ObjectiveTo prepare a set of statements for randomised clinical trials (RCT) integrity through an international multi-stakeholder consensus.MethodsThe consensus was developed via multi-country multidisciplinary stakeholder group composition and engagement; evidence synthesis of 55 systematic reviews concerning RCT integrity; anonymized two-round modified Delphi survey with consensus threshold based on the average percentage of majority opinions; and a final consensus development meeting. Prospective registrations: (https://osf.io/bhncy, https://osf.io/3ursn).ResultsThere were 30 stakeholders representing 15 countries from five continents including trialists, ethicists, methodologists, statisticians, consumer representatives, industry representatives, systematic reviewers, funding body panel members, regulatory experts, authors, journal editors, peer reviewers and advisors for resolving integrity concerns. Delphi survey response rate was 86.7% (26/30 stakeholders). There were 111 statements (73 stakeholder-provided, 46 systematic review-generated, 8 supported by both) in the initial long list, with eight additional statements provided during the consensus rounds. Through consensus the final set consolidated 81 statements (49 stakeholder-provided, 41 systematic review-generated, 9 supported by both). The entire RCT life cycle was covered by the set of statements including general aspects (n = 6), design and approval (n = 11), conduct and monitoring (n = 19), reporting of protocols and findings (n = 20), post-publication concerns (n = 12) and future research and development (n = 13).ConclusionImplementation of this multi-stakeholder consensus statement is expected to enhance RCT integrity.

BackgroundHyperandrogenism is frequently found in polycystic ovary syndrome (PCOS) and contributes to physical manifestations like hirsutism and obesity, along with infertility. This condition can result in anxiety, depression, and body image disorders, potentially leading to sexual dysfunction. The objective of this investigation was to assess the correlation among hirsutism, anthropometric characteristics, sexual dysfunction, and anxiety levels among infertile Indonesian women diagnosed with PCOS.MethodsFrom December 2021 to December 2022, a cross-sectional study was undertaken involving 71 infertile women diagnosed with PCOS at Yasmin Clinic, Dr. Cipto Mangunkusumo General Hospital in Jakarta, Indonesia. Hirsutism was assessed using the modified Ferriman-Gallwey (mFG) score; the anthropometric profile was assessed using BMI and waist-to-hip ratio. The assessment of sexual dysfunction was conducted using the Female Sexual Function Index (FSFI) questionnaire, while the evaluation of anxiety levels utilized the HAM-A questionnaires.ResultsIn this study, it was discovered that 53.3% of subjects experienced sexual dysfunction. However, there was no statistically significant relationship between hirsutism, anthropometric profile, and sexual dysfunction score in infertile women with PCOS (p > 0.05). Analysis of the overall FSFI domain score revealed that lubrication and satisfaction were lower in obese patients (p = 0.02 and p = 0.03), but this did not contribute to an overall sexual dysfunction score. Also, we found that subjects who experienced sexual dysfunction had a higher anxiety score (p < 0.005), with correlation analysis showing that Ferriman-Gallwey (FG) scores have a significant positive correlation with anxiety.ConclusionThere is no correlation between hirsutism, anthropometric profile, and sexual dysfunction in infertile Indonesian women diagnosed with PCOS. However, hirsutism could play a role in causing anxiety in Indonesian PCOS women. Additional investigation is required, as female sexual function is an intricate subject.

