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This review discusses epigenetic mechanisms and the relationship of infertility in men and women in relation to parameters pertaining to nutrition. The prevalence of infertility worldwide is 8-12 %, and one out of every eight couples receives medical treatment. Epigenetic mechanisms, aging, environmental factors, dietary energy and nutrients and non-nutrient compounds; more or less energy intake, and methionine come into play in the occurrence of infertility. It also interacts with vitamins B12, D and B6, biotin, choline, selenium, zinc, folic acid, resveratrol, quercetin and similar factors. To understand the molecular mechanisms regulating the expression of genes that affect infertility, the environment, the role of genotype, age, health, nutrition and changes in the individual's epigenotype must first be considered. This will pave the way for the identification of the unknown causes of infertility. Insufficient or excessive intake of energy and certain macro and micronutrients may contribute to the occurrence of infertility as well. In addition, it is reported that 5-10 % of body weight loss, moderate physical activity and nutritional interventions for improvement in insulin sensitivity contribute to the development of fertility. Processes that pertain to epigenetics carry alterations which are inherited yet not encoded via the DNA sequence. Nutrition is believed to have an impact over the epigenetic mechanisms which are effective in the pathogenesis of several diseases like infertility. Epigenetic mechanisms of individuals with infertility are different from healthy individuals. Infertility is associated with epigenetic mechanisms, nutrients, bioactive components and numerous other factors.

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OBJECTIVE: To examine the potential effects of lifestyle factors on male reproductive health. Evidence of a global decline in human sperm quality over recent decades has been accumulating. Environmental, occupational, and modifiable lifestyle factors may contribute to this decline. This review focuses on key lifestyle factors that are associated with male infertility such as smoking cigarettes, alcohol intake, use of illicit drugs, obesity, psychological stress, advanced paternal age, dietary practices, and coffee consumption. Other factors such as testicular heat stress, intense cycling training, lack of sleep and exposure to electromagnetic radiation from mobile phone use are briefly discussed. MATERIALS AND METHOD: A comprehensive literature search was performed to identify and synthesise all relevant information, mainly from within the last decade, on the major lifestyle factors associated with male infertility and semen quality. Database searches were limited to reports published in English only. A manual search of bibliographies of the reports retrieved was conducted to identify additional relevant articles. RESULTS: In all, 1012 articles were identified from the database search and after reviewing the titles and abstract of the reports, 104 articles met the inclusion criteria. Of these, 30 reports were excluded as the full-text could not be retrieved and the abstract did not have relevant data. The remaining 74 reports were reviewed for data on association between a particular lifestyle factor and male infertility and were included in the present review. CONCLUSION: The major lifestyle factors discussed in the present review are amongst the multiple potential risk factors that could impair male fertility. However, their negative impact may well be mostly overcome by behaviour modification and better lifestyle choices. Greater awareness and recognition of the possible impact of these lifestyle factors are important amongst couples seeking conception.

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OBJECTIVE: To summarise the latest evidence on the role of sperm DNA fragmentation (SDF) in male factor infertility, as SDF has been emerging as a valuable tool for male infertility evaluation. METHODS: A search of PubMed was conducted using the keywords 'sperm DNA fragmentation' and 'male infertility'. Studies in languages other than English were excluded. All identified studies were screened and clinical studies in humans were included. RESULTS: In all, 150 articles were included for analysis. Current evidence supports the association between high SDF and poor reproductive outcomes for natural conception and intrauterine insemination. Although the relationship between high SDF and in vitro fertilisation and intracytoplasmic sperm injection is less clear, the negative implication of high SDF on pregnancy loss is evident. Various treatment strategies have been attempted with varying success. The predictive value of SDF testing on outcomes of natural pregnancy and assisted reproduction illustrates its value in clinical practice. CONCLUSION: The significant role of SDF in male factor infertility is supported by current evidence. The beneficial role of SDF testing in selection of varicocelectomy candidates, evaluation of patients with unexplained infertility and recurrent pregnancy loss, selection of the most appropriate assisted reproductive technique with highest success rate for infertile couples, and assessment of infertile men with modifiable lifestyle factors or gonadotoxin exposure has been recently proposed.

