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Background: In the last 40 years, assisted reproductive techniques (ARTs) have emerged as potentially resolving procedures for couple infertility. This study aims to evaluate whether ART is associated with epigenetic dysregulation in the offspring. Methods. To accomplish this, we collected all available data on methylation patterns in offspring conceived after ART and in spontaneously conceived (SC) offspring. Results. We extracted 949 records. Of these, 50 were considered eligible; 12 were included in the quantitative synthesis. Methylation levels of H19 CCCTC-binding factor 3 (CTCF3) were significantly lower in the ART group compared to controls (SMD −0.81 (−1.53; −0.09), I2 = 89%, p = 0.03). In contrast, H19 CCCTC-binding factor 6 (CTCF6), Potassium Voltage-Gated Channel Subfamily Q Member 1 (KCNQ1OT1), Paternally-expressed gene 3 (PEG3), and Small Nuclear Ribonucleoprotein Polypeptide N (SNRPN) were not differently methylated in ART vs. SC offspring. Conclusion: The methylation pattern of the offspring conceived after ART may be different compared to spontaneous conception. Due to the lack of studies and the heterogeneity of the data, further prospective and well-sized population studies are needed to evaluate the impact of ART on the epigenome of the offspring.

A physical examination represents a fundamental step in diagnosing diseases. Due to the role that hormones play in the regulation of numerous biological processes in various organs and systems, endocrine diseases cause a variety of clinical manifestations that can be easily identified with a careful physical examination and can guide the clinician to specific diagnoses. Furthermore, the presence of specific clinical signs in various endocrine-metabolic diseases can predict the risk of developing comorbidities and serious adverse events. In this article, we present some of the main clinical signs of endocrine-metabolic diseases and the risk of comorbidities, summarizing the pathogenetic mechanisms that lead to their formation. The aim is to highlight how the identification of these specific signs can reduce the number of dynamic tests and the costs necessary to reach the diagnosis and allow the early identification of any complications associated with these diseases, improving the clinical management of affected patients.

Purpose: To prospectively investigate the effects of treatment with liraglutide, a glucagon-like peptide 1 (GLP1) analog, on reproductive and sexual function in men with metabolic hypogonadism who are of childbearing age. Materials and Methods: To accomplish this purpose, 110 men of childbearing age (18–35 years) with metabolic hypogonadism were enrolled and divided into three groups, according to their desire to have children. Group A was made up of men actively seeking fatherhood, Group B, of men who did not seek fatherhood, and Group C, of men who had already fathered a child. Group A patients were treated with gonadotropins (urofollitropin at 150 IU, three times a week, and human chorionic gonadotropin at 2000 IU, twice a week), Group B patients with liraglutide (3 mg daily), and Group C patients with transdermal testosterone (60 mg per day). All patients were treated for 4 months. Results: Patients treated with liraglutide (Group B) showed significant improvement in conventional sperm parameters, compared to baseline and Group A patients, and in the quality of erectile function compared to baseline and patients of Groups A and C. In addition, they had significantly higher levels of total testosterone and sex hormone-binding globulin serum levels after 4 months of treatment with liraglutide than those achieved by patients in the other two groups at the end of the respective treatments. Finally, Group B patients also showed significantly higher serum gonadotropin levels than the other groups. Conclusions: The results of this study showed, for the first time, the efficacy of liraglutide, a GLP1 analog, for the pharmacological treatment of male patients with metabolic hypogonadism. Liraglutide has also shown advantages over traditional treatments on both reproductive and sexual function and appears to offer greater benefits in terms of metabolic protection. These findings suggest that liraglutide is a useful drug for the treatment of obese males with metabolic hypogonadism.

