Reversible effects of the SARS-CoV-2 on semen parameters.

Despite that the SARS-CoV-2 pandemic has been controlled, it has affected a large proportion of the population, raising some concerns about potential sequelae in men at reproductive age. To contribute to the clarification of this issue, we performed a retrospective study comparing semen parameters values before and after confirmed SARS-CoV-2 infection in a large cohort of infertile men, compared to a control group that did not undergo SARS-CoV-2 infection. Wilcoxon test on paired samples and general linear regression model showed that SARS-CoV-2 infection has a detrimental effect on semen volume values (p < 0.005). However, semen volume seems to be significantly lower only during the first spermatogenic cycle after SARS-COV-2 infection (p < 0.005) and mainly in unvaccinated patients (p < 0.05). In addition, we detected alterations in progressive motility in patients infected with the alpha SARS-COV-2 strain (p < 0.05). In conclusion, our results show that although SARS-CoV-2 has a small effect on semen volume and sperm motility in infertile men, depending on the infectious strain or vaccination status, pre-infection values of semen parameters appear to be restored over one spermatogenic cycle after infection.

From pathophysiology to practice: addressing oxidative stress and sperm DNA fragmentation in Varicocele-affected subfertile men.

Varicocele can reduce male fertility potential through various oxidative stress mechanisms. Excessive production of reactive oxygen species may overwhelm the sperm's defenses against oxidative stress, damaging the sperm chromatin. Sperm DNA fragmentation, in the form of DNA strand breaks, is recognized as a consequence of the oxidative stress cascade and is commonly found in the ejaculates of men with varicocele and fertility issues. This paper reviews the current knowledge regarding the association between varicocele, oxidative stress, sperm DNA fragmentation, and male infertility, and examines the role of varicocele repair in alleviating oxidative-sperm DNA fragmentation in these patients. Additionally, we highlight areas for further research to address knowledge gaps relevant to clinical practice.

Male Reproductive Endocrine Disorders.

The endocrine system intricately regulates male sexual development and health which influences masculinization, sexual libido, muscle mass, bone density, and overall vitality. Disorders in the hypothalamic-pituitary-gonadal axis can lead to hypogonadism, gynecomastia, sexual dysfunction, and infertility. Testosterone replacement therapy can be considered for symptomatic hypogonadism but poses risks for azoospermia and polycythemia, along with uncertain impact on cardiovascular disease. Gynecomastia results from a high estrogen-to-androgen ratio, mostly from either excess estrogen or decreased androgens. Sexual dysfunction is more commonly secondary to psychological or metabolic disorders; consider workups to rule out endocrine etiologies including hypogonadism if indicated.

The impact of mitochondrial impairments on sperm function and male fertility: a systematic review.

BACKGROUND: Besides adenine triphosphate (ATP) production for sustaining motility, the mitochondria of sperm also host other critical cellular functions during germ cell development and fertilization including calcium homeostasis, generation of reactive oxygen species (ROS), apoptosis, and in some cases steroid hormone biosynthesis. Normal mitochondrial membrane potential with optimal mitochondrial performance is essential for sperm motility, capacitation, acrosome reaction, and DNA integrity. RESULTS: Defects in the sperm mitochondrial function can severely harm the fertility potential of males. The role of sperm mitochondria in fertilization and its final fate after fertilization is still controversial. Here, we review the current knowledge on human sperm mitochondria characteristics and their physiological and pathological conditions, paying special attention to improvements in assistant reproductive technology and available treatments to ameliorate male infertility. CONCLUSION: Although mitochondrial variants associated with male infertility have potential clinical use, research is limited. Further understanding is needed to determine how these characteristics lead to adverse pregnancy outcomes and affect male fertility potential.

What sperm parameters effect blastocyst formation and quality during ICSI with severe male infertility.

Sperm-derived genetic material contributes half of the genome to the embryo, hence it's crucial to investigate which sperm parameter influences blastocyst formation in the intracytoplasmic sperm injection (ICSI) cycles with severe male infertility. The retrospective study analyzed 296 ICSI cycles with severe oligoasthenoteratozoospermia (OAT) and 99 ICSI cycles with preimplantation genetic testing for aneuploidy (PGT-A). Following the correlation analysis, data stratifications were performed in the OAT ICSI subgroup. The results showed that the matching blastocyst in the OAT ICSI cycles had inferior sperm parameters. DFI and sperm morphology had an influence on the blastocyst formation rate and the high-quality blastocysts formation rate on Day6, but no significant effect on the blastocyst development on Day 5. The high-quality blastocysts formation rate and ratio of high-quality blastocyst on Day 6 were demonstrably better in the subgroup of the teratozoospermic morphology when DFI was within the normal range. In the case of the normal sperm morphology, no statistically significant difference was found in blastocyst development, although there were numerical differences within different DFI subgroups. It was concluded that the blastocyst quality and development declined with the decreased sperm qualities.

Interplay between male gonadal function and overall male health.

The process-of-male reproduction is intricate, and various medical conditions-have the potential to disrupt spermatogenesis. Moreover, infertility in males can serve as an indicator of-potential future health issue. Numerous conditions with systemic implications have been identified, encompassing genetic factors (such as Klinefelter Syndrome), obesity, psychological stress, environmental factors, and others. Consequently, infertility assessment-presents an opportunity for comprehensive health counseling, extending-beyond discussions about reproductive goals. Furthermore, male infertility has been suggested as a harbinger of future health problems, as poor semen quality and a diagnosis of-male infertility are associated with an increased risk of hypogonadism, cardiometabolic disorders, cancer, and even mortality. This review explores the existing-literature on the relationship between systemic illnesses and male fertility, impacting both clinical-outcomes and semen parameters. The majority of the literature analyzed, which compared gonadal function with genetic, chronic, infectious or tumoral diseases, confirm the association between overall male health and infertility.

Role of Anti-Müllerian Hormone in Male Reproduction and Sperm Motility.

Anti-Müllerian hormone (AMH) is secreted by Sertoli cells and is responsible for the regression of Müllerian ducts in the male fetus as part of the sexual differentiation process. Serum AMH concentrations are at their lowest levels in the first days after birth but increase after the first week, likely reflecting active Sertoli cell proliferation. AMH rises rapidly in concentration in boys during the first month, reaching a peak level at ∼6 months of age, and it remains high during childhood, then they will slowly decline during puberty, falling to low levels in adulthood. Serum AMH measurement is used by pediatric endocrinologist as a specific marker of immature Sertoli cell number and function during childhood. After puberty, AMH is released especially by the apical pole of the Sertoli cells toward the lumen of the seminiferous tubules, resulting in higher levels in the seminal plasma than in the serum. Recently, AMH has received increasing attention in research on male fertility-related disorders. This article reviews and summarizes the potential contribution of serum AMH measurement in different male fertility-related disorders.

Uncovering the link between inflammatory rheumatic diseases and male reproductive health: a perspective on male infertility and sexual dysfunction.

Inflammatory rheumatic diseases (IRDs) refer to a range of persistent disorders that have a major influence on several physiological systems. Although there is much evidence connecting IRDs to sexual dysfunction and fertility problems, research specifically focusing on male infertility in relation to these diseases is sparse. This review addresses the complicated connection between IRDs and male infertility, emphasising the physiological, psychological, and pharmacological aspects that influence reproductive health outcomes in men with rheumatic conditions. We explore the effects of IRDs and their treatments on many facets of male reproductive well-being, encompassing sexual functionality, semen characteristics, and hormonal balance. Additionally, we present a comprehensive analysis of the present knowledge on the impact of several categories of anti-rheumatic drugs on male reproductive function. Although there is an increasing awareness of the need of addressing reproductive concerns in individuals IRDs, there is a noticeable lack of research especially dedicated to male infertility. Moving forward, more comprehensive research is needed to determine the prevalence, risk factors, and mechanisms driving reproductive difficulties in males with IRDs. We can better assist the reproductive health requirements of male IRD patients by expanding our understanding of male infertility in the setting of rheumatic disorders and implementing holistic methods to care.

The impact of COVID-19 on male reproductive health: a Systematic Review.

OBJECTIVE: This systematic literature review aims to assess the impact of COVID-19 on male fertility. DATA SOURCES: The study draws upon data extracted from PubMed, SciELO, and LILACS databases. STUDY SELECTION: The review incorporates cross-sectional studies, cohort studies, and clinical trials, encompassing investigations related to the subject matter. The studies included were published between June 2020 and March 2023, and encompassed content in English, Portuguese, and Spanish. Exclusion criteria encompassed review articles, case reports, abstracts, studies involving animal models, duplicate articles, and letters to the editor. DATA COLLECTION: Data extracted included the author's name and publication year, the number of patients studied, patient age, the presence of COVID-19 in semen, observed hormonal changes, and alterations in seminal quality. CONCLUSIONS: While hormonal changes and a decline in seminal quality were observed in COVID-19 patients, the virus itself was not detected in semen in the analyzed articles, which contradicts certain findings in the existing literature. It is essential to note that methodologies in the studies were diverse, and, due to the novelty of this infection, it is premature to definitively ascertain its long-term effects on male fertility or whether fertility can recover after a period of convalescence. This underscores the necessity for further research, utilizing more robust methodologies such as cohort studies.

Signatures of metabolic diseases on spermatogenesis and testicular metabolism.

Diets leading to caloric overload are linked to metabolic disorders and reproductive function impairment. Metabolic and hormonal abnormalities stand out as defining features of metabolic disorders, and substantially affect the functionality of the testis. Metabolic disorders induce testicular metabolic dysfunction, chronic inflammation and oxidative stress. The disruption of gastrointestinal, pancreatic, adipose tissue and testicular hormonal regulation induced by metabolic disorders can also contribute to a state of compromised fertility. In this Review, we will delve into the effects of high-fat diets and metabolic disorders on testicular metabolism and spermatogenesis, which are crucial elements for male reproductive function. Moreover, metabolic disorders have been shown to influence the epigenome of male gametes and might have a potential role in transmitting phenotype traits across generations. However, the existing evidence strongly underscores the unmet need to understand the mechanisms responsible for transgenerational paternal inheritance of male reproductive function impairment related to metabolic disorders. This knowledge could be useful for developing targeted interventions to prevent, counteract, and most of all break the perpetuation chain of male reproductive dysfunction associated with metabolic disorders across generations.

Low-serum antimüllerian hormone is linked with poor semen quality in infertile men screened for participation in a randomized controlled trial.

OBJECTIVE: To investigate possible associations between serum antimüllerian hormone (AMH) concentration and semen quality in infertile men. Studies investigating the associations between serum AMH concentration and semen quality in infertile men have shown conflicting results. DESIGN: Infertile men were included during screening for participation in the First in Treating Male Infertility Study, a double-blinded, placebo-controlled, 1:1, single-center randomized controlled trial. SETTING: Not applicable. PATIENTS: At the screening visit, 400 participants produced a semen sample and had their serum analyzed for AMH concentration. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Serum AMH concentration and semen quality. RESULTS: All men were stratified according to serum AMH concentrations in quartiles (Q1-Q4). Men in the lowest quartile had a lower sperm concentration (1 × 106/mL) (Q1: 8.0 vs. Q2: 10.4 vs. Q3: 11.0 vs. Q4: 13.0), total sperm count (1 × 106) (Q1: 29.1 vs. Q2: 38.2 vs. Q3: 44.4 vs. Q4: 55.7), sperm motility (%) (Q1: 41 vs. Q2: 57 vs. Q3: 50 vs. Q4: 53), and progressive sperm motility (%) (Q1: 31 vs. Q2: 44 vs. Q3: 35 vs. Q4: 40) compared with the other quartiles. Moreover, men with a sperm concentration <2 million/mL had a lower serum AMH concentration compared with men having 2-16 × 106 /mL and >16 × 106/mL (31 pmol/L vs. 38 pmol/L vs. 43 pmol/L, respectively). In accordance, men with sperm motility <20% had a lower serum AMH concentration compared with men with sperm motility 20%-42%, and >42% (31 pmol/L vs. 43 pmol/L. vs. 39 pmol/L, respectively). CONCLUSION: This study shows that low serum AMH concentration is associated with poor semen quality in infertile men, which implies that serum AMH concentration may have clinical value during the evaluation of male infertility. CLINICAL TRIAL REGISTRATION NUMBER: NCT05212337.

Uncovering the Potential Mechanisms and Effects of Hyperuricemia and its Associated Diseases on Male Reproduction.

Male fertility and metabolic disorders, including obesity and diabetes, are closely connected. Since hyperuricemia and metabolic syndrome are strongly related, male fertility and hyperuricemia may, to some degree, be associated. According to recent studies, hyperuricemia imposes various effects on sex hormones, semen quality, and male erectile dysfunction. Some researchers claim that uric acid worsens male semen and raises the risk of erectile dysfunction (ED), while others state that it safeguards both penile erection and male semen. Additionally, it has been shown that gout and metabolic syndrome also raise the risk of ED. To clarify this controversy, the influence and potential mechanisms of hyperuricemia on ED, semen quality, sex hormone levels, and the effects of hyperuricemia-related disorders on ED will be comprehensively summarized.

Changes in Sperm Parameters with Time in Men with Normal and Abnormal Baseline Semen Analysis.

The association between paternal age and sperm quality in the population level has been previously studied. Only limited data exists regarding the intra-personal variations in semen parameters among fertile and infertile men over time. We aimed to assess trends over time in semen parameters among men with normal and abnormal baseline sperm parameters and investigate potential risk factors for sperm quality deterioration. This retrospective cohort study was conducted at a university-affiliated medical center in vitro fertilization (IVF) unit. Patients with at least two semen analyses (SA) performed > 1 year apart, with the last SA done between 2017 and 2021, were included. The study consisted of two main analyses-comparison of intra-patient's sperm parameters changes in men with normal and abnormal baseline SA (BSA) and analysis of risk factors for developing abnormal semen parameters over time in men who had normal BSA parameters. This study included a total of 902 men assessed for infertility with normal and abnormal BSA. The average time interval between tests was 1015 days (range 366-7709 days). Among individuals with normal BSA, there was a mild decline in most parameters-concentration (- 6.53 M/ml), motility (- 7.74%), and total motile count (TMC) (- 21.80 M) (p < 0.05 for all parameters). In contrast, a slight improvement in most parameters, except for concentration, was noted in men with abnormal BSA-volume (+ 0.21 ml), motility (+ 8.72%), and TMC (+ 14.38 M) (p < 0.05 for all parameters). Focusing on men with normal BSA, 33.5% of individuals developed abnormality in one or more of their sperm parameters over time, within a mean time of 1013 ± 661 days. We also found that only time between tests emerged as an independent prognostic factor for the development of abnormal SA later. Interestingly, sperm deterioration in participants in their third, fourth, and fifth decades of life with normal initial semen analysis was similar. Our study provides evidence of a decline in semen quality over time in individuals with normal BSA, in contrast to men with abnormal BSA. Longer time intervals between tests independently increase the risk of sperm abnormalities.

Association of abstinence time with semen quality and fertility outcomes: a systematic review and dose-response meta-analysis.

