Haitham Elbardisi

A multicenter study to evaluate oxidative stress by oxidation–reduction potential, a reliable and reproducible method

Seminal oxidative stress (OS) is well‐known to affect male fertility status. The discrepancy in OS measurement has hindered its clinical use as a quality indicator for semen. Some tests measured single markers of oxidants or reductants, leading to lack of standardization of results. Oxidation–reduction potential (ORP) is a better representative for OS as it provides an overall measure of the activity of both oxidants and reductants. ORP assessment by MiOXSYS has been introduced as a measure of OS with high specificity in differentiating fertile from infertile semen samples. This is a retrospective study comparing data from semen analysis and ORP measurements between two andrology laboratories in the USA and Qatar over a period of 12 months. The same protocol was followed by both laboratories. The USA dataset contained 194 patients and 51 fertile donors, while the Qatar dataset contained 400 patients and 50 fertile donors. In both datasets and in the combined dataset, the infertile group had significantly lower sperm concentration, total and progressive motility, and normal morphology as well as higher ORP levels compared to fertile men (p < 0.05). When comparing data from both centers, the infertile group showed significant difference between both datasets regarding progressive motility and morphology (p < 0.001). Also, the percentage of patients with abnormal semen volume, sperm count, total and progressive motility were significantly different between both datasets (p < 0.05). ORP levels showed no significant difference between both datasets (p < 0.08). ROC analysis indicated that ORP cutoff value of 1.42 mV/106/mL in the USA group, Qatar group, and combined dataset can accurately differentiate fertile from infertile semen groups. Although other semen parameters showed significant differences between the two centers, ORP remained consistent in both datasets individually or in combined data. This proves its reproducibility and reliability.

Varicocele among infertile men in Qatar

Objective of this retrospective study was to assess the presence and clinical grade of varicocele among Qatari and non‐Qatari men evaluated for infertility. Diagnosis of varicocele was performed clinically and confirmed via colour Doppler ultrasonography. A total of 455 infertile male patients (mean age 36.3 ± 7.6 years) were divided into either Qatari (n = 91, mean age 37.3 ± 9.1 years) or non‐Qatari (n = 364, mean age 36.0 ± 7.1 years) groups. Among all patients, 43.1% (n = 196) were confirmed to have varicocele, of which 40 were Qatari and 156 non‐Qatari. Among all patients, 171 (37.6%) presented with left‐sided varicocele and 25 (5.5%) with bilateral varicocele. Of the 196 patients with varicocele, grade I was given to 40 (20.4%), grade II to 68 (34.7%) and grade III to 88 (44.9%). Grade II and III varicocele were seen significantly more frequently than grade I among all patients and non‐Qatari patients (p < .05). Grade II varicocele was seen more frequently than grades I or III among Qatari patients, but difference was not significant. Grade III was seen significantly more frequently than grade I among patients with secondary infertility (p < .05). Varicocele is an important health issue in Qatar among both Qatari and non‐Qatari men.

Premature ejaculation in type II diabetes mellitus patients: association with glycemic control.

Background Premature ejaculation (PE) is a highly prevalent sexual dysfunction among patients with diabetes mellitus (DM). Despite this, the underlying mechanism of this association is poorly understood. In this study, we aimed to investigate the prevalence of PE in a group of patients with DM and explore possible associations linking both conditions together. Methods This was a prospective study of subjects recruited with advertisement pamphlets and whose sexual function was assessed using the international index of erectile function-5 (IIEF-5) and the Arabic index of premature ejaculation (AIPE) questionnaires together with stopwatch measured intravaginal ejaculatory latency time (ELT). Participants were divided into two groups; group A subjects had DM and group B were healthy adult males. Results A total of 488 subjects were recruited. Group A included 199 (40.8%) subjects, while group B included 289 (59.2%). The prevalence of PE and ED was significantly higher in group A subjects (P<0.001). Mean ELT ± standard deviation (SD) was 3.6±2.7 in group A versus 4.3±2.8 in group B (P<0.014). Diabetic patients with erectile dysfunction (ED) showed a significantly higher incidence of PE with significantly shorter ELT. Conclusions PE is more prevalent in diabetic patients. DM is a multi-systemic disorder with complications that could help explain the pathophysiology of PE.

Point-of-care whole-exome sequencing of idiopathic male infertility

PurposeNonobstructive azoospermia (NOA) affects 1% of the male population; however, despite state-of-the-art clinical assessment, for most patients the cause is unknown. We capitalized on an analysis of multiplex families in the Middle East to identify highly penetrant genetic causes.MethodsWe used whole-exome sequencing (WES) in 8 consanguineous families and combined newly discovered genes with previously reported ones to create a NOA gene panel, which was used to identify additional variants in 75 unrelated idiopathic NOA subjects and 74 fertile controls.ResultsIn five of eight families, we identified rare deleterious recessive variants in CCDC155, NANOS2, SPO11, TEX14, and WNK3 segregating with disease. These genes, which are novel to human NOA, have remarkable testis-specific expression, and murine functional evidence supports roles for them in spermatogenesis. Among 75 unrelated NOA subjects, we identified 4 (~5.3%) with additional recessive variants in these newly discovered genes and 6 with deleterious variants in previously reported NOA genes, yielding an overall genetic etiology for 13.3% subjects versus 0 fertile controls (p = 0.001).ConclusionNOA affects millions of men, many of whom remain idiopathic despite extensive laboratory evaluation. The genetic etiology for a substantial fraction of these patients (>50% familial and >10% sporadic) may be discovered by WES at the point of care.

Does the number of veins ligated during microsurgical subinguinal varicocelectomy impact improvement in pain post-surgery?

Background We examined the impact of the number of veins ligated during varicocelectomy on post-surgical improvement of pain in a group of men presenting with clinical varicocele and pain as an indication for surgery. Methods This is a retrospective study of patients presenting with clinical left varicocele to the male infertility unit at a teaching hospital in Qatar. Files of all patients who underwent sub-inguinal microsurgical varicocelectomy were retrieved and categorized into three groups indicating the number of spermatic veins ligated during varicocelectomy. The presence of pain was assessed during pre- and post-operation (at 3 and 6 months). Statistical analysis was performed using Kruskal-Wallis test (K) and Chi-square test (C). Results Out of 675 records, 207 (30.7%) patients did left varicocelectomy for pain. Their mean age was 35.3±9.2 years. Pain was assessed in 106/207 (51.2%) patients post operatively, of whom 89 (84%) reported complete resolution of symptoms. This improvement was maintained irrespective of the number of veins ligated during surgery (<5 veins: 90.0%, 5–10 veins: 81.5%, and >10 veins: 85.7%). Conclusions Microsurgical subinguinal varicocelectomy is a valid treatment method for patients with a symptomatic clinical varicocele. While a significant post-surgical (at 6 months) reduction of pain was detected, the number of veins ligated intraoperatively was not predictive of post-operative improvement of pain in this study population.

Outcome of microsurgical testicular sperm extraction in familial idiopathic nonobstructive azoospermia

The aim of the study was to evaluate the sperm retrieval rate by microsurgical testicular sperm extraction (TESE) in familial idiopathic nonobstructive azoospermia (NOA). One hundred and nineteen patients with idiopathic NOA who underwent microsurgical TESE over the past 5 years were included. Patients were then divided into two groups; Group ‘A’ with familial idiopathic NOA (11 families with two brothers in each family, 22 patients) and Group ‘B’ with nonfamilial idiopathic NOA (97 patients). Clinical data as well as data of microsurgical TESE were recorded. In Group ‘A’, the sperm retrieval rate was 9.1% (2/22 patients) compared to 45.4% in Group ‘B’ (44/97 patients) (P ≤ 0.05). The two patients in Group ‘A’ with successful sperm retrieval belonged to one family. The histopathological diagnosis was the same in the brothers in each family. It can be concluded that the testicular sperm retrieval rate in familial idiopathic NOA is significantly lower than in nonfamilial idiopathic NOA.

Sperm Retrieval in Ejaculatory Dysfunction

Ejaculatory dysfunction or the inefficient ejaculation of semen at the moment of sexual climax is the most prevalent form of male sexual dysfunction. It is a well-recognized consequence to a variety of clinical conditions and medical and surgical therapies. Four different types of ejaculatory dysfunctions occur; they include premature ejaculation, delayed ejaculation, retrograde ejaculation, and anejaculation. A thorough understanding of physiology and pathophysiology of ejaculation is necessary for effective management. A stepwise approach to therapy is generally favored which includes behavioral therapy, pharmacotherapy, penile vibratory stimulation, electroejaculation, and surgical sperm retrieval.

