Оценка эффективности и безопасности новой методики коррекции показателей сперматогенеза у пациентов, перенесших операцию Мармара

Report on varicocele and infertility

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

Alternate indications for varicocele repair: non-obstructive azoospermia, pain, androgen deficiency and progressive testicular dysfunction

Beneficial Effects of Microsurgical Varicocelectomy on Semen Parameters in Patients Who Underwent Surgery for Causes Other Than Infertility

Microsurgical varicocelectomy with intentional preservation of the testicular artery(ies) is regarded as the gold standard approach to varicocele repair. We sought to determine whether the number of testicular arteries preserved at the time of micro-surgical varicocelectomy predicts improvement in postoperative semen parameters. We analyzed the records of 334 infertile men who underwent varicocelectomy performed by a single surgeon using a subinguinal microsurgical technique between July 1996 and January 2003. We examined the association between the number of testicular arteries preserved at the time of varicocelectomy and serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), varicocele grade, testicular volume, and postoperative improvement in semen parameters. Unilateral, left-sided varicocelectomy was performed in 194 men, while bilateral varicocelectomy was performed in 140 men. Mean (+/-SE) sperm concentration (20.1 +/- 1.5 x 10(6)/mL to 26.7 +/- 1.9 x 10(6)/mL, P =.001), percent motility (24.7 +/- 1.0% to 30.9 +/- 1.2%, P =.001), and percent normal morphology (35.8 +/- 1.4% to 37.7 +/- 1.5%, P =.046) improved significantly following varicocelectomy. The mean number of preserved testicular arteries was 1.5 on the left (range, 1-4) and 1.5 on the right (range, 1-4). The number of testicular arteries preserved at the time of varicocelectomy did not correlate significantly with preoperative assessment of serum FSH, LH, varicocele grade, and testicular volume or with postoperative improvement in semen parameters. Our data indicate that preoperative parameters are not predictive of the number of testicular arteries identified at the time of microsurgery. These data also suggest that the number of arteries identified and preserved with meticulous spermatic cord dissection does not correlate with improvement in semen parameters.

Study question Can a Targeted nutraceutical supplementation improve semen parameters and enhance the chances of pregnancy in female partners? Summary answer A three-month targeted nutraceutical regimen improved semen quality and sperm DNA integrity, leading to improvements in pregnancy outcomes, including spontaneous and intrauterine insemination (IUI) conceptions. What is known already Elevated sperm DNA fragmentation index (DFI) is associated with reduced conception rates and increased miscarriage risks in assisted reproduction. Oxidative stress plays a key role in sperm DNA damage, contributing to male infertility. While various nutraceutical combinations have been investigated for their impact on semen parameters, findings remain inconsistent, and their clinical utility is yet to be firmly established. Further research is warranted to define their role in male reproductive health. Study design, size, duration This retrospective study was conducted at Sai Fertility Centre, India, from June 2023 to November 2024. A total of 150 male patients aged 28–42 years with sperm DFI >30% and whose spouses had experienced at least one unexplained miscarriage were included. Semen analysis and sperm DNA fragmentation assessments were performed before and after a three-month treatment regimen, followed by a two-month post-treatment follow-up. Participants/materials, setting, methods Participants received a daily nutraceutical combination for three months, consisting of vitamin D3 (600 IU), selenomethionine (40 mcg), coenzyme Q10 (100 mg), and astaxanthin (8 mg). Semen analysis was conducted following standard guidelines, and sperm DNA fragmentation was evaluated using the Sperm Chromatin Dispersion (SCD) Assay. Statistical analysis was performed using SPSS Statistics 27.0.1, with paired t-tests for pre- and post-treatment comparisons. Main results and the role of chance After three months of supplementation, significant improvements were observed in semen parameters, including an increase in semen volume from 2.35 mL to 2.89 mL (p < 0.001), total sperm count from 132.5 million to 170.2 million (p < 0.001), sperm concentration from 56 million/mL to 58 million/mL (p < 0.001), and progressive motility from 16.74% to 19.04% (p < 0.001). Additionally, sperm DNA fragmentation index (DFI) decreased by 37.9%, from 43.26% to 26.87% (p < 0.001), indicating improved sperm DNA integrity. No statistically significant changes were observed in total motility or sperm morphology. Among the 150 male participants, 24 female partners conceived spontaneously (16%), while 36 achieved pregnancies via intrauterine insemination (IUI) (24%). Furthermore, an inverse correlation between age and sperm DFI was noted. Limitations, reasons for caution This single-centre design limits the generalizability of findings. The absence of a control group restricts causal inference. While significant improvements in semen parameters were observed, pregnancy outcomes remained modest, necessitating larger, prospective trials.Female partners interventions would have influence in addition. Direct effect of nutraceuticals will be done in future study. Wider implications of the findings These results support the potential role of nutraceuticals in enhancing semen quality and sperm DNA integrity in men with infertility. Further studies, particularly in combination with assisted reproductive techniques, are warranted to validate these findings and establish clinical recommendations. Trial registration number Yes