BackgroundWomen with type 1 diabetes depend on insulin injections throughout their life. However, the recommendation for strict metabolic control of diabetes requires the administration of supra-physiological doses of insulin, which might result in insulin-mediated stimulation of androgen synthesis. Hyperandrogenism in women with type 1 diabetes may be associated with polycystic ovary syndrome (PCOS). This study was performed to investigate PCOS and its associated clinical symptoms and biochemical alterations in women with type 1 diabetes in the Palestinian Territories. This retrospective cohort study consists of 50 women with type 1 diabetes and 50 apparently healthy non-diabetic controls. Questionnaire interviews were conducted. The diagnosis of PCOS was based on chronic anovulation and biochemical evidence of hyperandrogenism. Serum total testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and insulin were measured by ELISA.ResultsThe mean waist-to-hip ratio and age at menarche were significantly higher in diabetic women than in non-diabetic controls (81.9 ± 7.9 and 13.9 ± 1.6 years vs. 78.8 ± 5.7 and 13.2 ± 1.2 years, and P = 0.045, P = 0.020, respectively). Oligomenorrhea, acanthosis nigricans, seborrhea, and hirsutism were more frequent in diabetics. The levels of total testosterone and insulin were significantly higher in diabetics (0.58 ± 0.11 ng/ml and 15.8 ± 12.4 mlU/ml vs. 0.44 ± 0.11 ng/ml and 10.8 ± 4.5 mlU/ml, P < 0.001 and P = 0.010, respectively). PCOS was present in 11 (22.0%) of diabetic women compared to 3 (6.0%) in non-diabetics (P = 0.044). Diabetic women with PCOS received higher doses of insulin than non-PCOS women (72.7 ± 23.9 vs. 55.0 ± 19.8 UI.cc/ml/day, P = 0.023). PCOS women showed more frequent oligomenorrhea (100% vs. 15.4%, P < 0.001) and higher levels of total testosterone and insulin (0.64 ± 0.09 and 23.1 ± 13.0 vs. 0.53 ± 0.11 and 14.1 ± 11.8, P = 0.023 and P = 0.041, respectively). PCOS cases were significantly more frequent in diabetic women receiving intensive insulin therapy than their counterparts with non-intensive insulin therapy (40.9% vs. 7.1%, P = 0.012).ConclusionIntensive insulin treatment in type 1 diabetes potentiates the development of PCOS and its related clinical and biochemical features particularly oligomenorrhea, hyperinsulinemia, and hyperandrogenemia.

BackgroundThis retrospective study aimed to compare the outcomes of day 3 double embryo transfer (DET) with single blastocyst transfer (SBT) during frozen embryo transfer (FET) cycles. A total of 999 women below the age of 38 years who underwent FET at Malaysia’s KL Fertility and Gynaecology Centre from January 2019 to December 2021 were analyzed. Patients with autologous eggs were recruited in the study. All the eggs were inseminated by intracytoplasmic sperm injection. The embryos were vitrified on day 3 cleavage-stage or blastocyst stage with Cryotop® method. The FET was performed following natural cycle (NC), modified natural cycle (m-NC), or hormone replacement therapy (HRT) cycles. The NC and m-NC groups received oral dydrogesterone for luteal phase support.ResultsThere were no statistical differences in the rates of positive pregnancy, clinical pregnancy, and ongoing pregnancy between the two groups. However, implantation rates were significantly higher in the SBT group (50.1% versus 37.6%, p < 0.05). The day 3 DET group had significantly higher multiple pregnancy rates (28.7% versus 1.1%, p < 0.05). Subgroup analysis of embryo transfers performed following NC, m-NC, or HRT cycles showed similar results.ConclusionsThis study suggests that SBT is the better choice for embryo transfers as it had higher implantation rates and its pregnancy rates were similar to day 3 DET. The SBT also significantly reduced the incidence of multiple pregnancies without compromising pregnancy rates.

BackgroundMeiotic and mitotic errors often lead to aneuploidy and mosaicism. In this context, the self-correction mechanism enables the embryo to preferentially retain and preserve euploid cells through processes such as apoptosis, necrosis, or marginalization. This mechanism is thought to minimize the chance of genetic abnormalities during cell development.Materials and methodsA literature search for articles written in English from January 2013 to October 2023 was conducted on PubMed, EBSCO, and Scopus, using the keywords “self-correction,” “self-repair,” “aneuploidy,” “mosaicism,” and “embryo.”ResultsA total of 308 articles were collected, out of which 5 retrospective and 1 prospective study were selected based on inclusion criteria.DiscussionsInvestigations showed that embryos remove chromosomally abnormal cells, supporting the self-correction mechanism. aCGH has been used in 4 studies to demonstrate the presence of self-correction in mosaic embryos. Furthermore, a higher relative viability of polyploidies than complex aneuploidies was observed, suggesting early discrimination against complex aneuploidy, particularly those arising from mitotic origins. However, there are doubts about the reliability of preimplantation genetic testing for aneuploidy at the blastocyst stage, as it may lead to a high rate of false positives and the discarding of "good" embryos.ConclusionsStudies showed a self-correction mechanism in human embryos through the ability to expel abnormal cells. Further investigation is needed to elucidate the underlying mechanisms and determine optimal strategies for preimplantation genetic testing to fully understand and optimize the use of self-correction mechanisms in embryo assessment and selection.

