The Association of HLA-G Gene Polymorphism and Its Soluble Form With Male Infertility

Successful reproduction depends on many factors. Male factors contribute to infertility in approximately 50% of couples who fail to conceive. Seminal plasma consists of secretions from different accessory glands containing a mixture of various cytokines, chemokines, and growth factors, which together can induce a local immune response that might impact on a male’s as well as a female’s fertility. Human leukocyte antigen (HLA)-G expression has been suggested as an immunomodulatory molecule that influences pregnancy outcome. The HLA-G gene encodes either membrane-bound or/and soluble proteins. The aim of this study was the evaluation of HLA-G polymorphisms and their impact on soluble HLA-G (sHLA-G) production. We tested the HLA-G polymorphism in three positions: rs1632947: c.-964G>A; rs1233334: c.-725G>C/T in the promoter region; rs371194629: c.∗65_∗66insATTTGTTCATGCCT in the 3′ untranslated region. We tested two cohorts of men: 663 who participated in in vitro fertilization (test material was blood or sperm), and 320 fertile controls who possessed children born after natural conception (test material was blood). Since 50% of men visiting assisted reproductive clinics have abnormal semen parameters, we wondered if men with normal sperm parameters differ from those with abnormal parameters in terms of HLA-G polymorphism and secretion of sHLA-G into semen. We found that certain rs1632947-rs1233334-rs371194629 HLA-G haplotypes and diplotypes were associated with male infertility, while others were protective. Normozoospermic men with the A-C-del haplotype and A-C-del/A-C-del diplotype secreted the most sHLA-G into semen (574.1 IU/mL and 1047.0 IU/mL, respectively), while those with the G-C-ins haplotype and G-C-ins/G-C-ins diplotype – the least (80.8 IU/mL and 75.7 IU/mL, respectively). Men with the remaining haplotypes/diplotypes secreted sHLA-G at an intermediate level. However, only in one haplotype, namely G-C-ins, did we observe strong significant differences in the concentration of sHLA-G in the semen of men with teratozoospermia compared to men with normal sperm parameters (p = 0.009). In conclusion, fertile men differ in the profile of HLA-G polymorphism from men participating in IVF. Among all HLA-G haplotypes, the most unfavorable for male fertility is the G-C-ins haplotype, which determines the secretion of the lowest concentration of the soluble HLA-G molecule. This haplotype may reduce sperm parameters.

Comparison of ICSI and Conventional IVF in Non-Male Factor Patients with Less Than Four Oocytes

Background: We aimed to analyse our clinical results for a particular subgroup of patients with poor ovarian response (POR) in order to clarify if lower number of oocytes is a drawback for proceeding to C-IVFMaterials and methods: In this retrospective study, patient files of all couples (#1733) who underwent oocyte retrieval between January 2017 and December 2019 were reviewed and 191 cases diagnosed with non-male factor infertility in which ≤3 cumulus-oocyte-complexes available for fertilisation were analysed. Exclusion criteria were: woman age>42, patients with a history of previous ART trial, prenatal genetic testing cycles and couples undergoing total cryopreservation for any indication. Three groups were constructed depending on the method of fertilisation and on semen quality as follows: IVF non-male factor (Group 1,n=77); ICSI non-male factor (Group 2, n=65); ICSI male factor- ICSI/MF n=49 according to WHO reference values. Main outcome parameters were: fertilisation rate, implantation rate and live birth rate. Results: Fertilisation rate per collected COC was significantly higher in group 1 compared to the other two groups (85,68%, 72,58%, 73,33% respectively, p=0,004). FR per inseminated oocyte also tended to be higher in group 1 but not reaching a statistically significant level. Both techniques yielded similar implantation rates (20,42%, 28,49%, 23,33% respectively, p=0,407) and live birth rates (26,8%, 30,6%, 31,1% respectively, p=0.643).Conclusions: In the presence of normal semen parameters, low egg number is not an indication to perform ICSI. The choice of fertilisation method should be based primarily on semen quality, in combination with the patient’s previous history regardless of the ovarian reserve.

Relationship Among Traditional Semen Parameters, Sperm DNA Fragmentation, and Unexplained Recurrent Miscarriage: A Systematic Review and Meta-Analysis

Several studies have explored the relationship among traditional semen parameters, sperm DNA fragmentation (SDF), and unexplained recurrent miscarriage (RM); however, the findings remain controversial. Hence, we conducted a meta-analysis to explore the relationship among traditional semen parameters, SDF, and unexplained RM. Multiple databases, including PubMed, Google Scholar, MEDLINE, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI), were searched to identify relevant publications. From the eligible publications, data were extracted independently by two researchers. A total of 280 publications were identified using the search strategy. According to the inclusion/exclusion criteria, 19 publications were eligible. A total of 1182 couples with unexplained RM and 1231 couples without RM were included in this meta-analysis to assess the relationship among traditional semen parameters, SDF, and unexplained RM. Our results showed that couples with unexplained RM had significantly increased levels of SDF and significantly decreased levels of total motility and progressive motility compared with couples without RM, although significant differences were not observed in the semen volume, sperm concentration, and total sperm count between couples with and without RM. The SDF assay may be considered for inclusion in evaluations of couples with unexplained RM.

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.

