Sperm Concentration In Men Research Articles

Optimal Restoration of Spermatogenesis following Testosterone Therapy using hCG and FSH

To study improvements in spermatogenesis in men with a history of testosterone therapy using a novel fertility treatment regimen. A single-center retrospective cohort analysis. Seventy-seven men with previous testosterone use seeking fertility treatment from January 2020 to March 2024. A treatment regimen of 3000IU human Chorionic Gonadotropin (hCG) and 75IU Follicle Stimulating Hormone (FSH) three times a week was utilized. The primary outcome measured was change in sperm concentration during hCG/FSH therapy. The secondary outcome measured was whether concurrent testosterone therapy during hCG/FSH therapy affected recovery of spermatogenesis. Within the entire cohort (n=77), 74% of men demonstrated improvements in their sperm concentrations. There was not a significant difference in recovery of sperm concentration in men who stayed on testosterone therapy during hCG/FSH reboot (No testosterone therapy [n=50], 74% improved vs. Concurrent testosterone therapy [n=27], 74% improved). We report optimal recovery of spermatogenesis with hCG/FSH therapy in infertile men with a history of testosterone use. Concurrent testosterone therapy does not impede hCG/FSH-mediated spermatogenic recovery.

Novel approach for oligospermia (NAPO) - Protocol for a randomized controlled trial

BackgroundInfertility affects millions of couples globally, with up to 40–50 % of cases linked to impaired semen quality. Insemination or in vitro fertilization are used frequently, regardless of the cause of infertility due to the lack of specific medical interventions for male infertility. Denosumab, an antibody blocking RANKL signaling, may enhance semen quality in infertile men. This randomized controlled trial evaluates if denosumab improves spermatogenesis in men with severely impaired semen quality identified by serum AMH levels as a predictive marker. MethodsNAPO is a single-center, sponsor-investigator-initiated, placebo-controlled, double-blinded randomized trial. Subjects will be randomized in a 2:1 fashion to receive either denosumab 60 mg subcutaneously or a placebo. The study will be carried out at the Division of Translational Endocrinology, Copenhagen University Hospital, Herlev, Denmark. The primary outcome of the study is defined as the difference in sperm concentration (millions/mL) at one spermatogenesis (80 days) after inclusion. DiscussionAn important step in addressing infertility is establishing a viable treatment option for male infertility. With this study, we describe the protocol for a planned RCT aimed at evaluating whether treatment with denosumab can improve sperm concentration in men with severely impaired semen quality. The results of this study will provide evidence crucial for future treatment in a patient group where treatment options are minimal at best. Trial registrationClinical Trials: NCT06300229. Registered on March 12, 2024. Clinical Trials Information System (CTIS): 2023-508325-27-00. Approved on December 19, 2023.