BackgroundEfficacy of clomiphene citrate (CC) in the treatment of male subfertility remains unclear, with inconsistent results in the literature and limited guidance from professional organizations. We sought to stratify the response to clomiphene in men based on their initial gonadotropins and semen parameters.MethodsWe conducted a retrospective analysis of 234 patients from an academic center who took CC for subfertility. Patients with pre-treatment and 3 months follow-up total testosterone (TT) and semen analyses were included. Patients with previous hormone therapy, genitourinary surgery, prior success in conceiving pregnancy, or only one semen analysis were excluded. Primary outcomes were magnitudes of improvement in TT and semen parameters at 3 months. Student’s t-test (alpha =0.05) was used for univariate analyses; multivariable linear regression was used for multivariate analysis.ResultsOne hundred and thirty-seven patients met inclusion criteria. Thirty-four percent of patients experienced improvement in sperm concentration after 3 months of CC treatment, 13% decreased, and 53% showed no change. Using a pre-treatment TT cutoff of 300 ng/dL and gonadotropin thresholds of 7 miU/mL, initial TT did not affect magnitude of improvement in semen parameters, while lower initial gonadotropins showed statistical improvement across all outcomes. Multivariate analysis showed pre-treatment follicle stimulating hormone (FSH) was inversely correlated with improvement in TT [odds ratio (OR): 2.64e-05, 95% confidence interval (CI): 1.32e-09 to 5.28e-01, P=0.04] and sperm concentration (OR: 0.22, 95% CI: 5.70e-02 to 8.48e-01, P=0.03). We also provide initial gonadotropin cutoffs that suggest statistical benefit from CC use.ConclusionsMen with lower gonadotropin levels may expect greater degree of improvement in both hormone and semen parameters with use of CC. Men with azoospermia do not benefit based on semen analyses alone. Degree of non-azoospermia does not affect magnitude of improvement. CC had decreasing efficacy at higher initial gonadotropin levels. These data may provide guidance in stratifying and counseling men for CC treatment.

Older Age Is Associated With Similar Improvements in Semen Parameters and Testosterone After Subinguinal Microsurgical Varicocelectomy

Varicocele is one of the most common causes of male infertility in which testicular function is progressively damaged. This study aims to investigate the effect of varicocelectomy and mast cell stabilizers on reducing sperm DNA fragmentation in infertile patients with varicocele. In this randomized clinical trial, after obtaining ethical approval and informed consent, infertile patients with varicocele were randomly assigned to three groups: varicocelectomy, 1 mg ketotifen, and varicocelectomy plus with 1 mg ketotifen for 3-month follow-up. Semen analysis and estimation of DNA fragmentation index (DFI) were obtained from all people in the studied time periods. In this study, 420 infertile patients with varicocele were included with an average age of 31.6 years. The results showed that sperm morphology, sperm motility, sperm count, and sperm DFI had significant differences after the intervention (p < 0.05). Also, the results of semen analysis for each group showed that there was a significant improvement in sperm morphology, motility, count, and DFI index of infertile people with varicocele after the intervention (p < 0.05). But the difference was statistically higher in the varicocelectomy plus with 1 mg ketotifen group than in the other groups (p < 0.01). The evidence and results of this study showed that the use of varicocelectomy plus ketotifen in infertile people with varicocele was more effective in improving Semen parameters than the use of mast cell stabilizers or varicocelectomy alone.

