INFLUENCE OF ADDING ZINC ARGINYLE-GLYCINATE TO IMPROVE EFFICACY OF BIOREGULATORY PEPTIDES OF THE PROSTATE GLAND IN TREATMENT OF PATIENTS WITH IMPAIRED SPERM PARAMETERS.

The drug Prostatilen® AC, rectal suppositories were developed on the basis of the previously registered medicine containing bioregulatory peptides of the prostate gland - Prostatilen® rectal suppositories, 3 mg, from whom it differs by the addition of аctive pharmaceutical ingredient zinc arginyle-glycinate dihydrochloride (ZAG). The aim of this study was to analyze the positive effect of adding ZAG to the drug in patients with impaired spermatogenesis. A total of 98 men aged 25-45 years (an average of 35.2±4.3 years) with a verified diagnosis of chronic abacterial prostatitis and related reproductive dysfunctions in the phase III, randomized, multicenter, open-label clinical trial was examined. The duration of participation of patients in the study was 14-16 days, the screening period was 2-3 days, the duration of therapy was 10 days, and the final examination was 2-3 days. A study group (n=49) received therapy with Prostatilen AC once daily, a control group (n=49) had Prostatilen once daily. All patients underwent conventional semen analysis before and after treatment. The obtained parameters were compared. During the analysis of the average statistical data in the comparison groups, it was found that treatment with Prostatilen AC leads to an increase in the total population of motile spermatozoa (cells A + B + C) by 14.3%, and the reference drug Prostatilen contributes to an increase in this indicant by 4.1% compared with the results of a screening examination with significantly higher efficiency in increasing the relative count of spermatozoa with a fast progressive motility (After therapy Prostatilen/Prostatilen AC p=0.0004). Prostatilen AC showed significantly higher efficiency in terms of increasing the count of normal forms of spermatozoa in the ejaculate than the reference drug Prostatilen (After therapy Prostatilen/Prostatilen AC p=0.0118). In patients who received the drug Prostatilen AC the number of abnormal forms of spermatozoa decreased by 12.4% (After therapy - 55.57%), and in the comparison group (drug Prostatilen) by 6.5% (After therapy - 58.90%) with significant decrease in forms of abnormal spermatozoa with head, acrosome, or neck pathology for Prostatilen AC compared to control. Prostatilen AC compared to Prostatilen had a statistically significant and clinically significantly superior efficacy in relation to initially impaired sperm parameters (improve of sperm motility, restoration of morphologically normal sperm, decrease in forms of abnormal spermatozoa with head, acrosome or neck pathology). This drug could be recommended to use in the treatment of patients in whom chronic prostatitis occurs with concomitant disorders of sexual and reproductive functions.

[Clinical efficacy of Jujing Decoction on teratospermia: An investigation based on the theory of "yin forming"].

