Oligoasthenoteratozoospermia Research Articles

#241 : Impact of Antioxidants in Improving Semen Parameters Like Count, Motility and DNA Fragmentation in Sub-Fertile Males: A Randomized, Double Blind, Placebo Controlled Clinical Trial

Background and Aims: Male infertilities are solely responsible for 20-30% of infertility cases. Oxidative damage of sperm DNA is positively linked with oligoasthenoteratozoospermia (OAT), and male infertility. The antioxidants are being explored worldwide to combat OAT, sperm DNA fragmentation and reactive oxygen species. The objective of the study was to assess the effectiveness of an antioxidant blend in improving sperm count, semen parameters and reducing DNA fragmentation index (DFI) in sub-fertile males. Method: A prospective, double-blind, randomized, placebo-controlled trial was conducted in 300 sub-fertile males (25–45 years) from ten study sites in India. Subjects were randomized in either the antioxidant blend treatment group or placebo group. We assessed changes in sperm count, motility, normal morphology, semen volume, and percent DFI before and after treatment (90 days). To further stratify data on different criteria post hoc analysis was performed. Statistical analysis was performed using SPSS 10.0 software. Results: There were improvements in sperm count, semen volume, sperm motility, and sperm normal morphology in the treatment group. There was improvement in sperm count in severe oligospermia subjects (sperm count < 5 million/mL, 5–10 million/mL, 10.1–15 million/mL), and high-extremely higher baseline DFI (20–30%, 31–40% and above 40%), as per post hoc analysis. There was no premature discontinuation and adverse events were reported during the study, indicating safety and well-tolerability of treatment. Conclusion: Study results confirmed the well-researched fact of antioxidants being effective to reduce oxidative stress and thus improve sperm DNA integrity and also improved semen parameters particularly in males aged 40 and above.

The association between levels of samarium, hafnium, tungsten and rhenium in seminal plasma and the risk of idiopathic oligo-astheno-teratozoospermia in men of childbearing age.

Oligo-astheno-teratozoospermia (OAT) is a global public health problem, which affects 30% men of childbearing age. Meanwhile, with the rapid development of industry and economy, the contents of rare earth elements (REEs) in the environment are increasing. However, little is known about the associations between REEs levels and OAT risk. To evaluate the associations between the levels of four REEs (samarium (Sm), hafnium (Hf), tungsten (W), rhenium (Re)) in seminal plasma and OAT risk, from October 2021 to November 2022, semen samples from 924 men of childbearing age (460 controls and 464 cases) were collected from the reproductive center of the First Affiliated Hospital of Anhui Medical University. Inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure the levels of Sm, Hf, Re and W in seminal plasma. Bayesian kernel machine regression (BKMR) was conducted to explore the joint effects of levels of four REEs in seminal plasma on the risk of OAT and select the one exerting a major role; generalized linear regression models (GLM) with log link function were employed to investigate the association of every REE level in seminal plasma and OAT risk; sankey diagram and linear regression models were utilized to describe the associations between the levels of four REEs and the indexes of sperm quality. The levels of four REEs in seminal plasma were higher in the case group than levels in the control group (pSm = 0.011, pHf = 0.040, pW = 0.062, pRe = 0.001, respectively). In BKMR analysis, theOAT risk increased when the overall levels of four REEs were higher than their 55th percentile compared to all of them at their 50th percentile, and Re level played a major role in the association. Additionally, Re level in seminal plasma was positively associated with theOAT risk in the single element model after adjustment of covariates (medium vs. low: OR (95% CI) = 1.55 (1.10, 2.18); high vs. low: OR (95% CI) = 1.69 (1.18, 2.42)). Lastly, the sankey diagram and linear regression models revealed that Sm level was negatively associated with the PR%, total sperm count and total progressively motile sperm count; Hf level was negatively associated with the PR%; W and Re levels were negatively associated with the PR% and total motility, and Re level was positively associated with abnormal morphology rate. Men of childbearing age with OAT had higher levels of Sm, Hf and Re in seminal plasma than those in the control group. An increasing trend for theOAT risk was observed with an increase in mixture levels of Sm, Hf, W and Re, and Re exposure level played a major role in the association whether in BKMR model or single element model. Additionally, the levels of these four REEs were negatively associated with the indexes of sperm quality.