Background: Varicocele is one of the most prevalent and correctable causes of male infertility, often associated with impaired spermatogenesis and elevated sperm DNA fragmentation index (DFI). Its detrimental impact on sperm quality results from oxidative stress and venous reflux within the pampiniform plexus. Microsurgical varicocelectomy has emerged as the preferred surgical intervention, offering precise anatomical correction with minimal complications. While its effectiveness in improving semen parameters is well documented, its influence on natural conception requires further clinical exploration. Objective: To evaluate the effect of microsurgical varicocelectomy on semen quality, sperm DNA integrity, and natural pregnancy outcomes in infertile men with clinical varicocele. Materials and Methods: A prospective observational study was conducted at Civil Hospital, Bahawalpur, from January to June 2024. Ninety infertile males aged 25–45 years with clinical varicocele, oligoasthenozoospermia, and baseline DFI &gt;20% were included. Patients with azoospermia, previous varicocelectomy, or systemic illness affecting fertility were excluded. All participants underwent microsurgical subinguinal varicocelectomy performed by a single experienced surgeon under general anesthesia. Pre- and postoperative semen analyses were performed to assess sperm count, motility, morphology, and DFI. Pregnancy achievement was monitored over a six-month follow-up. Data were analyzed using paired t-tests and chi-square tests, with p &lt; 0.05 considered significant. Results: The mean age of participants was 34.28 ± 5.60 years, and mean BMI was 24.01 ± 3.27 kg/m². Significant postoperative improvements were observed in sperm count (8.09 ± 4.00 to 25.90 ± 7.73 million/mL, p &lt; 0.001), motility (35.39 ± 8.72% to 54.24 ± 8.35%, p &lt; 0.001), morphology (5.68 ± 2.46% to 13.32 ± 4.07%, p &lt; 0.001), and DFI (29.86 ± 5.91% to 17.96 ± 4.30%, p &lt; 0.001). Pregnancy was achieved in 32 (36%) patients. No statistically significant association was found between pregnancy outcomes and variables such as age, obesity, infertility duration, or varicocele grade. Conclusion: Microsurgical varicocelectomy significantly improves semen parameters and sperm DNA integrity, supporting its role as an effective intervention to enhance natural fertility in men with clinical varicocele.

The impact of ipsilateral testicular atrophy on semen analysis and DNA fragmentation response to varicocele repair

Propecia may induce spermatogenic failure

Study question Can we use artificial intelligence models to predict semen upgrading after microsurgical varicocele repair? Summary answer A machine learning model performed well in predicting clinically meaningful post-varicocelectomy semen upgrade using pre-operative hormonal, clinical, and semen analysis data. What is known already Varicocele repair is recommended in the presence of a clinical varicocele together with at least one abnormal semen parameter, and male infertility. Unfortunately, up to 50% of men who meet criteria for repair will not see meaningful benefit in outcomes despite successful surgery. Nomograms exist to help predict success, but these are based out of single-center databases, do not incorporate hormonal data, and are rarely designed to predict pre-defined, clinically meaningful improvements in semen parameters. Study design, size, duration Data were collected from an international, multi-center retrospective cohort. A total of 240 men were identified. Data from 160 men from Miami, USA and 80 men from Toronto, Canada were included. Data was collected from 2006 to 2020. Participants/materials, setting, methods We collected pre and postoperative clinical data following varicocele surgery. Clinical upgrading was defined as an increase in sperm concentration that would allow a couple to access new reproductive technologies/techniques. The tiers used for upgrading were 0–1million/cc (Intracytoplasmic Sperm Injection), 1–5 million (In Vitro Fertilization), 5–15 million (Intrauterine Insemination), and &amp;gt;15 million (Natural conception). Artificial intelligence models were trained and tested using R to predict which patients upgraded after surgery. Main results and the role of chance 51% of men underwent bilateral varicocele repair. The majority of men had grade 2 varicocele on the left, and (when present) a grade 1 varicocele on the right. Overall, 47% of men experienced an upgrade following varicocele surgery, 47% did not change, and 6% downgraded. The data from Miami were used to create a random forest model for predicting clinically significant upgrade in sperm concentration. The most informative model parameters were preoperative FSH, sperm concentration, and surgical laterality. The model identified three clinical categories: men with unfavorable, intermediate, and favorable features to predict varicocele upgrade. On external validation using data from Toronto, the model accurately predicted upgrade in 87% of men with favorable features, and in 49% and 36% of men with intermediate and unfavorable features, respectively. Overall, the model performed well on external validation with an AUC of 0.72 and good calibration. Calibration plots, using cross-validation, define how well the predicted probabilities match the actual probability of sperm concentration upgrade. The random forest model was run twelve times. All model characteristics are the mean of ten model runs with the highest and lowest performing runs removed. The model was translated to an online calculator that can be used by clinicians. Limitations, reasons for caution One limitation to our study is that we were not able to predict total motile sperm count (TMSC), which has been shown to perform slightly better than concentration at predicting assisted reproduction outcomes. By focusing on clinically significant upgrading, this difference should be minimized. Wider implications of the findings: Predicting the chances of clinically significant semen upgrading after varicocele repair is essential for patients and clinicians to understand. Several men undergo surgery with no subsequent benefit, which may lead to a delay in definitive treatment with IVF/IUI. Understanding their chances will help couples make better informed decisions moving forward. Trial registration number Not applicable

Sperm count and sperm motility in incidental high-grade varicocele

The effect of antioxidants on male factor infertility: the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial