Characteristic of spermogram parameters in men with reproductive pathology in age-related aspect

Introduction. The prevalence of andrological diseases among adolescents and young adults resulting in lowered reproductive potential has been noted to progressively increase. At the same time, the number of couples starting to manage reproductive issues after 35–40 years of age highlighting the onset of male androgen deficiency continues to rise. Therefore, the analysis of spermogram as the key element in assessing male reproductive potential is better to conduct at different age periods of man's life.Aim: to compare spermogram parameters in different age groups of patients with reproductive pathology.Materials and Мethods. The analysis of spermograms in adolescents with left-sided grade II–III varicocele aged 17 years and in infertile males aged 22–48 years was performed. Semen analysis was conducted in accordance with the standards of the 5 th edition of the World Health Organization and included the following parameters: semen volume (ml), sperm concentration (million/ml), total sperm count (million), acidity, viscosity, progressive motility, total motility, viability, morphology, detected mucus, leukocytes, amyloid bodies, lecithin grains as well as sperm aggregation and agglutination. The stained preparations were used to assess the morphology of spermatozoa and spermatogenesis cells. According to the spermogram data obtained, the following conclusions were drawn: normozoospermia, oligozoospermia, asthenozoospermia, teratozoospermia. Statistical analysis was performed by using Statistica 10.0 software (StatSoft Inc., USA). The normality distribution was assessed using the χ2 test. Quantitative parameters were presented as arithmetic means and standard deviations (M ± SD). Assessing significance of differences was performed by using the Student's t-test, whereas inter-parameter correlation relations were analyzed by using the linear Pearson's correlation coefficient. A significance level between inter-group parameters was set at p < 0.05.Results. It was found that adolescents with varicocele vs. adult men had significantly decreased ejaculate volume. In particular, the average ejaculate volume in adolescents and adult men was 2.32 ± 1.22 ml and 3.50 ± 1.44 ml, respectively, so that the larger number of young patients were noted to have ejaculate volume below 1.5 ml. Compared to young subjects, aged patients had decreased sperm concentration (35.88 ± 25.74 versus 72.20 ± 49.32 million/ml) and total sperm count (120.58 ± 91.72 versus 173.07 ± 163.92 million). Young patients were found to have significantly superior data in all categories of sperm motility, whereas infertile men were diagnosed with impaired sperm motility. In particular, adolescents were featured with the average number of spermatozoa displaying fast and slow translational movement comprising 17.12 ± 11.04 % and 29.30 ± 12.29 %, respectively, the proportion of progressive motility spermatozoa was 46.20 ± 19.82 %. In contrast, similar parameters in adult men were 5.10 ± 6.36 %, 19.80 ± 9.61 %, and 24.95 ± 11.23 %, respectively. In infertile men prevalence of lacked spermatozoa with rapid forward movement was 46 (46.0 %), in adolescents – 8 (8.6%), whereas rate of immotile spermatozoa in infertile men, on average, accounted for 53.10 ± 14.56 %, in adolescents – 34.40 ± 21.83 %. In addition, adolescents with varicocele had significantly fewer spermatozoa with normal morphology – 14.14 ± 8.06 % (in adult men – 30.08 ± 17.94 %), there were more abundant defects in the sperm head – 58.01 ± 12.43 % (in men – 48.83 ± 18.95 %) and flagella – 17.24 ± 6.31 % (in men – 10.29 ± 6.21 %). The data obtained showed that adolescents were more often diagnosed with normozoospermia – in 49 (52.7 %) cases, in infertile men – in 12 (12.0 %) cases, whereas in aged men asthenozoospermia was detected in 82 (82.0 %) cases, in adolescents – 5 (5.4 %) cases.Conclusion. The abnormalities in the spermogram revealed in adolescents may be associated with unestablished spermatogenesis. Normozoospermia more common in adolescents with varicocele may evidence about preserved reproductive potential. Impaired sperm motility in aged patients seems to be related to the formation of oxidative stress and damage to spermatozoa by reactive oxygen species due to combined age-related changes, cumulation of the negative effects of environmental and lifestyle factors, as well as comorbidities.

