Propecia may induce spermatogenic failure

PD24-03 A PREOPERATIVE PROGNOSTIC NOMOGRAM FOR PREDICTING CHANGES IN SEMEN PARAMETERS IN INFERTILE MEN AFTER VARICOCELE REPAIR

STUDY QUESTIONWhat thresholds for total sperm count, sperm concentration, progressive motility, and total progressive motile sperm count (TPMC) are associated with earlier time-to-conception in couples undergoing fertility evaluation?SUMMARY ANSWERValues well above the World Health Organization (WHO) references for total sperm count, concentration, and progressive motility, and values up to 100 million for TPMC were consistently associated with earlier time-to-conception and higher conception rates.WHAT IS KNOWN ALREADYAlthough individual semen parameters are generally not able to distinguish between fertile and infertile men, they can provide clinically useful information on time-to-pregnancy for counseling patients seeking fertility treatment. Compared to the conventional semen parameters, TPMC might be a better index for evaluating the severity of male infertility.STUDY DESIGN, SIZE, DURATIONWe used data from a longitudinal cohort study on subfertile men from 2002 to 2017 and included 6061 men with initial semen analysis (SA) in the study.PARTICIPANTS/MATERIALS, SETTING, METHODSMen from subfertile couples who underwent a SA within the study period were included, and 5-year follow-up data were collected to capture conception data. Couples were further categorized into two subgroups: natural conception (n = 5126), after separating those who achieved conception using ART or IUI; natural conception without major female factor (n = 3753), after separating those with severe female factor infertility diagnoses. TPMC was calculated by multiplying the semen volume (ml) by sperm concentration (million/ml) and the percentage of progressively motile sperm (%). Cox proportional hazard models were used to report hazard ratios (HRs) with 95% CIs before and after adjusting for male age, the number of previous children before the first SA, and income. Using the regression tree method, we calculated thresholds for total sperm count, sperm concentration, progressive motility, and TPMC to best differentiate those who were more likely to conceive within 5 years after first SA from those less likely to conceive. We also plotted continuous values of semen parameters in predicting 5-year conception rates and time-to-conception.MAIN RESULTS AND THE ROLE OF CHANCEOverall, the median time to conception was 22 months (95% CI: 21–23). A total of 3957 (65%) couples were known to have achieved conception within 5 years of the first SA. These patients were younger and had higher values of sperm concentration, progressive motility, and TPMC. In the overall cohort, a TPMC of 50 million best differentiated men who were more likely to father a child within 5 years. Partners of men with TPMC ≥50 million had a 45% greater chance of conception within 5 years in the adjusted model (HR: 1.45; 95% CI: 1.34–1.58) and achieved pregnancy earlier compared to those men with TPMC < 50 million (median 19 months (95% CI: 18–20) versus 36 months (95% CI: 32–41)). Similar results were observed in the natural conception cohort. For the natural conception cohort without major female factor, the TPMC cut-off was 20 million. In the visual assessment of the graphs for the continuous semen parameter values, 5-year conception rates and time-to-conception consistently plateaued at higher values of sperm concentration, total sperm count, progressive motility, and TPMC compared to the WHO reference levels and our calculated thresholds. For TPMC, values up to 100–150 million were still associated with a better conception rate and time-to-conception in the visual assessment of the curves.LIMITATIONS, REASONS FOR CAUTIONThere was limited information on female partners and potential for inaccuracies in capturing less severe female infertility diagnoses. Also we lacked details on assisted pregnancies achieved outside of our healthcare network (with possible miscoding as ‘natural conception’ in our cohort). We only used the initial SA and sperm morphology, another potentially important parameter, was not included in the analyses. We had no information on continuity of pregnancy attempts/intention, which could affect the time-to-conception data. Finally, most couples had been attempting conception for >12 months prior to initiating fertility treatment, so it is likely that we are underestimating time to conception. Importantly, our data might lack the generalizability to other populations.WIDER IMPLICATIONS OF THE FINDINGSOur results suggest that a TPMC threshold of 50 million sperm provided the best predictive power to estimate earlier time-to-conception in couples evaluated for male factor infertility. Higher values of sperm count, concentration and progressive motility beyond the WHO references were still associated with better conception rates and time-to-conception. This provides an opportunity to optimize semen parameters in those with semen values that are low but not abnormal according to the WHO reference values. These data can be used to better inform patients regarding their chances of conception per year when SA results are used for patient counseling.STUDY FUNDING/COMPETING INTEREST(S)None.TRIAL REGISTRATION NUMBERN/A.

