The association between inflammation of the male reproductive system and oligozoospermia has been frequently reported in the clinical work-up of male infertility. To improve sperm parameters in infertile patients with genital inflammation, many phytochemical and nutraceutical drugs are currently being used. However, their use is still empirical and no conclusive data have been provided about their efficacy. The treatment with steroid anti-inflammatory drugs might be useful in reducing inflammation and improving sperm parameters, thus increasing the fertility outcome. The aim of this study was to evaluate if glucocorticoid treatment improves seminal parameters in infertile oligozoospermic patients presenting signs of accessory gland inflammation at genital ultrasound. A total of 90 infertile patients were enrolled in the study. They presented normal testicular volume, normal FSH plasma levels, the presence of various degrees of oligozoospermia, associated with scrotal and trans-rectal ultrasound signs indicative of accessory gland inflammation, but negative microbiological analysis on semen and/or prostatic secretions. Patients were randomly allocated into three groups of treatment, receiving, respectively, 5, 12.5, and 25 mg daily oral Prednisone for one month. Seminal parameters were evaluated at admission and after treatment. In patients undergoing Prednisone treatment at a daily dose of 5 mg we observed a significant increase in total sperm count. At a daily dose of 12.5 mg, Prednisone treatment improved sperm concentration, total sperm count, and the percentage of sperm motility. Twenty-five mg of Prednisone led to significant improvement in all the sperm parameters, except for semen volume. These results clearly demonstrate that Prednisone treatment can significantly improve sperm parameters in a selected population of oligozoospermic patients. These findings suggest that Prednisone treatment should be considered in idiopathic oligozoospermic patients with supposed normal spermatogenesis and accessory gland inflammatory alterations, in order to improve sperm parameters and fertility outcome.
Grande G et al., 2026·The Journal of clinical endocrinology and metabolism·Free to read
Male factor infertility (MFI) is frequently labelled idiopathic when evaluation relies primarily on semen analysis, potentially overlooking endocrine and pathophysiological mechanisms relevant for targeted management.
To phenotypically define MFI and develop a pathophysiology-based classification aimed at reducing idiopathic infertility following comprehensive evaluation.
Prospective monocentric cohort study conducted at a tertiary referral academic centre.
Eight hundred male partners of infertile couples evaluated between October 2024 and January 2026 after exclusion of isolated female factor infertility.
Prevalence of MFI categories, hormonal patterns across phenotypes, and proportion of idiopathic infertility after comprehensive work-up.
All patients underwent standardized clinical evaluation, hormonal assessment (total testosterone, FSH, LH), testicular ultrasound, and complete semen analysis. Microbiological testing, transrectal ultrasound, and genetic analyses were performed according to guidelines.
Primary spermatogenic failure was the most prevalent category (56.0%), followed by infection/inflammation (22.4%) and hypogonadotropic hypogonadism (8.5%). Idiopathic infertility was identified in only 5.3% of cases. Distinct endocrine profiles were observed, with high-FSH spermatogenic failure representing the dominant phenotype.
Comprehensive phenotyping markedly reduces the proportion of patients classified as having idiopathic infertility and identifies clinically relevant subgroups. This prospective study provides validation of a pathophysiology-based classification and supports a shift toward endocrine-integrated diagnostic strategies in male infertility, with potential implications for targeted management.
Rocca MS et al., 2026·Journal of translational medicine·Free to read
Standard semen analysis has little prognostic value in distinguishing fertile from infertile men. Furthermore, in men with semen parameters within the reference ranges, it cannot distinguish fertile men from infertile men, i.e. partners of couples with idiopathic infertility. Oxidative stress, mitochondrial dysfunction, sperm telomere shortening, and DNA fragmentation have been proposed as contributors to impaired male fertility. However, these biomarkers have not been evaluated as a whole in subjects with normal semen parameters, partners of fertile and infertile couples.
To characterise a multidimensional panel of sperm biomarkers-including sperm telomere length (STL), mitochondrial DNA copy number (mtDNAcn), reactive oxygen species (ROS), lipid peroxidation (LP), sperm chromatin dispersion (SCD), and respiratory control ratio (RCR)-and to identify whether these parameters might discriminate, in men with normal semen parameters, infertile men from fertile controls.
A total of 150 men with semen parameters within the normal ranges were enrolled: 47 male partners of couples with idiopathic infertility and 103 fertile controls. STL and mtDNAcn were quantified by qPCR; ROS were assessed using OxiSperm®II with semiquantitative imaging; LP was measured spectrophotometrically in seminal plasma; SCD was used to determine DNA fragmentation; and mitochondrial function was evaluated by oxygen consumption and RCR. Correlations between biomarkers and semen parameters were analysed using Pearson or Spearman coefficients, and intergroup comparisons were adjusted for age.
