The Egyptian IVF-ET Center

Oxidative stress (OS) is established as a key factor in the etiology of both male and female infertility, arising from an imbalance between reactive oxygen species (ROS) production and the endogenous antioxidant (AOX) defenses. In men, OS adversely affects sperm function by inducing DNA damage, reducing motility, significantly impairing sperm vitality through plasma membrane peroxidation and loss of membrane integrity, and ultimately compromising overall sperm quality. In women, OS is implicated in various reproductive disorders, including polycystic ovary syndrome, endometriosis, and premature ovarian failure, leading to diminished oocyte quality, disrupted folliculogenesis, and poorer reproductive outcomes. Antioxidant therapy represents a promising intervention to mitigate the harmful effects of ROS on reproductive health in additions to its easy accessibility, safety, and low cost. Despite several findings suggesting improvements in fertility potential with AOX therapy, the data remains inconclusive regarding optimal dosage and combination, duration of treatment, and the specific patient populations most likely to benefit. In this review, we discuss the role of AOXs in the management of infertile couples, focusing on their biological mechanisms, potential adverse effects, therapeutic efficacy, and clinical applications in improving reproductive outcomes in both natural conception and medically assisted reproduction. Additionally, we highlight the current practice patterns and recommendations for AOX supplementation during the course of infertility treatment. Further, we provide an overview on the limitations of the current research on the topic and insights for future studies to establish standardized AOX regimens and to assess their long-term impact on key outcomes such as live birth rates and miscarriage rates.

In this systematic review and meta-analysis, we investigated the relationship between varicocele and sperm DNA fragmentation (SDF) alongside conventional semen parameters. A comprehensive systematic search was conducted to identify articles on SDF in men with varicocele published in the Scopus and PubMed databases. This included observational studies investigating levels of SDF as a primary outcome and conventional semen parameters as secondary outcomes in men with varicocele compared to men without varicocele. Out of 476 retrieved articles, 40 met our inclusion criteria, with 35 included in our quantitative synthesis. Our analysis revealed that men with varicocele showed significantly higher SDF than men without varicocele (mean difference [MD] 15.34, 95% confidence interval [95% CI]: 9.74-20.9; p<0.001). The evaluation of SDF using different assays did not affect the results (p=0.7). Our results indicated a significant effect of varicocele on sperm concentration (MD -29 million/mL, 95% CI: -37, -21; p<0.001), total sperm count (MD -188 million/ejaculate, 95% CI: -325, -52; p=0.007), sperm vitality (MD -5.7%, 95% CI: -8.6, -2.8; p<0.001), total sperm motility (MD -17%, 95% CI: -29.0, -5.3; p=0.004), progressive sperm motility (MD -17%, 95% CI: -23,-11, p<0.001), normal sperm forms (MD -3.1%, 95% CI: -4.3, -1.8, p<0.001) and abnormal sperm forms (MD 2.25%, 95% CI: 0.77, 3.73; p=0.003). However, semen volume and the total motile sperm count were not significantly different between both groups (MD -113 million/ejaculate, 95% CI: -244.0, 18.1; p=0.09). Varicocele negatively impacts male fertility by increasing SDF. Our study supports using SDF analysis in patients with varicocele to aid clinicians in deciding on varicocele repair.

There have been many significant scientific advances in the diagnostics and treatment modalities in the field of male infertility in recent decades. Examples of these include assisted reproductive technologies, sperm selection techniques for intracytoplasmic sperm injection, surgical procedures for sperm retrieval, and novel tests of sperm function. However, there is certainly a need for new developments in this field. In this review, we discuss advances in the management of male infertility, such as seminal oxidative stress testing, sperm DNA fragmentation testing, genetic and epigenetic tests, genetic manipulations, artificial intelligence, personalized medicine, and telemedicine. The role of the reproductive urologist will continue to expand in future years to address different topzics related to diverse questions and controversies of pathophysiology, diagnosis, and therapy of male infertility, training researchers and physicians in medical and scientific research in reproductive urology/andrology, and further development of andrology as an independent specialty.

