-39.94). The clinical pregnancy rate, was significantly (p value 0.022) higher in the study group than in the control group with an odds ratio of 1.79 (CI 95% 1.05-3.06) and NNT 9.57 (CI 95% 5.03-98.99). CONCLUSION: That laser-assisted hatching by thinning of the zona pellucida may be a suitable method to improve the ICSI-ET outcomes, in term of the implantation and the pregnancy rates, in cases of endometriosis. CLINICAL TRIAL REGISTRATION: Pan African Clinical Trials Registry (PACTR), http://www.pactr.org/ATMWeb/appmanager/atm/atmregistry?dar=true&tNo=PACTR201502001022393 , PACTR201602001467322.

MicroRNA expression analysis in endometriotic serum treated mesenchymal stem cells.

Endometriosis is defined by presence of endometrial-like-tissue outside the uterus. Recently, ectopic endometriotic lesions have been suggested to originate by abnormal differentiation of endometrial mesenchymal stem cells (eMSCs). MicroRNAs (miRNAs) play an important role in the pathophysiology of endometriosis. Through a PCR array approach, we aimed to assess the differential expression of microRNAs in human eMSC treated in culture with sera derived from women with severe endometriosis. Sera were collected from five patients with severe endometriosis and three control women and added individually in the culture medium to conduct experimental and control eMSC sets, respectively. Regular microscopic follow-up for cell morphology was performed. SYBR Green based real-time PCR array was used to assess the expression of 84 miRNAs. Bioinformatics analysis was done to predict the target genes of the significantly dysregulated miRNAs and their enriched biological processes and pathways. Thirty-two miRNAs were found significantly dysregulated in experimental cultures. Functional enrichment analysis revealed several endometriosis associated biological processes and pathways were enriched by target genes of these miRNAs. In conclusion, treatment of human eMSCs with sera of severe endometriosis cases affects the expression of certain miRNAs and their target genes. This may result in altering cell functions and consequently, endometriosis development.

Is mini-mental score examination scoring a new predictor of uncontrolled hypertension?

Essential hypertension is an important risk factor for target organ damage. The brain is among the target organs infrequently visited. The authors evaluated whether an abnormal Mini-Mental Score Examination (MMSE) score predicts uncontrolled hypertension even if office blood pressure is normal. Seventy-seven hypertensive patients were included. The cognitive function of each patient was assessed using MMSE and a customized brain magnetic resonance imaging study. Patients were classified into normal cognitive function group and mild, moderate, and severe cognitive impairment groups. A significance level of P=.05 was used. There was a higher percentage of uncontrolled BP in every cognitive impairment class. In patients older than 65 years, MMSE score had a sensitivity and specificity of 94% and 83%, respectively, in the prediction of uncontrolled hypertension. MMSE is a simple test to run in the clinic to predict whether patients have well-controlled blood pressure.

Long-term outcomes (>2 years) of atrial fibrillation ablation using a multi-electrode ablation catheter in patients with paroxysmal atrial fibrillation.

PURPOSE: Catheter ablation for paroxysmal atrial fibrillation (PAF) is an effective treatment. Favourable outcomes at 6-12 months post-ablation have been reported using the multi-electrode catheter 'pulmonary vein ablation catheter (PVAC)' but little is known about longer term outcomes. There are also limited data on quality of life (QoL) post-atrial fibrillation (AF) ablation beyond 2 years of follow-up. METHODS: Two hundred three consecutive patients (77 % male, mean age 57.7 ± 11 years) who had a PAF ablation were included. Patients underwent conventional pulmonary vein isolation (PVI) (n = 128) or PVAC ablation (n = 75). Patients' symptoms were scored at baseline, at clinic follow-up and on questionnaire follow-up using the validated Canadian Cardiovascular Society Severity of AF (CCS-SAF) scale. The 'AF Effect on QualiTy of life' (AFEQT) questionnaire was used on questionnaire follow-up. RESULTS: Mean questionnaire follow-up was 854 ± 176 days with 74 % response rate. The majority of patients (91.6 % overall) were highly symptomatic at baseline with CCS-SAF class 3 or 4 symptoms. CCS-SAF class on follow-up questionnaire decreased significantly from baseline for both groups (mean 1.69 ± 1.7 for PVAC and 1.45 ± 1.5 for PVI, p = 0.001 and p < 0.001, respectively) with no difference between groups (p = 0.52) and the majority being class 0 or 1 (59.9 % overall). Mean AFEQT questionnaire scores were similar between both groups (78.1 ± 25 vs. 82 ± 23, p = 0.35). Total procedure time was significantly shorter in the PVAC group (135 ± 54 vs. 178 ± 43 min, p < 0.001). CONCLUSION: There was a comparable and significant improvement in QoL post-ablation in patients who underwent ablation using PVAC catheter and conventional techniques.