Seminal calbindin 2 level in azoospermia and oligoasthenoteratozoospermia and its correlation with seminal and hormonal parameters.

We aimed to assess seminal calbindin 2 (CALB 2) expression in men with different semen parameters as well as its correlation with reproductive hormones in azoospermic patients and different semen parameters in oligoasthenoteratozoospermic patients. CALB 2 is also known as calretinin and 29 kDa calbindin. This prospective study was performed on 96 cases from the andrology outpatient clinic divided into 3 groups as follows: group 1 including 32 non obstructive azoospermic (NOA) patients, group 2 including 32 patients with oligoasthenoteratozoospermia (OAT), and Group 3 including normozoospermic individuals as controls. Semen analysis and estimation of seminal CALB 2 concentrations by enzyme linked immunosorbent assay (ELISA) technique were performed for all participants. Reproductive hormones were measured in nonobstructive NOA patients. The mean seminal CALB 2 level was higher in OAT patients compared to NOA patients and controls (7.8 ± 1.30 ng/ml, 7.3 ± 0.80 and 7.4 ± 1.0, respectively). Furthermore, the study had shown strong positive correlations between CALB 2 and sperm normal forms in controls and OAT patients. In contrast, there was no significant correlation between seminal CALB 2 and any of the reproductive hormones measured in NOA patients. Seminal CALB 2 may play a role in increasing the abnormal forms in OAT patients.

Varicocelectomy outcomes among patients with azoospermia and severe oligasthenoteratozoospermia.

Varicocele is a reversible cause of male infertility. However, there are conflicting data available concerning the benefit of varicocele repair for patients with nonobstructive azoospermia (NOA) and severe oligoasthenoteratozoospermia (OAT). To address the benefit of varicocelectomy in patients with severe OAT and NOA with regard to their semen parameters and surgical sperm retrieval rate in those who underwent testicular sperm extraction (TESE) or testicular sperm aspiration (TESA). This retrospective cohort study was conducted on a sample of 13 patients diagnosed with NOA and severe OAT who underwent varicocelectomy for infertility treatment with no prespecified exclusion criteria. Thirteen patients were enrolled. Five patients were diagnosed with NOA; eight were diagnosed with severe OAT. For improvements in the semen parameters postoperatively, the semen concentration of all patients was significantly increased compared to the preoperative concentration (3.59 ± 10.0.8 vs. 0.25 ± 0.31, P = 0.02) and the remaining parameters were unchanged. Regarding sperm retrieval, three patients underwent TESE and two patients underwent TESA, in which all had positive results. Varicocele repair was found to improve the semen parameters in patients with NOA and severe OAT and produced a successful surgical sperm retrieval rate in all patients who underwent TESA or TESE.

The Association Between the Levels of Oxidative Stress Indicators (MDA, SOD, and GSH) in Seminal Plasma and the Risk of Idiopathic Oligo-asthenotera-tozoospermia: Does Cu or Se Level Alter the Association?

Epidemiological studies on the associations between the levels of oxidative stress (OS) indicators (MDA, SOD, and GSH) in seminal plasma and the risk of idiopathic oligo-asthenotera-tozoospermia (OAT) are still inconsistent. Additionally, whether the associations can be altered by the status of essential trace elements is still unknown. To investigate the relationship between MDA, SOD, and GSH levels in seminal plasma and the risk of idiopathic OAT, and further to examine whether levels of iron (Fe), copper (Cu), and selenium (Se) in seminal plasma can alter the associations. A total of 148 subjects (75 idiopathic OAT cases and 73 controls) were included in this study. Seminal plasma samples from all the participants were measured for levels of MDA, SOD, GSH, Fe, Cu, and Se. Unconditional logistic regression models were used to examine the associations between three oxidative stress indicators and the risk of idiopathic OAT. Bayesian kernel machine regression was performed to determine the joint effects of levels of three OS indicators on the risk of idiopathic OAT. Subgroup analyses were performed to explore whether the above associations can be different when Fe, Cu, and Se were in different levels. The level of MDA in seminal plasma was positively associated with the risk of idiopathic OAT, with adjusted odds ratio (OR) and 95% confidence interval (CI) of 2.38 (1.17, 4.83), and SOD and GSH levels were not associated with the risk of idiopathic OAT. In BKMR analyses, we found a significant positive association between the mixture of MDA, SOD, and GSH levels and the risk of idiopathic OAT at concentrations below the 65th percentile, while a negative association at concentrations above it. In subgroup analysis, a positive association was observed between MDA levels in seminal plasma and the risk of idiopathic OAT in the high-Cu group (adjusted OR = 3.66, 95%CI = 1.16, 11.57), while no significant association was found in the low-Cu group (adjusted OR = 1.43, 95%CI = 0.44, 4.58). Additionally, a negative association was found between GSH levels in seminal plasma and the risk of idiopathic OAT in the high-Se group (adjusted OR = 0.34, 95%CI = 0.11, 0.99), while no significant association was observed in the low-Se group (adjusted OR = 1.96, 95%CI = 0.46, 8.27). The levels of MDA, SOD, and GSH in seminal plasma were associated with the risk of idiopathic OAT, and the levels of Cu and Se in seminal plasma may alter the associations.