Semen parameters did not differ significantly between male partners of fertile and infertile couples. compared to men of fertile couples, men of infertile couples exhibited significantly shorter STL (0.57 ± 0.59 vs 1.21 ± 1.13, p_adj = 0.001) and higher oxidative stress, with both ROS (8300.9 ± 4214.8 vs 6555.3 ± 3394.3, p_adj = 0.027) and LP (88.33 ± 55.50 vs 40.29 ± 46.98, p_adj < 0.001) markedly elevated. mtDNAcn, SCD, and RCR showed no difference between the groups. Across the entire cohort, STL correlated negatively with ROS and LP and positively with RCR. ROS correlated negatively with total sperm count, motility and RCR, and positively with LP. LP displayed the strongest pattern of associations, correlating negatively with concentration, total count, motility, STL and RCR, and positively with age and volume.
Among men with normal semen analysis, partners of couples with idiopathic infertility exhibit a distinct sperm molecular profile characterised by telomere shortening and oxidative imbalance. STL, ROS and LP emerged as age-independent biomarkers associated with infertility status and showed promising discriminatory ability in this cohort, supporting their integration as second-level tests to complement routine semen analysis in cases of normozoospermia.
Ponce MR et al., 2026·Andrology·Free full text on PubMed Central
Transgender individuals assigned male at birth (AMAB) may choose to preserve their fertility prior to starting gender-affirming hormone therapy (GAHT). However, limited data exist regarding the baseline reproductive and hormonal characteristics of this population before and after GAHT.
To characterize semen quality and hormonal profiles in transgender AMAB individuals prior to GAHT and compare findings with cisgender men and with transgender individuals who discontinued GAHT for at least 3 months.
This retrospective study included transgender AMAB individuals from two tertiary andrology centers who underwent sperm cryopreservation before GAHT initiation (treatment-naïve group). Clinical evaluation included anthropometric measures, testicular volume assessment, varicocele detection, and sex hormone measures. Semen parameters were analyzed according to WHO criteria and compared with those of cisgender men and previously treated transgender individuals.
Thirty-two treatment-naïve transgender AMAB individuals were included. Hormonal parameters were generally within reference ranges. Only 46.9% of treatment-naïve individuals met WHO criteria for normozoospermia, compared with 75.5% of cisgender controls. Compared with nine previously treated individuals, estradiol levels were higher and seminal volume lower. A higher frequency of seminal abnormalities was observed, although not statistically significant.
A substantial proportion of treatment-naïve transgender AMAB individuals exhibited impaired semen parameters prior to GAHT initiation. Prior GAHT exposure showed a trend toward poorer semen quality. These findings support early fertility counseling and preservation in transgender individuals prior to GAHT initiation.
Besides gonadal involvement (hypogonadism, male factor infertility, and testicular hypotrophy), patients with Klinefelter syndrome (KS) may suffer from several extra-gonadic complications, including neoplastic events.
The aim of this review is to summarize all major clinical evidence dealing with the association between KS and neoplastic diseases and provide practical suggestions for the management of patients with KS regarding neoplastic risk.
This narrative review was conducted through a comprehensive search of the PubMed database, using combinations of the following keywords: "Klinefelter syndrome," "cancer," "neoplasm," "breast cancer," "germ cell tumor," "lymphoma," and "testosterone replacement therapy".
KS is associated with a higher risk of breast cancer and mediastinal germ cell tumors and an apparent higher risk of hematological malignancies, in particular non-Hodgkin lymphoma and leukemia. Evidence on testicular cancer is limited, with no clear increase in risk attributable to KS, while prostate cancer has a lower risk and lower mortality rate.
Given the complexity of the syndrome and the limited available evidence, regular clinical follow-up with targeted investigations when clinically indicated may facilitate early diagnosis and management of associated comorbidities.
Foresta C et al., 2000·Molecular and cellular endocrinology
The aim of this study was to individuate parameters able to distinguish oligozoospermic subjects who will respond to follicle-stimulating hormone (FSH) therapy. A group of 135 oligozoospermic subjects was divided in three groups considering basal FSH and inhibin B concentrations: group A (normal FSH and inhibin B) characterized by moderate hypospermatogenesis sometimes associated to partial spermatidic arrest; group B (high FSH and normal inhibin B) characterized by hypospermatogenesis associated or not to spermatogonial/spermatocytic arrest; group C (high FSH and low inhibin B) characterized by severe hypospermatogenesis. Seventy-eight patients were treated with FSH at the dose of 75 IU on alternate days while 57 were treated with the same dose every day for 3 months. After FSH treatment a significant increase in ejaculated sperm concentration was observed only in oligozoospermic subjects with normal basal FSH and inhibin B plasma levels (group A) showing a testicular cytological picture of moderate hypospermatogenesis. In these subjects no differences in sperm production were observed between the two protocols of therapy. In the remaining patients of group A, characterized by hypospermatogenesis associated with maturation arrest at spermatidic level and in group B and C, no increase in sperm concentration was observed after therapy. These data suggest that FSH treatment may have a role in oligozoospermic subjects only when the spermatogenetic alterations consist in germ cell depopulation without maturative disturbances and with normal FSH concentrations.
Caldarola G et al., 2017·Dermatology (Basel, Switzerland)
Recent evidence indicates that a systemic state of inflammation may impair fertility, but data about psoriatic males are scarce.
