Use of empirical medical therapies for idiopathic male infertility in Australia and New Zealand.

OBJECTIVE: Idiopathic male infertility is common, yet there is no approved treatment. This study aimed to understand practice patterns towards empirical medical therapy (EMT) for idiopathic male infertility in Australia and New Zealand (NZ). DESIGN: Clinical members of the Endocrine Society of Australia, Fertility Society of Australia & NZ, and Urological Society of Australia & NZ were invited to complete a survey. Questions included demographics, EMT practice habits, and thoughts regarding infertility case scenarios. Unadjusted group differences between specialists, those with and without additional training in male infertility, and frequency of managing it were evaluated. RESULTS: Overall, 147 of 2340 members participated (6.3%); majority were endocrinologists and gynaecologists. Participants were experienced; 35% had completed additional training in male infertility and 36.2% reported they frequently manage male infertility. Gynaecologists were more likely to manage male infertility and attend education courses than endocrinologists and urologists. Beliefs about the effect of EMT on sperm concentration and pregnancy did not differ between speciality types. Many respondents considered all patient scenarios suitable for EMT. Of medications, hCG and clomiphene were selected most. Two respondents indicated they would use testosterone to treat male infertility. CONCLUSIONS: This study demonstrates common use of EMT in Australia and NZ for idiopathic male infertility. The breadth of responses reflects a lack of consensus within the current literature, highlighting the need for further research to clarify their role in the management of idiopathic male infertility.

A multi-modal approach to investigate Desmodium gangeticum's influence on stress-induced male infertility: In vivo, in vitro, and in silico assessments.

Physical and psychological stress has an inverse relation with male libido and sperm quality. The present study investigates the potential fertility-enhancing properties of Desmodium gangeticum (DG) root extracts in male Wister rats subjected to immobilization-induced stress (SIMB). DG roots were extracted using n-hexane (HEDG), chloroform (CEDG), and water (AEDG). In the pilot study, aphrodisiac protentional was investigated at two doses (125 and 250 mg kg-1) of each extract. In the main study, the HEDG and AEDG at 125 and 250 mg kg-1 were challenged for the stress by immobilization (SIMB), for 6 h daily over 28 days. Parameters assessed included aphrodisiac effects, gonadosomatic index (GSI), semen quality, sperm quantity, fructose content, serum hormonal levels, testicular oxidative stress, and testicular histopathology. Additional in silico studies, including the lipid solubility index, molecular docking, molecular dynamics, and SymMap studies were conducted for validation. HEDG demonstrated significant aphrodisiac activity, improved - GSI, sperm quality and quantity, and fructose content, serum testosterone levels, histological changes induced by SIMB in the testes. Swiss ADME studies indicated Gangetin (a pterocarpan) had a high brain permeation index (4.81), a superior docking score (-8.22), and higher glide energy (-42.60), compared with tadalafil (-7.17). The 'Lig fit Prot' plot in molecular dynamics simulations revealed a strong alignment between Gangetin and phosphodiesterase type 5 (PDE5). HEDG exerts aphrodisiac effects by increasing blood testosterone levels and affecting PDE5 activity. The protective effects on spermatozoa-related parameters and testicular histological changes are attributed to the antioxidant and anti-inflammatory properties, of pterocarpan (gangetin).

Management of Male Fertility in Hypogonadal Patients on Testosterone Replacement Therapy.

Testosterone is crucial in regulating several body functions in men, including metabolic, sexual, and cardiovascular functions, bone and muscle mass, and mental health. Therefore, optimizing testosterone levels in men is an important step to maintaining a healthy body and mind, especially as we age. However, traditional testosterone replacement therapy has been shown to lead to male infertility, caused by negative feedback in the hypothalamic-pituitary-gonadal (HPG) axis. Recent advances in research have led to the discovery of many new methods of administration, which can have more or less suppressive effects on the HPG axis. Also, the usage of ancillary medications instead of or after testosterone administration might help maintain fertility in hypogonadal patients. The goal of this narrative review is to summarize the newest methods for optimizing fertility parameters in patients undergoing treatment for hypogonadism and to provide the necessary information for healthcare providers to make the right treatment choices.