Quality of ejaculate of male patients with type 2 diabetes mellitus (DM), vaccinated with GamCovidVac (Sputnik V)

Background: New coronavirus infection (Covid-19) in patients with diabetes type 2 mellitus (DM) often has severe clinical course and manifestation. This comorbidity is a reasonable indication for vaccination. Male patients are often concerned about the vaccination impact on their fertility, so the current research of this issue seems to be essential and relevant.Aims: To evaluate the quality of ejaculate in type 2 diabetes mellitus (DM) patients, vaccinated by GamCovidVac (Sputnik V).Materials and Methods: The pilot observational prospective study included 30 males with type 2 diabetes mellitus (DM). The study continued from February 2021 till June 2021. The research design involved medical history analysis, glycated hemoglobin (HbA1c) tests, total testosterone level in blood measurement, semen analysis (sperm count test). Group comparison was performed by Wilcoxon Signed Ranks Test. The differences were considered statistically significant at p<0.05.Results: After vaccination 19 patients (63%) demonstrated a temperature rise which lasted for 2 days; 26 patients (87%) complained of tenderness in the injections site which lasted up to 5 days. Though a few patients reported general somatic side effects after the vaccination, there have been no statistically significant deviations in sperm count, viability, function and morphology. The levels of glycated hemoglobin and total testosterone remained unchanged.Conclusion: The study revealed no negative impact of GamCovidVac on ejaculate quality, total testosterone level and compensation of carbohydrate metabolism.

SEMEN ANALYSIS; CORNER STONE IN EVALUATING INFERTILITY

Objective: To study the patterns and distribution of various abnormal semen parameters in infertile males. Study Design: Cross sectional study. Place and Duration of Study: Department of Pathology, Combined Military Hospital, Karachi, from Nov 2019 to Oct 2020. Methodology: The study included 364 patients who presented with primary and secondary infertility. Consecutive convenient sampling was done. Semen analysis was performed using World Health Organization latest guidelines. Samples were categorized as normospermia, azoospermia, oligospermia, asthenozoospermia and necrospermia. Results: The study comprised of 364 samples of infertile males. Normal sperm count was observed in 317 (87%) males, azoospermia in 28 (7.6%) and oligospermia in 19 (5.2%) males. Low ejaculated volume and higher non-motile sperms were noted in oligospermia samples in comparison with normospermia samples. Asthenozoospermia was observed in 102 (28%) and oligoasthenospermia was noted in 15 (4.1%) samples. Conclusion: Good quality semen analysis is a corner stone to diagnose the cause of male infertility.Sperm concentration and motility are the important markers of normal male reproductive system and are related to each other.

The Efficacy and Safety of Letrozole or Anastrozole in The Treatment of Specific Male Infertility Patients: Meta-Analysis and Systematic Review

Background: Letrozole (LE) or anastrozole (AZ) is clinically beneficial in male infertility patients with a low testosterone-estradiol ratio (T/E2). Many scholars believe it has the potential to become one of the effective drugs to treat male infertility. But some relevant research results are different or even the opposite. Study Question: The purpose of this report is to evaluate the efficacy and safety of letrozole or anastrozole in the treatment of specific male infertility patients. Data Sources: We performed a comprehensive literature search using PubMed, Embase, Cochrane, CNKI, VIP, CBM, and Wanfang Date through August 2021 for all studies.Study Design: We conducted a systematic review with meta- analysis of the all available literature reporting sperm conventional parameters, gonadotropin and testosterone levels, and/or the pregnancy rate. Results: The total of 10 studies involving 280 patients were included. LE or AZ administration increased significantly sperm concentration, total sperm count, and serum luteinizing hormone, follicle-stimulating hormone, testosterone levels and T / E2 compared with baseline values, but E2 levels were significantly reduced. In contrast, LE or AZ did not have any significant effect on sperm concentration and motility and pregnancy rate, but improved total sperm count, sperm morphology, compared to the control group, which included studies done with Selective estrogen receptor modulators (SEMR) or testosterone undecanoate (TU). Conclusion: LE or AZ may be effective in the treatment of low T / E2 male infertility, perhaps better than other anti-estrogen or exogenous testosterone supplementation. In addition, we should pay special attention to the changes of E2 during treatment.

FSHB Genotype Identified as a Relevant Diagnostic Parameter Revealed by Cluster Analysis of Men With Idiopathic Infertility