Effect of antioxidants on semen parameters in men with oligo-astheno-teratozoospermia: a network meta-analysis.

Although antioxidants are largely used in subfertile men with oligo-astheno-teratozoospermia (OAT), the choice among different molecules is challenged by the lack of comparative head-to-head studies. The network meta-analysis (NMA) can overcome limitations of pairwise meta-analyses, since it incorporates direct and indirect evidence into a single model generating an effectiveness hierarchy. To assess with a NMA the effects of antioxidants in improving seminal parameters in idiopathic OAT. PubMed, Scopus, Cinahl, and Cochrane Library databases were searched for randomized controlled trials (RCTs) comparing any antioxidant treatment to each other or placebo in men with at least one idiopathic seminal abnormality. Data were included in a random-effects NMA, where efficacy of treatments was ranked by surface under the cumulative ranking curve (SUCRA). 29 RCTs provided information on 2045 men (mean age: 33.5 years) with idiopathic OAT and 19 antioxidant preparations. Compared to placebo, l-carnitine, especially in combination with l-acetyl-carnitine (LAC), had the highest SUCRA for sperm concentration, progressive motility, and morphology. Folate was the only other compound effective on sperm concentration. Vitamin E+selenium or zinc had the highest SUCRA for total motility. A contribution on progressive motility was revealed for pentoxifylline and vitamin E+CoQ10.

A novel nonsense mutation of PNLDC1 associated with male infertility due to oligo-astheno-teratozoospermia in a consanguineous Chinese family.

Learning points for clinicians PARN-like ribonuclease domain-containing exonuclease 1 (PNLDC1) forms a trimmer of piRNAs mediating 3'-splicing and plays an important role in meiosis and spermatogenesis. Here, we identified a novel nonsense PNLDC1 variant in a patient with Oligo-astheno-teratozoospermia (OAT) and poor clinical outcomes of intracytoplasmic sperm injection (ICSI) from a consanguineous Chinese family.

CFAP70 is a solid and valuable target for the genetic diagnosis of oligo-astheno-teratozoospermia in infertile men.

Male infertility is a worldwide population health concern, but its aetiology remains largely understood. Although CFAP70 variants have already been reported in two oligo-astheno-teratozoospermia (OAT) individuals by sequencing, animal evidence to support CFAP70 as a credible OAT-pathogenic gene is lacking. Cfap70-KO mice were generated to explore the physiological role of CFAP70. CFAP70 variants were detected in infertile men with OAT by whole exome sequencing and Sanger sequencing confirmation. Cfap70-truncated mice were further generated to explore the pathogenicity of the nonsense variant of CFAP70 identified in the proband. Here, we demonstrate that Cfap70-KO mice are sterile mainly due to OAT and further identify a Chinese infertile man carrying a homozygous nonsense variant (c.2962C>T/p.R988X) of CFAP70. Cfap70-truncated mice lacking 5-8 tetratricopeptide repeats (TPRs) mimic the patient's symptoms. CFAP70 is required for the biogenesis of spermatid flagella partially by regulating the expression of OAT-associated proteins (e.g., QRICH2), assisting the cytoplasmic preassembly of the calmodulin- and radial spoke-associated complex (CSC), and controlling the manchette localization of axoneme-related proteins. Moreover, we suggest that CFAP70-associated male infertility could be overcome by intracytoplasmic sperm injection (ICSI) treatment. Overall, we demonstrate that CFAP70 is necessary to assemble spermatid flagella and that CFAP70 gene could be used as a diagnostic target for male infertility with OAT in the clinic. This study was supported by the National Key Research and Development Project (2019YFA0802101 to S.C), Open Fund of Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education (to S.C), Central Government to Guide Local Scientific and Technological Development (ZY21195023 to B.W), and Basic Research Projects of Central Scientific Research Institutes (to B.W).