OBJECTIVE: To study the clinical efficacy of Jujing Decoction (JJD) based on the theory of "yin forming" in the treatment of teratospermia and its effects on semen parameters, sperm morphology, sperm DNA fragmentation index (DFI) and the ultrastructure of sperm mitochondria. METHODS: We randomly divided 40 patients with teratospermia into a blank control group (n = 16) and a JJD group (n = 24), the former treated by reproductive health guidance and the latter with JJD, respectively. After 12 weeks of intervention, we observed the clinical effects and changes in the semen volume, sperm concentration, percentages of progressively motile sperm (PMS) and morphologically abnormal sperm (MAS), sperm DFI and the ultrastructure of sperm mitochondria, and analyzed the data obtained based on the "yin forming" theory. RESULTS: The total effectiveness rate was significantly higher in the JJD than in the blank control group (87.50% vs 6.66%, P < 0.05). Compared with the baseline, the patients after treated with JJD showed significant improvement in semen volume (ï¼»3.27 ± 1.14ï¼½ vs ï¼»4.16 ± 1.84ï¼½ ml, P < 0.05), sperm concentration (ï¼»38.85 ± 15.88ï¼½ vs ï¼»39.35 ± 14.58ï¼½ × 106/ml, P < 0.05), PMS (ï¼»37.47 ± 2.74ï¼½% vs ï¼»42.55 ± 7.07ï¼½%, P < 0.05), MAS (ï¼»97.43 ± 1.01ï¼½% vs ï¼»95.52 ± 0.85ï¼½%, P < 0.05), acrosomal integrity (ï¼»45.27 ± 5.14ï¼½% vs ï¼»51.88 ± 4.48ï¼½%, P < 0.05), and DFI (ï¼»25.53 ± 6.89ï¼½% vs ï¼»17.68 ± 2.38ï¼½%, P < 0.05), while the blank controls exhibited only slightly increased semen volume (ï¼»3.67 ± 1.77ï¼½ vs ï¼»4.40 ± 1.78ï¼½ ml) and sperm concentration (ï¼»37.24 ± 9.31ï¼½ vs ï¼»38.32 ± 10.54ï¼½ ×106/ml), but no significant improvement in the other parameters (P> 0.05). Before treatment, folded and discontinuous sperm acrosomal membrane was observed under the transmission electron microscope in the sperm mitochondria of the two groups of patients, the mitochondria stacked and differently sized in the neck and disorderly arranged and some obviously swollen around the tail microtubule. After treated with JJD, the ultrastructure of sperm mitochondria was significantly improved, with relative continuity and integrity of the acrosomal membrane and well-arranged and relatively intact and uniform-sized mitochondria in the neck and tail. CONCLUSION: Jujing Decoction can increase the semen volume, sperm concentration and percentage of progressively motile sperm, reduce the percentage of morphologically abnormal sperm and sperm DFI, improve sperm acrosomal integrity, maintain the stability of sperm ultrastructure and protect the structure of sperm mitochondria.

[Efficacy of Jujing Decoction combined with lipoic acid in the treatment of asthenospermia and teratospermia].

OBJECTIVE: To observe the clinical efficacy of Jujing Decoction combined with lipoic acid in the treatment of asthenospermia and teratospermia. METHODS: Fifty patients with asthenospermia and teratospermia meeting the inclusion criteria were randomly divided into a blank control (n = 10) and a medication group (n = 40), the former provided with fertility guidance and the latter treated with Jujing Decoction combined with lipoic acid. After 12 weeks of treatment, the clinical therapeutic effects were evaluated by comparing the semen volume, sperm concentration, percentages of progressively motile sperm (PMS) and morphologically abnormal sperm (MAS), rate of acrosome integrity, sperm DNA fragment index (DFI) and pregnancy rate between the two groups. RESULTS: Compared with the control group, the medication group achieved a significantly higher overall effectiveness rate (10% ï¼»1/10ï¼½ vs 88.89% ï¼»32/36ï¼½, P < 0.05) and pregnancy rate (0% ï¼»0/10ï¼½ vs 8.33% ï¼»3/36ï¼½, P < 0.05) after treatment. The medication group also showed remarkably increased PMS from (21.04 ± 6.49)% to (32.66 ± 7.05)%, decreased MAS from (98.31 ± 1.28)% to (96.52 ± 1.11)%, elevated acrosome integrity from (42.18 ± 16.67)% to (60.42 ± 11.61)%, and reduced sperm DFI from (21.92 ± 6.96)% to (12.37 ± 3.79)%, all with statistically significant differences compared with the blank control group. CONCLUSION: Jujing Decoction combined with lipoic acid can significantly improve sperm motility, reduce MAS and DFI and increase the pregnancy rate through antioxidant stress, and has a high clinical safety.

Effect of Letrozole on sperm parameters, chromatin status and ROS level in idiopathic Oligo/Astheno/Teratozoospermia.

BACKGROUND: This study investigates the effect of letrozole on hormone profiles, semen parameters, body mass index (BMI), degree of oxidative stress and sperm chromatin integrity in men with idiopathic oligo/astheno/teratozoospermia (iOAT) and T:E2 ratio ≤ 10. MATERIALS AND METHODS: This study is a longitudinal, prospective, interventional and open-labelled clinical trial. Semen samples were collected from 20 iOAT men with low serum testosterone (T) to estradiol (E2) ratio (T:E2 ratio ≤ 10). The participants were treated with 2.5 mg letrozole orally per day for 3 months. Then, sperm parameters, hormone profiles, BMI, chromatin integrity and intracellular reactive oxygen species (ROS) level were assessed pre- and post- treatment. The chromatin integrity was evaluated by assessment of DNA fragmentation (with TUNEL assay) and protamine deficiency (with Chromomycin A3, CMA3). Also, the intracellular ROS levels were investigated by 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. Finally, the differences between the parameters evaluated before and after letrozole treatment were analyzed with the t-test and the Wilcoxon signed-rank test. RESULTS: Sperm concentration, percentage of sperm motility and its normal morphology increased significantly after letrozole treatment. Moreover, serum testosterone level increased but estradiol level decreased significantly following treatment. The mean of T:E2 ratio improved 1600%. Also, letrozole treatment significantly reduced the percentage of sperm TUNEL positivity and sperm CMA3 positivity. While no significant difference was observed between intracellular ROS levels and BMI before and after treatment. Finally, as a notable result, four spontaneous pregnancies (20%) were achieved after treatment. CONCLUSIONS: Letrozole treatment can effectively increase spontaneous pregnancies by improving sperm parameters and sperm chromatin integrity in men with iOAT and T:E2 ratio ≤ 10. TRIAL REGISTRATION: Trial registration: IRCT, IRCT20191030045283N1. Registered 16 November 2019 - Retrospectively registered, https://fa.irct.ir/user/trial/43484/view.

Coenzyme Q10 effect on semen parameters: Profound or meagre?

Coenzyme Q10 has shown promise in treating male infertility; however, there are inconsistencies across the published data. We undertook a quantitative meta-analysis by pooling data from three placebo-controlled randomised clinical trials (RCTs) in order to evaluate the efficacy of CoQ10 in improving semen parameters. Sperm count, sperm motility, sperm forward motility, sperm morphology and CoQ10 level in the seminal plasma were measured and quantitatively correlated with CoQ10 oral administration. Pooled analysis showed a significant impact of CoQ10 in improving sperm motility and forward motility, without a significant impact on sperm count, sperm morphology, ejaculate volume or seminal plasma level of CoQ10. Efficacy assessment suggested that CoQ10 shows better results at higher doses and when administered for a period of more than 3 months but not longer than 6 months. We conclude that CoQ10 has a profound effect on sperm motility and a meagre effect on all other parameters. Therefore, CoQ10 can be used for treating asthenozoospermic infertility with the dosage and duration depending upon the severity of the disorder and the patient's response to the treatment.

Efficacy of the Oestrogen Antagonist Tamoxifen on Sperm Parameters in Patients with Idiopathic Oligoathenoteratozoospermia.

BACKGROUND: The oestrogen antagonist tamoxifen has been suggested as an empiric treatment option for treating idiopathic oligoathenoteratozoospermia (iOAT). OBJECTIVES: To analyse the use of tamoxifen in iOAT. METHOD: Fifty-seven men receiving tamoxifen for iOAT were recruited from 2016 to 2017 in a retrospective, single-centre setting. Hormone and semen analysis was performed before and after 3 months of treatment. RESULTS: After a 3-month treatment, serum levels of testosterone (3.4 ng/mL [2.7-4.8] vs. 5.3 [3.1-7.1]; p = 0.026), follicle stimulating hormone (FSH; 7.6 [5.9-11.5] vs. 15.9 mIU/mL [8.4-19.9]; p = 0.003) and luteinizing hormone (4.5 [3.3-6.6] vs. 7.6 mIU/mL [4.8-10.7]; p = 0.007) significantly increased. At a cut-off of >8.8 mIU/mL, serum levels of FSH were predictive for an improved sperm motility (OR 0.229 [95% CI 0.068-0.773]; p  = 0.018) and serum levels of inhibin B were predictive for an improved total sperm count at a cut-off of <82 ng/L (OR 18.0 [95% CI 1.267-255.744]; p = 0.033). During an 11 month-follow-up, patients receiving tamoxifen showed a clinical pregnancy rate of 42%, leading to a live birth rate of 56% of all pregnant women. Twenty-three per cent of all patients reported non-serious adverse events. CONCLUSIONS: Tamoxifen is effective in improving the total sperm count as well as motility and can thus be safely used as empiric medical therapy in iOAT.