BACKGROUND: Infertility affects 186 million people worldwide, with male factors contributing to 50% of infertility cases. Semen analysis is a key for diagnosing male factor infertility, but sperm parameters can be influenced by ejaculatory abstinence (EA) duration. Shortening or prolonging EA can impact on semen quality and assisted reproductive technology (ART) outcomes, but the optimal EA duration remains unclear, particularly for infertility patients. OBJECTIVES: This study conducts a comprehensive meta-analysis to explore the impact of varying abstinence durations on semen quality and fertility outcomes. METHODS: Three English database (PubMed, Embase, and Cochrane Central Register of Controlled Trials) as well as four Chinese database (China National Knowledge Infrastructure, Chinese Scientific Journals database, WanFang database, and Chinese Biomedical Literature database) were searched from 2000 to August 2023. The classical meta-analysis and "one-stage" dose-response meta-analysis were conducted to compare the associations of different abstinence durations (short-term abstinence vs. long-term abstinence) on semen quality in healthy adult and different type of infertile patients. RESULTS: There were 85 eligible studies were finally included. The meta-analysis of volume (mean difference [MD] = -0.95 mL, 95% confidence interval [CI]: -1.16 to -0.74 mL), total sperm count (TSC) (MD = -102.45×106, 95% CI: -117.98×106 to -86.91×106), sperm concentration (SC) (MD = -11.88×106/mL, 95% CI: -18.96×106/mL to -4.80×106/mL), DNA fragmentation index (DFI) (MD = -2.37%, 95% CI: -4.73% to -0.01%) in healthy men showed a significant decrease with different abstinence durations (short-term abstinence vs. long-term abstinence). The meta-analysis of infertile men showed significant decrease in volume in various subgroups (MD range: -0.73 to -1.17 mL) with P < 0.01; TSC (MD = -61.93×106, 95% CI: -88.84×106 to -35.01×106), SC (MD = -5.39×106/mL, 95% CI: -9.97×106 to -0.81×106/mL), DFI (MD = -5.63%, 95% CI: -10.19% to -1.06%) in unexplained infertility subgroup; significant increase in viability (MD = 6.14%, 95% CI: 3.61% to 8.68%) in the unexplained infertility subgroup. The dose-response meta-analysis showed that TSC in oligozoospermia showed a nonlinear increase (coefficient from 3.38 to -5.76, P from 0.02 to 0.22) and the truncation point was around the 4th to 5th abstinence day. The percentage of progressive motile sperm (PR) in asthenozoospermia showed a significant decrease (coefficient = -2.39, 95% CI: -4.28 to -0.50). For fertility outcomes of different ARTs, only the clinical pregnancy rate (CPR) in the intrauterine insemination (IUI) subgroup showed a significant decrease around the 3rd day (coefficient = 0.85, 95% CI: 0.75 to 0.97). CONCLUSIONS: Short-term abstinence may be associated with limited improvements in semen quality in healthy men but could be more beneficial for infertile men, especially within the first 4 days of abstinence. Caution is urged in making definitive conclusions about the causal relationship between abstinence time and semen quality changes due to potential confounding and interactions.

What advances may the future bring to the diagnosis, treatment, and care of male sexual and reproductive health?

Over the past 40 years, since the publication of the original WHO Laboratory Manual for the Examination and Processing of Human Semen, the laboratory methods used to evaluate semen markedly changed and benefited from improved precision and accuracy, as well as the development of new tests and improved, standardized methodologies. Herein, we present the impact of the changes put forth in the sixth edition together with our views of evolving technologies that may change the methods used for the routine semen analysis, up-and-coming areas for the development of new procedures, and diagnostic approaches that will help to extend the often-descriptive interpretations of several commonly performed semen tests that promise to provide etiologies for the abnormal semen parameters observed. As we look toward the publication of the seventh edition of the manual in approximately 10 years, we describe potential advances that could markedly impact the field of andrology in the future.