P-026 Effect of Microsurgical Varicocele Ligation in Patients with Isolated Oligozoospermia

Abstract Study question Is varicocelectomy effective in improving the semen quality of patients with isolated oligozoospermia (IO)? Summary answer Varicocelectomy is a valid option for infertile men with clinical varicocele and documented IO considering the significant improvement in semen concentration. What is known already Varicocele is the leading correctable cause of male factor infertility and its surgical treatment has been associated with sound improvement in semen quality and fertility potential. While varicocelectomy is clearly indicated in men with abnormal semen parameters, its effect on men with isolated abnormalities is less commonly assessed. Study design, size, duration The charts of 1521 patients who underwent microsurgical subinguinal varicocelectomy for clinically palpable varicocele between 2011-2021 were retrospectively reviewed. Infertile patients with IO were included in the study group, while data from patients with oligoasthenoteratozoospermia (OAT) were utilized for comparison. Participants/materials, setting, methods Men with azoospermia, a history of genitourinary infection, and those utilizing peri-operative fertility medications were excluded. The collected data included patient's demographics, varicocele grade and veins’ sizes, and their semen (semen analysis, WHO 2010; sperm DNA fragmentation, Halosperm) and hormone parameters before and up to 6 months after varicocelectomy. Data were analyzed using Wilcoxon Signed Ranks test and chi-squared tests. A p value <0.05 was considered significant. Main results and the role of chance A total of 96 patients with IO and 123 patients with OAT were included in the study. Patients with IO had a mean age of 32.5 ± 7 years, and an average testis volume of 15.6ml. The varicocele was of grades 2 and 3 in 58% and 38% of patients. Among the IO group, a significant increase in sperm concentration was identified postoperatively (p = 0.01). Surprisingly, results revealed a significant decrease in sperm total motility, however, the postoperative median was still within the normal range (45.5%). No significant changes were observed in other semen or hormone parameters. When a comparison was made with the OAT group, 83% of patients with IO had an improvement in sperm concentration compared to 63.9% of patients in OAT group following varicocelectomy (P = 0.044). However, a higher percentage of patients showed an improvement in total motility among the OAT group (67.6%) in comparison to the IO group (42.9%) (p = 0.04). Limitations, reasons for caution Results were obtained from a relatively small sample size. However, varicocele treatment is not necessarily considered as the first treatment option in men with mild or isolated derangements in semen quality. Wider implications of the findings Results of this study shed the light on the effect of varicocele treatment in men with isolated oligozoospermia and hence may be beneficial for patient counselling in the clinic. Trial registration number not applicable

P-016 WHO 2021-based comprehensive appraisal of sperm factor parameters’ association with embryological and clinical outcomes. A single center study of 4013 PGT-A cycles