Impacts of COVID-19 and SARS-CoV-2 on male reproductive function: a systematic review and meta-analysis protocol

IntroductionCOVID-19 pandemic caused by SARS-CoV-2 has become a global health challenge. SARS-CoV-2 can infect host cells via the ACE2 receptor, which is widely expressed in the corpus cavernosum, testis and male reproductive tract, and participates in erection, spermatogenesis and androgen metabolism. Also, the immune response and persistent fever resulting from COVID-19 may lead to damage of the testicular activity, consequently compromising male fertility.Methods and analysisPubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal database, Chinese Biomedical Databases and Wanfang Data will be systematically searched for observational studies (case–control and cohort) published up to March 2021 in English or in Chinese literature on the impacts of COVID-19 and SARS-CoV-2 on male reproductive function. This protocol will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines and Meta-analysis of Observational Studies in Epidemiology. The primary outcome will be semen parameters, and the additional outcomes will include: (a) detection of SARS-COV-2 in semen, (b) male sexual hormones, (c) sperm DNA fragmentation index, (d) erectile function, (e) evaluation of testis and also the male genital tract. Two reviewers will independently extract data from the included studies based on a predesigned data extraction form. The risk of bias of included studies will be evaluated through the Newcastle-Ottawa Scale for observational studies. Review Manager software V.5.3 will be used for statistical analysis. Q statistic and I² test will be performed to assess the heterogeneity among studies. Sensitivity analysis will be used to explore the robustness of pooled effects. We will use the Grading of Recommendations Assessment, Development and Evaluation system to assess the quality of evidence.Ethics and disseminationEthical approval is not required and results will be published in a peer-reviewed journal.PROSPERO registration numberCRD42021245161.

Curcumin Along With Fe3O4 Nanoparticles Improved Sperm Parameters In Rats With Testicular Ischemia

Background: Ischemic/reperfusion (I/R) in testicular tissue is one reason for the worldwide increase in male infertility. In the present study, we assessed the effects of curcumin and Fe3O4 nanoparticles (NPs) on sperm parameters in rats with I/R damage. Materials and Methods: Forty-eight adult male rats were divided into two groups (n=24 per group): control and torsion/detorsion. The control and torsion/detorsion groups were divided into four subgroups include sham, Fe3O4 NPs, curcumin, and Fe3O4 NPs+curcumin. After the rats were sacrificed, semen was collected from their epididymal tissues to assess sperm viability, motility, concentration, and morphology. Results: Curcumin significantly improved viability, motility, and normal sperm morphology in rats with I/R damage compared to the control group; however, it did not have a significant effect on sperm concentration (P<0.001). Fe3O4 NPs alone decreased all sperm parameters in the control and I/R rats (P<0.001). However, concomitant administration of Fe3O4 nanoparticles with curcumin significantly improved sperm parameters in rats with I/R damage (P<0.001). Conclusion: The increase in all semen parameters in the experimental groups with concomitant use of Fe3O4 NPs plus curcumin indicated that green synthesis of NPs could be recommended for future clinical studies.

Semen parameters in male partners of sub-fertile couples.

Objective: To evaluate the frequency of semen parameters in male partners of in sub-fertile couples. Study Design: Cross-sectional study. Setting: Department of Gynaecology, Bakhtawar Ameen Hospital, Multan. Period: July 2019 to July 2020. Material & Methods: Infertile couples from at least 12 months were selected for study. A team of Gynaecologist, andrologist and endocrinologist assessed the couples. In male partner, general physical examination, endocrine factor, genetic assessment, accessory gland infection and testicular dysfunction were evaluated. Semen sample was sent to laboratory for semen analysis. Results: In a total of 169 sub-fertile couples, the mean age of male and female partner were 37.98±4.54 years and 32.51±3.78 years respectively. Mean duration since marriage was 5.17±4.51 years. Abnormal semen parameters such as azoospermia, oilgo-azoospermia, asthenozoospermia, teratozoospermia and aspermia were noted 21 (12.4%), 26 (15.4%), 48 (28.4%), 18 (10.7%) and 10 (5.9%) subjects respectively. There were 46 (27.2%) subjects with normal semen parameters. Conclusion: Most of the male sub-fertile subjects had asthenozoospermia. More than one fourth of the subjects had normal semen parameters.

Estimation of haemodynamic changes in varicocele testis and results after microsurgical sub-inguinal varicocelectomy

Introduction: Varicocele is among the most frequently encountered, surgically correctable causes of male infertility. Since varicocele is a primary abnormality of testicular vessels, a thorough understanding of haemodynamic changes in the microcirculation of varicocele testis is needed. Objectives: To estimate changes in the microcirculation of varicocele testis and correlate them with symptomatic and semen parameters changes before and after varicocelectomy. Material and methods: This prospective, observational study includes 47 patients of age group 18–40 years who underwent microsurgical varicocelectomy during June 2016 to April 2018 at a tertiary medical institute. Testicular haemodynamic was evaluated using a colour spectral doppler study (PSV-Peak systolic velocity/ESV-End diastolic velocity/RI-Resistive index/PI-Pulsatility index). Semen analysis parameters and testicular blood flow were compared with pre-operative values. Results: RI in the capsular artery of varicocele affected testis, which was 0.61 ± 0.11 (mean ± SD), significantly reduced to 0.56 ± 0.09 (mean ± SD) in post-operative follow-up, indicating improved perfusion. Pre-operative sperm density was noted to be 15.94 ± 7.88 (mean ± SD), which improved to 28.41 ± 10.99, Progressive sperm motility from 33.81 ± 10.88 to 38.32 ± 9.21 and morphology from 36.13 ± 10.68 to 41.43 ± 9.29 on 6-month follow-ups ( p < 0.05). Conclusion: Varicocele testis is associated with altered testicular haemodynamic, which insults spermatogenesis. Microsurgical varicocelectomy with testicular artery and lymphatic preservation leads to correction of this altered haemodynamic state and improves the testicular microcirculation.