BackgroundConsidering the close link between polycystic ovary syndrome (PCOS) and metabolic syndrome considerable research has been devoted to studying the pattern of fat distribution in PCOS.ObjectivesThe study aims to assess the usefulness of dual-energy X-ray absorptiometry (DEXA) based regional fat distribution indices as a predictor of the development of PCOS.MethodsThis case–control study recruited diagnosed cases of PCOS using Rotterdam Criteria (cases n = 86) and healthy age-matched controls (n = 90). DEXA was performed in both groups for assessment of total and regional body fat distribution after undergoing ultrasonography (USG) and baseline/biochemical evaluation.ResultsThe study revealed a significant difference between cases and controls in trunk fat percentage (40.2% ± 9.1% vs 26.5% ± 9.1%; p < 0.001), android fat percentage (42.4% ± 41%vs 27.8% ± 1.51%; p < 0.001), total fat percentage (43.8% ± 8% vs28.5% ± 1.6%; p < 0.001), fat mass/ht2 (fat mass index) (8.82 ± 3% vs 4.8 ± 1.7%; p < 0.001), android/gynoid ratio (1.05 ± 0.1 vs 0.7 ± 0.2; p < 0.001), and trunk/limb fat mass ratio (1.06 ± 0.3 vs 0.69 ± 0.3; p 0.001). Multivariate analysis revealed a significant relation of trunk fat mass with android % fat, gynoid fat mass, and android-gynoid ratio.ConclusionsThe study demonstrates that there is a central pattern of fat distribution in patients with PCOS while the overall fat might not be increased which is well analyzed by DEXA. Hence, we suggest its use in the initial diagnostic workup and follow-up of PCOS patients for their body fat distribution and content.

BackgroundSurgery is the main line of treatment of endometriosis. Patients with stage IV endometriosis have more extensive adhesions, which make the surgery difficult. There are no accurate non-invasive predictive preoperative parameters of stage IV endometriosis and no consensus has been reached.Therefore, the aim of the present study was to evaluate and detect preoperative non-invasive parameters for the detection of stage IV endometriosis.Patients and methodsIn the present study, we included 150 females admitted for surgical removal of endometriosis. We scored and classified endometriosis into four stages according to the revised ASRM classification. We compared between baseline characteristics of patients with different stages of endometriosis, and then we selected the best combination of diagnostic and predictive parameters of stage IV endometriosis.ResultsPredictors of stage IV endometriosis and indicators for safety surgery were as follows: VAS ≥ 4 (p < 0.001), fixed uterus (p = 0.005), fixed ovarian cysts (p < 0.001), tender uterosacral ligament nodule (p < 0.001), tender rectovaginal septum nodule (p = 0.003), bilateral endometriosis (p < 0.001), and sum of sizes of endometriotic nodules (p < 0.001).ConclusionFixed uterus, fixed ovarian cysts, tender uterosacral ligament nodule, tender rectovaginal septum nodule, bilateral endometriosis, and indications for surgery were significantly considered adequate predictive markers for stage IV endometriosis.

BackgroundFolliculogenesis is an intricate process that involves the development and maturation of ovarian follicles in females. During folliculogenesis, multiple factors including hormones, growth factors, and signaling pathways regulate the growth and maturation of follicles. In recent years, microRNA, short non-coding RNA molecules, has gained attention due to its roles in the physiology and pathophysiology of various diseases in humans. It is known to have an important part in ovarian health and illness and its functions extend to several cellular processes.Main bodyIn this overview, we look at the importance of microRNAs in ovarian illnesses and how they function during follicle growth in the ovaries. Short RNA molecules (22 nucleotides) called microRNAs may influence several mRNA targets in different biological processes. The expression patterns of these small non-coding RNAs undergo dynamic changes during the several phases of follicular development; they play a function in post-transcriptional gene regulation. Follicle development, follicular atresia (regression of the follicles), and ovulation are all intricately regulated by the dynamic expression of distinct miRNAs throughout the various phases of folliculogenesis.The role of microRNAs (miRNAs), which are known to regulate gene expression, has recently come to light as crucial in the development and advancement of a number of ovarian diseases. Abnormalities of the human ovary, such as ovarian cancer, polycystic ovary syndrome (PCOS), and endometriosis, have prompted extensive research into the dysregulation of microRNAs. Endometriosis is associated with miRNAs that are known to have a role in processes such as invasion, cell growth, cell adhesion, angiogenesis, and epithelial-mesenchymal transition. The disturbance of target gene expression resulting from abnormal miRNA production is a potential factor contributing to cancer development. Some microRNAs (miRNAs) differ in expression levels between women with polycystic ovary syndrome and healthy controls, indicating that miRNAs may play a role in the development of PCOS.ConclusionExtensive research carried out over the last 20 years has illuminated the roles of microRNAs (miRNAs), demonstrating their critical importance in controlling gene expression and the cell cycle. Changes in the quantities of microRNAs (miRNAs) may affect the aggressiveness of cancer and contribute to a variety of gynecological disorders. It appears that microRNAs hold potential as diagnostic biomarkers and treatment potential for various ovarian diseases.