Abstract Study question What is the impact of sperm parameters and paternal age on all embryological and clinical outcomes during ICSI-cycles with aneuploidy testing? Summary answer Reduced basal/post swim-up motility and patients with concentration+morphology+motility <5th-percentile (based on WHO-2021) are associated with poorer embryological outcomes and cumulative-live-birth-rate per concluded PGT-A cycle. What is known already Previous studies reported an association between oligoasthenoteratozoospermia (OAT), obstructive azoospermia (OA) and non-obstructive azoospermia (NOA) and poorer fertilization/blastulation rates, but no impact on euploidy rates at the blastocyst stage. Similarly, the clinical outcomes were mostly independent from sperm characteristics when euploid blastocysts are transferred. The data about paternal age effect are controversial, varying between absent and severe embryological/clinical impact. Moreover, little is known about the association between each semen analysis parameters and embryological/clinical outcomes. Lastly, most of the evidence to date was based on WHO 2010 criteria, recently updated by WHO 2021, and did not mention cumulative-live-birth-rates (CLBR) per cycle. Study design, size, duration Retrospective study at a single private center involving 4013 ICSI+PGT-A cycles with own-oocytes conducted by 3101 couples (2013-2021). The primary embryological outcome was euploid-blastocyst-rate (EBR) per cohort of inseminated oocytes. The primary clinical outcome was CLBR per concluded cycle (i.e., LB achieved or no transferable/all transferred blastocysts). Intermediate embryological/clinical outcomes were also tested. All parameters were analyzed as continuous variables. For some analyses we categorized paternal age (<38/38-44/>44 years) and sperm factor (WHO-2021 parameters<5th percentile). Participants/materials, setting, methods GnRH-antagonist ovarian-stimulation, ICSI, trophectoderm biopsy without zona-pellucida drilling in day3, qPCR/NGS-based analysis to report non-mosaic aneuploidies (segmental aneuploidies reported from 2017 onwards; N = 1991 cycles) and vitrified-warmed euploid single-blastocyst-transfers were conducted. Semen analysis (volume, concentration, total sperm per ejaculate, basal/post swim-up motility, morphology), sperm characteristics (ejaculated/FNA/TESE; fresh/frozen), DNA-fragmentation-index (DFI, outlined via Tunel-test; N = 188 cycles), paternal BMI and age were investigated for their association with embryological/clinical outcomes adjusted for confounders via linear/logistic regressions. Main results and the role of chance Maternal and paternal age were 38.9±3.2(range:23-45) and 41.9±5.7(25-72) years, 10±6.3(1-44) cumulus-oocyte-complexes were retrieved and 7.3±4.6(1-32) metaphase-II oocytes inseminated. Cycles showing all parameters >5th-percentile were 47.1%(N = 1890), concentration<5th-percentile were 3.7%(N = 149), motility<5th-percentile were 3.9%(N = 155), morphology<5th-percentile were 10.1%(N = 405), concentration+motility<5th-percentile were 1.7%(N = 70), concentration+morphology<5th-percentile were 6.2%(N = 248), motility+morphology<5th-percentile were 5.0%(N = 70), concentration+motility+morphology<5th-percentile were 19.9%(N = 797), OA and NOA were 1.4%(N = 56) and 1.0%(N = 41), respectively. The only confounder upon EBR per cohort of metaphase-II oocytes was maternal age. Only basal/post swim-up motility was associated with this outcome. When categorized, only concentration+morphology<5th-percentile (-2.7%,95%CI -5.1 to -0.3%, adjusted-p=0.03), concentration+morphology+motility<5th-percentile (-4.0%,95%CI -5.5 to -2.6%, adjusted-p<0.01), OA (-5.5%,95%CI -10.3 to -0.7%, adjusted-p=0.03) and NOA (-5.8%,95%CI -11.4 to -0.1%, adjusted-p=0.05) showed significantly poorer results. Maternal age and number of metaphase-II oocytes were the confounders upon the chance to obtain ≥1 euploid blastocyst and ≥1 LB among concluded cycles. Only basal/post swim-up motility was associated with this outcome. When categorized, only concentration+morphology+motility<5th-percentile showed significantly lower chances (multivariate-OR:0.74,95%CI 0.61-0.90, adjusted-p<0.01 and multivariate-OR:0.74,95%CI 0.59-0.92, adjusted-p<0.01). No association was reported between semen parameters/sperm factor categories and 1PN/³3PN rates, day5-7 blastocyst-rate, morphological quality, outcomes per euploid transfer. Paternal age categories were associated with day5-blastocyst (N = 1131/3308,34.2%, N = 1179/3644,32.4%, and N = 919/3127,29.4%) and AA-blastocyst rates (N = 1732/3308,52.4%, N = 1815/3644,49.8%, and N = 1387/3127,44.4%) in men <38/38-44/>44 years, respectively (p < 0.01). Limitations, reasons for caution Some confounders were unbalanced among the study groups but accounted for in linear/logistic regressions. 9% of the cycles were not concluded by the time of abstract drafting. The sample size in the groups of surgically-retrieved sperm is limited, in part because NOA patients due to genetic causes were not included. Wider implications of the findings By comprehensively accounting for sperm factor characteristics, this report provides reproductive professionals with useful figures to counsel infertile couples about their chance of success during IVF. These estimates are useful for the decision-making process regarding the most effective clinical strategies to apply. Further studies including more NOA/OA patients are warranted. Trial registration number not applicable

Clinical Pregnancy Is Not Associated with Sperm Quality in POSEIDON Group 1 and 2 Patients

