ABSTRACT
The clinical effect of sperm DNA damage in assisted reproduction has been a controversial topic during recent decades, leading to a variety of clinical practice recommendations. While the ...latest European Society of Human Reproduction and Embryology (ESHRE) position report concluded that DNA damage negatively affects assisted reproduction outcomes, the Practice Committee of the American Society for Reproductive Medicine (ASRM) does not recommend the routine testing of DNA damage for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Herein, our aim was to perform a systematic review and meta‐analysis of studies investigating whether sperm DNA damage affects clinical outcomes in IVF and ICSI, in order to contribute objectively to a consistent clinical recommendation. A comprehensive systematic search was conducted according to PRISMA guidelines from the earliest available online indexing year until March 2020, using the MEDLINE‐PubMed and EMBASE databases. We included studies analysing IVF and/or ICSI treatments performed in infertile couples in which sperm DNA damage was well defined and assessed. Studies also had to include information about pregnancy, implantation or live birth rates as primary outcomes. The NHLBI‐NIH quality assessment tool was used to assess the quality of each study. Meta‐analyses were conducted using the Mantel–Haenszel method with random‐effects models to evaluate the Risk Ratio (RR) between high‐DNA‐damage and control groups, taking into account the 95% confidence intervals. Heterogeneity among studies was evaluated using the I2 statistic. We also conducted sensitivity analyses and post‐hoc subgroup analyses according to different DNA fragmentation assessment techniques. We identified 78 articles that met our inclusion and quality criteria and were included in the qualitative analysis, representing a total of 25639 IVF/ICSI cycles. Of these, 32 articles had sufficient data to be included in the meta‐analysis, comprising 12380 IVF/ICSI cycles. Meta‐analysis revealed that, considering IVF and ICSI results together, implantation rate (RR = 0.74; 95% CI = 0.61–0.91; I2 = 69) and pregnancy rate (RR = 0.83; 0.73–0.94; I2 = 58) are negatively influenced by sperm DNA damage, although after adjustment for publication bias the relationship for pregnancy rate was no longer significant. The results showed a non‐significant but detrimental tendency (RR = 0.78; 0.58–1.06; I2 = 72) on live birth rate. Meta‐analysis also showed that IVF outcomes are negatively influenced by sperm DNA damage, with a statistically significant impact on implantation (RR = 0.68; 0.52–0.89; I2 = 50) and pregnancy rates (RR = 0.72; 0.55–0.95; I2 = 72), although the latter was no longer significant after correction for publication bias. While it did not quite meet our threshold for significance, a negative trend was also observed for live birth rate (RR = 0.48; 0.22–1.02; I2 = 79). In the case of ICSI, non‐significant trends were observed for implantation (RR = 0.79; 0.60–1.04; I2 = 72) or pregnancy rates (RR = 0.89; 0.78–1.02; I2 = 44), and live birth rate (RR = 0.92; 0.67–1.27; I2 = 70). The current review provides the largest evidence to date supporting a negative association between sperm DNA damage and conventional IVF treatments, significantly reducing implantation and pregnancy rates. The routine use of sperm DNA testing is therefore justified, since it may help improve the outcomes of IVF treatments and/or allow a given couple to be advised on the most suitable treatment. Further well‐designed controlled studies on a larger number of patients are required to allow us to reach more precise conclusions, especially in the case of ICSI treatments.
Summary
The present updated systematic review and meta‐analysis aims to summarize the evidence from published studies with low risk for any important bias (based on methodological quality assessment) ...investigating the potential associations of adiposity with sperm quality and reproductive hormones. We conducted a systematic search of the literature published in MEDLINE‐PubMed and EMBASE through June 2019. Based on the criteria in our review, 169 eligible publications were used for data ion. Finally, 60 articles were included in the qualitative analysis and 28 in the quantitative analysis. Our systematic review results indicated that overweight and/or obesity were associated with low semen quality parameters (i.e., semen volume, sperm count and concentration, sperm vitality and normal morphology) and some specific reproductive hormones (e.g., inhibin B, total testosterone and sex hormone‐binding globulin). Overweight and/or obesity were also positively associated with high estradiol concentrations. Meta‐analysis indicated that overweight and/or obesity categories were associated with lower sperm quality (i.e., semen volume, sperm count and concentration, sperm vitality, total motility and normal morphology), and underweight category was likewise associated with low sperm normal morphology. In conclusion, our results suggest that maintaining a healthy body weight is important for increasing sperm quality parameters and potentially male fertility.