The protocols commonly used in assisted reproductive technology (ART) consist of long-term embryo culture up to the blastocyst stage after the insemination of all mature oocytes, the freezing of all the embryos produced, and their subsequent transfer one by one. These practices, along with preimplantation genetic testing, although developed to improve the live birth rate (LBR) and reduce the risk of multiple pregnancies, are drawing attention to the possible increase in obstetric and perinatal risks, and adverse epigenetic consequences in offspring. Furthermore, ethical–legal concerns are growing regarding the increase in cryopreservation and storage of frozen embryos. In an attempt to reduce the risk associated with prolonged embryo culture and avoid embryo storage, we have chosen to inseminate a limited number of oocytes not exceeding the number of embryos to be transferred, after two days or less of culture. We retrospectively analyzed 245 ICSI cycles performed in 184 infertile couples with a female partner aged ≥40 from January 2016 to July 2021. The results showed a fertilization rate of 95.7%, a miscarriage rate of 48.9%, and a LBR of 10% with twin pregnancies of 16.7%. The cumulative LBR in our group of couples was 13%. No embryos were frozen. In conclusion, these results suggest that oocyte selection and embryo transfer at the cleaving stage constitute a practice that has a LBR comparable to that of the more commonly used protocols in older women who have reduced ovarian reserve.

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Background: Selenium (Se) is an essential component of selenoenzymes, which have catalytic and antioxidant functions. A low Se status has been reported in patients with chronic autoimmune thyroiditis (AT) who benefit from Se supplementation. The role of Se in male reproduction is still a matter of debate. Although Se and selenoenzymes ensure sperm viability and protect against increased oxidative stress, only a few studies have assessed the effects of the administration of Se alone on sperm parameters, providing contrasting results. Aim: The aim of this study was to assess the effects of oral Se supplementation on conventional sperm parameters and DNA fragmentation (SDF) in patients with AT of reproductive age with normal thyroid function. Patients and Methods: Only patients with AT and normal thyroid function were selected for this study. All included patients underwent oral Se supplementation at the dose of 83 µg once daily (Syrel®, IBSA) for six months. Sperm conventional parameters, SDF, and thyroid function were assessed before and at the end of the treatment. Results: Twenty AT patients with normal weight were enrolled. After Se supplementation, they showed a higher sperm concentration, a higher percentage of sperm with progressive motility, and a higher percentage with normal morphology. They also had lower semen leukocyte concentration, and a lower percentage of spermatozoa with DNA fragmentation compared with pre-treatment values. Free-thyroxine serum levels increased significantly, whereas free triiodothyronine showed an upward trend. The thyroid-stimulating hormone did not change significantly. Conclusion: Se supplementation may represent a possible non-hormonal therapeutic choice for the treatment of male infertility, although further studies are needed to confirm this evidence. The possible thyroid hormone dependency of these findings needs to be clarified.

Follicle-stimulating hormone (FSH) is a therapeutic option in patients with idiopathic oligozoospermia and normal FSH serum levels. However, few studies have evaluated which dose of FSH is more effective. The aim of this study was to compare the clinical efficacy of the two most frequently used FSH treatment regimens: 75 IU daily vs. 150 IU three times a week. Patients were retrospectively assigned to two groups. The first group (n = 24) was prescribed highly purified FSH (hpFSH) 75 IU/daily (Group A), and the second group (n = 24) was prescribed hpFSH 150 IU three times a week (Group B) for three months. Before and after treatment, each patient underwent semen analysis, evaluation of the percentage of DNA-fragmented spermatozoa, assessment of testicular volume (by ultrasonography), and measurement of FSH and total testosterone (TT) serum levels. Treatment with hpFSH significantly improved conventional sperm parameters. In detail, sperm concentration increased significantly after treatment only in Group A, whereas total sperm count, percentage of spermatozoa with progressive motility, normal morphology, or alive improved significantly in both groups. Interestingly, the percentage of sperm DNA fragmentation decreased significantly in both groups after treatment with hpFSH. FSH serum levels were expectably higher at the end of the treatment than before hpFSH was administered to both groups. Remarkably, TT serum levels only increased significantly in Group A. Finally, testicular volume was significantly higher in Group A after treatment, while it did not change significantly compared to baseline in Group B. The percentage of FSH responders did not differ significantly between the two groups (8/24 vs. 6/24). The daily administration of hpFSH 75 IU seems more effective than using 150 IU three times a week. However, this therapeutic scheme implies a higher number of injections and slightly higher costs.