Temporal Effects of Clomiphene Citrate on Testosterone and Semen Parameters

ABSTRACT Introduction In men with secondary hypogonadism or impaired sperm concentrations, clomiphene citrate (CC) is often prescribed off-label to improve testosterone levels and fertility parameters. Prior studies have largely focused on outcomes in the short term (∼3 months). Longer-term efficacy of CC use is less clear, particularly if and when improvement may reach a plateau. Objective We sought to determine the magnitude of improvement in total testosterone and sperm concentration in men taking CC for fertility optimization 3, 6, 9, and 12-month interval follow-up. Methods With IRB approval, we retrospectively evaluated men presenting to an academic andrology clinic for fertility evaluation who were prescribed CC from January 2016 through May 2021. We identified men with 3, 6, 9, and 12-month follow-up data for total testosterone (TT) and 3, 6, and 9-month follow-up semen analyses. Mean absolute change in TT and sperm concentration are reported, along with 95% confidence intervals. Men with previous genitourinary procedures or hormone therapy were excluded. Paired t-tests were used to compare change in TT and sperm concentration at each time point to baseline, and statistical significance was set at p<0.05. Results CC (25 mg qd or 50 mg qod) was prescribed to 235 men seeking fertility optimization during the 5-year period. Mean age was 37.7 (SD 6.7, range 24-52). Of these 235, data for TT at 3, 6, 9, and 12 months were available for 25 men, and semen analyses at 3, 6, and 9 months were available for 26 men. Baseline TT at time of prescription was 358±145 ng/dL, and baseline sperm concentration was 13±17.2 M/mL. In the subset of 25 men with long-term follow-up data, a statistically significant improvement in TT was identified at 3 months (+62.7 ng/dL, 95% CI: 0.49-125.0 ng/dL, p=0.048), and additional benefit was seen at 6 months (+181.8 ng/dL, 95% CI: 114.1-249.5 ng/dL, p<0.01) followed by plateau at 9 and 12 months (Figure A). Improvement in sperm concentration was first noted at 9 months of treatment with CC (+20.7 M/mL, 95% CI: 10.2-31.2 M/mL, p<0.01) (Figure B). At no point were there improvements of semen volume and % motility at any follow-up. Conclusions In men prescribed CC for fertility optimization, we observed a maximal improvement in TT at 6 months, followed by plateau. Sperm concentrations showed a statistically significant improvement at 9 months. Our results suggest that longer duration of CC therapy may be needed to fully appreciate a benefit from CC treatment. Our study is limited by retrospective analysis, absence of controls, and small sample size. Work is under way to examine long-term follow-up data of CC in men seeking treatment for hypogonadism rather than optimization of fertility. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: JNM: Antares Pharma, Boston Scientific, and Endo Pharmaceuticals

Analysis of leukocyte and sperm telomere length in oligozoospermic men.

Telomere length is considered one of the most relevant biological markers of genomic stability since it protects DNA from impairment and also ensures chromosome alignment during DNA replication. The negative impact of telomere shortening on sperm quality has been suggested as an important indicator of male infertility. Therefore, we aimed to assess leucocyte and sperm telomere length (LTL&STL), as well as sperm parameters, DNA damage and protamine deficiency in men with oligozoospermia as compared to fertile men. Our results demonstrated a significant reduction in sperm parameters (concentration, motility, morphology), LTL & STL and a significant increase in sperm DNA damage and protamine deficiency in oligozoospermic men compared with fertile individuals. These outcomes revealed that low sperm concentration in men is possibly a sign of impaired meiotic and/or meiotic division during the spermatogenesis process. It is not only associated with proper chromatin packaging but also with telomere length as a key player in the process of mitosis and meiosis, assisting in chromosomal alignment, pairing, synapsis and crossing over during spermatogenesis.

Association of Alcohol Intake and Semen Parameters in Men With Primary and Secondary Infertility: A Cross-Sectional Study.

Alcohol consumption has commonly been associated with semen parameters. However, the association between alcohol intake and semen parameters in primary and secondary infertile men remains unclear. In this study, 776 infertile men from China were grouped according to alcohol intake: abstainers, moderate drinkers (<9 units/week, up to approximately 100 g of ethanol) and heavy drinkers (≥9 units/week). Semen parameters, including semen volume, sperm concentration, total sperm count, progressive motility and normal morphology were investigated. Alcohol consumption and other lifestyle factors were assessed by questionnaire. Logistic regression models were applied. There was no significant association between alcohol consumption and semen parameters in men with primary infertility. Smaller testis volumes and lower sperm concentrations were found among moderate and heavy drinkers in the secondary infertility group than among abstainers. After adjustment for potential confounders, men with secondary infertility and heavy alcohol consumption had a higher risk of abnormal sperm concentrations (OR = 3.72; 95% CI, 1.04, 13.37). These findings suggest that alcohol intake may decrease sperm concentrations in men with secondary infertility, whereas no association was found in men with primary infertility. It may be beneficial for clinicians to advise male patients with secondary infertility who are seeking fertility treatment to avoid heavy alcohol consumption.

Effect of folate deficiency on promoter methylation and gene expression of Esr1, Cav1, and Elavl1, and its influence on spermatogenesis.

