FSH Therapy in Male Factor Infertility: Evidence and Factors Which Might Predict the Response.

Follicle-stimulating hormone (FSH) administration is applied in the management of subjects affected by hypogonadotropic hypogonadism. Whilst this application is widely recognized and established alone or in combination with human chorionic gonadotropin (hCG), a similar strategy is empirically advocated in idiopathic male factor infertility (MFI). In this setting, FSH therapy has been used to increase sperm quantity, quality, and pregnancy rate when FSH plasma concentrations are below 8 IU/L and when the seminal tract is not obstructed. In the literature, several studies suggested that giving FSH to patients with idiopathic MFI increases sperm count and motility, raising the overall pregnancy rate. However, this efficacy seems to be limited, and about 10-18 men should be treated to achieve one pregnancy. Thus, several papers suggest the need to move from a replacement approach to an overstimulating approach in the management of FSH therapy in idiopathic MFI. To this aim, it is imperative to determine some pharmacologic markers of FSH efficacy. Furthermore, it should be useful in clinical practice to distinguish, before starting the treatment, among patients who might respond or not to FSH treatment. Indeed, previous studies suggest that infertile men who have normal levels of gonadotropins in plasma might not respond to FSH treatment and about 50% of patients might be defined as "non-responders". For these reasons, identifying predictive markers of FSH action in spermatogenesis and clinical markers of response to FSH treatment is a fascinating area of study that might lead to new developments with the aim of achieving personalization of the treatment of male infertility. From this perspective, seminal parameters (i.e., spermatid count), testicular cytology, genetic assessment, and miRNA or protein markers in the future might be used to create a tailored FSH therapy plan. The personalization of FSH treatment is mandatory to minimize side effects, to avoid lost time with ineffective treatments, and to improve the efficacy, predicting the most efficient dose and the duration of the treatment. This narrative review's objective is to discuss the role of the different putative factors which have been proposed to predict the response to FSH treatment in idiopathic infertile men.

Male contraception: Focus on behavioral and barrier methods.

INTRODUCTION: Male contraception includes various methods designed to prevent pregnancy by focusing on the male's role in reproduction. RESULTS: Behavioral methods, such as withdrawal and periodic abstinence, offer non-invasive alternatives that require self-control and precise timing to avoid depositing sperm in the female reproductive tract during fertile periods. However, these methods generally have low effectiveness and rely heavily on user adherence and experience. The male condom, a barrier method, provides both contraception and protection against sexually transmitted infections. Its effectiveness relies on correct and consistent use. DISCUSSION: Access to comprehensive sexual education and medical counseling is essential to dispel the stigma surrounding contraceptive use and correct misconceptions, ensuring proper usage and ultimately contributing to better reproductive health outcomes.

Diabetes and male fertility disorders.

Couple infertility is a common condition, defined as being unable to conceive after 12 months of regular unprotected sexual intercourse. Male Factor Infertility (MFI) is responsible, alone or in combination with female factors, for about half of the overall cases of couple infertility. MFI is gradually increasing in prevalence, with a notable decline in semen parameters over the last decades. The aetiologies behind the finding of decreasing sperm counts are difficult to pinpoint but might be due in part to increasing rates of overweight and obesity in men of childbearing age. Diabetes mellitus (DM) is a common and chronic metabolic disease, whose prevalence is also gradually increasing, rising up to 10% of the population. The International Diabetes Federation estimates that there are currently more than 500 million people living with DM worldwide, the vast majority of whom suffering from type 2 DM (T2DM). There is growing awareness of the relationship between unhealthy lifestyle, in particular unhealthy diet, and MFI. Starting from all these premises, the aim of this narrative review is to describe the current evidence on the link between DM and MFI, both in terms of DM as a cause of/a risk factor for MFI and of MFI as a possible predictive marker for T2DM. Finally, we will discuss the risk of DM as a consequence of the therapy of MFI or assisted reproductive techniques.

Noninvasive Indices of MASLD Are Associated With Hypogonadism in Male Patients With Type 2 Diabetes Mellitus.

CONTEXT: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease, affecting one-fourth of the adult population worldwide. Recent data found an association between MASLD and hypogonadism, but this relation in patients with type 2 diabetes mellitus (T2DM) is still unclear. OBJECTIVE: To evaluate in men with T2DM the association between total testosterone (TT) and noninvasive indices of hepatic steatosis (Fatty Liver Index [FLI], Hepatic Steatosis Index [HSI], Dallas Steatosis Index [DSI]) and fibrosis (AST to Platelet Ratio Index [APRI], Fibrosis-4 Index [FIB-4]), and their predictive cutoff values in identifying hypogonadism. METHODS: Cross-sectional study on 189 men with T2DM, without history of liver diseases and alcoholism, recruited on an outpatient basis. Interventions were andrological evaluation, metabolic parameters, TT, and liver indices. The main outcome measures were comparison of steatosis and fibrosis indices with testosterone levels and presence of hypogonadism. Receiver operating characteristic curves were used to identify cutoff values of liver indices in predicting low testosterone (<12 nmol/L). RESULTS: FLI, HSI, and DSI were negatively related with TT and were higher in the low-testosterone group than in the normal-testosterone group (FLI: 74.1 [61.4-93.5] vs 56.5 [32.1-78.2], P < .001; HSI: 41.5 [39.2-45.9] vs 40.1 [36.6-43.2], P = .005; DSI: 0.45 [-0.08-+1.04] vs -0.07 [-1.02-+0.58], P < .001). FLI and DSI also correlated with clinical symptoms of hypogonadism. No differences between groups were observed for APRI and FIB-4. FLI ≥63 was the best parameter as predictive index of low TT (sensitivity 73%, specificity 64%). CONCLUSION: We found an association between noninvasive indices of steatosis and hypogonadism in patients with T2DM. These indices could be used to direct the patients to andrological evaluation.

Case report: Obstructive azoospermia as the first presentation of Von Hippel-Lindau disease.

We report the case of a 38-year-old man whose diagnostic workup for primary infertility led to the discovery of obstructive azoospermia due to bilateral papillary cystadenoma of the epididymis (PCE). Given the rarity of this finding and because PCE could be a manifestation of Von Hippel-Lindau disease (VHL), although the patient had no family or personal history of VHL, the VHL gene was tested, and a known pathogenetic variant (c.464-1G>A; p.)? was found. Screening for other Von Hippel-Lindau disease-associated neoplasms revealed bilateral retinal capillary hemangioblastomas, clear cell renal cell carcinoma, and multiple pancreatic cysts. In this case, an accurate diagnostic workup for male infertility allowed the detection of a rare life-threatening syndrome, already presenting with several silent neoplasms. For this reason, this case report may be useful for reproductive medicine specialists in the management of male infertility.