Introduction and ObjectivesAbout 30-75% of infertile men are diagnosed with idiopathic infertility, thereby lacking major causative factors to explain their impaired fertility status. In this study, we used a large cohort of idiopathic infertile men to determine whether subgroups could be identified by an unbiased clustering approach and whether underlying etiologic factors could be delineated.Patients and MethodsFrom our in-house database Androbase®, we retrospectively selected patients (from 2008 to 2018) with idiopathic male infertility (azoo- to normozoospermia) who fit the following selection criteria: FSH ≥ 1 IU/l, testosterone ≥ 8 nmol/l, ejaculate volume ≥ 1.5 ml. Patients with genetic abnormalities or partners with female factors were excluded.For the identified study population (n=2742), we used common andrologic features (somatic, semen and hormonal parameters, including the FSHB c.-211G&gt;T (rs10835638) single nucleotide polymorphism) for subsequent analyses. Cluster analyses were performed for the entire study population and for two sub-cohorts, which were separated by total sperm count (TSC) thresholds: Cohort A (TSC ≥ 1 mill/ejac; n=2422) and Cohort B (TSC &lt; 1 mill/ejac; n=320). For clustering, the partitioning around medoids method was employed, and the quality was evaluated by average silhouette width.ResultsThe applied cluster approach for the whole study population yielded two separate clusters, which showed significantly different distributions in bi-testicular volume, FSH and FSHB genotype. Cluster 1 contained all men homozygous for G (wildtype) in FSHB c.-211G&gt;T (100%), while Cluster 2 contained most patients carrying a T allele (&gt;96.6%). In the analyses of sub-cohorts A/B, two clusters each were formed too. Again, the strongest segregation markers between the respective clusters were bi-testicular volume, FSH and FSHB c.-211G&gt;T.ConclusionWith this first unbiased approach for revealing putative subgroups within a heterogenous group of idiopathic infertile men, we did indeed identify distinct patient clusters. Surprisingly, across all diverse phenotypes of infertility, the strongest segregation markers were FSHB c.-211G&gt;T, FSH, and bi-testicular volume. Further, Cohorts A and B were significantly separated by FSHB genotype (wildtype vs. T-allele carriers), which supports the notion of a contributing genetic factor. Consequently, FSHB genotyping should be implemented as diagnostic routine in patients with idiopathic infertility.

Novel enhancer for male fertility dysfunction in STZ diabetic rats

This new study evaluated effect of aqueous leaves extracts of Chrozophora tinctoria (L.) Rafin on male reproductive hormones and histological features of the testis diabetic rats. The results obtained showed remarkable increased of sperm count, viability and motility after treatment. Testosterone, FSH and LH hormones also increased with oral administration of the plant extract at dose 70 mg/kg of body weight. The results suggested the anti hyperglycemic property of the extract as well as its positive effect to maintain male hormones concentrations. Histological examination of the testis revealed improvement of spermatogenesis and Leydig cell proliferation with all doses of the extract. However, the histoarchitecture of the testis rats received 70 and 90 mg/kg of the plant extract, was found to be similar to the healthy group. These findings suggest that the extract can maintain the damage fertility in diabetic rats. These promising results may explain the use of this plant in the future for therapeutic treatment of diabetes complications associated subfertility.

KIF3B gene silent variant leading to sperm morphology and motility defects and male infertility

Sperm structural and functional defects are leading causes of male infertility. Patients with immotile sperm disorders suffer from axoneme failure and show a significant reduction in sperm count. The kinesin family member 3B (KIF3B) is one of the genes involved in the proper formation of sperm with a critical role in intraflagellar and intramanchette transport. A part of exon 2 and exons 3–5 of the KIF3B encodes a protein coiled-coil domain that interacts with IFT20 from the IFT protein complex. In the present study, the coding region of KIF3B coiled-coil domain was assessed in 88 oligoasthenoteratozoospermic patients, and the protein expression was evaluated in the mature spermatozoa of the case and control groups using immunocytochemistry and western blotting. According to the results, there was no genetic variation in the exons 3–5 of the KIF3B, but a new A &gt; T variant was identified within the exon 2 in 30 patients, where nothing was detected in the control group. In contrast to healthy individuals, significantly reduced protein expression was observable in oligoasthenoteratozoospermic (OAT) patients carrying variation where protein organization was disarranged, especially in the principal piece and midpiece of the sperm tail. Besides, the protein expression level was lower in the patients’ samples compared to that of the control group. According to the results of the present study the NM_004798.3:c.1032A &gt; T, p.Pro344 = variant; which has been recently submitted to the Clinvar database; although synonymous, causes alterations in the transcription factor binding site, exon skipping, and also exonic splicing enhancer-binding site. Therefore, KIF3B can play an important role in spermatogenesis and the related protein reduction can cause male infertility.