The role of oral antioxidants in the improvement of sperm parameters in infertile men.

PURPOSE: A variety of pathologic conditions may increase oxidative stress in semen resulting in structural modifications to spermozoa's plasma membrane that interfere with sperm motility, morphology, and count. Antioxidants are currently being marketed to treat male infertility. In semen, antioxidants may decrease oxidative stress and potentially improve sperm parameters. In this narrative, mini-review we evaluated the effectiveness of antioxidants in infertility. METHODS: This mini-review of the current literature has been carried out through searching of the PubMed and Google scholar databases. RESULTS AND CONCLUSIONS: The literature review suggests that there is evidence that oral antioxidants such as selenium, carnitine, zinc, coenzymeQ10, vitamins E and C, etc. alone or in combinations, improve sperm count, motility, morphology as well as pregnancy rates in infertile men with idiopathic oligoasthenospermia. Unfortunately, most of these studies are poorly designed, limited by sample size, varying in dosage, differing in primary end points, and most notably lacking live birth data. Importantly, large randomized, well-designed, placebo-controlled trials are needed.

Dapagliflozin ameliorates diabetes-induced spermatogenic dysfunction by modulating the adenosine metabolism along the gut microbiota-testis axis.

Male infertility is one of the most common complications of diabetes mellitus (DM). Dapagliflozin is widely used to manage the type II DM. This study aimed to assess the dapagliflozin's effects on the spermatogenesis by administering either dapagliflozin (Dapa) or vehicle (db) to male db/db mice, and using littermate male db/m mice as the control (Con). We further performed the integrative analyses of the cecal shotgun metagenomics, cecal/plasmatic/testicular metabolomics, and testicular proteomics. We found that dapagliflozin treatment significantly alleviated the diabetes-induced spermatogenic dysfunction by improving sperm quality, including the sperm concentration and sperm motility. The overall microbial composition was reshaped in Dapa mice and 13 species (such as Lachnospiraceae bacterium 3-1) were regarded as potential beneficial bacteria. Metabolites exhibited modified profiles, in which adenosine, cAMP, and 2'-deoxyinosine being notably altered in the cecum, plasma, and testis, respectively. Testicular protein expression patterns were similar between the Dapa and Con mice. In vivo results indicated that when compared with db group, dapagliflozin treatment alleviated apoptosis and oxidative stress in testis tissues by down-regulating 2'-deoxyinosine. This was further validated by in vitro experiments using GC-2 cells. Our findings support the potential use of dapagliflozin to prevent the diabetes-induced impaired sperm quality and to treat diabetic male infertility.

Antioxidants for male infertility: therapeutic scheme and indications. A retrospective single-center real-life study.

BACKGROUND: This single-center real-life study was conducted to evaluate the most effective combination of nutraceuticals and the most appropriate indications for the treatment of male infertile patients. METHODS: Infertile patients aged 20-55 years were treated with a combination of antioxidants (Androlen®; Enfarma, Misterbianco, Catania, Italy) (group A), with Androlen® (Enfarma) and a mixture of fibrinolytic molecules (Lenidase®, Enfarma) (group B), or Androlen® (Enfarma) and other molecules different from those used for the patients of the group B (group C). Patients were also subdivided according to the presence of varicocele, mild testicular hypotrophy, idiopathic infertility, and chronic male accessory gland infection. RESULTS: Forty-three patients were enrolled. In the overall analysis, only progressive motility significantly improved after therapy. Subgroup analysis showed a significant increase in progressive motility, total motile sperm count (TMSC), and in the percentage of alive spermatozoa after treatment in the group A. Progressive motility improved significantly in patients with varicocele, while the TMSC in patients with varicocele and those with idiopathic infertility. The percentage of alive spermatozoa increased in patients with testicular hypotrophy. CONCLUSIONS: Treatment with antioxidants increased progressive sperm motility, especially in patients with varicocele or idiopathic infertility.

Silk Fibroin Encapsulated Icariin Nanoparticles Mitigate Bisphenol A-Induced Spermatogenesis Dysfunction.

Bisphenol A (BPA) is a prevalent endocrine disruptor found in natural environments. Exposure to BPA has been associated with male infertility. The natural phytochemical icariin (ICA) has demonstrated significant promise for the treatment of male infertility. However, its effectiveness is limited due to its low bioavailability, poor water solubility, and insufficient targeting abilities. Herein, novel nanoparticles are generated from the natural silk fibroin, which are used to load ICA. The efficient drug delivery system (ICA-SNPs) result in significantly focused drug distribution to spermatogonium, enhancing the anti-infertility properties of ICA, and can effectively mitigate spermatogenesis dysfunction induced by BPA, control serum sex hormone levels, and enhance testicular ultrastructure. Additionally, the ICA-SNPs restore spermatogenesis dysfunction primarily via the hormone biosynthesis, spermatogonium meiosis process, and glycerophospholipid metabolism.

Pathophysiology of obesity-related infertility and its prevention and treatment by potential phytotherapeutics.

BACKGROUND: Obesity is a complex multifactorial disease in which the accumulation of excess body fat has adverse health effects, as it can increase the risk of several problems, including infertility, in both men and women. Obesity and infertility have risen together in recent years. Against this background, the present review aims to highlight the impact of obesity on infertility and the underlying pathophysiology of obesity-related infertility (ORI) in men and women, and to provide readers with knowledge of current trends in the effective development of phytotherapeutics for its treatment. METHODS: We thoroughly searched in PubMed, MEDLINE, Scopus, EMBASE, and Google Scholar to find all relevant papers on ORI and the therapeutic effects of phytotherapeutics on ORI in men and women. RESULTS: The extensive search of the available literature revealed that obesity affects reproductive function through several complex mechanisms such as hyperlipidaemia, hyperinsulinaemia, hyperandrogenism, increased body mass index, disruption of the hormonal milieu, systemic inflammation, oxidative stress, alterations in epigenetics and dysbiosis. On the other hand, several studies reported that phytotherapeutics has a broad therapeutic spectrum of action by improving sex hormone homeostasis, ovarian dysfunction, menstrual cycle and inhibiting ovarian hyperplasia, as well as down-regulating ovarian apoptosis, inflammation and oxidative stress, and controlling metabolic dysfunction in obese women. Male infertility is also addressed by phytotherapeutics by suppressing lipogenesis, increasing testosterone, 3ß-HSD and 17ß-HSD levels, improving sperm parameters and attenuating testicular dyslipidaemia, oxidative stress, inflammation and germ cell apoptosis. CONCLUSIONS: In the present review, we discussed the effects of obesity on reproductive dysfunction in men and women and the underlying pathophysiology of ORI. In addition, the therapeutic effect of phytotherapeutics against ORI was highlighted.

Adverse drug reactions on male fertility.

For several years, fertility disorders have been on the increase worldwide. These disorders affect both sexes, but are more pronounced in men; and in half of cases the etiology is unknown. The role of drugs in male infertility has been little studied to date. Most of the available data comes from experimental animal studies, with all their limitations. With the exception of a few drugs, such as certain anticancer agents, human data are rare. This article describes the mainly drugs known to have deleterious effects on male fertility, the mechanisms leading to these effects and methods used to assess the risk of drug-induced male infertility. It underlines the need for further work in experimental research, clinical trials and post-marketing surveillance to improve our knowledge of drugs that induce male infertility. Although these adverse effects are not life-threatening, they can have a significant impact on patients' lives.

