Phase angle at bioelectric impedance analysis is associated with detrimental sperm quality in idiopathic male infertility: a preliminary clinical study.

Background: In 2020, 38% of adults were affected by obesity, while infertility globally affected 1 in 6 people at some stage of their lives.Body mass index (BMI) provides an easy but occasionally inaccurate estimation of body composition. To achieve a more precise assessment, bioelectric impedance analysis serves as a validated tool that administers electrical energy through surface electrodes. Phase angle as a function of the relationship between tissues resistance and reactance, is a trustworthy predictor of body composition and cell membrane integrity. Objectives: We aim to assess whether there is an association between phase angle and seminal parameters, as well as sperm DNA fragmentation percentage. Design: Semen samples of 520 idiopathic infertile patients were analyzed according to 2021 World Health Organization guidelines and evaluated for sperm DNA fragmentation rate. Each participants underwent bioelectric impedance analysis. Results: Median age was 40 years old, median BMI was 26.3 kg/m2, median phase angle was 6.2°. In the logistic regression analysis adjusted for age and total intracorporeal water, phase angle (continuous) was significantly associated with oligozoospermia (odds ratio [OR]:0.4; p<0.01) and sperm morphology (OR: 0.65; p=0.05) and slightly with sperm DNA fragmentation (OR: 0.98; p=0.07). In subgroup analysis, the logistic regression analysis adjusted for the mentioned parameters showed that a phase angle between 6.2 and 7 (°) (OR: 0.63; p=0.02) and >7 (°) (OR: 0.12; p<0.01) were associated with a reduced risk of oligozoospermia compared to values <6.2 (°). Similarly, a phase angle between 6.2 and 7 (°) (OR: 0.57; p< 0.01 and OR: 0.58; p= 0.01) and PA > 7 (°) (OR: 0.12; p= 0.03 and OR: 0.21; p< 0.01) were associated with a reduced risk of lower sperm concentration and lower total sperm count, respectively, compared to a phase angle < 6.2 (°). Conclusion: Our study suggests a negative association between phase angle and detrimental sperm parameters in male idiopathic infertility.

What Does Intracytoplasmic Sperm Injection Change in Embryonic Development? The Spermatozoon Contribution.

The intracytoplasmic sperm injection (ICSI) technique was invented to solve severe male infertility due to altered sperm parameters. Nowadays, it is applied worldwide for the treatment of couple infertility. ICSI is performed with any available spermatozoon from surgery or ejaculated samples, whatever are the sperm motility, morphology or quantity. The aim of the present review was to study if embryo development and kinetics would be modified by (1) ICSI under the technical aspects, (2) the micro-injected spermatozoa in connection with male infertility. From published data, it can be seen that ICSI anticipates the zygote kinetics Furthermore, because fertilization rate is higher in ICSI compared to conventional in vitro fertilization (IVF), more blastocysts are obtained for clinical use in ICSI. Sperm and spermatozoa characteristics, such as sperm parameters, morphology and vitality, DNA content (levels of sperm DNA fragmentation, microdeletions, and chromosomal abnormalities), RNA content, epigenetics, and sperm recovery site (testicular, epididymis, and ejaculated), have an impact on fertilization and blastocyst rates and embryo kinetics in different ways. Even though ICSI is the most common solution to solve couples' infertility, the causes of male infertility are crucial in building a competent spermatozoa that will contribute to normal embryonic development and healthy offspring.

Lipidomic Profile of Human Sperm Membrane Identifies a Clustering of Lipids Associated with Semen Quality and Function.

Reduced sperm motility and/or count are among the major causes of reduced fertility in men, and sperm membranes play an important role in the spermatogenesis and fertilization processes. However, the impact of sperm lipid composition on male fertility remains under-investigated. The aim of the present study was to perform a lipidomic analysis of human sperm membranes: we performed an untargeted analysis of membrane lipid composition in fertile (N = 33) and infertile subjects (N = 29). In parallel, we evaluated their serum lipid levels. Twenty-one lipids were identified by their mass/charge ratio and post-source decay spectra. Sulfogalactosylglycerolipid (SGG, seminolipid) was the most abundant lipid component in the membranes. In addition, we observed a significant proportion of PUFAs. Important differences have emerged between the fertile and infertile groups, leading to the identification of a lipid cluster that was associated with semen parameters. Among these, cholesterol sulfate, SGG, and PUFAs represented the most important predictors of semen quality. No association was found between the serum and sperm lipids. Dietary PUFAs and SGG have acknowledged antioxidant functions and could, therefore, represent sensitive markers of sperm quality and testicular function. Altogether, these results underline the important role of sperm membrane lipids, which act independently of serum lipids levels and may rather represent an independent marker of reproductive function.