Abstract Study question To compare PGT-A outcomes of Physiological ICSI (PICSI) and magnetic activated cell sorting (MACS) sperm selection techniques to a control of normal sperm DNA fragmentation. Summary answer PGT-A outcomes did not differ between using normal sperm DNA fragmentation semen to the semen processed by PICSI or MACS. What is known already Sperm DNA fragmentation can negatively affects pre-implantation embryo development in all stages after ICSI. Advanced sperm selection techniques like PICSI and MACS are thought to be efficient to improve fertilization, cleavage, and blastocyst formation rates in cases with abnormal SDF. It has become evident that a blastocyst's aneuploidy is not only contributed by the oocyte,but can also be caused by the sperm.The relation between sperm selection techniques such as PICSI or MACS and blastocyst euploidy is not investigated yet. Study design, size, duration A prospective randomized controlled trial of 351 ICSI cycles in a private fertility center, from October 2019 to December 2022. Cases were included in the study if: female had ≥5 MII oocytes, male had abnormal sperm DNA fragmentation (SDF) index (&amp;gt;20% by TUNEL assay), all blastocysts (≥4BB) had trophoectoderm biopsy. Participants/materials, setting, methods Included cases were randomized on the day of ICSI to PICSI or MACS group, along with a control arm of cases with normal SDF needed for comparison. PGT-A was done using Illumina platform (Miseq), and the results were reviewed by artificial intelligence (Cooper Surgical). Cases were categorized according to the female age into 2 subgroups(&amp;lt;35, and &amp;gt; 35 years). Statistical analysis of all pre-implantation embryo development parameters and PGT-A results were done using SPSS. Main results and the role of chance We found no significant differences between the female age, male age, count, motility, SDF, no. mature oocytes between the studied groups. Limitations, reasons for caution The results included all pre-implantation embryo parameters but, subsequent post-implantation events like implantation, pregnancy and miscarriage rates will add more data about the competency of the resulted embryos. Wider implications of the findings The usage of advanced sperm selection techniques like PICSI or MACS has showed comparable results to that of normal SDF cases, through eliminating the adverse effects of SDF on ICSI and PGT-A outcomes. Trial registration number NCT05494216

Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method. A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4-6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians.

PurposeSystematic reviews and meta-analyses (SRMAs) are used to generate evidence-based guidelines. Although the number of SRMAs published in the literature has increased dramatically in the last decade, the training and the experience of the researchers performing the SRMAs are usually not explained in the SRMAs’ methodology, and this may be a source of bias. Although some studies pointed out the need for quality control of SRMAs and training in proper statistical methods, to the best of our knowledge, no study has reported the importance of training the researchers that conduct the SRMAs. The aim of this study is to describe a training program designed to impart the essential knowledge and skills required for the conduct of an SRMA and to assess the need for, and outcome of, such a training.Materials and MethodsResearchers were trained for use of Scopus, study eligibility, assessment of the quality of evidence (QoE) through the Cambridge Quality Checklist for observational studies, as well as the Cochrane Risk of Bias tool, the Consolidated Standards of Reporting Trials (CONSORT) guidelines, and the Jadad score for randomized controlled trials (RCTs), Population, Intervention, Comparison, Outcome (PICO) questions and data extraction. A total of 35 of them were approved to join a planned SRMA. At the end of the SRMA, they were administered 43 multiple-choice questions (MCQs) on demographics, motivation for participation in the SRMA, self-perceived change in knowledge before and after conducting the SRMA, and self-assessment of performance. The senior researchers then revised the spreadsheet of the SRMA and, based on the mistakes found, organized a training focused on the correct assessment of the study design, where 43 researchers (9 joined midway) and 11 trainees with no experience in conducting SRMA attended. They all were tested through a 5 MCQ assessment that was administered before and after the training. Those scoring poorly were re-trained and re-tested, and only those scoring satisfactorily were admitted to further SRMAs.ResultsApproximately 54.3% of the participants were medical doctors (MD), 31.4% were urologists and 48.6% had previous experience with SRMAs. Joining an international collaborative study was the main motivation, chosen by 19.7% of researchers. The results of the self-perceived change in knowledge showed a significant improvement in the use of Scopus, checklists for QoE, PICO questions, data required to perform a meta-analysis, and critical reading of scientific articles. Also, the majority of the researchers ranked the quality of their work as high. The pre-test results of the 5 MCQ showed a low score, which was not different from that achieved by a group of fresh trainees (median, 2; IQR 1–3 vs. median, 1; IQR, 1–2; p=0.3). Post-training there was significant improvement in both groups (researchers: median, 4; IQR, 3–5 vs. median, 2; IQR, 1–3; p<0.001; trainees: median, 4; IQR, 3–4 vs. median, 1; IQR, 1–2; p=0.02). Out of the 44 researchers, 12 (27.3%) scored poorly (≤3). After re-training, all of them scored satisfactorily (>3) and were admitted to subsequent SRMAs.ConclusionsAt the end of our model, 100% of researchers participating in this study were validated to be included in a meta-analysis. This validation required the involvement of the MT, two meetings, a self-evaluation survey, and one or two sets of objective tests with explanations and corrections. Our results indicate that even well-trained clinicians are naïve when it comes to the methodology of SRMA. All the researchers performing an SRMA need comprehensive training that must cover each aspect of the SRMA methodology. This paper provides a replicable training program that could be used by other investigators to train the researchers to perform high-quality SRMAs.