Combined evaluation of prolactin-induced peptide (PIP) and extracellular signal-regulated kinase (ERK) as new sperm biomarkers of FSH treatment efficacy in normogonadotropic idiopathic infertile men.

PURPOSE: Nearly, 40% of the causes of male infertility remain idiopathic. The only suggested treatment in idiopathic oligo- and/or asthenozoospermia in normogonadotropic patients is the FSH. In the current clinical practice, efficacy is exclusively assessable through semen analysis after 3 months of treatment. No molecular markers of treatment efficacy are appliable in clinical practice. The aim of the present work is to evaluate the combination of extracellular signal regulated kinase (ERK) 1 and 2 and prolactin inducible peptide (PIP) as potential markers of idiopathic infertility and FSH treatment efficacy. METHODS: Western blot and confocal microscopy were performed to analyze the modulation of PIP and ERK1/2 in idiopathic infertile patients (IIP) sperm cells. Taking advantage of mass spectrometry analysis, we identified these proteins unequivocally in sperm cells. RESULTS:  We demonstrated a significant decrease of both PIP protein and of ERK1/2 levels in spermatozoa obtained from IIP in comparison to healthy fertile patients (HFP). Conversely, we reported a significant increase of these markers comparing infertile patients before and after 3 months of FSH treatment. Importantly, this correlated with an increase in total number of sperm and sperm motility after FSH treatment. Finally, we identified of PIP and ERK2 proteins in sperm samples by proteomic analysis. CONCLUSIONS: The combined evaluation of ERK1/2 and PIP proteins might represent a useful molecular marker to tailor FSH treatment in the management of male normogonadotropic idiopathic infertility.

Effect of Medicago sativa seed powder (Plus vitamin E vs. vitamin E alone) on semen analysis in men with idiopathic infertility: A double blind randomized clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Different parts of the alfalfa plant (Medicago sativa L.), especially its seeds, have been introduced as a semen quality enhancer in the folk medicine of different regions of Iran as well as in the traditional Persian medicine (PM) books. The seeds of this plant are also used in many combined medicines to treat male infertility in PM. AIM OF THE STUDY: This study was designed to investigate the effect of M. sativa seed powder plus vitamin E vs. vitamin E alone on semen analysis of men with idiopathic infertility. MATERIALS AND METHODS: In this randomized clinical trial, 60 participants were randomly divided into two groups and then received M. sativa seed powder (6 g daily) or placebo for three months, as add-on to vitamin E (100 U). Results of semen analysis (sperm total count, motility, and morphology as well as semen volume) of these two groups and their changes were compared before and after treatment as the primary outcome. The number of pregnancies after one month and probable side effects were also assessed. RESULTS: After 12 weeks, sperm total count changed from 36.2 ± 21.8 × 106/ml to 48.5 ± 19.1 × 106/ml in M. sativa and from 39.5 ± 23.5 × 106/ml to 41.2 ± 20.9 × 106/ml in placebo, percentage of normal morphology changed from 1.8 ± 0.8% to 2.6 ± 1.2 % in M. sativa and from 2.0 ± 0.9% to 2.6 ± 1.2% in placebo and percentage of motile sperm changed from 36.5 ± 11.8 % to 39.7 ± 12.0% in M. sativa and from 39.3 ± 10.1 % to 38.1 ± 12.1% in placebo. The improvements in M. sativa group are significantly better than placebo group (P = 0.00, 0.01 and 0.04, respectively). However, semen volume decreased in both groups, but its changes were not significant. The number of pregnancies was four in the intervention and zero in placebo group. One case with abdominal bloating and one with respiratory allergy withdrew from the intervention group. No other adverse effect was reported. CONCLUSIONS: In this study, significant improvement was detected in sperm parameters (except semen volume) of men with idiopathic infertility in M. sativa plus vitamin E group in compare to vitamin E alone after 12 weeks. These findings suggest that the M. sativa, as a complementary therapy, may have a beneficial effect on semen quality. More clinical trials with larger sample size are needed.