Infertility is a global public health issue, affecting 15% of all couples of reproductive age. Male factors, including decreased semen quality, are responsible for ~25% of these cases. The dietary ...pattern, the components of the diet and nutrients have been studied as possible determinants of sperm function and/or fertility.
Previous systematic reviews have been made of the few heterogeneous low-quality randomized clinical trials (RCTs) conducted in small samples of participants and investigating the effect of specific nutrients and nutritional supplements on male infertility. However, as yet there has been no systematic review of observational studies.
A comprehensive systematic review was made of the published literature, from the earliest available online indexing year to November 2016, in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. We have included cross-sectional, case-control and prospective and retrospective studies in which fertile/infertile men were well defined (men with sperm disorders, sperm DNA damage, varicocele or idiopathic infertility). The primary outcomes were semen quality or fecundability. With the data extracted, we evaluated and scored the quality of the studies selected. We excluded RCTs, animal studies, review articles and low-quality studies.
A total of 1944 articles were identified, of which 35 were selected for qualitative analysis. Generally, the results indicated that healthy diets rich in some nutrients such as omega-3 fatty acids, some antioxidants (vitamin E, vitamin C, β-carotene, selenium, zinc, cryptoxanthin and lycopene), other vitamins (vitamin D and folate) and low in saturated fatty acids and trans-fatty acids were inversely associated with low semen quality parameters. Fish, shellfish and seafood, poultry, cereals, vegetables and fruits, low-fat dairy and skimmed milk were positively associated with several sperm quality parameters. However, diets rich in processed meat, soy foods, potatoes, full-fat dairy and total dairy products, cheese, coffee, alcohol, sugar-sweetened beverages and sweets have been detrimentally associated with the quality of semen in some studies. As far as fecundability is concerned, a high intake of alcohol, caffeine and red meat and processed meat by males has a negative influence on the chance of pregnancy or fertilization rates in their partners.
Male adherence to a healthy diet could improve semen quality and fecundability rates. Since observational studies may prove associations but not causation, the associations summarized in the present review need to be confirmed with large prospective cohort studies and especially with well-designed RCTs.
Objective To compare the microRNA (miRNA) expression profile in spermatozoa from three infertile populations vs. a group of fertile men. Design Evaluation of the expression level of 736 miRNAs in ...human spermatozoa using TaqMan quantitative reverse transcription–polymerase chain reaction. Setting University research facility. Patient(s) Semen samples with a single seminal alteration were collected from infertile individuals: asthenozoospermic (n = 10), teratozoospermic (n = 10), and oligozoospermic (n = 10). Intervention(s) None. Main Outcome Measure(s) Correlation of the expression level of each miRNA with seminal parameters, age, and chromosome instability; clustering of the individuals according to their miRNA expression profiles and influence of the seminogram, age, chromosome instability, and assisted reproductive technology outcome in the clustering; analysis of the differentially expressed miRNAs (DE-miRNAs) in each infertile population; genome annotation of these DE-miRNAs; and ontological analysis of their predicted targets. Result(s) The hsa-miR-34b-3p correlated with age, the hsa-miR-629-3p with sperm motility, and the hsa-miR-335-5p, hsa-miR-885-5p, and hsa-miR-152-3p with sperm concentration. The individuals clustered into two groups, and only the seminogram was differentially distributed. We identified 32 DE-miRNAs in the asthenozoospermic group, 19 in the teratozoospermic group, and 18 in the oligozoospermic group. The up-regulated miRNAs presented an enriched localization in introns, affecting relevant genes for spermatogenesis. The predicted targets of the DE-miRNAs contained critical genes associated to infertility, and their ontological analysis revealed significantly associated functions related to the seminal alterations of each group. Conclusion(s) Spermatozoa from patients with seminal alterations exhibit a differential miRNA profile. This provides new evidence that miRNAs have an essential role in spermatogenesis, contributing to the mechanisms involved in human fertility.