[Huanshao Capsules combined with levocarnitine for the treatment of asthenospermia, oligospermia and teratozoospermia].

OBJECTIVE: To observe the clinical effects of Huanshao Capsules (HSC) combined with levocarnitine (LC) on asthenospermia, oligospermia, teratozoospermia, and the semen parameters of the patients. METHODS: This randomized controlled clinical study included 186 infertility patients with spleen and kidney asthenia. We randomly divided them into three groups of equal number and treated them orally with HSC at the dose of 3 capsules tid, LC at 10 ml tid, and HSC+LC, respectively, all for 12 weeks. At 4, 8, and 12 weeks after treatment, we obtained the semen parameters from the patients and compared them among the three groups. RESULTS: Totally, 180 of the patients completed the study, 61 in the HSC, 59 in the LC and 60 in the HSC+LC group. After 12 weeks of medication, the patients of the HSC+LC group showed an increase of 42.77% in the semen volume, 142.37% in sperm concentration, 28.61% in sperm motility, and 24.39% in the percentage of grade a+b sperm and a decrease of 6.27% in the percentage of morphologically abnormal sperm as compared with the baseline (P <0.05). The patients treated with HSC+LC showed significantly more improvement in all the above parameters than those treated with LC alone (P <0.05) as well as in sperm motility and the percentage of progressively motile sperm than those treated with HSC alone (P <0.05). The HSC group exhibited remarkable improvement in the above parameters after treatment as compared with the baseline (P <0.05) and higher semen volume and sperm concentration than the LC group (P <0.05). CONCLUSIONS: Huanshao Capsulescombined with levocarnitinedeserves a wide clinical application as a safe and efficacious therapy forasthenospermia, oligospermia,and teratozoospermia.

European Academy of Andrology guideline Management of oligo­astheno­teratozoospermia

Oligo­astheno­teratozoospermia is frequently reported in men from infertile couples. Its etiology remains, in the majority of cases, unknown with a variety of factors to contribute to its pathogenesis. The aim of this European Academy of Andrology guideline was to provide an overview of these factors and to discuss available management options.

Association between total globozoospermia and sperm chromatin defects.

Globozoospermia is a severe sperm morphological anomaly leading to primary infertility and low fertilisation following intracytoplasmic sperm injection (ICSI). This phenotype is observed in less than 0.1% of infertile men and is determined by small, round-headed spermatozoa with absence of an acrosomal cap, acrosome protease and also cytoskeletal proteins. Failure of oocyte activation is considered as the main cause of fertilisation failure in these individuals post-ICSI. Therefore, artificial oocyte activation (AOA) along with ICSI is commonly implemented. However, based on previous report, fertilisation rate remains low despite implementation of ICSI-AOA. Therefore, other mechanisms like sperm chromatin packaging and DNA fragmentation may account for low fertilisation and development post-ICSI-AOA. Therefore, this study aims to assess and compare the degree of sperm protamine deficiency and DNA fragmentation in large population of infertile men with total globozoospermia (30 globozoospermic men presenting with 100% round-headed spermatozoa) with 22 fertile individuals using chromomycin A3 and TUNEL assay respectively. Results clearly show that mean of sperm concentration and percentage of sperm motility were significantly lower, while percentage of sperm abnormal morphology, protamine-deficient and DNA-fragmented spermatozoa were significantly higher in infertile men with globozoospermia compared to fertile men. Therefore, increased sperm DNA damage in globozoospermia is likely related to defective DNA compaction and antioxidant therapy before ICSI-AOA could be recommended as an appropriate option before ICSI-AOA.