Exploring the Potential of Plant Bioactive Compounds against Male Infertility: An In Silico and In Vivo Study.

Infertility is a well-recognized multifactorial problem affecting the majority of people who struggle with infertility issues. In recent times, among infertility cases, the male factor has acquired importance, and now it contributes to approximately half of the infertility cases because of different abnormalities. In the current study, we used natural phytochemicals as potential drug-lead compounds to target different receptor proteins that are involved in the onset of male infertility. A set of 210 plant phytochemicals were docked counter to active site residues of sex hormone-binding globulin, a disintegrin and metalloproteinase 17, and DNase I as receptor proteins. On the basis of binding scores and molecular dynamics simulation, the phytochemicals tricin, quercetin, malvidin, rhamnetin, isorhamnetin, gallic acid, kaempferol, esculin, robinetin, and okanin were found to be the potential drug candidates to treat male infertility. Molecular dynamics simulation showed tricin as a strong inhibitor of all selected receptor proteins because the ligand-protein complexes remained stabilized during the entire simulation time of 100 ns. Further, an in vivo study was designed to evaluate the effect of tricin in male rats with nicotine-induced infertility. It was explored that a high dose of tricin significantly reduced the levels of alanine transaminase, aspartate transaminase, urea, creatinine, cholesterol, triglyceride, and low-density lipoprotein and raised the level of high-density lipoprotein in intoxicated male rats. A high dose of tricin also increased the reproductive hormones (i.e., testosterone, luteinizing hormone, follicle-stimulating hormone, and prolactin) and reduced the level of DHEA-SO4. The phytochemical (tricin, 10 mg/kg body weight) also showed significant improvement in the histo-architecture after nicotine intoxication in rats. From the current study, it is concluded that the phytochemical tricin could serve as a potential drug candidate to cure male infertility.

[Comparative analysis of antibiotic therapy and cytokine therapy (the drug Superlymph) for male infertility associated with male accessory gland infection].

AIM: To compare the effects of cytokine and antibacterial therapy on semen parameters and additional functional tests in patients with infertility due to male accessory gland infections (MAGI) who are preparing for assisted reproductive technologies (ART). MATERIALS AND METHODS: A randomized, prospective, controlled clinical trial without blinding was carried out. A total of 60 men from infertile couples with MAGI who were preparing to ART was included in the study. In the main group (n=30) patients received Superlymph, 1 suppository of 25 units, 2 times a day for 20 days. In the control group (n=30), the antibacterial drug Doxycycline 100 mg 2 times a day for 28 days was given. After the end of therapy on day 33+/-3, a repeated sperm analysis, MAR test, a test for reactive oxygen species in the ejaculate and sperm DNA fragmentation, and bacteriological examination of sperm was performed. In addition, a survey for adverse events was carried out. The significance of differences in initial and final parameters and differences between groups was assessed using the Students t-test, Wilcoxon test and Mann-Whitney U-test depending on the data distribution. The Shapiro-Wilk test was done to investigate the normality of data distribution. Fisher's exact test was used to compare categorical variables. RESULTS: The final analysis included data from 53 patients (n=28 in the main group and n=25 in the control group). In both groups, a significant decrease in the level of free oxygen radicals in the ejaculate was noted (p=0.031), which was more pronounced in the main group. There were no differences in other semen parameters. Eradication of the microorganism according to bacteriological examination occurred in 57.1% of patients in the main group and in 88% of those in the control group (p=0.016). In patients receiving monotherapy with Superlymph, there was a significant decrease in the sperm DNA fragmentation index and the concentration of leukocytes in the ejaculate. In patients receiving antibacterial therapy, there was a significant increase in ejaculate volume, a decrease in the proportion of IgG-associated sperm and leukocyte concentration. CONCLUSION: Many issues of diagnosis and treatment of MAGI have not been thoroughly studied and are poorly standardized. Considering the problems of increasing antibiotic resistance, alternative treatment options are needed. Cytokine therapy (the drug Superlymph) is an effective alternative method of monotherapy for male infertility due to MAGI and is optimal for quickly preparing a couple for ART protocol, given its positive effect on oxidative stress and the index of sperm DNA fragmentation. The prospect of combination therapy with antibiotics and Superlymph seems promising.