Objective: To evaluate the changes of conventional sperm parameters in men who referred to an andrology reference center in Catania (Eastern Sicily, Italy) in the decade 2011–2020. Methods: For this purpose, we selected–retrospectively and randomly–the reports of 1409 semen analyses performed according to the 2010 WHO criteria. Data on sperm concentration, total sperm count, progressive sperm motility, and percentage of normal forms were analyzed using linear regression of the raw and logarithmic-transformed data. The sperm parameters were subsequently pooled in two five-year periods (2011–2015 and 2016–2020) and compared with each other. Finally, the influence of the city of residence was assessed on five-year pooled data. Main results: A slight but non-significant decline of total sperm count (−2.26 million/year, p = 0.065) and the percentage of spermatozoa with normal morphology (−0.08%/year, p = 0.057) was observed. In contrast, a significant increase of progressive sperm motility (+0.28%/year, p = 0.008) over time was found. The total sperm count of the quinquennium 2016–2020 was significantly lower. and an upward trend of progressive sperm motility was found. compared to the years 2011–2015. No changes in sperm concentration and morphology occurred in the years 2011–2015 vs. 2016–2020. Sperm conventional parameters did not differ when the five-year pooled data were analyzed according to the town of residence. Conclusions: Divergent trends of total sperm count and progressive sperm motility over time were found in patients from Eastern Sicily. This may point out the need of assessing whether a time-dependent change of biofunctional sperm parameters occurs to really understand the trend of sperm quality over time.

Cardiovascular diseases are the main cause of mortality in the Western population, so the attempt to find a marker capable of predicting their early onset is not surprising. It is known that arteriogenic erectile dysfunction (ED) precedes the onset of a major coronary event by several years. However, a marker that is able to early identify those patients who should undergo further diagnostic investigations is, to date, missing. Recent research on this topic has focused on the role of the mean platelet volume (MPV), a marker of platelet activity that is high in most vascular diseases, such as coronary artery disease (CAD), stroke, peripheral artery disease (PAD), and ED. The basic pathophysiological mechanism of all these clinical conditions is atherosclerosis. Platelets play a central role in amplifying this process both indirectly by stimulating endothelial cells to produce inflammatory cytokines and chemokines, and directly through the expression of membrane receptors and the release of molecules that contribute to the formation of atherosclerotic plaque. The objective of this review is to critically analyze the evidence on the role of MPV in predicting the diagnosis and severity of vasculogenic ED and the possibility of using this simple marker as a first step to start a diagnostic process aimed at assessing the cardiovascular risk in these patients.

There is increasing data in favour of follicle-stimulating hormone (FSH) therapy in patients with oligo-asthenozoospermia and normal-range gonadotropins in order to increase sperm count and above all sperm motility. Some studies showed an improvement in DNA fragmentation and spontaneous pregnancy. Recently, biosimilar FSH has been marketed with the same indications. We performed a retrospective multicentric case-control study involving 147 asthenozoospermic patients between 18 and 45 years of age. A total of 97 patients were treated with biosimilar FSH 150 UI three times a week for 3 months, while 50 control subjects received no treatment. Patients were evaluated at baseline and after 3 months with semen analysis including DNA fragmentation, testicular colour Doppler ultrasound, and blood tests. Spontaneous pregnancies were recorded during a further follow-up period of 6 months. Treated patients showed after treatment a statistically significant increase in sperm concentration, total sperm count, and total motile sperm, as well as improved progressive motility and non-progressive motility. DNA fragmentation showed a significant reduction. Conversely, in the control group, no significant change was found. Pregnancy rate was significantly higher in treated patients. These data suggest comparable efficacy of biosimilar FSH in the treatment of male infertility, however, larger studies are needed to confirm our results.