[Isolated teratozoospermia: is there a role for antioxidant therapy?]

Recently, literature has emerged that offers contradictory findings of idiopathic forms of isolated teratozoospermia that may confuse clinicians. Some researchers argue that at 0-1% of normal forms of spermatozoa, morphology itself cannot be a prognostic indicator of fertility, either in the planning of natural pregnancy, or when used in assisted reproduction. In this connection, the possible causes of teratozoospermia and alternative therapies are being actively sought, in addition to known invasive and costly procedures. There is convincing evidence that reactive oxygen species overproduction is associated with the occurrence of abnormal spermatozoa in the ejaculate. An abnormal morphology can be accompanied by damage to the sperm DNA, impaired chromatin condensation, and associated unsuccessful pregnancy outcomes. Most of the studies show that using antioxidants results in positive changes. This literature review highlights the role of oxidative stress and DNA fragmentation in the formation of morphologically abnormal spermatozoa. The authors discuss drug interventions to treat teratozoospermia and present their own recommendations for antioxidant therapy in the clinical management of idiopathic forms of male infertility.

[Using L- and acetyl-L-carnintines in combination with clomiphene citrate and antioxidant complex for treating idiopathic male infertility: a prospective randomized trial].

The most common cause of male infertility is idiopathic oligo-, and or astheno-, and /or teratozoospermia. In such cases, anti-estrogens, antioxidants (vitamins and trace elements) or carnitines are used, but the evidence on their effectiveness is inconsistent; there are currently no published studies exploring their concurrent use. AIM: To investigate the efficacy and safety of the L- and acetyl-L-carnitine complex, vitamins A, E, C, selenium, zinc and other antioxidants ("SpermActin" + "More than vitamins") in combination with clomiphene citrate (CC) in managing male idiopathic infertility in the form of oligo, and/or astheno-, and/or teratozoospermia. MATERIALS AND METHODS: The study comprised 173 men from infertile couples aged 25-45 years who were divided into two groups - the study group (n=88) and control group (n=85). All the patients were examined according to the WHO recommendations. Patients of the study group received L-carnitine fumarate (1 g), acetyl-L-carnitine (0.5 g) twice daily, a complex of vitamins and microelements and CC 25 mg twice daily orally. Patients of the control group were administered the same dosages of CC and a complex of vitamins. Ejaculate was evaluated before and after 3-4 months of treatment. Six months after the start of treatment, information about the onset or absence of pregnancy over the last six months was collected via telephone or online survey. RESULTS: Co-administration of L- and acetyl-L-carnitines concurrently with CC and antioxidant complex (vitamins and minerals) in patients with idiopathic oligo- and/or asteno- and/or teratozoospermia provides some additional positive effect on the concentration of spermatozoa, more pronounced in patients with multiple impaired semen parameters - oligoasthenoteratozoospermia, but does not improve the morphology, progressive sperm motility and pregnancy rates compared to patients receiving basic treatment.

[Stimulation of a spermatogenesis in men at a pathospermia and infertility].

THE PURPOSE: to investigate of the methods of treatment, directed on increase in quantity of spermatozoa in an ejaculate. MATHERIALS AND METHODS: for this purpose used clomifene and combinations of recombinant FSH with chorionic gonadotrophin (HCG) in 60 men with infertility. RESULTS: Efficiency of monotherapy by clomiphene was higher and made 20% for conception, and 63% for oligoteratozoospermia. Efficiency of the combined therapy of HCG in combination with recombinant FSH was 40% for conception, and 87% for oligoteratozoospermia. The efficiency of the combined therapy by recombinant FSH and HCG in cases of the previous inefficiency monotherapy HCG and clomifene for oligoteratozoospermia made 65%. SUMMARY: The combined therapy of HCG in combination with recombinant FSH is al most effective. At the same time the studied types of the stimulating therapy are safe and don't lead to development of side effects.