The aim of this study was to assess gonadal function in psoriatic males implementing our knowledge about fertility in these subjects.
Male psoriatic patients, aged between 18 and 55 years, and a group of healthy subjects matched for age, BMI and geographic origin were enrolled. All subjects underwent a complete physical and andrological examination, standard semen analysis, complete microbiological analysis and ultrasound evaluation of sexual glands. Seminal levels of soluble urokinase-type plasminogen activator receptor (suPAR) and serum levels of testosterone, estradiol (E2), sex hormone-binding globulin (SHBG), luteinizing hormone and follicle-stimulating hormone were also assessed.
Fifty patients and 50 controls fulfilled the inclusion criteria and were enrolled in our study. Testosterone and SHBG were found to be significantly decreased in patients with psoriasis compared with the control group. Higher levels of E2 were also reported in psoriatic patients. Total sperm count, sperm motility and percent of spermatozoa with normal morphology were significantly reduced in patients compared to controls. suPAR levels were significantly increased in patients compared to controls and found to be above the reference limits. Ultrasound signs of inflammation of the accessory glands were observed in 35/50 patients with psoriasis and in none of the controls.
Our study suggests that untreated psoriasis may impair male fertility. We also found that this might be due to an impact of systemic inflammation on the hormonal profile and on sexual accessory gland inflammation.
The association between male accessory gland infection/inflammation (MAGI) and infertility is well-known in clinical practice. Standard semen analysis, leukocytospermia, and microbiological tests are often not enough accurate for a diagnosis. A large amount of biochemical parameters in seminal plasma have been suggested as inflammation markers, however, there is not yet a sensitive and specific biomarker that accurately identifies MAGI. We investigated the presence of soluble urokinase-type plasminogen activator receptor (suPAR), known marker of systemic inflammation, in the seminal plasma to evaluate its possible involvement in urogenital tract inflammation. On the basis of andrological evaluation, including spermiogram and ultrasound findings, we selected 76 patients with MAGI and 30 healthy men as control group. Patients were classified according to the results of the semen culture in group A (n = 28) presenting a bacterial MAGI and group B (n = 48) with abacterial MAGI. C-reactive protein (CRP), total protein (TP), procalcitonin (PCT), leukocytes peroxidase (LP), and suPAR concentrations were assayed on seminal plasma. Spermiogram parameters were significantly lower in the patients with MAGI than in controls. CRP, TP, PCT, and LP did not differ in MAGI vs.
suPAR was detectable in all semen samples; it was significantly increased in A and B groups (86.6 ± 30.7 ng/mL vs. 39.7 ± 17.2 ng/mL) with an inverse correlation with sperm parameters. We selected by receiver operating characteristic curve a suPAR cut-off value of 55.3 ng/mL as a diagnostic threshold for the diagnosis of MAGI. We report in this study the first evidence of suPAR presence in seminal plasma, focusing on its interesting role as reliable and sensitive marker of inflammation for the differential diagnosis of MAGI.
To evaluate the effects of treatment with FSH on seminal parameters and spontaneous pregnancy in male infertility.
Prospective, controlled, randomized clinical study.
Infertility center at a university hospital.
PATIENT(S): One hundred twelve men affected by idiopathic oligozoospermia.
INTERVENTION(S): Patients were randomized into two groups: 62 subjects were treated with 100 IU of recombinant human FSH on alternate days for 3 months, and 50 patients did not receive any treatment. Semen analysis was performed in all subjects at the end of this period of treatment and after the following 3 months. Subjects who had not reached spontaneous pregnancy underwent assisted reproductive techniques.
MAIN OUTCOME MEASURE(S): Seminal parameters, testicular cytologic analysis, FSH, LH, T, and inhibin B concentrations.
RESULT(S): The treatment group considered as a whole did not show modifications in sperm parameters. However, a subgroup of these (30, 48.4%) had a significant increase of sperm count (responder group). In the period including 3 months after the withdrawal of FSH therapy, we observed a significantly higher spontaneous pregnancy rate in the responder group (5 of 30 [16.7%]) with respect to nonresponder and nontreated groups (1 of 32 [3.1%] and 2 of 50 [4.0%], respectively). Furthermore, the improvement of seminal parameters in the responder group allowed these patients to undergo less frequent IVF-ET/intracytoplasmic sperm injection.
CONCLUSION(S): Results from this controlled, randomized clinical trial show that FSH therapy does not improve sperm concentration or pregnancy rate when infertile male patients are chosen solely by the clinical criteria of idiopathic oligospermia and normal FSH concentration. Subgroup analysis, however, does indicate that patients without maturation arrest in addition to the clinical scenario do benefit from medical therapy.
Male Fertility › Male Factor Treatment › Medical Management · Therapeutics › Anti-Infective and Anti-Inflammatory Agents › Immune Modulating Agents
G De Filpo
PMID 28125168 28125168 DOI 10.1111/andr.12300 10.1111/andr.12300 Milardi et al. 2017, Milardi 2017
00240q980