MP55-12 DOES VARICOCELECTOMY IMPROVE SEMEN PARAMETERS IN ADOLESCENTS WITH GRADE 3 VARICOCELE?

Study question Does Body Mass Index (BMI) affect the semen parameter outcome after microsurgical varicocelectomy in infertile men? Summary answer BMI significantly affects the quality of semen parameters of infertile men with varicocele. However, it does not influence the outcome of varicocele repair. What is known already Varicocele is the most common correctable cause for male infertility. It has been proven that varicocele affects different semen parameters which can be corrected by varicocelectomy, thus restoring male fertility potential. Obesity is another well-known risk factor for male infertility. Both varicocele and obesity can affect semen parameters through similar pathophysiological mechanisms including hyperthermia and increased seminal oxidative stress. Although, varicocele was found to be negatively correlated with BMI, the effect of BMI on varicocele management was not investigated. Study design, size, duration This retrospective study of 1170 patients presenting with male factor infertility to a tertiary medical center over a period of 8 years. The inclusion criteria were patients who underwent microsurgical varicocelectomy for infertility. Patients with a genetic abnormality, history of chemotherapy or radiotherapy or leukocytospermia were excluded. Participants/materials, setting, methods 813 patients were recruited and grouped according to BMI international score into Group A (n = 251patients, BMI < 25kg/m2), Group B (n = 289patients, BMI 25-29.9kg/m2), Group C (n = 183patients, BMI 30-34.9kg/m2 ) and Group D (n = 90patients, BMI>34.9kg/m2) Semen analysis, sperm DNA fragmentation(SDF), hormonal profile were collected pre-and 3 months post-operatively. Chi-squared test, Spearman correlations and Mann-Whitney test were used for statistical analysis of the study data. p-value <0.05 was considered significant. Main results and the role of chance The patients’ mean age was 35.87±8.17 years. High-grade varicocele (II and III) was significantly more prevalent in the lower BMI groups (group A and B, p < 0.001). BMI showed significant negative correlation with sperm concentration (r=-196, p < 0.0001), total motility (r=-117, p = 0.001) and progressive motility (r=-107, p = 0.002). The basal pre-operative investigations showed significant difference between the obesity groups as regards sperm concentration (p < 0.001), total motility (p = 0.003) and progressive motility (p = 0.037). The more obese groups (Groups C and D) showed the poorest semen parameters. Postoperatively, all groups showed significant improvement in sperm concentration (A:p=0.03, B:0.01, C:<0.001, D:0.01). Total and progressive motility were only significant in Groups A (p = 0.06, <0.0001 respectively), B (p < 0.0001, 0.03 respectively) and C (p < 0.0001, <0.0001 repectively) while in Group D, total motility was improved clinically but did reach statistical significance (p = 0.07) and progressive motility didn’t show improvement. Morphology was significantly improved in only Group B (p = 0.02). There was no significant difference between the 4 groups as regards the median improvement of semen parameters postoperatively except for morphology which improved significantly more in the less obese patients (p = 0.002). Limitations, reasons for caution The main limitation is the retrospective design of the study. Wider implications of the findings In infertile patients with varicocele, obesity is an additional factor that leads to worse semen parameters, thus weight reduction may help in these cases. Clinicians should not be discouraged to go for varicocelectomy in obese patients based on the improvement in semen parameters post-varicocelectomy in all obesity groups. Trial registration number Not applicable