The Potential Role of Circulating MicroRNAs in Male Rat Infertility Treated with Kaempferia parviflora

Background. Therapeutic strategies based on herbal plants and diets containing sufficient amounts of antioxidants and essential vitamins are very important factors in treating reproduction and male infertility worldwide. Thus, the aim of this study was to investigate the potential effects of Kaempferia parviflora (KP) on the role of some microRNAs in treated and nontreated infertile rats. In addition, the correlation of expressed microRNAs with sperm count, sperm motility, and sperm viability was identified. The probable use of these microRNAs as a diagnostic marker for predicting the clinical response of infertility to the treatment with KP was also achieved. Methods. In the present study, the potential effects of Kaempferia parviflora (KP) at different doses (140, 280, and 420 mg/kg) for six weeks on male rats with subinfertility were explored. In addition, the effect of KP on the expression of circulating microRNAs and its correlation with the parameters of sexual infertility was identified by performing both in vitro and in vivo assays. In vitro antioxidant activity, sperm functional analysis, serum testosterone, and expression of circulating microRNAs were conducted using colorimetric, ELISA, and real-time RT-PCR analysis, respectively. Results. Kaempferia parviflora (KP) at nontoxic doses of 140–420 mg/kg/day for six weeks significantly improved serum testosterone and epididymal sperm parameters (sperm count, motility, and sperm viability), increased testicular weight, and provided a reduction in the percentage of abnormal spermatozoon in infertile male rats. The expression of miR-328 and miR-19b significantly decreased, and miR-34 significantly increased in infertile rats treated with KP compared to infertile nontreated rats. After six weeks of KP therapy, the change in the expression levels of miRNAs was correlated positively with higher levels of serum testosterone and the measures of epididymal sperm parameters. The respective area under the receiver operating characteristic curve (AUC-ROC) was applied to predict the potential use of miR-328, miR-19b, and miR-34 in the diagnosis of male infertility in treated and nontreated infertile male rats. The data showed that AUC cutoff values of 0.91 for miR-328, 0.89 for miR-19b, and 0.86 for miR34 were the best estimated values for the clinical diagnosis of male rats with infertility. In rats treated with KP for six weeks, AUC cutoff values of 0.76 for miR-328, 0.79 for miR-19b, and 0.81 for miR-34 were the best cutoff values reported for the clinical response of infertility to KP therapy after six weeks. Conclusions. In this study, the improvement of male infertility might proceed via antioxidant and antiapoptotic pathways, which significantly improve spermatogenesis and aphrodisiac properties of males. In addition, the expression of miRNAs, miR-328, miR-34, and miR-19b, in KP-treated and nontreated infertile rats significantly correlated with increased serum testosterone levels and epididymal sperm parameters as well. MicroRNAs, miR-328, miR-34, and miR-19b, might be related to oxidative and apoptotic pathways that proceeded in spermatogenesis. Thus, the use of miRNAs could have a role as diagnostic, therapeutic, and predictive markers for assessing the clinical response of Kaempferia parviflora treatment for six weeks. This may have potential applications in the therapeutic strategies based on herbal plants for male infertility. However, in subsequent studies, the genetic regulatory mechanisms of the expressed miRNAs should be fully characterized.

Case Report on Primary Infertility with Hypothyroidism and Diabetes Mellitus

Introduction: Infertility is the inability, by natural means, of an animal to reproduce. Typically, adult species are not in their normal state of health. A woman who is unable to conceive well will define infertility as unable to bear a full-term pregnancy. Because of any ejaculating disease, and any declining sperm count, men are directly liable for 30-40% infertility. The WHO estimates the overall prevalence of primary infertility in India at 3.9% and 16.8%. Fertility estimates differ widely between India and 3.7% in Utter Pradesh and Maharashtra. Case Presentation: On 9/12/2020, a 38-year-old female came for In Vitro Fertilization with a known case of primary infertility in AVBR Hospital, Wardha. Her complaint was inability to conceive for 4 years, irregular menses, headache, sleep disturbance, loss of appetite. She was admitted for in-vitro fertilization therapy for the 2nd cycle. She had a history of hypothyroidism for 8 years for which she has been taking Thyrox 50mg OD tablet and has Diabetes Mellitus for one year since she is taking Metformin 500mg BD tablet. Instead, she has no concerns about asthma, tuberculosis, epilepsy, etc. On 9/12/2020, she underwent an embryo transfer. Diagnostic Evaluation: The diagnostic hysteroscopy was conducted at the private hospital in Amravati 2 years ago. She has been diagnosed with nullipara for 4 years as a primary infertility. She has already undergone 2 cycles of Intra Uterine Insemination (IUI) and 1 cycle of in vitro fertilization. Hysterosalpingography: Both fallopian tubes are normal & patent uterus is normal. Conclusion: There is multifactorial infertility. In both men and women, anatomy, physiology, the environment, hormones and genetics all play a role in causing infertility. Therefore, in the coming years, it is a very important problem and research in this zone is very essential.