This study aims to investigate the effect of folate deficiency on the male reproductive function and the underlying mechanism. A total of 269 screened participants from 421 recruitments were enrolled in this study. An animal model of folate deficiency was constructed. Folate concentration was measured in the ejaculate, and its association with semen parameters was then determined. The expression and promoter methylation status of ESR1, CAV1, and ELAVL1 were also evaluated. Results showed that seminal plasma folate level was significantly lower among subjects with azoospermia than those with normozoospermia. Low folate level was significantly correlated with low sperm concentration in men with normozoospermia. Folate deficiency significantly reduced the expression of ESR1, CAV1, and ELAVL1, which are critical to spermatogenesis. However, low folate levels did not increase the methylation levels of the promoter regions of ESR1, CAV1, and ELAVL1 in human sperm DNA. Thus, folate deficiency impairs spermatogenesis may partly due to inhibiting the expression of these genes. Thus future research should determine the significance of sufficient folate status in male fertilization and subsequent pregnancy outcomes.

Influence of malignant tumors occurring in the reproductive age on spermiogenesis: studies on patients with testicular tumor and lymphoma

The application of chemo- and radiotherapy results in good survival prognosis for young men with malignant tumors, but long-term gonadoxic effect has to be considered. In addition, malignant disease itself has a negative impact on spermiogenesis. The aim of the authors was to examine the spermiogenetic effect of the most common tumors occurring in the reproductive age in men: testicular cancer, Hodgkin disease and non-Hodgkin disease. Spermiogram of men with testicular cancer (N = 68), Hodgkin disease (N = 37) and non-Hodgkin disease (N = 14) who were referred for sperm cryopreservation were analysed in the Reproductive Andrology Laboratory of the authors. Azoospermia was found in 11.8% of all patients (N = 119), while 58.8% of the patients had oligozoospermia even before the treatment. Sperm concentration of men with testicular cancer was significantly lower than those with lymphomas (32.8 M/mL vs. 24.9 M/mL, p = 0.03). There was no difference in sperm concentration between the Hodgkin and non-Hodgkin lymphoma groups. Spermiogenetic defect is more pronounced in men with testicular cancer than those with lymphomas. Cryopreservation before treatment for fertility preservation should be offered for all reproductive aged men with malignant disease, especially for those with testicular cancer.

Drinking-Water Disinfection By-products and Semen Quality: A Cross-Sectional Study in China

Background: Exposure to disinfection by-products (DBPs) has been demonstrated to impair male reproductive health in animals, but human evidence is limited and inconsistent.Objective: We examined the association between exposure to drinking-water DBPs and semen quality in a Chinese population.Methods: We recruited 2,009 men seeking semen analysis from the Reproductive Center of Tongji Hospital in Wuhan, China, between April 2011 and May 2012. Each man provided a semen sample and a urine sample. Semen samples were analyzed for sperm concentration, sperm motility, and sperm count. As a biomarker of exposure to drinking-water DBPs, trichloroacetic acid (TCAA) was measured in the urine samples.Results: The mean (median) urinary TCAA concentration was 9.58 (7.97) μg/L (interquartile range, 6.01–10.96 μg/L). Compared with men with urine TCAA in the lowest quartile, increased adjusted odds ratios (ORs) were estimated for below-reference sperm concentration in men with TCAA in the second and fourth quartiles (OR = 1.79; 95% CI: 1.19, 2.69 and OR = 1.51; 95% CI: 0.98, 2.31, respectively), for below-reference sperm motility in men with TCAA in the second and third quartiles (OR = 1.46; 95% CI: 1.12, 1.90 and OR = 1.30; 95% CI: 1.00, 1.70, respectively), and for below-reference sperm count in men with TCAA in the second quartile (OR 1.62; 95% CI: 1.04, 2.55). Nonmonotonic associations with TCAA quartiles were also estimated for semen parameters modeled as continuous outcomes, although significant negative associations were estimated for all quartiles above the reference level for sperm motility.Conclusion: Our findings suggest that exposure to drinking-water DBPs may contribute to decreased semen quality in humans.Citation: Zeng Q, Wang YX, Xie SH, Xu L, Chen YZ, Li M, Yue J, Li YF, Liu AL, Lu WQ. 2014. Drinking-water disinfection by-products and semen quality: a cross-sectional study in China. Environ Health Perspect 122:741–746; http://dx.doi.org/10.1289/ehp.1307067

Seminal Plasma Cobalamin Significantly Correlates With Sperm Concentration in Men Undergoing IVF or ICSI Procedures

Mild hyperhomocysteinemia is caused by B vitamin deficiencies. We hypothesize that these biochemical derangements detrimentally affect spermatogenesis. Therefore, the aim of this study was to investigate the folate, cobalamin, pyridoxine, and homocysteine concentrations in blood and seminal plasma and the associations between these biomarkers and semen parameters in men participating in an in vitro fertilization or intracytoplasmic sperm injection program. From 73 men (median age [range]: 37 years [28-53]), blood and semen samples were obtained for the determination of serum and red blood cell (RBC) folate, serum total cobalamin, whole-blood pyridoxal-5'-phosphate, plasma total homocysteine (tHcy), and serum total testosterone. Semen analysis included sperm concentration, motility, and morphology according to World Health Organization criteria. The B vitamins and tHcy concentrations were significantly correlated in blood but not in seminal plasma. The serum and RBC folate concentrations were significantly correlated also with the total folate concentration in seminal plasma (r = .44; P < .001 and r = .39; P < .001, respectively). Likewise, the total cobalamin concentration in serum and seminal plasma was significantly correlated (r = .55; P = .001). Of interest is that the total cobalamin concentration in seminal plasma was significantly correlated with the sperm concentration (r = .42; P < .001). This is in contrast to the absence of significant associations between the other vitamins and tHcy in blood and seminal plasma and any of the semen parameters. These findings suggest that folate and cobalamin are transferred from the blood to the male reproductive organs and emphasize the role of cobalamin in spermatogenesis in human.

P-591: The effect of sperm improve on sperm concentration

Male factor infertility is a common yet often neglected entity. The importance of the micronutrients, zinc and folic acid as well as vitamin E, on spermatogenesis has been demonstrated in various studies. The objective of this study was to determine the effect of Sperm Improve, a combination comprising vitamin E, folic acid and zinc, on the sperm concentration in men. A retrospective, interventional study was performed on men attending a Cape Town fertility clinic. Three groups of men were identified: namely, group A sperm concentration<10 million/ml, group B sperm concentration 10-19 million/ml and group C sperm concentration ≥20 million/ml. The three groups of patients were each assigned to receive a 3 month course of Sperm Improve. Before and after treatment, standardized semen samples were obtained for sperm concentration, motility and morphology according to the Tygerberg strict criteria. The main outcome measure was the effect of treatment on the sperm concentration per ml. Other outcome measures included the effect of treatment on sperm morphology and motility. Statistical analysis was carried out using the Statistical Package for the Social Science (SPSS) version 10. The number and percentage of qualitative variables, and the mean and standard deviation (SD) of quantitative data were calculated. Comparisons between mean values of quantitative variables were calculated using the Student’s t-test, while the chi-square (X2) test was used for qualitative data. A 95% confidence interval was calculated where applicable. All tests of significance used were at the 5% level of significance. Fifty seven men were included in the study. Group A comprised twenty one men, group B comprised 5 men and group C comprised thirty one men. All three groups were comparable with respect to the mean age of men and women. In group A the mean sperm concentration before treatment was 3.5 million/ml and after three months of treatment the mean sperm concentration was 16.9 million/ml (p=0.01). In group B the mean sperm concentration before treatment was 13.3 million/ml and after three months of treatment the mean sperm concentration was 15.6 million/ml (p=0.78). In group C the mean sperm concentration before treatment was 73.1 million/ml and after three months of treatment the mean sperm concentration was 62.8 million/ml (p=0,42). The mean morphology in group A was 3.4% before treatment and 3.7% after treatment (p=o.623). In group B the mean morphology before treatment was 4% and after treatment 3.6% (p=0.788). In group C the mean morphology before treatment was 5.1% and after treatment 4.9% (p=0.849). The mean motility in group A was 42.3% before treatment and 46.8% after treatment (p =0.366). In group B the mean motility before treatment was 47% and after treatment 36% (p=0.388). In group C the mean morphology before treatment was 48.8% and after treatment 50.8% (p=0.643). Conclusion: Treatment with Sperm Improve has been shown to be beneficial in patients with sperm concentration<10 million/ml. Treatment did not affect sperm morphology or motility. Further randomised placebo controlled studies are needed to determine the optimal dosage and efficacy of this treatment option.