BackgroundPGT-A has become an important part of IVF treatments. Despite its increased use, there are contradicting results on its role in improving reproductive outcomes of ART cycles. Given that aneuploidy is a main limiting factor for IVF success, we aimed to study the predictive factors of aneuploidy in infertile patients undergoing IVF and hence highlight the patients who would benefit the most from genetic testing.ResultsA retrospective analysis of 1242 blastocysts biopsied in the setting of PGT-A cycles was performed. The euploid group included 703 embryos, while the aneuploid group had 539 embryos. The factors included in the analyses were the couple’s history as well as the embryo characteristics. The primary outcome was the rate of aneuploid embryos per patient’s history as well as per embryo characteristics. The aneuploidy rate (AR) in our cohort was 43.4%. The woman’s age was found to be a significant predictor (OR 1.045, 95% CI 1.008–1.084, p = 0.016). Biopsy on day 5 as well as degree of expansion 3 was also found to affect significantly (OR 0.724, 95% CI .541–.970, p = 0.03 and OR 2.645, 95% CI 1.252–5.585, p = 0.011). Lack of consanguinity decreased the AR by an OR 0.274 with 95% CI .137–.547, p < 0.001. The number of blastocysts available, trophectoderm quality, embryo grade, gonadotropins as well as trigger used were not found to be significant predictors (p = 0.495, 0.649, 0.264, 0.717 and 0.659 respectively).ConclusionAdvanced female age, consanguinity, the day of embryo biopsy, and the degree of blastocyst expansion were all found to affect the incidence of AR. The age of the male partner, cause of infertility, and grade of embryo at biopsy were not found to correlate with aneuploidy.

BackgroundIncreased surgical efficacy has led to a remarkable increase in the usage of minimally invasive surgical procedures since their inception. The use of simulation in surgical teaching has grown significantly during the past 10 years. Several laparoscopic simulators have been built. Virtual reality (VR) simulators and box trainers (BTs), often known as pelvic trainers, are the two primary training modalities used in hospitals and clinical training institutes for the development and acquisition of laparoscopic skills. Our study aimed to evaluate the proper sequence of pelvic trainers and VR simulator training to improve laparoscopic gynecological skills.MethodologyWe carried out this pilot study at the Virtual Endoscopic Simulation and Skills Acquisition Laboratory at the Obstetrics and Gynecology Department in the Kasr Al Ainy Hospital, Faculty of Medicine, Cairo University, Egypt, from February to August 2022. All residents with minimal or without laparoscopic experience (twenty residents) were divided into two groups and classified as (group A versus group B). Group A’s training began with a pelvic trainer, which was tested using a checklist. Later, the group trained on a virtual reality simulator, which tested them using an electronic autoassessment. After training on a virtual reality simulator and passing an electronic autoassessment test, group B moved on to pelvic trainers and had a checklist-based assessment.ResultsWe compared pelvic trainer tasks between the training groups, and detected no significant differences in camera navigation, cutting pattern, peg transfer, or running stitches (P values 0.646, 0.341, 0.179, and 0.939 respectively); when we compared VR simulator tasks between the training groups, there were no significant differences in camera navigation, cutting pattern, peg transfer, or running stitches (P values 0.79, 0.3, 0.33, and 0.06, respectively).ConclusionThere was no difference in training, between residents who started on a pelvic trainer or the VR simulator; therefore, both could be used in laparoscopic training with no preferred order.Trial registrationThe trial was registered at clinicaltrials.gov with the name “Pelvic trainer vs VRS” and the identifier “NCT05255614.” The registration date was January 19, 2022, and the trial was prospectively registered. URL: https://register.clinicaltrials.gov/prs/app/action/ViewOrUnrelease?uid=U0004GED&ts=22&sid=S000BR5D&cx=t6mc14