The use of inositols in endocrinological clinical practice is increasingly widespread. Most of the existing evidence concerns myoinositol (MYO), the most abundant form in nature, especially in women with polycystic ovarian syndrome. We have previously shown that MYO increases sperm motility in patients with asthenozoospermia by the increase of sperm mitochondrial membrane potential (MMP), a biofunctional sperm parameter closely associated to sperm motility. The aim of this study was to evaluate the effects of D-chiro-inositol (DCI), another biologically active isoform of inositols, on sperm MMP, as data on this matter has never been released so far. To accomplish this, semen samples from 15 patients with asthenozoospermia and 15 healthy normozoospermic men were incubated with increasing concentrations of DCI (0, 75, and 750 µg/mL) or phosphate buffer saline for 30 min. Incubation with DCI significantly improved sperm MMP at lower concentrations, and with shorter incubation length than those used in our similar MYO studies. In conclusion, these findings indicate that DCI positively impacts on sperm mitochondrial function in vitro. Studies aimed at assessing the role of DCI in the treatment of asthenozoospermia in-vivo are warranted.

Background: Recent studies have supported the beneficial effects of a short abstinence period on sperm parameters. The aim of this study was to assess sperm motility, morphology and DNA fragmentation before and after swim-up of a second ejaculate obtained after a short abstinence period in normozoospermic men and oligo-astheno-teratozoospermic (OAT) patients. Material and methods: Semen analyses and swim-up preparations of two consecutive semen samples (collected within 1 h) were carried out in 30 normozoospermic and 35 OAT patients enrolled in an assisted reproductive technique (ART) program. Results: Compared to the first ejaculate, the second sample showed a higher percentage of spermatozoa with normal form (p &lt, 0.01) and lower percentage of spermatozoa with DNA fragmentation (p &lt, 0.01) in normozoospermic men, whereas a higher percentage of spermatozoa with progressive motility (p &lt, 0.001) and normal morphology (p &lt, 0.0001) was found in OAT patients. Swim-up separation showed a lower DNA fragmentation rate (p &lt, 0.05) in the second ejaculate in normozoospermic men, whereas the second ejaculate of OAT patents showed an increase in normally-shaped spermatozoa (p &lt, 0.01) and lower percentage of spermatozoa with fragmented DNA (p &lt, 0.001) compared to the first one. Conclusions: Swim-up separation of a second ejaculate collected within 1 h might be suggested for ART procedures, especially in OAT patients.

Male infertility is a widespread condition among western countries. Meta-regression data show that sperm concentration and total sperm count have halved in the last decades. The reasons of this decline are still unclear. The evaluation of testicular function in pre-pubertal children may be effective in the timely detection of Sertoli cell (SC) disfunction, which anticipates the diagnosis of male infertility. The aim of this Special Issue is to gather together in vitro evidence on SC physiology, causes of SC dysfunction, and to suggest a practical approach to be adopted in children.

Background: Arterial erectile dysfunction (ED) is an early sign of vascular damage. Rare evidence has been published so far as to whether subclinical hypothyroidism (SCH) affects arterial erectile function. Therefore, the objective of this study was to fill this gap. Methods: Patients with arterial ED and SCH were consecutive enrolled and randomly divided into Group A (n = 20) and Group B (n = 20). Group A was treated with levo-thyroxine (LT4) at the dose of 1 &micro, g/kg/day for six months, whereas patients of the group B did not receive any treatment. Thyroid stimulating hormone (TSH), free-thyroxine (FT4), peak systolic velocity (PSV), International Index of Erectile Function 5-item version (IIEF-5) score, mean platelet volume (MPV), and total cholesterol were evaluated at enrollment (T0) and after six months (T1). Patients without hypertension, diabetes mellitus, dyslipidemia, not on drugs, and with normal total testosterone (TT) values were included in this study. Results: Group A and B did not differ for age (61.2 &plusmn, 4.8 vs. 60.3 &plusmn, 5.6 years), body-mass index (28.7 &plusmn, 2.5 vs. 28.3 &plusmn, 2.6 Kg/m2), and serum TT levels (481.2 &plusmn, 54.0 vs. 492.1 &plusmn, 59.7 ng/dL). At T0, serum TSH levels (6.5 &plusmn, 1.2 vs. 6.0 &plusmn, 1.0 &micro, IU/mL), FT4 (8.8 &plusmn, 0.6 vs. 8.8 &plusmn, 0.6 pmol/L), PSV (26.5 &plusmn, 1.4 vs. 25.8 &plusmn, 2.1 cm/s), IIEF-5 score (8.2 &plusmn, 1.7 vs. 9.0&plusmn, 1.7), and total cholesterol (167.8 &plusmn, 21.7 vs. 171.6 &plusmn, 21.3 mg/dL) did not significantly differ in patients of Group A vs. those of Group B. MPV was significantly higher in Group A than in Group B (12.3 &plusmn, 0.3 vs. 11.8&plusmn, 0.7 fL). At T1, Group A showed significantly lower TSH (2.26 &plusmn, 0.5 &micro, IU/mL), MPV (9.5 &plusmn, 0.3 fL), and total cholesterol (137.8 &plusmn, 29.2 mg/dL) and significantly higher FT4 (9.3 &plusmn, 0.4 pmol/L), PSV (40.0 &plusmn, 2.6 cm/s), and IIEF-5 score (20.2 &plusmn, 3.6) compared to pre-treatment values. None of these endpoints showed significant change at T1 compared to T0 in patients of group B. Conclusions: Lt4 therapy is associated with an improvement of the erectile function at the vascular level, a decrease in MPV and total cholesterol. LT4 therapy should be considered in patients with arterial ED and SCH.