Lifestyle risk factors for erectile and sexual function include smoking, excessive alcohol consumption, lack of physical activity, psychological stress, and adherence to unhealthy diets. In the ...present study, we evaluated the effects of mixed nuts supplementation on erectile and sexual function. Eighty-three healthy male aged 18-35 with erectile function assessment were included in this FERTINUTS study sub-analysis; a 14-week randomized, controlled, parallel feeding trial. Participants were allocated to (1) the usual Western-style diet enriched with 60 g/day of a mixture of nuts (nut group;
= 43), or (2) the usual Western-style diet avoiding nuts (control group;
= 40). At baseline and the end of the intervention, participants answered 15 questions contained in the validated International Index of Erectile Function (IIEF), and peripheral levels of nitric oxide (NO) and E-selectin were measured, as surrogated markers of erectile endothelial function. Anthropometrical characteristics, and seminogram and blood biochemical parameters did not differ between intervention groups at baseline. Compared to the control group, a significant increase in the orgasmic function (
-value = 0.037) and sexual desire (
-value = 0.040) was observed during the nut intervention. No significant differences in changes between groups were shown in peripheral concentrations of NO and E-selectin. Including nuts in a regular diet significantly improved auto-reported orgasmic function and sexual desire.
Background
Telomeres are essential for the integrity of chromosome ends during cell division and their involvement in different processes linked to aging has been established. These chromosome ...components are involved in spermatogenesis and seem to play an important role in fertilization and embryo development. Telomere length is shortened with each cell division. Recently, short sperm telomere length has been proposed as a potential biomarker of male infertility.
Objectives
To conduct a systematic review and meta‐analysis of studies exploring the association between spermatozoa and/or leukocyte telomere length with sperm quality parameters and different infertility conditions.
Material and methods
A systematic review and meta‐analysis was conducted with studies from Medline‐PUBMED and Cochrane Library databases until May 2022. Eligible studies included cohort, cross‐sectional and case–control studies, and telomere length in spermatozoa and/or leukocytes cells was defined as the exposure. Semen quality parameters or infertility conditions (e.g., oligozoospermia, asthenozoospermia, teratozoospermia, or other spermatogenic impairment combinations) were defined as the outcomes.
Results
Twenty‐three observational studies were included. In the qualitative analysis, high heterogeneity was observed between studies regarding the associations between telomere length and semen parameters in different normozoospermic/fertile and oligozoospermic/infertile populations. In the meta‐analysis, spermatozoa and leukocyte telomere length were shorter in infertile individuals than in fertile individuals (mean difference 95% confidence interval: –1.43 –1.66 to –1.21, p‐value <0.001 and –1.67 –2.02 to –1.31, p‐value <0.001, respectively). Moreover, in terms of sperm telomere length, these differences were also significant between individuals with a normal seminogram and individuals with a low quantity of spermatozoa in the ejaculate (–0.97 –1.32, –0.61, p‐value <0.001).
Conclusion
The current systematic review and meta‐analysis suggests the potential role of spermatozoa or leukocyte telomere length as a reliable biomarker of semen quality, which may help distinguish between infertility conditions beyond the routine semen analysis.
Objective To characterize the microRNA (miRNA) expression profile in spermatozoa from human fertile individuals and their implications in human fertility. Design The expression levels of 736 miRNAs ...were evaluated using TaqMan arrays. Ontologic analyses were performed to determine the presence of enriched biological processes among their targets. Setting University research and clinical institutes. Patient(s) Ten individuals with normal seminogram, standard karyotype, and proven fertility. Intervention(s) None. Main Outcome Measure(s) Expression levels of 736 miRNAs, presence of enriched metabolic routes among their targets, homogeneity of the population, influence of demographic features in the results, presence of miRNA stable pairs, and best miRNA normalizing candidates. Result(s) A total of 221 miRNAs were consistently present in all individuals, 452 were only detected in some individuals, and 63 did not appear in any sample. The ontologic analysis of the 2,356 potential targets of the ubiquitous miRNAs showed an enrichment of processes related to cell differentiation, development, morphogenesis, and embryogenesis. None of the miRNAs were significantly correlated with age, semen volume, sperm concentration, motility, or morphology. Correlations between samples were statistically significant, indicating a high homogeneity of the population. A set of 48 miRNA pairs displayed a stable expression, a particular behavior that is discussed in relationship to their usefulness as fertility biomarkers. Hsa-miR-532-5p, hsa-miR-374b-5p, and hsa-miR-564 seemed to be the best normalizing miRNA candidates. Conclusion(s) Human sperm contain a stable population of miRNAs potentially related to embryogenesis and spermatogenesis.
