Reduced Seminal Concentration of CD45pos Cells after Follicle-Stimulating Hormone Treatment in Selected Patients with Idiopathic Oligoasthenoteratozoospermia

The present study evaluated the conventional sperm parameters and the seminal concentration of CD45pos cells (pan-leukocyte marker) of infertile patients with idiopathic oligoasthenoteratozoospermia (OAT). The patients were arbitrarily divided into three groups treated with recombinant follicle-stimulating hormone FSH: α (Group A = 20 patients), recombinant FSH-β (Group B = 20 patients), and highly purified human FSH (Group C = 14 patients). All treated groups achieved a similar improvement of the main sperm parameters (density, progressive motility, and morphology), but only the increase in the percentage of spermatozoa with normal morphology was significant compared to the baseline in all three examined groups. Moreover, all groups had a significant reduction of the seminal concentration of CD45pos cells and of the percentage of immature germ cells. Before and after the treatment, the concentration of CD45pos cells showed a positive linear correlation with the percentage of immature germ cells and a negative correlation with the percentage of spermatozoa with regular morphology. These results demonstrate that treatment with FSH is effective in patients with idiopathic OAT and that there are no significant differences between the different preparations. The novelty of this study is in the significant reduction of the concentration of CD45pos cells observed after the treatment

Controversy and Consensus on Indications for Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations

Purpose: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. Materials and Methods: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. Results: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. Conclusions: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians

Controversy and consensus on the management of elevated sperm DNA fragmentation in male infertility: A global survey, current guidelines, and expert recommendations

Purpose Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. Materials and Methods An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method. Results A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4–6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. Conclusions This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians

Effetti della nicotina sulla funzione spermatica in vitro

L obiettivo dello studio è stato quello di valutare, in vitro, gli effetti della nicotina sulla motilità degli spermatozoi e sui parametri non convenzionali del liquido seminale. Sono stati valutati i migliori spermatozoi, selezionati mediante capacitazione, di 10 uomini normozoospermici, sani e non fumatori. Gli spermatozoi sono stati sono stati esposti a concentrazioni crescenti di nicotina (0, 1, 10 e 100 ng/ml) per 3 e 24 ore. Dopo l incubazione sono stati valutati la motilità progressiva, e mediante citofluorimetria a flusso i parametri non convenzionali: potenziale di membrana mitocondriale, vitalità, esternalizzazione della fosfatidilserina, apoptosi tardiva, grado di compattazione della cromatina e frammentazione del DNA. La nicotina ha ridotto, in modo concentrazione-dipendente, la motilità progressiva a partire dalla concentrazione più bassa (1 ng/nl). Allo stesso modo, ha ridotto la percentuale di spermatozoi vitali ed ha aumentato il numero di spermatozoi in apoprosi tardiva, con alterata compattazione della cromatina o frammentazione del DNA già dopo 3 ore di incubazione. Questi effetti sono stati osservati ad una concentrazione simile (100 ng/ml) a quella trovata nel plasma seminale di uomini fumatori (70 ng/ml), ad eccezione degli effetti sulla frammentazione del DNA, dove gli effetti sono stati osservati anche ad una concentrazione inferiore (10 ng/ml) di nicotina. La nicotina può essere considerata dunque come un componente del fumo di sigaretta che ha effetti nocivi sulla funzione riproduttiva maschile

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

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

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

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 inves-tigations 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

Thyroid Hormones and Spermatozoa: In Vitro Effects 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