P-25: Semen attributes and sperm hyaluronic acid binding after 2-3 days and 1 day abstinences in 418 normozoospermic and oligozoospermic men

We have evaluated the effects of abstinence period on motile sperm concentrations and sperm fertilizing potential in husbands of couples treated with intrauterine insemination. Comparison of semen attributes and sperm biochemical markers of maturity and zona pellucida binding ability, in first day (2-3 days abstinence) and second day (1 day abstinence) semen samples of husbands of couples treated with IUI. Sperm concentration and motility were evaluated by CASA (Hamilton-Thorne). Sperm maturity was assessed by HspA2 chaperone measurements (reflects proportion of mature sperm) and sperm creatine kinase (CK) activity (reflects cytoplasmic retention in immature sperm). Sperm fertilizing potential was measured by hyaluronic acid (HA) binding (proportion of sperm able to bind to the zona pellucida of oocytes) using the HBA slide assay (MidAtlantic Diagnostics). Statistical evaluations by paired T-test and Wilcoxon ranked sum test were performed by the Sigma Stat program (Jandel Scientific Co). All values are expressed as mean±SEM. The mean sperm concentrations in the 1D vs. 2-3D groups were 51.8±1.8x106 vs. 62.9±2.4 X 106 sperm/mL (N=418 men, P<0.001). The decline in sperm concentrations after 1D vs. longer abstinence periods has been well established. However, detailed analysis of the large group of 418 men revealed previously unobserved improvements in oligozoospermic and asthenozoospermic men. The 2-3D vs. 1D sperm concentrations in men of the <20x106 sperm/mL semen oligozoospermic range (N=84 men) were: 12.4±0.61 vs. 18.6±2.1 (p=0.03). However, in men in the >20x 106 sperm/mL normozoospermic range, there was a decline in 2-3D vs. 1D abstinence groups: 75.27±2.6 vs. 59.93±2.63; (P<0.001). The mean sperm motilities in the 2-3D and 1D groups (N=221) were unchanged: 53.3±1.1% vs. 55.7±1%. However, similar to the sperm concentration data, the asthenozoospermic men revealed an improvement in sperm motility after 1D abstinence. In the <40% motility range (N=45), the 2-3D vs. 1D motilities were 30.7±2.2% vs. 39.7±2.2% (P<0.001). However, in the >40% motility range, (N=176) the motilities were similar: 61.6±0.8% vs. 59.9±2.9. The mean values for CK activity, a marker of diminished sperm maturity and surplus cytoplasm, in the 2-3 D vs. 1 D groups were 0.31±0.05 vs. 0.43±0.04 CK IU/108 sperm (P<0.001, N=402), indicating a lower proportion of immature sperm after 2-3D abstinence. Similarly, the other sperm maturity marker, HspA2 ratio, showed a mean overall decline from the 2-3D to the 1D samples from 39.4% to 27.9% (P<0.006, N=405). With respect to sperm-hyaluronic acid binding, which reflects the proportion of sperm able to bind to the zona pellucida, there was only a slight decline in the 2-3D vs. 1D groups from 89.7±0.8 to 87.4± 0.9% (P< 0.01, N=181). In general, there is an abstinence-related decline in sperm concentrations and motility. However, analysis of the present large population of 415 men suggests that in oligozoospermic and asthenozoospermic men there are improvements in sperm concentration and motility, respectively, with short term abstinence. These data, along with those for the sperm maturity attributes, indicate that abstinence-related variations do not substantially affect the efficacy of IUI treatment in oligozoospermic and asthenozoospermic men, who benefit most from this therapeutic modality.

Efficacy and Safety of Recombinant Human Follicle-Stimulating Hormone in Men With Hypogonadotropic Hypogonadism: A Meta-Analysis of 4 Trials in Europe, Australia, USA and Japan

(1) To assess the efficacy and safety of recombinant human follicle-stimulating hormone (r-hFSH; follitropin alfa, freeze-dried formulation) in increasing sperm concentration in men with hypogonadotropic hypogonadism (HH). (2) To assess the impact of baseline data on outcome data.