The paradox of the Italian clinical embryologist in the national public health system: hints towards harmonization of a postgraduate educational curriculum.

Clinical embryologists are highly trained laboratory professionals with multiple roles, including laboratory, clinical, biobanking and quality system management. In most European countries, clinical embryologists are trained to work in Medically Assisted Reproduction (MAR) centres without a specifically dedicated educational path. The criteria required for employment vary according to the educational structure and the public or private nature of the centre. We have herein described the educational profile required by Italian clinical embryologists to work in MAR centres of the National Health System (NHS). Public centres currently represent 36% of all the Italian MAR clinics. According to the Italian law, a future clinical embryologist must achieve a 3-4 year unpaid post-graduate specialization in a different field, choosing from Genetics, Microbiology, Clinical Pathology or Nutrition. Accesses to the above-mentioned post-graduate courses are themselves very limited. Clinical embryologists are basically trained by senior colleagues. This situation makes inevitably difficult to recruit laboratory staff in NHS centres. Moreover, it represents an emblematic example of the need for an equal training curriculum, possibly ensuring a comparable education quality, mobility of trainees and dissemination of skills for clinical embryologists all over Europe.

Exposure to multiple metals/metalloids and human semen quality: A cross-sectional study.

BACKGROUND: Exposure to metals/metalloids, including essential and nonessential elements, has been associated to male reproductive health in animals. However, findings from human studies are inconsistent. OBJECTIVES: To investigate the impact of exposure to multiple metals/metalloids at environmental levels on the conventional human semen-quality parameters. MATERIALS AND METHODS: Men living in rural or industrial areas were recruited by personalized letters. No exclusion criteria were applied. Each man provided one semen sample and one blood sample. We analyzed the semen sample both to determine conventional sperm parameters (concentration, progressive motility and normal forms) and to quantify lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), nickel (Ni), vanadium (V) and selenium (Se) levels. The levels of these metals/metalloids were also quantified in venous blood and spermatozoa samples. Associations between the blood/seminal plasma metal/metalloid levels and semen quality parameters were assessed using confounder adjusted logistic regression models. Correlation and interactions between blood/seminal plasma and semen metal/metalloid levels were investigated using the Spearman's correlation. RESULTS: We found a positive association of seminal plasma cadmium level with lower Total count (OR = 4.48, 95%CI 0.25-80); whereas lead (OR = 4.51, 95%CI 0.86-23) and cadmium (OR = 3.45, 95%CI 0.77-16) seminal plasma levels had a positive association with progressive sperm motility. Overall, these associations remained suggestive after adjustment, though statistically unstable risks. Finally, we found weak interactions between beneficial effects of Se and detrimental ones only for Cd and Pb blood level on sperm concentration, total sperm count and progressive sperm motility. CONCLUSIONS: Our findings suggest that environmental exposure to Pb and Cd contributes to a decline in human semen quality, whereas Se can have beneficial effects. Measurements of metals/metalloids in the seminal fluid may be more predictable of semen quality than conventional blood measurements.

Evaluation of seminal fluid leukocyte subpopulations in patients with varicocele.

Varicocele is a common cause of sperm damage. Some studies showed higher concentration of seminal leukocytes in patients with varicocele. The aim of the study was to evaluate seminal leukocyte subpopulations in patients with varicocele. We enrolled 20 patients with varicocele and 20 age-matched healthy men. Sperm analysis was conducted according to the World Health Organization (WHO) 2010 criteria. We evaluated seminal leukocyte subpopulations and bio-functional sperm parameters by flow cytometry. Patients with varicocele had significantly lower sperm concentration and total number than controls. Regarding seminal leukocyte subpopulations, patients with varicocele had a significantly lower percentage of CD8+ and CD16+ leukocytes and a significantly higher percentage of CD4+ leukocytes than controls. As for bio-functional sperm parameters, we found that patients with varicocele had a significantly lower percentage of alive spermatozoa compared to the control group. These results may explain the increased level of cytokines in the seminal plasma of patients with varicocele.

FSH therapy for idiopathic male infertility: four schemes are better than one.