The aim of this experimental study was to evaluate whether infertile patients may benefit from the evaluation of bio-functional sperm parameters in addition to the conventional semen analysis. To accomplish this, we evaluated the correlation between conventional and bio-functional sperm parameters based on their percentile distribution in search of a potential threshold of these latter that associates with conventional sperm parameter abnormalities. The study was conducted on 577 unselected patients with infertility lasting at least 12 months. We identified cut-off values according to the median of the population for mitochondrial membrane potential (MMP), number of alive spermatozoa, and chromatin abnormality. High MMP (HMMP) (&ge, 46.25%) was associated with sperm concentration, sperm count, progressive motility, and normal form. Low MMP (LMMP) (&ge, 36.5%) was found to be associated with semen volume, sperm concentration, total sperm count, progressive motility, total motility, and normal form. The number of alive spermatozoa (&ge, 71.7%) was associated with sperm concentration and progressive motility whereas abnormal chromatin compactness (&ge, 21.10%) was associated with sperm concentration, total sperm count, and progressive motility. The data would suggest that, for every increase in the percentile category of sperm concentration, the risk of finding an HMMP&le, 46.25 is reduced by 0.4 and by 0.66 for a total sperm count. This risk is also reduced by 0.60 for every increase in the percentile category of sperm progressive motility and by 0.71 for total sperm motility. Each increment of percentile category of the following sperm parameter was followed by a decrease in the risk of finding an LMMP&le, 36.5: sperm concentration 1.66, total sperm count 1.28, sperm progressive motility 1.27, total sperm motility 1.76, and normal form 1.73. Lastly, the data showed that, for every increase in the percentile category of total sperm count, the risk of finding an abnormal chromatin compactness &le, 21.10 is reduced by 1.25 (1.04&ndash, 1.51, p &lt, 0.05) and an increase of total sperm motility is associated with a reduced risk by 1.44 (1.12&ndash, 1.85, p &lt, 0.05). Results suggest a correlation between bio-functional and conventional sperm parameters that impact the sperm fertilizing potential. Therefore, the evaluation of bio-functional sperm parameters by flow cytometry may be useful to explain some cases of idiopathic male infertility.

Introduction: The role of nutraceuticals in the treatment of male infertility, especially in the “idiopathic form”, remains the subject of significant debate. Many antioxidants improve sperm motility but the exact mechanism by which they act is still unclear. Although several studies have shown a correlation between sperm motility and mitochondrial function, the effects of antioxidant therapy on mitochondrial membrane potential (MMP) are poorly studied. The first aim of this review was to evaluate the efficacy of antioxidants on mitochondrial function and, consequently, on sperm motility in male infertile patients. Material and Methods: we performed a systematic search of all randomized controlled and uncontrolled studies available in the literature that reported sperm motility and MMP at baseline and after antioxidant administration in-vivo and in-vitro in patients with idiopathic asthenozoospermia. Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar and Scopus databases were used. Results: Unexpectedly, among 353 articles retrieved, only one study met our inclusion criteria and showed a significant effect of myoinositol on both MMP and sperm motility. We then summarized the main knowledge on anatomy and metabolism of sperm mitochondria, techniques allowing to assess sperm mitochondria function and its relationships with low sperm motility. Finally, we paid special attention to the effect of antioxidant/prokinetic molecules for the treatment of asthenozoospermia. Conclusions: This is the first systematic review that has attempted to evaluate the effects of antioxidants on MMP and sperm motility. Although results are not conclusive due to the dearth of studies, the close relationship between mitochondria and sperm motility is clear. The investigation of this correlation could provide valuable information to be exploited in clinical practice for the treatment of male infertility.

Purpose: The aim of this study was to compare the initial request for sexual consultation with the final diagnosis and to evaluate the limits of the active andrological anamnesis concerning unclassified male sexual dysfunction. Methods: In this 12-year observational retrospective study, we collected data from patients referring to an andrological outpatient clinic, evaluating the requests, perceptions, needs, and self-diagnosis at their first visit and comparing them with the final diagnosis reached after a complete clinical, laboratory, and instrumental investigation. Results: A total of 11,200 patients were evaluated. The main request of andrological consultation was erectile dysfunction (ED) (52%), followed by premature ejaculation (PE) (28%), and low sexual desire (11.5%). Among the patients seeking help for ED, about 30% were ultimately found to have a different type of dysfunction and 24% were diagnosed with an &ldquo, unmet need&rdquo, which included issues not present in the current nosography nonetheless affecting sexual and relational life. Among the patients referring for PE, the final diagnosis was lifelong PE for the large majority of them, regardless of whether initially they thought to have an acquired form. Several of those who sought consultation for acquired PE were frequently found to be able to compensate for lifelong PE by a subsequent coitus or were able to induce orgasm in the partner with different modalities. Among the patients referring for low sexual desire, only 57.5% were confirmed to have it, 23% had ED and 18.5% showed a raised threshold of penile sensitivity. Conclusions: The results of this study show that the reason for consultation is frequently misleading and raise the relevance of being aware of the so-called &ldquo, unmet needs&rdquo, and to discuss with the patient and the couple to explore the sexual history behind the self-diagnosis. These findings also suggest the need to expand the current taxonomy of male sexual dysfunctions.

Introduction: Osteoporosis is increasingly prevalent in the elderly, with fractures mostly occurring in women and men who are older than 55 and 65 years of age, respectively. The aim of this review was to examine the evidence regarding the influence of hormones on bone metabolism, followed by clinical data of hormonal changes in the elderly, in the attempt to provide possible poorly explored diagnostic and therapeutic candidate targets for the management of primary osteoporosis in the aging population. Material and methods: An extensive Medline search using PubMed, Embase, and Cochrane Library was performed. Results: While the rise in Thyroid-stimulating hormone (TSH) levels has a protective role on bone mass, the decline of estrogen, testosterone, Insulin-like growth factor 1 (IGF1), and vitamin D and the rise of cortisol, parathyroid hormone, and follicle-stimulating hormone (FSH) favor bone loss in the elderly. Particularly, the AA rs6166 FSH receptor (FSHR) genotype, encoding for a more sensitive FSHR than that encoded by the GG one, is associated with low total body mass density (BMD), independently of circulating estrogen. A polyclonal antibody with a FSHR-binding sequence against the β-subunit of murine FSH seems to be effective in ameliorating bone loss in ovariectomized mice. Conclusions: A complete hormonal assessment should be completed for both women and men during bone loss evaluation. Novel possible diagnostic and therapeutic tools might be developed for the management of male and female osteoporosis.

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.

Background: The clinical practice shows that many low-dose ACTH-stimulation tests have a false positive result. The aim of the study was to determine the diagnostic accuracy of a low-dose ACTH-stimulation test in the diagnosis of adrenal insufficiency and to define its optimal cut-off. Methods: We analyzed data from 103 patients undergoing 1 &micro, g ACTH-stimulation test. Four patients had adrenal insufficiency (AI) upon follow up: Two primary, and two secondary AI. Cortisol serum levels were evaluated at time 0, 20&rsquo, and 30&rsquo, after the injection of 1 &micro, g i.v. of ACTH. The sensitivity, specificity, accuracy, and positive and negative predictive values of the test were calculated for both 20&rsquo, sampling. The receiver operating characteristic (ROC) curve was obtained to assess the sensitivity and specificity of low-dose ACTH-stimulation test in the diagnosis of adrenal insufficiency at different cut-off values. Results: Considering 500 nmol/L as the standard cut-off value, low-dose ACTH stimulation test showed a 100% sensitivity and a 67.3% specificity, with a high rate of false positive results. ROC curve analysis showed that the cut-off of 401.5 nmol/L is the best compromise between sensitivity (100%) and specificity (93.9%). Conclusions: By using a cut-off value of 401.5 nmol/L for the low-dose ACTH stimulation test, the number of false positive patients decreased significantly, but the sensitivity remained high.

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.

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-&alpha, 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 &micro, M/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-&alpha, 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 &micro, M/mL) and they were confirmed at the concentration of 45 &micro, M/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.

Experimental evidence has shown that the IGF1 receptor (IGF1R) is involved in testicular development during embryogenesis. More recently, data gathered from mice granulosa cells and zebrafish spermatogonia suggest that IGF1R has a role in Follicle-stimulating hormone (FSH) signaling. No evidence has been reported on this matter in Sertoli cells (SCs) so far. The aim of the study was to evaluate the role, if any, of the IGF1R in FSH signaling in SCs. The effects of FSH exposure on myosin-phosphatase 1 (MYPT1), ERK 1/2, AKT308, AKT473, c-Jun N-terminal kinase (JNK) phosphorylation and on anti-M&uuml, llerian hormone (AMH), inhibin B and FSH receptor (FSHR) mRNA levels were assessed with and without the IGF1R inhibitor NVP-AEW541 in purified and functional porcine neonatal SCs. Pre-treatment with NVP-AEW541 inhibited the FSH-induced MYPT1 and ERK 1/2 phosphorylation, decreased the FSH-dependent Protein kinase B (AKT)308 phosphorylation, but did not affect the FSH-induced AKT473 and JNK phosphorylation rate. It also interfered with the FSH-induced AMH and FSHR down-regulation. No influence was observed on the FSH-stimulated Inhibin B gene expression. Conclusion. These findings support the role of theIGF1R in FSH signaling in porcine SCs. The possible influence of IGF1 stimulation on the FSH-mediated effects on SCs should be further explored.

In recent years, a growing number of studies seem to support the beneficial effects of a very short abstinence period on sperm parameters, especially in patients with oligo-asthenozoospermia (OA). On this basis, the aim of this study was to evaluate the effects of a short period of abstinence (1 h) on intracytoplasmic sperm injection (ICSI) outcomes in infertile patients with severe OA. We performed a retrospective study on 313 ICSI cycles in which couples were divided into two different groups based on sperm parameters of the male partners. Group 1 included normozoospermic men or male partners with a mild OA (n = 223). Group 2 included male partners with severe OA (n = 90). They were asked to provide a second consecutive ejaculation after 1 h from the first one. The best ejaculate was used to perform ICSI. We found a significant increase of total (p &lt, 0.001) and progressive motility (p &lt, 0.001) in the second ejaculate of patients of Group 2 compared with those of the first one. Spermatozoa of the second ejaculate were chosen for ICSI for all patients in Group 2. We found statistically significant improvement of clinical pregnancy rate (p = 0.001) and embryo quality (p = 0.003) in couples in Group 2 compared to those of Group 1. No statistically significant difference was found in fertilization, implantation, live birth delivery, and miscarriage rates between the two groups. Therefore, a second semen sample collected after a very short time-interval in patients with severe OA allowed us to obtain significantly higher clinical pregnancy rate with improved embryo quality compared to normozoospermic men or patients with mild OA. Fertilization, implantation, live birth delivery, and miscarriage rates were similar between the two groups. The present study shows that a second consecutive ejaculate could represent a simple strategy to obtain better sperm parameters and assisted reproductive technology (ART) outcomes in infertile patients with mild-severe OA.