Sperm concentration in Latvian military conscripts as compared with other countries in the Nordic–Baltic area

Recent studies of semen quality in men from the general population gave rise to the hypothesis of an East-West gradient in semen quality in the Nordic-Baltic area, with the highest sperm counts in Estonia, Lithuania and Finland, and the lowest in Denmark (30% difference in mean concentration). Genetic, lifestyle-related and environmental factors - alone or in combination - were suggested to be responsible for these differences. The aim of this study was to assess sperm concentration in men from the general population in Latvia and to investigate the impact of ethnic and lifestyle-related factors on this marker of male reproductive health. A total of 133 military conscripts from Latvia were investigated. We found that sperm counts among Latvian adolescents were at the same level (mean 74, median 63 x 10(6)/mL) as those previously reported from Estonia, Lithuania and Finland. Sperm concentration was somewhat higher than in Sweden without reaching the level of statistical significance (mean difference 3 x 10(6)/mL; 95% CI: -10, 16 x 10(6)/mL), and statistically significantly higher that in Denmark (mean difference: 17 x 10(6)/mL; 95% CI: 5, 2 x 10(6)/mL). The study also revealed an impact of ethnic factors on sperm numbers. Sperm concentration was significantly higher in men with both parents born in Latvia (77 +/- 60 x 10(6)/mL), compared with men with both parents born outside Latvia (55 +/- 45 x 10(6)/mL, p = 0.03).

Impact of therapy and androgen receptor polymorphism on sperm concentration in men treated for testicular germ cell cancer: a longitudinal study.

Testicular cancer (TC) patients have a high survival rate, and the question of post-therapy recovery of sperm production and its dependence on genetic predisposition is of major interest. Ejaculates were obtained from 112 TC patients at one or more of the following time points: post-orchidectomy, or 6, 12, 24, 36 and 60 months post-therapy. The lengths of the androgen receptor (AR) function modulating CAG and GGN repeats in leukocyte DNA were also analysed. No significant decrease in sperm concentration was seen in men who received 1-2 cycles of adjuvant chemotherapy (ACT). Radiotherapy (RT) or more than two cycles of chemotherapy (HCT) caused an initial decline in sperm concentration, which returned to pre-treatment levels 2-5 years after therapy. In the HCT group, sperm concentration 12-24 months post-treatment (T(12-24)) was inversely correlated with CAG length (rho = -0.72, P = 0.03). The type of treatment, but not the concentration at T(0), was an independent predictor of sperm concentration at T(6) (P < 0.0005) and T(12-24) (P = 0.004). ACT did not induce a significant decline in sperm concentration. After HCT and RT, a significant reduction of sperm concentration was observed, recovering to pre-treatment levels 2-5 years post-treatment. In HCT-treated patients, the AR CAG length influenced the recovery of spermatogenesis.

Inverse correlation between sperm concentration and number of androgen receptor CAG repeats in normal men.

Androgens are essential for the maintenance of normal spermatogenesis. Androgen action is mediated by the androgen receptor (AR), which in the testis is expressed by Leydig, peritubular, and Sertoli cells. The fact that sperm numbers range from 20 up to 300 million/mL in normal men without any indication of changed endocrine parameters led us to assume that genetic variability of transduction of androgen signaling could be important. We therefore compared the variable number of CAG repeats in the AR with sperm concentrations in men with normal ejaculate parameters (62 fathers and 69 volunteers participating in clinical trials). In multivariate analysis CAG repeat length did not differ between the volunteers (19.4 +/- 3.1) and the fathers (20.6 +/- 3.0), but was significantly correlated to sperm concentrations with a coefficient of -0.25. When compared with a group of infertile men with (n = 14) or without (n = 30) a family history of infertility, no such correlation was found. These results indicate that men with short CAG repeats have the highest sperm output within the normal fertile population. Polymorphisms of the AR contribute to the efficiency of spermatogenesis in normal men, but do not play a predominant role in male infertility.