It is well-established that testicular spermatozoa are immature and acquire motility and fertilization capabilities during transit throughout the epididymis. The epididymis is a duct-like organ that ...connects the testis to the vas deferens and is comprised of four anatomical regions: the initial segment, caput, corpus, and cauda. Sperm maturation occurs during epididymal transit by the interaction of sperm cells with the unique luminal environment of each epididymal region. In this review we discuss the epididymis as an essential reproductive organ responsible for sperm concentration, maturation (including sperm motility acquisition and fertilizing ability), protection and storage. Importantly, we also discuss specific characteristics and roles of epididymal-derived exosomes (epididymosomes) in establishing sperm competency within the intricate process of reproduction. This review suggests that an increasing body of evidence is working to develop a complete picture of the role of the epididymis in male reproduction, offspring health, and disease susceptibility.
Dietary phytoestrogens are bioactive compounds with estrogenic activity. With the growing popularity of plant-based diets, the intake of phytoestrogen-rich legumes (especially soy) and legume-derived ...foods has increased. Evidence from preclinical studies suggests these compounds may have an effect on hormones and health, although the results of human trials are unclear. The effects of dietary phytoestrogens depend on the exposure (phytoestrogen type, matrix, concentration, and bioavailability), ethnicity, hormone levels (related to age, sex, and physiological condition), and health status of the consumer. In this review, we have summarized the results of human studies on dietary phytoestrogens with the aim of assessing the possible hormone-dependent outcomes and health effects of their consumption throughout a lifespan, focusing on pregnancy, childhood, adulthood, and the premenopausal and postmenopausal stages. In pregnant women, an improvement of insulin metabolism has been reported in only one study. Sex hormone alterations have been found in the late stages of childhood, and goitrogenic effects in children with hypothyroidism. In premenopausal and postmenopausal women, the reported impacts on hormones are inconsistent, although beneficial goitrogenic effects and improved glycemic control and cardiovascular risk markers have been described in postmenopausal individuals. In adult men, different authors report goitrogenic effects and a reduction of insulin in non-alcoholic fatty liver patients. Further carefully designed studies are warranted to better elucidate the impact of phytoestrogen consumption on the endocrine system at different life stages.
The cold‐adapted bacterium Pseudomonas sp. ID1 produces the extracellular exopolysaccharide ID1 (EPS ID1) with cryoprotective activity. This study was designed to optimize the vitrification/in‐straw ...warming protocol of in vitro‐produced (IVP) blastocysts by adding EPS ID1 to the vitrification media. Day 7‐expanded blastocysts were vitrified/warmed using the VitTrans device after the addition of 0 or 100 μg/mL EPS ID1 to the vitrification media. Blastocysts vitrified by the Cryotop method and fresh non‐vitrified blastocysts served as controls. Outcomes were assessed in the warmed embryos in terms of survival rates and mRNA relative abundances of BAX, BCL2, GPX1, and CDX2 genes. No differences in survival rates were observed at 3 h post‐warming between vitrification treatments. At 24 h post‐warming, the addition of EPS prior to vitrification with the VitTrans device produced similar survival rates to Cryotop‐vitrified embryos and similar hatching rates to fresh non‐vitrified or Cryotop‐vitrified embryos. No differences emerged in BCL2 gene expression. Lower BAX (p < .05) and higher GPX1 (p < .05) and CDX2 (p < .1) gene expression were observed in expanded and/or hatched blastocysts derived from VitTrans‐EPS‐vitrified embryos when compared to those from the non‐supplemented group. In conclusion, addition of EPS not only promoted blastocyst survival and hatching after VitTrans vitrification/warming but also modified the expression of genes associated with better embryo quality.
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