Geographical differences in semen characteristics of 13 892 infertile men

Abstract Objective: To assess the relationship between geographical differences and all semen parameters, across 13,892 infertile men of 84 diverse nationalities, recruited at a specialised tertiary hospital that represents the main healthcare provider in Qatar. Male infertility is an important and global public health problem. Despite this, there is a significant scarcity of epidemiological male infertility and semen analysis research in the Middle East and North Africa (MENA) region, as well as geographical comparisons with other parts of the world. Patients and methods: Retrospective study of semen findings of 13 892 infertile men assessed at the Male Infertility Unit at Hamad Medical Corporation, in Qatar between January 2012 and August 2015. Based on country of origin, patients were categorised into those from the MENA region (n = 8799) and non-MENA patients (n = 5093). The two groups were compared across demographic features and semen characteristics: age, sperm volume, sperm total motility, sperm progressive motility (PMot), abnormal sperm forms (ABF), and sperm DNA fragmentation (SDF). Results: The whole sample’s mean (SD) age was 35.7 (0.7) years, sperm concentration was 32.3 (0.25) × 106 sperm/mL, total motility was 45.4 (0.2)%, sperm PMot was 25.1 (0.2)%, and ABF was 79.9 (0.2)%. Overall, 841 patients had azoospermia (6.05%), 3231 had oligospermia (23.3%), 4239 had asthenospermia (30.5%) and 6772 had teratospermia (48.7%). SDF (1050 patients) was abnormal in 333 patients (31.7%). MENA patients were significantly younger than their non-MENA counterparts and had a greater semen volume. Non-MENA patients had significantly higher sperm counts, total motility and PMot, and lower ABF. SDF showed no statistical difference between the two groups. MENA patients had significantly higher prevalence of oligospermia, asthenospermia, and teratospermia; and lower prevalence of normal sperm concentration, normal motility, and normal morphology. Throughout the 4 years of the study, MENA patients constantly had significantly lower sperm counts; generally lower sperm total motility percentage and generally lower quality sperm morphology. We compared patients by age (≤40 and >40 years): in the patients aged ≤40 years, the same results as for the overall study were reproduced; in the >40-years group, the same results were reproduced with the exception of morphology, which was not significantly different between the MENA and non-MENA patients. Conclusion: Semen quality is generally lower in male infertility patients from the MENA region compared to non-MENA regions.

Oxidation–reduction potential and sperm DNA fragmentation, and their associations with sperm morphological anomalies amongst fertile and infertile men

Abstract Objective: To assess seminal oxidation–reduction potential (ORP) and sperm DNA fragmentation (SDF) in male infertility and their relationships with sperm morphology in fertile and infertile men. Patients and methods: Prospective case-control study comparing the findings of infertile men (n = 1168) to those of men with confirmed fertility (n = 100) regarding demographics and semen characteristics (conventional and advanced semen tests). Spearman rank correlation assessed the correlation between ORP, SDF, and different morphological indices. Means of ORP and SDF were assessed in variable levels of normal sperm morphology amongst all participants. Results: Infertile patients had a significantly lower mean sperm count (32.7 vs 58.7 × 106 sperm/mL), total motility (50.1% vs 60.4%), and normal morphology (5.7% vs 9.9%). Conversely, infertile patients had significantly higher mean head defects (54% vs 48%), and higher ORP and SDF values than fertile controls. ORP and SDF showed significant positive correlations and significant negative correlations with sperm head defects and normal morphology in infertile patients, respectively. ORP and SDF were significantly inversely associated with the level of normal sperm morphology. Using receiver operating characteristic curve analysis, ORP and SDF threshold values of 1.73 mV/106 sperm/mL and 25.5%, respectively, were associated with 76% and 56% sensitivity and 72% and 72.2% specificity, respectively, in differentiating <4% from ≥4% normal morphology. Conclusion: A direct inverse relationship exists between seminal ORP and SDF with various levels of normal sperm morphology. Using ORP and SDF measures in conjunction with standard semen morphology analysis could validate the result of the fertility status of patients.

Clinical implication of DNA fragmentation in male infertility

Recently, sperm DNA fragmentation (SDF) has been recognized as an important marker of sperm quality that can be used as a predictive factor for fertility in men. Although some controversies exist regarding the role of SDF in infertility, the fact remains that semen from infertile men possess a higher level of SDF than fertile controls (1,2). Elevated SDF may not only contribute to higher rates of failed fertilizations and spontaneous pregnancy loss, but it can also affect assisted reproductive techniques (ART) outcomes in terms of oocyte fertilization, embryo quality, clinical pregnancy and live birth rate. However, controversy still exists regarding the association between SDF and the outcomes of intracytoplasmic sperm injection (ICSI) (3,4).