This study is aimed at establishing the effects of varying sperm quality on IVF-ICSI/IMSI outcomes in unexpected poor ovarian responder subjects of POSEIDON groups 1 and 2. In the present study, 1,263 couples with female partners who fulfilled the POSEIDON group 1 and 2 criteria were recruited. All couples underwent ICSI or IMSI at Morula IVF Jakarta Clinic, Indonesia. Patients were subsequently classified into six groups, according to semen conditions of the respective male partners: (1) normozoospermic, (2) teratozoospermia, (3) oligoasthenoteratozoospermia (OAT), (4) asthenozoospermia, (5) severe OAT, and (6) cryptozoospermia. Laboratory and clinical outcomes of the IVF-ICSI/IMSI program were then evaluated. Early and late embryonic development parameters including the number of fertilization, cleavage and blastocyst stages, and blastocyst quality differed significantly among the different sperm quality groups ( p < 0.05 ). No difference was observed in the number of embryo transfers and clinical pregnancy among the studied groups ( p > 0.05 ). Our study has demonstrated the effect of sperm quality on embryo development at the early and later stages; however, the clinical pregnancy was not impaired in the unexpected poor responders of POSEIDON groups 1 and 2.

The Effect of L-carnitine supplement on seminal fluid parameters in males with infertility

Background: Male infertility is a significant problem affecting 7.5% of the male population. Approximately 60% of these cases are idiopathic and related to sperm dysfunctions such as oligo-astheno-teratozoospermia (OAT).Aim: The aim of this study was to verify the effect of L-carnitine on sperm parameters in patients who presented with infertility.Patients and Methods: The clinical trial study conducted on a total 142 men but 8 patients with varicocele were excluded. So this study was conducted on the remainder 134 patients presenting with infertility due to idiopathic oligo-astheno-zoospermia (mean age± SD: 30.6 ± 6.07), who didn't use L-carnitine previously. Sample divided into 2 groupd (70 patients treated with L carnitine and 64 with placebo). L-carnitine was prescribed orally at a daily dose of 2 gm/day for 3 months. Before onset of drug intake and after the ending of the L-carnitine treatment, semen analysis was performed. Results: Seminal fluid analysis has been done before treatment and then 3 months after treatment. The mean values of sperm count, total motility and normal morphology of astheno-spermic and oligo-astheno-teratospermic were found significantly at (p<0.05). There is a trend toward an improvement in seminal fluid parameters was noted when comparing baseline with 3 months points in both the placebo and the carnitine arm.The results of the present study clearly demonstrated that L-carnitine at a daily dose of 2 gm/day for a treatment period of 3 months can improve sperm concentration, sperm count, percentage of actively motile sperm, and progressive motile sperm count among men with idiopathic oligo- and/or astheno-zoospermia.Conclusion: The present study concluded that L-carnitine at a daily dose of 2 gm/day for a treatment period of 3 months had positive effect and can be treat infertility.

Homozygous frameshift variant in POC1B causes male infertility with oligoasthenoteratozoospermia in human and mice.

Several different mutations in the proteome of centriole 1 centriolar protein B (POC1B) have been linked to cone dystrophy or cone-rod dystrophy (CORD). However, mutations in POC1B that are associated with both CORD and oligoasthenoteratozoospermia (OAT) have not been reported previously. Here, whole-exome sequencing was performed to identify a homozygous frameshift variant (c.151delG) in POC1B in the two brothers who had been diagnosed with both CORD and OAT from a consanguineous family. Transcript and protein analyses of biological samples from the two patients carrying the variant showed that POC1B protein is lost in sperm cells. The system CRISPR/Cas9 was utilized to create poc1bc.151delG/c.151delG knock-in (KI) mice. Notably, poc1bc.151delG/c.151delG KI male mice presented with OAT phenotype. Additionally, testicular histology and transmission electron microscopy analysis of the testes and sperm indicated that Poc1b mutation results in abnormal formation of acrosomes and flagella. Collectively, according to our experimental data on human volunteers and animal models, biallelic mutations in POC1B can cause OAT and CORD in mice and humans.