OBJECTIVE: The aim of this article is to propose an algorithm that aids the clinician to choose the best therapeutic scheme of follicle-stimulating hormone (FSH) in the treatment of men with idiopathic infertility, based on testicular volume (TV) and serum total testosterone concentrations; highlighting the potential role of additional therapy with hCG in a sequential temporal scheme. MATERIALS AND METHODS: We subdivided patients in four clinical groups: patients with normal TV and serum testosterone concentrations (A); patients with normal TV and reduced serum testosterone concentrations (B); patients with reduced TV and serum testosterone concentration (C); patient with low TV e normal serum testosterone concentrations (D). Then, we administered to each group a specific therapeutic scheme. Group A: treated with FSH alone for at least 3 months; group B: treated with hCG alone twice a week for 3 months and addition of FSH for poor responders (unmodified sperm parameters); group C: treated ab initio with FSH and hCG until the pregnancy was reached; group D: treated with FSH alone for 3 months and addition of hCG for moderate poor responders (increased TV but unmodified sperm parameters) or second cycle of FSH for 3 months for severe poor responders (unmodified TV and sperm parameters). After 6 months we evaluated the therapeutic response in term of sperm parameters normalization rate, spontaneous pregnancy rate, and sperm DNA fragmentation normalization rate. RESULTS: 40% of patients became normozoospermic after treatment, while 30% achieved spontaneous pregnancy. B was the group that best responded to treatment in terms of normalization of seminal parameters; while the highest spontaneous pregnancy rate was obtained from the D group. B group also obtained the highest sperm DNA fragmentation normalization rate. CONCLUSIONS: To date, no reliable predictors of response to treatment with FSH exist, but TV and serum testosterone concentrations can help the clinician to choose the best therapeutic scheme for men with idiopathic infertility. The groups treated with a sequential temporal scheme (B and D groups) showed better clinical results compared with two groups treated with conventional schemes (A and C groups).

Management and Treatment of Varicocele in Children and Adolescents: An Endocrinologic Perspective.

Pediatric varicocele has an overall prevalence of 15%, being more frequent as puberty begins. It can damage testicular function, interfering with Sertoli cell proliferation and hormone secretion, testicular growth and spermatogenesis. Proper management has a pivotal role for future fertility preservation. The aim of this review was to discuss the diagnosis, management and treatment of childhood and adolescent varicocele from an endocrinologic perspective, illustrating the current evidence of the European Society of Pediatric Urology (ESPU), the European Association of Urology (EAU), the American Urological Association (AUA) and the American Society for Reproductive Medicine (ASRM) scientific societies. According to the ASRM/ESPU/AUA practice committee, the treatment of adolescent varicocele is indicated in the case of decreased testicular volume or sperm abnormalities, while it is contraindicated in subclinical varicocele. The recent EAS/ESPU meta-analysis reports that moderate evidence exists on the benefits of varicocele treatment in children and adolescents in terms of testicular volume and sperm concentration increase. No specific phenotype in terms of testicular volume cut-off or peak retrograde flow (PRF) is indicated. Based on current evidence, we suggest that conservative management may be suggested in patients with PRF < 30 cm/s, testicular asymmetry < 10% and no evidence of sperm and hormonal abnormalities. In patients with 10-20% testicular volume asymmetry or 30 < PRF ≤ 38 cm/s or sperm abnormalities, careful follow-up may ensue. In the case of absent catch-up growth or sperm recovery, varicocele repair should be suggested. Finally, treatment can be proposed at the initial consultation in painful varicocele, testicular volume asymmetry ≥ 20%, PRF > 38 cm/s, infertility and failure of testicular development.

Testosterone levels after treatment with urofollitropin in infertile patients with idiopathic mild reduction of testicular volume.

INTRODUCTION: A reduction of testicular volume (TV) represents an important clinical sign, which may hide sperm abnormalities and predispose to hypogonadism. AIM: The primary purpose of this study was to evaluate the serum levels of total testosterone after treatment with urofollitropin in selected patients with male infertility and idiopathic mild reduction of testicular volume. METHODS: In this 1-year-long prospective design, patients with abnormal sperm parameters, mild reduction in TV (8-12 mL) and normal gonadotropin, and total testosterone (TT) serum levels were recruited in this study. Patients treated for 4 months with urofollitropin were included in group A, those treated with intracytoplasmatic sperm injection due to a female-factor infertility were included in group B. Hormone values, sperm parameters, and TV were detected at baseline (T0), after 4 (T1) and 12 months (T2) in group A and at T0 and T2 in group B. RESULTS: Group A (n = 80) showed increased follicle-stimulating hormone (FSH) at T1 and sperm morphology at T1 and T2 compared to T0 (all p < 0.05). Group B (n = 50) had lower TT and higher FSH levels at T2 compared to T0 (all p < 0.05). At T2, TT, VT, total sperm count, progressive motility, total motility, and sperm morphology were higher in group A compared to group B (all p < 0.05). CONCLUSION: Reduced TV may predispose to infertility and hypogonadism. FSH treatment may improve Sertoli and Leydig cell function and prevent the development of hypogonadism.

Effects of GH and IGF1 on Basal and FSH-Modulated Porcine Sertoli Cells In-Vitro.

Several lines of evidence suggest that insulin-like growth factor 1 (IGF1) is involved in Sertoli cell (SC) proliferation and that its receptor (IGF1R) could mediate follicle-stimulating hormone (FSH) effects. To examine the role of the growth hormone (GH)-IGF1 axis on SC function, we evaluated the effects of GH and IGF1 on basal and FSH-modulated SC proliferation, as well as on anti-Müllerian hormone (AMH) and inhibin B expression and secretion in-vitro. SCs from neonatal pigs were incubated with (1) placebo, (2) 100 nM highly purified urofollitropin (hpFSH), (3) 100 nM recombinant GH (rGH), (4) 100 nM recombinant IGF1 (rIGF1), (5) 100 nM hpFSH plus 100 nM rGH, (6) 100 nM hpFSH plus 100 nM rIGF1, for 48 h. We found that IGF1, but not FSH nor GH, stimulated SC proliferation. Furthermore, an inhibitory effect of FSH, GH and IGF1 on AMH secretion, and a stimulatory role of FSH and IGF1, but not GH, on inhibin B secretion were found. These results suggest that the GH-IGF1 axis influences basal and FSH-modulated SC proliferation and function. We speculate that SC proliferation occurring in childhood might be supported by the increased serum IGF1 levels observed during this period of life.

Thyroid Hormones and Spermatozoa: In VitroEffects on Sperm Mitochondria, Viability and DNA Integrity.

The aim of this study wasto assess the in vitro effects of levothyroxine (LT4) on conventional and bio-functional sperm parameters and its implications on fertility. Patients with male idiopathic infertility were enrolled and subjected to examination of the seminal fluid and capacitation according to the WHO 2010 criteria and flow cytometric sperm analysis for the evaluation of bio-functional sperm parameters. LT4 significantly increased the percentage of spermatozoa with high mitochondrial membrane potential (MMP), decreased the percentage of spermatozoa with low MMP and increased sperm motility already at a concentration of 0.9 pmol L-1. Therefore, LT4 significantly reduced sperm necrosis and lipid peroxidation ameliorating chromatin compactness. These effects of LT4 were evident at a concentration of 2.9 pmol L-1, close to the physiological free-thyroxine (FT4) concentrations in the seminal fluid of euthyroid subjects. We showed a beneficial role of thyroid hormones on sperm mitochondrial function, oxidative stress and DNA integrity. The results of this in vitro study could have a clinical application in patients with idiopathic infertility, clarifying the role of thyroid function on male fertility.

Poor Efficacy of L-Acetylcarnitine in the Treatment of Asthenozoospermia in Patients with Type 1 Diabetes.

Introduction. In recent years, research has focused on the impact that diabetes mellitus (DM) has on male reproductive function. The available evidence has mainly considered type 2 DM (DM2). However, we have previously shown that type 1 DM (DM1) also affects male reproductive health. Given the efficacy of carnitine in the treatment of male infertility, a topic that merits further investigation is its role in the treatment of infertile patients with DM1. Aim. To investigate the efficacy of carnitines for the treatment of asthenozoospermia in DM1 patients. Methods. This was a two-arm single-blind, randomized control trial. The patients enrolled in this study were assigned to the group receiving L-acetylcarnitine (LAC) (1.5 g daily for 4 months) or to the group receiving LAC (same dosage) plus L-carnitine (LC) (2 g daily for 4 months). Serum-glycated hemoglobin levels did not differ significantly after either of the two treatments given. Administration of LAC plus LC showed greater efficacy on progressive sperm motility than single therapy (increase 14% vs. 1% after treatment, respectively). Discussion. The results of this study showed that the administration of LAC plus LC is more effective than the administration of LAC alone. The lower efficacy of LAC alone could be due to the lower overall administered dosage. Alternatively, a selective defect of carnitine transporters at an epididymal level could be hypothesized in patients with DM1. Further studies are needed to clarify this point.

Early Identification of Isolated Sertoli Cell Dysfunction in Prepubertal and Transition Age: Is It Time?

The male transitional phase is of fundamental importance for future fertility. This aspect is largely neglected in clinical practice. This opinion aims to shed light on these issues. The children frequently complete the transition phase with a slight reduction of testicular volume. The system of detecting testicular volume is often inadequate. These patients evidently complete puberty in an incomplete way because they do not reach an adequate testicular volume, albeit in the presence of adequate height and regular secondary sexual characteristics.

Environment and Male Fertility: Effects of Benzo-α-Pyrene and Resveratrol on Human Sperm Function In Vitro.

Lifestyle, cigarette smoking and environmental pollution have a negative impact on male fertility. Therefore, the aim of this study was to evaluate the in-vitro effects of benzo-α-pyrene (BaP) and aryl hydrocarbon receptor (AHR) agonists on motility and bio-functional sperm parameters. We further assessed whether resveratrol (RES), an AHR antagonist and antioxidant molecule, had any protective effect. To accomplish this, 30 normozoospermic, healthy, non-smoker men not exposed to BaP were enrolled. Spermatozoa of 15 men were incubated with increasing concentrations of BaP to evaluate its effect and to establish its dose response. Then, spermatozoa of the 15 other men were incubated with BaP (15 µM/mL), chosen according to the dose-response and/or RES to evaluate its antagonistic effects. The effects of both substances were evaluated after 3 h of incubation on total and progressive sperm motility and on the following bio-functional sperm parameters evaluated by flow cytometry: Degree of chromatin compactness, viability, phosphatidylserine externalization (PS), late apoptosis, mitochondrial membrane potential (MMP), DNA fragmentation, degree of lipoperoxidation (LP), and concentrations of mitochondrial superoxide anion. Benzo-α-pyrene decreased total and progressive sperm motility, impaired chromatin compactness, and increased sperm lipoperoxidation and mitochondrial superoxide anion levels. All these effects were statistically significant at the lowest concentration tested (15 µM/mL) and they were confirmed at the concentration of 45 µM/mL. In turn, RES was able to counteract the detrimental effects of BaP on sperm motility, abnormal chromatin compactness, lipid peroxidation, and mitochondrial superoxide. This study showed that BaP alters sperm motility and bio-functional sperm parameters and that RES exerts a protective effect on BaP-induced sperm damage.

Erectile dysfunction, physical activity and physical exercise: Recommendations for clinical practice.

Erectile dysfunction could be an early sign of endothelial dysfunction and, therefore, of cardiovascular disease, with which it shares many risk factors. Among reversible risk factors, physical inactivity is one of the most important. Regular physical exercise has been shown to improve erectile function through different mechanisms involving glucose and lipid metabolism, regulation of arterial pressure, production of nitric oxide and hormonal modulation. Furthermore, exercise shows a synergistic effect with the drugs commonly used in the treatment of impotence. Since many patients with erectile dysfunction may have underlying cardiovascular disease, the evaluation of individual cardiovascular risk is mandatory before prescribing physical exercise. When exercise is not contraindicated, the most appropriate protocol must be chosen, considering the individual characteristics of the patient. Both aerobic and anaerobic/resistance protocols have proven effective. However, meta-analytic studies show that aerobic exercise with moderate-to-vigorous intensity is the most effective in improving erection. Testosterone is an important modulator of physical performance, and its blood levels must always be evaluated in patients with erectile dysfunction.

Epigenetics of Male Fertility: Effects on Assisted Reproductive Techniques.

During the last decades the study of male infertility and the introduction of the assisted reproductive techniques (ARTs) has allowed to understand that normal sperm parameters do not always predict fertilization. Sperm genetic components could play an important role in the early stages of embryonic development. Based on these acquisitions, several epigenetic investigations have been developed on spermatozoa, with the aim of understanding the multifactorial etiology of male infertility and of showing whether embryonic development may be influenced by sperm epigenetic abnormalities. This article reviews the possible epigenetic modifications of spermatozoa and their effects on male fertility, embryonic development and ART outcome. It focuses mainly on sperm DNA methylation, chromatin remodeling, histone modifications and RNAs.

Urogenital infections in patients with diabetes mellitus: Beyond the conventional aspects.

Diabetes mellitus (DM) is a widespread disease in our country. Urogenital infections, including urinary tract infections, vaginitis, balanitis, balanoposthitis, and male accessory gland infections, show a higher risk of occurrence in patients with DM that non-diabetic subjects. Both non-drug-related and drug-related mechanisms are involved in their pathogenesis. These conditions may impact on glucose control and islets function in DM and more likely develop into adverse complications. A throughout microbial characterization, including the drug-sensitivity test, is required for a proper management. To reduce the risk of recurrence, combined treatment, including antibiotic, anti-inflammatory, and fibrinolytic molecules, should be prescribed also to the sexual partner. The choice of the antidiabetic drug to prescribe should take into consideration the presence of urogenital infections. In conclusion, urogenital infections may more likely lead to complication in diabetic than non-diabetic patients, affect fertility and glucose control. Therefore, they need proper management.