Sperm count and sperm motility in incidental high-grade varicocele

Background: One of the most commonly employed medical therapies for idiopathic male infertility are antiestrogens. Tamoxifen as estrogen receptor blockers have been used as empiric treatments for male infertility, acting through blocking estrogen receptor at the hypothalamus and pituitary levels and so preventing the important negative feedback of estrogens to the pituitary and hypothalamus as a result that leading to gonadotropin releasing hormone (GnRH) stimulation and pulsatile release of luteinizing hormone (LH)/follicle-stimulating hormone (FSH). Objective: To assess tamoxifen role in the treatment of men with primary infertility who are normogonadotropic. as it is widely prescribed drug for that purpose as well as to evaluate possible patient’s criteria for a better response to tamoxifen. Methods: One hundred twenty-three patients with idiopathic primary infertility and normal FSH, LH, and testosterone serum levels were enrolled in this prospective study. All patients received 20 mg tamoxifen daily as a single dose for at least 3 months, and semen analysis (total sperm concentration, total number of progressive motile sperms and percentage of normal sperm morphology) as well hormones levels were evaluated, with the values being compared with those before treatment. Results: Overall, there was no statistically-significant improvement in semen parameters 3 months after treatment (P>0.05); however, patients with pretreatment lower normal FSH level of (1.7-6.85 mIU/ml) and those with pretreatment sperm concentration of (five to ten million per ml) showed statistically significant improvement in sperm concentration after tamoxifen therapy (p=0.044 and p=0.012 respectively). Conclusion: Tamoxifen is an acceptable treatment for idiopathic male infertility. A better response can be expected in patients with pretreatment lower normal FSH level of (1.7-6.85 miu/ml) and sperm concentration of 5-10 million per ml. It might be used as first line treatment to enhance sperm concentration, giving its availability and lower cost in comparison to other hormonal therapies. Keywords: Male Infertility, tamoxifen, empirical treatment Citation: Al-Anbary LA. Tamoxifen as empirical treatment in males with primary infertility and normal gonadotropic hormonal levels: A prospective study. Iraqi JMS. 2021; 19(2): 230-236. doi: 10.22578/IJMS.19.2.12

Clomiphene citrate (CC) is commonly used off-label for the treatment of male infertility, yet there is limited data to guide patient selection. To identify a subset of patients more likely to benefit from CC, we aimed to define predictors of improvement in semen parameters among men receiving CC. We retrospectively analysed 151 men treated with at least 25mg CC daily for male infertility and/or hypogonadism at two institutions between 2004 and 2014. Men previously on testosterone were excluded. The primary outcome was change in semen parameters. Variables included baseline patient characteristics, pre-treatment hormone profiles and pre-treatment semen analyses. A total of 77 men met inclusion criteria. Median length of therapy was 2.8months. There was significant improvement in sperm concentration (14-21million/ml; p=0.002) and total motile count (TMC; 13-28 million; p=0.04). One third of patients who began with fewer than 5 million motile spermatozoon improved to a TMC>5 million, increasing reproductive options to include intrauterine insemination. Patient characteristics, pre-treatment hormone profile and degree of oligozoospermia did not predict treatment response. While no predictors of improvement were identified, clinically useful response rates are described for use in shared decision-making.

RANKL has been suggested as a novel regulator of male reproduction, and a recent randomized controlled trial (RCT) showed that the RANKL-inhibitor denosumab, normally used to treat osteoporosis, can improve semen quality in infertile men with high anti-Müllerian hormone (AMH) and small testicles. Therefore, this RCT aimed to investigate the effect of denosumab in men with severe oligospermia prospectively selected by serum AMH and testicular size. A double-blinded, placebo-controlled, single-center RCT, including 42 men with oligospermia with the main endpoint of improving sperm concentration. The groups were randomized 2:1 to receive either a single subcutaneous injection of denosumab 60 mg (n = 28) or a placebo treatment (n = 14) for 80 days. Thirty-nine men completed the study, with 26 assigned to the denosumab group and 13 to the placebo group. No differences in sperm concentration or total sperm count were found at day 80 between those treated with denosumab or placebo. Additionally, there were no differences in serum testosterone, LH, FSH, inhibin B, or AMH. Men treated with denosumab or placebo experienced an increase in both sperm concentration and total sperm count but not serum inhibin B from baseline to day 80. This RCT showed that denosumab did not improve sperm concentration or alter reproductive hormones compared to placebo. Denosumab is not superior to the vitamin D- and calcium-supplemented men in the placebo group.