Seminal Calbindin 2 in Infertile Men With Varicocele: A Prospective Comparative Study

The present study compared seminal calbindin 2 (CALB 2) levels and semen parameters in men with and without varicocele. CALB 2 is also known as calretinin and 29 kDa calbindin. The study was a case-control study conducted from April (2021) to March (2022) in the andrology department at Beni-Suef University hospital. The study included four matched groups: group (I) were controls (fertile normozoospermic men without varicocele) (n=24). Group (II) were fertile normozoospermic men with varicocele (n=24). Group (III) were infertile oligoasthenoteratozoospermia (OAT) men without varicocele (n=24). Group (IV) were infertile OAT men with varicocele (n=24). The lowest levels of seminal CALB 2 were found in patients with severe oligozoospermia which showed a statistically significant difference when compared to seminal CALB 2 in patients with normal, mildly low, or moderately low sperm counts. There were significant negative correlations between sperm concentration, sperm motility and percentage of normal sperm forms and seminal CALB 2. Seminal plasma CALB 2 may play a role in the negative impact of varicocele on the semen parameters especially sperm concentration, sperm motility and percentage of sperm normal forms. Future studies are needed to verify these findings.

TENT5D disruption causes oligoasthenoteratozoospermia and male infertility.

Oligoasthenoteratozoospermia (OAT) is one of the most complex aggregators of male gametic problems. However, the genetic etiology of OAT is still largely unknown. To reveal the new genetic factors responsible for male infertility owning to OAT and reveal the outcomes of the affected patients from intracytoplasmic sperm injection (ICSI). Two infertile men with typical OAT were recruited in 2018 and retrospected a cohort that included 47 patients with OAT from 2013 to 2021. Fifty healthy men with proven fertility served as control subjects. To identify the novel pathogenic variants, whole-exome sequencing and Sanger sequencing were used. In silico analysis revealed the affecting of the variants. Field emission scanning electron microscopy was employed to observe the morphological defects of the spermatozoa. Immunofluorescence was used to analyze the expression and localization of the related protein. CRISPR/Cas9 was used to generate the mouse model. ICSI was used as a treatment for the patients and to assess the effects of the pathogenic variant on fertilization and embryo development. We identified a loss-of-function mutation NM_001170574.2:c.823G>T (p.Glu275*) in X-linked TENT5D from two patients with OAT. This variant is highly deleterious and has not been found in the human population. The count of patients' spermatozoa is dramatically decreased and displays multiple morphologic abnormalities with poor motility. Tent5d knockout mice are infertile and exhibit parallel defects. ICSI could rescue the infertility of the Tent5d knockout male mice. Moreover, the proband was treated with ICSI and achieved a successful pregnancy outcome for the first time. Subsequent mutation screening identified no TENT5D mutations among 47 additional patients with OAT and 50 control subjects. Mutation in TENT5D results in OAT and male infertility, and this terrible situation could be rescued by ICSI.

A novel loss-of-function variant in PNLDC1 inducing oligo-astheno-teratozoospermia and male infertility.

Male infertility is a major reproductive disorder, which is clinically characterized by highly heterogeneous phenotypes of abnormal sperm count or quality. To date, five male patients with biallelic loss-of-function (LOF) variants of PARN-like ribonuclease domain-containing exonuclease 1 ( PNLDC1 ) have been reported to experience infertility with nonobstructive azoospermia. The aim of this study was to identify the genetic cause of male infertility with oligo-astheno-teratozoospermia (OAT) in a patient from a Chinese Han family. Whole-exome and Sanger sequencing analyses identified a homozygous LOF variant (NM_173516.2, c.142C>T, p.Gln48Ter) in PNLDC1 . Hematoxylin and eosin staining revealed that the spermatozoa of the patient with OAT had an irregular head phenotype, including microcephaly, head tapering, and globozoospermia. Consistently, peanut agglutinin staining of the spermatozoa revealed a complete or partial loss of the acrosome. Furthermore, the disomy rate of chromosomes in the patient's spermatozoa was significantly increased compared with that of a fertile control sample. We reported an LOF variant of the PNLDC1 gene responsible for OAT.

“SINGLE CASE STUDY - EFFICACY OF SHATAVARYADI CHURNA IN SHUKRADUSTI AND SHUKRAKSHAYA WITH SPECIAL REFERENCE TO OLIGOASTHANOTARATOZOOPERMIA.”