[Use of the antioxidant complex Androdoz in men with fertility impairments].

INTRODUCTION: Infertility is a global problem, affecting more than 15% of sexually active couples worldwide. The frequency of the male factor reaches 40-50% and continues to increase. Fertility problems with unknown causes are referred as idiopathic. AIM: To evaluate the possibility of using the Androdoz antioxidant complex in men with infertility. MATERIALS AND METHODS: A retrospective analysis of the medical records of 32 infertile men aged 21 to 45 years (average of 27.8 +/- 6.7 years) with pathospermia was carried out. Antioxidant complex Androdoz was prescribed 2 capsules bid with meals according to the package insert for up to 3 months. The results were assessed after 3 and 12 months (follow-up period) from the start of therapy. In addition to ejaculate analysis, all patients underwent digital rectal examination, transrectal ultrasound of the prostate and ultrasound of the scrotum, microscopic examination of ejaculate and expressed prostate secretions, and PCR-based assay of urethral swab (Androflor). The zinc concentration in seminal plasma, as well as the total antioxidant capacity of sperm, was also evaluated. Damage to sperm chromosomes was characterized by DNA fragmentation using an assessment of sperm chromatin dispersion. RESULTS: Based on the results of a comparative analysis of ejaculate, it was revealed that taking Androdoz complex not only had a positive effect on sperm motility and viability, but also led to a decrease in the percentage of sperm with DNA fragmentation to a level of less than 15%, and significantly increased the total antioxidant capacity of the ejaculate. CONCLUSIONS: The use of Androdoz antioxidant complex in men with reproductive disorders improves the qualitative and quantitative markers of the sperm analysis and the morphological state of the male reproductive system, and allows to replenish the lack of vitamins. The most important effect of Androdoz complex appears after 3 months.

[Evaluation of long-term results of using the drug Fertiwell: impact on the likelihood of conception and pregnancy outcome].

INTRODUCTION: Current methods of treating male infertility have limited efficiency, since they are aimed to individual stages of the pathogenesis. Preparations based on testicular regulatory polypeptides are the most physiological and universal, owing to a complex effect on the self-regulation of testicular tissue. AIM: To study the delayed efficiency and safety of therapy with Fertiwell in patients with pathospermia and to assess the frequency of conception and pregnancy outcome in their partners based on the collection, analysis and interpretation of medical data. MATERIALS AND METHODS: A telephone survey of patients participating in the phase III clinical trial was carried out. The fact of conception in a couple was assessed over a period of 1 to 9 months after completion of therapy, as well as time from completion of the course to conception, pregnancy outcomes, newborn health outcomes. RESULTS: In the period from 1 to 9 months after completion of therapy, pregnancy occurred in 17 out of 34 couples (50%) in the Fertiwell group and in 13 out of 42 couples (30.95%) in the placebo group. This difference was statistically and clinically significant (p<0.05). All pregnancies resulted in a live birth. The median time from completion of the course to conception was 4 months in Fertiwell group and 6 months in the placebo group. There were no significant differences in anthropometric parameters of newborns between the two groups (p>0.05). CONCLUSION: When using the drug Fertiwell, pregnancy and live birth rate was significantly higher (2.23 times) compared to the control group. There was a trend toward earlier pregnancies in partners of men receiving Fertiwell. Thus, this drug can be recommended for the treatment of men with idiopathic infertility as monotherapy, as well as in combination with assisted reproductive technologies.