INTRODUCTION AND OBJECTIVE: Exogenous testosterone (T) therapy is typically long-acting and causes azoospermia in up to 65% of the men. Natesto, dosed three times a day, is a short-acting, FDA approved nasal testosterone available since 2015. We hypothesized that Natesto can preserve spermatogenesis due to its short-acting property.METHODS: We prospectively enrolled hypogonadal men aged 18-55 years with two serum T levels < 300 ng/dL (drawn before 10 AM), symptoms, and 2 semen analyses (SA) with total motile sperm counts (TMSC) > 5 million in a phase IV clinical trial. Eligible men received Natesto for 6 months. Serum T, luteinizing hormone (LH), follicle stimulating hormone (FSH), 17-hydroxyprogesterone (17-OHP), 2 SA, and testis volume were collected at baseline and after 3 and 6 months of therapy. Symptoms were evaluated using the international index of erectile function 6 (IIEF-6) and the short form 36 (SF-36) questionnaires. The primary endpoints were change in T, LH, FSH, sperm concentration, sperm motility, and TMSC. Secondary end points were change in symptoms, testis volume, and adverse events (AEs). Data are presented as means (SD), t-test was used to compare changes after 3 and 6 months, p<0.05 was considered significant.RESULTS: In total, 102 men were screened, and 60 men (age 19-55 years) enrolled. Of the 60 men, 44 completed 3 months, 33 completed 6 months, and 17 dropped out. Mean serum T increased from hypogonadal at baseline to 3 and 6 months (p=0.005), LH and FSH decreased (p=0.03) but remained within the normal range (2-5 IU/mL). Most importantly, semen parameters remained unchanged after 3 and 6 months of T therapy. Only 3 (7.5%) men had severe oligospermia and one (2.5%) became azoospermic but recovered at 6 months after discontinuation. Testis volume and intratesticular T (serum 17-OHP) were maintained at 3 and 6 months. There was improvement across all sub-domains of the IIEF as well as improvement in questions related to energy in the SF-36. A total of 10 men dropped out due to nasal irritation.CONCLUSIONS: This phase IV clinical trial demonstrated that Natesto increased serum T, improved hypogonadal symptoms, maintained gonadotropins, testis volume, intratesticular testosterone and semen parameters. Natesto, and other short acting forms of testosterone therapy may help hypogonadal men maintain fertility.

Science linking environmental contaminant exposures with fertility and reproductive health impacts in the adult male