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OBJECTIVE: To review sperm DNA fragmentation (SDF) testing as an important sperm function test in addition to conventional semen analysis. High SDF is negatively associated with semen quality, the fertilisation process, embryo quality, and pregnancy outcome. Over recent decades, different SDF assays have been developed and reviewed extensively to assess their applicability and accuracy as advanced sperm function tests. Amongst them, the standardisation of the terminal deoxynucleotidyl transferased UTP nick-end labelling (TUNEL) assay with a bench top flow cytometer in clinical practice deserves special mention with a threshold value of 16.8% to differentiate infertile men with DNA damage from fertile men. MATERIALS AND METHODS: A systematic literature search was performed through the PubMed, Medline, and ScienceDirect databases using the keywords 'sperm DNA fragmentation' and 'laboratory assessment'. Non-English articles were excluded and studies related to humans were only included. RESULTS: Of the 618 identified, 87 studies (original research and reviews) and in addition eight book chapters meeting the selection criteria were included in this review. In all, 366 articles were rejected in the preliminary screening and a further 165 articles related to non-human subjects were excluded. CONCLUSION: There are pros and cons to all the available SDF assays. TUNEL is a reliable technique with greater accuracy and as an additional diagnostic test in Andrology laboratories along with basic semen analysis can predict fertility outcome, and thus direct the choice of an assisted reproductive technology procedure for infertile couples. Also, the TUNEL assay can be used as a prognostic test and results are beneficial in deciding personalised treatment for infertile men.

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OBJECTIVE: To assess seminal oxidation-reduction potential (ORP) and sperm DNA fragmentation (SDF) in male infertility and their relationships with sperm morphology in fertile and infertile men. PATIENTS AND METHODS: Prospective case-control study comparing the findings of infertile men (n = 1168) to those of men with confirmed fertility (n = 100) regarding demographics and semen characteristics (conventional and advanced semen tests). Spearman rank correlation assessed the correlation between ORP, SDF, and different morphological indices. Means of ORP and SDF were assessed in variable levels of normal sperm morphology amongst all participants. RESULTS: Infertile patients had a significantly lower mean sperm count (32.7 vs 58.7 × 106 sperm/mL), total motility (50.1% vs 60.4%), and normal morphology (5.7% vs 9.9%). Conversely, infertile patients had significantly higher mean head defects (54% vs 48%), and higher ORP and SDF values than fertile controls. ORP and SDF showed significant positive correlations and significant negative correlations with sperm head defects and normal morphology in infertile patients, respectively. ORP and SDF were significantly inversely associated with the level of normal sperm morphology. Using receiver operating characteristic curve analysis, ORP and SDF threshold values of 1.73 mV/106 sperm/mL and 25.5%, respectively, were associated with 76% and 56% sensitivity and 72% and 72.2% specificity, respectively, in differentiating <4% from ≥4% normal morphology. CONCLUSION: A direct inverse relationship exists between seminal ORP and SDF with various levels of normal sperm morphology. Using ORP and SDF measures in conjunction with standard semen morphology analysis could validate the result of the fertility status of patients.

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OBJECTIVE: To explore the current evidence concerning the effect of oral antioxidant supplementation on various male fertility outcomes, as antioxidants are widely available compounds that are commonly used for the treatment of male infertility. MATERIALS AND METHODS: PubMed, Medline and Cochrane electronic databases were searched according to a modified Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines looking for studies investigating the effect of antioxidant therapy on infertile men. The studies were explored looking for antioxidants: (i) types and doses; (ii) mechanism of action and rationale for use; and (iii) effect on the different outcome measures reported. RESULTS: In all, 26 studies reported a significant positive effect of antioxidant therapy on basic semen parameters, advanced sperm function, outcomes of assisted reproductive therapy, and live-birth rate. Vitamin E, vitamin C, carnitines, N-acetyl cysteine, co-enzyme Q10, zinc, selenium, folic acid and lycopene were most commonly used. The vitamins' mechanism of action and reported doses is presented in Table 1, Table 2. CONCLUSION: Antioxidants generally have a favourable effect on male fertility. Further studies are needed to identify the optimal antioxidant regimen that can be used safely and efficiently in clinical practice.