The need to have children is of great priority in families hence treatment of infertility has become a global concern. The couple not able to reproduce, experiences the feeling of frustration and disappointment which increase oxidative stress level thereby worsening the condition. Rutu, Kshetra, Ambu and Bija these are the four things which are necessary for the normal pregnancy. Bija means both male and female fertility factors i.e., Sukra and Artava respectively. In Ayurvedic classics eight types of Sukradosha are enumerated. This classification is based upon two methods,first one is based upon involvement of Doshas of shukra,Tanu,Alpa, Ruksh, Phenil etc.and next is based upon involvement of Doshas in shukra e.g. Vataj, Pittaj,shleshmaja, shukradusti etc. Shukra is described as Seventh dhatu in our classics. Among the Seven Dhatus, Shukra Dhatu is considered as important one. Shuddha Shukra is one of the most necessary factors for the healthy progeny. Shukradushti caused by vitiation of Vata pitta dosha and becomes diminished state of quality and quantity of Shukra dathu. Oligoasthenoteratozoospermia (OAT) is a condition in which the semen sample has Oligozoospermia, which is low sperm count, Asthenozoospermia, which is poor motility and teratozoospermia, which is abnormal morphology of sperm. Nowadays Oligoasthenoteratozoospermia is the most common condition in both developing and developed countries. Here explained the successful case study of shukradushti of using ayurvedic formulation.

The association between reactive oxygen species and α-tocopherol treatment in a sample of infertile Iraq male

Male infertility estimated about 20-70% of couples or >30 million men worldwide. The goal of this study was to elucidate the interrelations between oxidative stress (O.S) in seminal fluid and antioxidant inducing disruption of spermatogenesis. Twenty four infertile patients aged (23-41) years were involved in this study. Which were received α- tocopherol (vitamin E). This group (vit E group) was sub classified according to the WHO criteria (2010) into three different subgroups: oligoasthenoteratozoospermia (OAT) Asthenoteratozoo- spermia (A.T), and Asthenozoospermia (Astheno.). The control group consist of samples obtained from healthy donors of proven fertility (n=23). The main parameters were determined in seminal fluid of infertile patients and healthy men are the sperm and seminal plasma Malondialdehyde (MDA) concentration, and vitamin E concentration in seminal plasma. The results showed that, there was a high significant decrease (p≤0.001) in sperm parameters (concentration, progressive motility and normal morphology), and vitamin E concentration in infertile group compared with that fertile group.After analyzing the statistically difference in the different measured parameters between the vit E group after treatment, in comparison with that of before treatment; the following was observed A high significant increase (p≤0.001) were found in progressive motility, sperm [MDA] (MDAp), vitamin E concentration, and significant increase (P ≤0.05) in the sperm concentration. From all of these observations, it can be concluded that O.S contributes most likely to sperm damage and may be responsible for poor seminal fluid characteristic of the infertile patients involved in the present study. Antioxidants α-tocopherol (vitamin E) plays an important role in the improvement of seminal fluid parameters.

Impact of antioxidants in improving semen parameters like count, motility and DNA fragmentation in sub-fertile males: a randomized, double-blind, placebo-controlled clinical trial.

Clinical Trials Registry-India Identifier: CTRI/2020/12/029590.

The effect of pentoxifylline and calcium ionophore treatment on sperm cell biology in oligoasthenoteratozoospermia samples.

The objective of this study was to assess the effects of pentoxifylline (PTX) and Ca2+ ionophore (CI) A12387 treatment on some biological characteristics of sperm cells in oligoasthenoteratozoospermia (OAT) patients. After processing, each sample was divided into four groups: 1, control; 2, exposed to 3.6 mM PTX; 3, exposed to 5 μm calcium ionophore (CI); and 4, exposed to both PTX and CI; 30 min at 37°C. Sperm motility was measured before and after preparation. Acrosome reaction (AR), status of sperm vacuoles, mitochondrial membrane potential (MMP) and DNA fragmentation were assessed using PSA-FITC staining, motile sperm organelle morphology examination (MSOME), JC-1 staining and sperm chromatin dispersion (CSD) test, respectively. Treatment with PTX and CI led to increased and decreased sperm motility, respectively (P < 0.05). Furthermore, vacuole status and rates of sperm DNA fragmentation were not significantly different among groups (P > 0.05). Moreover, the data showed that the rates of AR and disrupted MMP were significantly different between groups (P < 0.05). In conclusion, in vitro application of PTX not only did not have any adverse effects on sperm cell biology characteristics, but also can rectify the harmful effect of CI.