MP74-13 PREDICTORS OF SUCCESS AFTER MICROSCOPIC SUBINGUINAL VARICOCELECTOMY

OBJECTIVE: The improvement in semen parameters after varicocelectomy varies considerably among patients. This study aimed to evaluate the association between preoperative follicle-stimulating hormone (FSH) levels and improvement in total motile sperm count (TMSC) following microscopic subinguinal varicocelectomy, along with other clinical, hormonal, and semen parameters. MATERIAL and METHODS: A retrospective analysis was conducted on 103 infertile men who underwent microscopic subinguinal varicocelectomy between January 2010 and December 2025. Patients were categorized into two groups according to the presence or absence of postoperative TMSC improvement. Total motile sperm count improvement was defined as an upgrade to a higher fertility category or a ≥50% increase in TMSC in the natural pregnancy group. Preoperative demographic characteristics, hormone levels (FSH, luteinizing hormone [LH], testosterone), and semen parameters were compared between groups. Factors associated with TMSC improvement were analyzed using univariate and multivariate logistic regression mo RESULTS: Postoperative TMSC improvement was observed in 36 patients (35.0%). Patients with TMSC improvement had lower preoperative FSH levels and significantly higher sperm concentration and TMSC values. In multivariate analysis, lower FSH levels (OR: 0.815; 95% CI: 0.650–0.925; p=0.020), higher preoperative sperm concentration (OR: 1.145; 95% CI: 1.065–1.310; p=0.002), and higher preoperative TMSC (OR: 1.127; 95% CI: 1.015–1.240; p=0.001) were identified as independent predictors of TMSC improvement. Varicocele grade and laterality were not significantly associated with postoperative outcomes. CONCLUSION: Preoperative FSH levels and baseline semen parameters are significant predictors of TMSC improvement after varicocelectomy. Follicle-stimulating hormone may serve as a clinically useful surrogate marker of spermatogenic reserve when selecting candidates for varicocelectomy and counseling patients regarding postoperative expectations. Keywords: varicocelectomy, total motile sperm count, follicle-stimulating hormone, predictor

Clinical and histopathological evidence suggest that the male reproductive system may be negatively impacted in patients with coronavirus disease (COVID-19). The objective of this study is to investigate the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on semen parameters by comparing semen analyses before and after COVID-19 diagnosis in the same patient. We retrospectively analyzed 342 semen analyses by reviewing medical records. The study included two groups of patients: (i) those who underwent two consecutive semen analyses within 6 months, one before (n = 114) and one after (n = 114) COVID-19 diagnosis, and (ii) a control group (n = 114) that was age-matched and did not receive a diagnosis of COVID-19. The study results indicated a significant decrease in semen volume, total sperm count per ejaculate, progressive motile sperm count, total motile sperm count, and normal sperm morphology after SARS-CoV-2 infection in comparison to their respective values before the infection. Subgroup analyses showed that the duration of COVID-19 diagnosis (short-term vs. long-term) did not impact the changes in semen parameters. However, fever during the COVID-19 process had a negative effect on semen parameters, particularly sperm concentration, unlike in patients without fever. In conclusion, our findings suggest that SARS-CoV-2 infection is associated with a decline in semen quality, which may potentially impact male fertility. Furthermore, it's important to note that the negative effects on semen parameters may persist in the long-term. Our results also indicate that fever during active infection could be a significant risk factor that negatively affects spermatogenesis.

In this study, we aimed to assess the effect of SARS-CoV-2 infection on semen parameters in one group of patients before and after infection. Patients were screened if they had a semen analysis performed between October 1, 2019, and December 1, 2020, in the assisted reproduction unit and later had positive polymerase chain reaction (PCR) test for SARS-CoV-2 infection. The patients' semen parameters were recorded before and after SARS-CoV-2 infection, along with degrees of SARS-CoV-2 infection, dates of SARS-CoV-2 infection, durations between the treatment for SARS-CoV-2 infection and the second semen analysis, time of symptom onset, duration of their symptoms, ages, comorbidities, and any medications patients were taking. Forty-one patients were included in the study. The mean age of the patients was 31.29±5.95 years. The mean duration from first semen analysis to the PCR test was 7.74±3.03 months. The mean duration between the PCR test and later semen analysis was 2.35±1.35 months. The median sperm concentration for the patients before and after SARS-CoV-2 infection were 24 mil/ml and 13 mil/ml, respectively (p<0.001). The normal morphology percentage before infection was 3.16±0.92, while it was 2.44±1.04 after infection (p=0.011). In 26 patients, the period from the time of infection to the second semen analysis was over 70 days, while this period was less than 70 days in the other 15 patients. In both patient groups, a significant decrease was detected in the sperm concentrations and total sperm count. In the semen samples we assessed, we observed a significant decrease in the mean sperm concentration, total sperm count, and mean percentage of samples with normal morphology after SARS-CoV-2 infection.

Male infertility as a window to health