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OBJECTIVE: To evaluate various methods of operative sperm retrieval in men with non-obstructive azoospermia (NOA) and to determine the optimal surgical approach in terms of effectiveness, morbidity, and complications. MATERIALS AND METHODS: PubMed and Cochrane databases were searched to identify five recent reviews and meta-analyses evaluating outcomes for sperm retrieval in men with NOA. RESULTS AND CONCLUSION: Micro-TESE is the most efficient method for retrieving sperm but requires special expertise and can be traumatic for the testes. Conventional biopsies are twice more likely to retrieve sperm than fine-needle aspiration. Testicular aspiration performed by multiple passes into the testis is traumatic and is not efficient for sperm retrieval. Needle-aspiration biopsy and open real-time testicular mapping by the single seminiferous tubule technique can offer less traumatic methods for sperm retrieval, which can be tried before proceeding to micro-TESE. The first attempt at sperm retrieval is the best chance the patient has and should combine various techniques sequentially to give the highest chance of success with the least morbidity.

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OBJECTIVE: In this review, we investigate the advantage of varicocele repair prior to assisted reproductive technologies (ART) for infertile couples and provide cost analysis information. MATERIALS AND METHODS: We searched the following electronic databases: PubMed, Medline, Excerpta Medica Database (Embase), Cumulative Index to Nursing and Allied Health Literature (CINAHL). The following search strategy was modified for the various databases and search engines: 'varicocele', 'varicocelectomy', 'varicocele repair', 'ART', 'in vitro fertilisation (IVF)', 'intracytoplasmic sperm injection (ICSI)'. RESULTS: A total of 49 articles, including six meta-analyses, 32 systematic reviews, and 11 original articles, were included in the analysis. Bypassing potentially reversible male subfertility factors using ART is currently common practice. However, varicocele may be present in 35% of men with primary infertility and 80% of men with secondary infertility. Varicocele repair has been shown to be an effective treatment for infertile men with clinical varicocele, thus should play an important role in the treatment of such patients due to the foetal/genetic risks and high costs that are associated with increased ART use. CONCLUSION: Varicocele repair is a cost-effective treatment method that can improve semen parameters, pregnancy rates, and live-birth rates in most infertile men with clinical varicocele. By improving semen parameters and sperm structure, varicocele repair can decrease or even eliminate ART requirement.

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OBJECTIVE: Verification of the effect of EmbryoGlue (EG) transfer medium enriched with hyaluronan on the embryo transfer success rate. DESIGN: A prospective study. SETTING: Fertimed, Fertility Treatment Centre, Olomouc. METHODS: 484 patients undergoing IVF + ET were engaged who were divided according to the medium used during transfer: Sage or Vitrolife culture medium (n = 135) and EG transfer medium (n = 349). The influence of other factors was also evaluated: age, number of received oocytes, percentage of fertilised oocytes, endometrium height on the day of transfer, number of preserved embryos, number of transferred embryos and the length of cultivation (48, 72, 96, 120 h). These factors were considered quantitative variables while the method of hormone stimulation, the type of culture medium and the application of EG were considered qualitative (categorical) variables. RESULTS: With the use of EG the chances of conception increased by approximately 9%. The negative effect of higher age on implantation proportion and the positive effect of cultivation prolongation were proven. The effect of EG on miscarriages was not proven. The probability of miscarriage diminished with higher oocyte fertilisation. The culture medium used (Sage or Vitrolife) before the application of EG does not affect the gravidity result. CONCLUSION: Using the transfer medium of EmbryoGlue before embryo transfer affects the pregnancy rate (PR) in a positive manner. The influence on pregnancy loss with the application of EG was not proven.

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Spermatozoa and lentiviruses are two of nature's most efficient gene delivery vehicles. Both can be genetically modified and used independently for the generation of transgenic animals or gene transfer/therapy of inherited disorders. Here we show that mature spermatozoa can be directly transduced with various pseudotyped lentiviral vectors and used in in vitro fertilisation studies. Lentiviral vectors encoding Green Fluorescent Protein (GFP) were shown to be efficiently processed and expressed in sperm. When these transduced sperm were used in in vitro fertilisation studies, GFP expression was observed in arising blastocysts. This simple technique of directly transducing spermatozoa has potential to be a powerful tool for the study of early and pre-implantation development and could be used as a technique in transgenic development and vertical viral transmission studies.