Gonadotropins in the Management of Couple Infertility: Toward the Rational Use of an Empirical Therapy.

Although epidemiology shows that both men and woman can experience infertility, the female partner usually experiences most of the diagnostic and therapeutic burden. Thus, management of couple infertility is a unique example of gender inequality. The use of exogenous gonadotropins in assisted reproductive technology (ART) to induce multifollicular growth is well consolidated in women, but the same is not done with the same level of confidence and purpose in infertile men. Indeed, the treatment of idiopathic male infertility is based on an empirical approach that involves administration of the follicle-stimulating hormone (FSH) in dosages within the replacement therapy range. This treatment has so far been attempted when the endogenous FSH serum levels are within the reference ranges. According to the most recent evidence, a "substitutive" FSH administration may not be effective enough, while a stimulatory approach could boost spermatogenesis over its basal levels without adverse extragonadal effects. This article aims to describe the rationale behind the empirical application of gonadotropins in couple infertility, highlighting the need for a change in the therapeutic approach, especially for the male partner.

Leydig cell metabolic disorder act as a new mechanism affecting for focal spermatogenesis in Klinefelter syndrome patients: a real world cross-sectional study base on the age.

Background: Klinefelter's syndrome (KS) was once considered infertile due to congenital chromosomal abnormalities, but the presence of focal spermatozoa changed this. The key to predict and promote spermatogenesis is to find targets that regulate focal spermatogenesis. Objective: To explore the trend of fertility changes in KS patients at different ages and identify potential therapeutic targets. Methods: Bibliometric analysis was used to collect clinical research data on KS from the Web of Science Core Collection (WoSCC) from 1992 to 2022. A cross-sectional study was conducted on 75 KS patients who underwent microscopic testicular sperm extraction (mTESE) from 2017 to 2022 in the real world. The reproductive hormones, testicular histopathology, androgen receptors, insulin-like factor 3 (INSL3) receptors and sperm recovery rate (SRR) were analyzed. Results: Male infertility, dysplasia, Sertoli cells, Leydig cells, testosterone and spermatogenesis were the research focuses related to KS. Luteinizing hormone (LH), testosterone, and INSL3 were evaluation indicators of Leydig cell function that fluctuate with age. Testosterone and LH peaked at ages 13-19 and 30-45, while INSL3 only peaked at ages 13-19. 27 patients (27/75) recovered sperm through mTESE and experienced SRR peaks at the ages of 20, 28, 34, and 37. The SRR of fibrosis patients was 46.15%, fatty degeneration was 7.14%, and melanosis was 40.00%. The INSL3 and androgen receptors were highly expressed and roughly balanced in focal spermatogenesis. Conclusion: Abnormal metabolism of Leydig cells led to imbalanced expression of INSL3 and androgen receptors, which might be a potential target for spermatogenesis in KS.

[Medical treatments for male infertility]. / Traitements médicaux de l'homme infertile.

BACKGROUND: Treatments to stimulate spermatogenesis and antioxidant food supplements are often offered to infertile patients either before sperm extraction surgery to improve results, or as part of medically assisted reproduction or spontaneous fertility to increase the likelihood of a live birth. METHODS: A bibliographic search limited to English-language literature on men published before 5/2023 was carried out, including clinical trials, literature reviews and meta-analyses on spermatogenesis-stimulating molecules and antioxidant treatments. RESULTS: Several medical treatments seem capable of improving male fertility: they act mainly by stimulating spermatogenesis through hormones, or by reducing the effects of oxidative stress. With regard to oligoasthenozoospermia, the literature shows that certain hormonal treatments stimulating spermatogenesis are useful. In the case of non-obstructive azoospermia, the value of treatment depends on the patient's FSH and testosterone levels. AOX supplementation appears to improve certain spermogram parameters and have an impact on pregnancy and live birth rates. CONCLUSION: This review should help urologists gain a better understanding of the various medical treatments and enable them to define an appropriate therapeutic strategy, tailored to the patient and the couple, in order to obtain the best results.

