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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 references38

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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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            A systematic review and meta-analysis to determine the effect of sperm DNA damage on in vitro fertilization and intracytoplasmic sperm injection outcome

            Sperm DNA damage is prevalent among infertile men and is known to influence natural reproduction. However, the impact of sperm DNA damage on assisted reproduction outcomes remains controversial. Here, we conducted a meta-analysis of studies on sperm DNA damage (assessed by SCSA, TUNEL, SCD, or Comet assay) and clinical pregnancy after IVF and/or ICSI treatment from MEDLINE, EMBASE, and PUBMED database searches for this analysis. We identified 41 articles (with a total of 56 studies) including 16 IVF studies, 24 ICSI studies, and 16 mixed (IVF + ICSI) studies. These studies measured DNA damage (by one of four assays: 23 SCSA, 18 TUNEL, 8 SCD, and 7 Comet) and included a total of 8068 treatment cycles (3734 IVF, 2282 ICSI, and 2052 mixed IVF + ICSI). The combined OR of 1.68 (95% CI: 1.49–1.89; P < 0.0001) indicates that sperm DNA damage affects clinical pregnancy following IVF and/or ICSI treatment. In addition, the combined OR estimates of IVF (16 estimates, OR = 1.65; 95% CI: 1.34–2.04; P < 0.0001), ICSI (24 estimates, OR = 1.31; 95% CI: 1.08–1.59; P = 0.0068), and mixed IVF + ICSI studies (16 estimates, OR = 2.37; 95% CI: 1.89–2.97; P < 0.0001) were also statistically significant. There is sufficient evidence in the existing literature suggesting that sperm DNA damage has a negative effect on clinical pregnancy following IVF and/or ICSI treatment.
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              Paternal obesity negatively affects male fertility and assisted reproduction outcomes: a systematic review and meta-analysis.

              This systematic review investigated the effect of paternal obesity on reproductive potential. Databases searched were Pubmed, Ovid, Web of Science, Scopus, Cinahl and Embase. Papers were critically appraised by two reviewers, and data were extracted using a standardized tool. Outcomes were: likelihood of infertility, embryo development, clinical pregnancy, live birth, pregnancy viability, infant development, sperm; concentration, morphology, motility, volume, DNA fragmentation, chromatin condensation, mitochondrial membrane potential (MMP), and seminal plasma factors. Thirty papers were included, with a total participant number of 115,158. Obese men were more likely to experience infertility (OR = 1.66, 95% CI 1.53-1.79), their rate of live birth per cycle of assisted reproduction technology (ART) was reduced (OR = 0.65, 95% CI 0.44-0.97) and they had a 10% absolute risk increase of pregnancy non-viability. Additionally, obese men had an increased percentage of sperm with low MMP, DNA fragmentation, and abnormal morphology. Clinically significant differences were not found for conventional semen parameters. From these findings it can be concluded that male obesity is associated with reduced reproductive potential. Furthermore, it may be informative to incorporate DNA fragmentation analysis and MMP assessment into semen testing, especially for obese men whose results suggest they should have normal fertility.
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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
                : F1000 Faculty Rev-670
                Affiliations
                [1 ]Department of Urology, Weill Cornell Medicine, 525 E. 68th Street, New York, NY, 10011, USA
                Author notes

                No competing interests were disclosed.

                Author information
                https://orcid.org/0000-0002-7084-2743
                Article
                10.12688/f1000research.17076.1
                6524745
                31143441
                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.

                History
                : 13 May 2019
                Funding
                The author(s) declared that no grants were involved in supporting this work.
                Categories
                Review
                Articles

                infertility,male infertility,azoospermia,varicocelectomy,sperm dna fragmentation,semen analysis,capacitation,assisted reproductive technology

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