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      Recent advances in understanding and managing male infertility

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          Abstract

          Infertility is a prevalent condition affecting an estimated 70 million people globally. The World Health Organization estimates that 9% of couples worldwide struggle with fertility issues and that male factor contributes to 50% of the issues. Male infertility has a variety of causes, ranging from genetic mutations to lifestyle choices to medical illnesses or medications. Recent studies examining DNA fragmentation, capacitation, and advanced paternal age have shed light on previously unknown topics. The role of conventional male reproductive surgeries aimed at improving or addressing male factor infertility, such as varicocelectomy and testicular sperm extraction, have recently been studied in an attempt to expand their narrow indications. Despite advances in the understanding of male infertility, idiopathic sperm abnormalities still account for about 30% of male infertility. With current and future efforts examining the molecular and genetic factors responsible for spermatogenesis and fertilization, we may be better able to understand etiologies of male factor infertility and thus improve outcomes for our patients.

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          Most cited references 38

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          Sperm chromatin damage impairs human fertility. The Danish First Pregnancy Planner Study Team.

          To examine the relationship between sperm chromatin defects, evaluated by the flow cytometric (FCM) sperm chromatin structure assay (SCSA), and the probability of a pregnancy in a menstrual cycle (fecundability). Follow-up study. The Section of Toxicology and Biomedical Sciences, ENEA Casaccia, Rome, Italy, and the Department of Occupational Medicine, Aarhus University Hospital, Aarhus, Denmark. Two hundred fifteen Danish first pregnancy planners with no previous knowledge of their fertility capability. None. Semen samples were collected at enrollment to measure semen volume, sperm concentration, motility, and morphology (by microscopy), as well as chromatin susceptibility to in situ, acid-induced partial denaturation by the FCM SCSA. Time to pregnancy was evaluated during a 2-year follow-up period. Demographic, medical, reproductive, occupational, and lifestyle data were collected by questionnaire. Fecundability was correlated with SCSA-derived parameters. Fecundability declines as a function of the percentage of sperm with abnormal chromatin and becomes small when aberrant cells are >40%. Optimal sperm chromatin packaging seems necessary for full expression of the male fertility potential. The SCSA emerged as a predictor of the probability to conceive in this population-based study.
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            Varicocele and male factor infertility treatment: a new meta-analysis and review of the role of varicocele repair.

            Varicocele is a common condition, found in many men who present for infertility evaluation. To assess the effect of varicocelectomy on male infertility. A literature search was performed using Embase and Medline. Literature reviewed included meta-analyses and randomized and nonrandomized prospective (controlled and noncontrolled) studies. In addition, a new meta-analysis was performed. Four randomized controlled trials reporting on pregnancy outcome after repair of clinical varicoceles in oligozoospermic men were identified. Using the random effect model, the combined odds ratio was 2.23 (95% confidence interval [CI], 0.86-5.78; p=0.091), indicating that varicocelectomy is moderately superior to observation, but the effect is not statistically significant. We identified 22, 17, and 5 prospective studies reporting on sperm concentration, total motility, and progressive motility, respectively, before and after repair of clinical varicocele. The random effect model combined improvement in sperm concentration was 12.32 million sperm per milliliter (95% CI, 9.45-15.19; p<0.0001). The random effect model combined improvement in sperm total and progressive motility were 10.86% (95% CI, 7.07-14.65; p<0.0001) and 9.69% (95% CI, 4.86-14.52; p=0.003), respectively. These results indicate that varicocelectomy is associated with a significant increase in sperm concentration as well as total and progressive motility. Prospective studies also show that varicocelectomy reduces seminal oxidative stress and sperm DNA damage as well as improving sperm ultramorphology. Studies indicate that a microsurgical approach to a varicocele repair results in less recurrence and fewer complications than other techniques. Although there is no conclusive evidence that a varicocele repair improves spontaneous pregnancy rates, varicocelectomy improves sperm parameters (count and total and progressive motility), reduces sperm DNA damage and seminal oxidative stress, and improves sperm ultramorphology. The various methods of repair are all viable options, but microsurgical repair seems to be associated with better outcomes. Copyright © 2011. Published by Elsevier B.V.
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              Comparison of reproductive outcome in oligozoospermic men with high sperm DNA fragmentation undergoing intracytoplasmic sperm injection with ejaculated and testicular sperm.

              To investigate the effectiveness of intracytoplasmic sperm injection (ICSI) using testicular sperm as a strategy to overcome infertility in men with high sperm DNA fragmentation (SDF).
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Project AdministrationRole: Writing – Original Draft Preparation
                Role: ConceptualizationRole: SupervisionRole: Writing – Review & Editing
                Journal
                F1000Res
                F1000Res
                F1000Research
                F1000Research
                F1000 Research Limited (London, UK )
                2046-1402
                16 May 2019
                2019
                : 8
                Affiliations
                [1 ]Department of Urology, Weill Cornell Medicine, 525 E. 68th Street, New York, NY, 10011, USA
                Author notes

                No competing interests were disclosed.

                Article
                10.12688/f1000research.17076.1
                6524745
                399a6b76-aa3c-4570-9e25-c6cc7714f18c
                Copyright: © 2019 Fainberg J and Kashanian JA

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                The author(s) declared that no grants were involved in supporting this work.
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