Clomiphene Citrate in the Management of Infertility in Oligospermic Obese Men with Hypogonadism: Retrospective Pilot Study.

Background and Objectives: Obesity is a significant risk factor for hypogonadism and infertility that is further associated with reduced semen quality. The aim of this study is to evaluate the effect of clomiphene citrate (CC), prescribed for treating infertility, on serum testosterone and semen parameters, particularly in oligospermic obese hypogonadal men. Materials and Methods: A retrospective analysis of data related to men (n = 53) who underwent CC treatment for infertility and hypogonadism (testosterone < 300 ng/dL) was performed. Patients with obesity (BMI ≥ 30 kg/m2) and sperm concentration ≤ 15 × 106/mL were included for analysis. Results: The overall results showed that, in oligospermic obese men (n = 31), treatment with CC significantly improved baseline sperm concentration (4.5 ± 6.8 × 106/mL vs. 11.4 ± 15.5 × 106/mL, p < 0.05) and motility (31.5% ± 21.5% vs. 42.6% ± 14.7%, p < 0.05). Furthermore, subsequent examination of oligospermic hypogonadal obese men treated with CC (n = 13) revealed substantial improvements in baseline serum testosterone levels (193.8 ± 59.3 ng/dL vs. 332.7 ± 114.8 ng/dL, p < 0.05) along with an increase in sperm concentration, total motility, and normal morphology. Conclusions: The results of this retrospective study suggest that CC treatment not only improves chances of fertility outcomes by substantially improving semen parameters but also increases total serum testosterone levels in oligospermic obese men without any supplemental and expensive testosterone replacement therapy.

Antioxidant activity of Flemingia praecox and Mucuna pruriens and their implications for male fertility improvement.

Globally, 15-24% couples are unable to conceive naturally and 50% of cases of this problem are due to infertility in males. Of this, about 50% of male infertility problems are developed due to unknown reasons called as idiopathic infertility. It is well established that, reactive oxygen species (ROS) have negative impact on male fertility and are involved in 80% of total idiopathic male infertility cases. Medicinal plants are considered as an alternative approach for mitigating the health problems. The plants with good antioxidant capacity can improve the male infertility symptoms generated by ROS. Such medicinal plants can be used to alleviate the symptoms of male infertility with their diverse phytoconstituents. Mucuna pruriens is a well-accepted herb, with its seeds being used to improve the male fertility in various ways and one of the ways is by eliminating the ROS. In our field survey, another plant, Flemingia praecox, although less known, its roots are used in all problems related to the male fertility by tribal people of the Gadchiroli district of Maharashtra, India. The study was conducted to determine in vitro antioxidant potential of F. praecox and compared the results with the well-established male fertility improving plant M. pruriens with special emphasis on medicinally important roots of F. praecox and seeds of M. pruriens. The objective of the study was investigated by studying their total phenol (TPC) and flavonoid (TFC) content, antioxidant parameters (DPPH, FRAP, ABTS, DMPD, ß-carotene bleaching and TAA) and finally DNA damage protection capacity of the plant extracts was studied. The plant parts used for the medicinal purposes have been investigated along with other major parts (leaves, stem and roots of both the plants) and compared with synthetic antioxidants, BHA, BHT and ascorbic acid. Moreover, the inhibition of two male infertility enzyme markers, PDE5 and arginase by F. praecox root and M. pruriens seed extract was also studied in vitro. The results showed that F. praecox possesses higher antioxidant activity than M. pruriens in the majority of studies as observed in TFC, DPPH, TAA, ABTS and DMPD assays. However, M. pruriens seeds showed best results in TPC, FRAP and DNA damage protection assay. F. praecox root extract also gave better PDE5 inhibition value than M. pruriens seeds. This study will help to establish the authenticity of F. praecox used by tribal people and will encourage its further use in managing the male infertility problems.