Naif Alhathal

Antioxidant therapy in male infertility: fact or fiction?

Infertile men have higher levels of semen reactive oxygen species (ROS) than do fertile men. High levels of semen ROS can cause sperm dysfunction, sperm DNA damage and reduced male reproductive potential. This observation has led clinicians to treat infertile men with antioxidant supplements. The purpose of this article is to discuss the rationale for antioxidant therapy in infertile men and to evaluate the data on the efficacy of dietary and in vitro antioxidant preparations on sperm function and DNA damage. To date, most clinical studies suggest that dietary antioxidant supplements are beneficial in terms of improving sperm function and DNA integrity. However, the exact mechanism of action of dietary antioxidants and the optimal dietary supplement have not been established. Moreover, most of the clinical studies are small and few have evaluated pregnancy rates. A beneficial effect of in vitro antioxidant supplements in protecting spermatozoa from exogenous oxidants has been demonstrated in most studies; however, the effect of these antioxidants in protecting sperm from endogenous ROS, gentle sperm processing and cryopreservation has not been established conclusively.

Is sperm dna damage associated with IVF embryo quality? A systematic review

PurposeSperm DNA damage is common amongst infertile men and may adversely impact natural reproduction, IUI-assisted reproduction and to a lesser degree IVF pregnancy. The objective of this study was to examine the influence of sperm DNA damage on embryo quality and/or development at IVF and ICSI.MethodsWe conducted a systematic review of studies that evaluated sperm DNA damage and embryo development and/or quality after IVF and/or ICSI.ResultsWe identified 28 studies (8 IVF, 12 ICSI and 8 mixed IVF-ICSI studies) that evaluated the relationship between sperm DNA damage and embryo quality. These 28 studies evaluated 3226 treatment cycles (1033 IVF and 873 ICSI, 1320 mixed IVF-ICSI cycles) and demonstrated highly variable characteristics. In 11 of the 28 studies (1/8 IVF, 5/12 ICSI and 5/8 mixed IVF-ICSI studies), sperm DNA damage was associated with poor embryo quality and/or development, whereas the remaining 17 studies showed no relationship between sperm DNA damage and embryo quality and/or development.ConclusionsThis systematic review indicates that the evaluable studies are heterogeneous and that overall, there is no consistent relationship between sperm DNA damage and embryo quality and/or development. The data also suggest that the influence of sperm DNA damage on embryo quality/development may be more significant in ICSI compared to IVF cycles.

Antisperm antibodies are not associated with pregnancy rates after IVF and ICSI: systematic review and meta-analysis

BACKGROUNDnSeveral studies have examined the relationship between direct antisperm antibody (ASA) levels in semen and pregnancy rate after advanced assisted reproductive technologies (ARTs) but the results have been inconsistent. The aim of our study was to further evaluate the relationship between ASA and pregnancy after IVF or ICSI by systematic review and meta-analysis.nnnMETHODSnWe conducted a systematic Medline search of all relevant full papers on direct semen ASA and pregnancy after IVF or ICSI. Three investigators independently reviewed the papers, followed by group discussion to choose the included papers. Meta-analysis was performed to get an odds ratio (OR) for the effect of ASA on pregnancy using IVF or ICSI.nnnRESULTSnThe study identified and analyzed 16 valid studies (10 IVF and 6 ICSI). The study characteristics (including the ASA cutoff values) were heterogeneous. Our meta-analysis revealed that the combined OR for failure to achieve a pregnancy using IVF or ICSI in the presence of positive semen ASA was 1.22 (95% CI: 0.84, 1.77) and 1.00 (95% CI: 0.72, 1.38), respectively. The overall (IVF + ICSI) combined OR was 1.08 (95% CI: 0.85, 1.38).nnnCONCLUSIONnThis systematic review and meta-analysis indicate that semen antisperm antibodies are not related to pregnancy rates after IVF or ICSI, suggesting that both forms of ART remain viable options for infertile couples with semen ASA. However, additional, well-designed prospective studies using appropriate ASA cutoff levels are needed to further address this issue.

High prevalence of isolated sperm DNA damage in infertile men with advanced paternal age

BackgroundSperm DNA damage is associated with male infertility, lower pregnancy rates and pregnancy loss.ObjectiveThe primary aim of our study was to evaluate the prevalence of sperm DNA damage in younger and older men with normozoospermia.Design, Setting and ParticipantsWe obtained semen from 277 consecutive non-azoospermic men presenting for sperm DNA testing.Outcome Measurements and Statistical AnalysisThe main outcome measures included sperm % DNA fragmentation index (%DFI, using sperm chromatin structure assay), sperm concentration, motility and morphology, and, paternal age.Results and LimitationsSperm % DFI was positively correlated with paternal age (ru2009=u20090.20, Pu2009<u20090.001) and inversely correlated % progressive motility (ru2009=u2009−0.16, Pu2009=u20090.01). Sperm %DFI was significantly higher in older (≥40xa0years) compared to younger (<40xa0years) normozoospermic men (17u2009±u200913 vs. 12u2009±u20098, respectively Pu2009=u20090.008), whereas, sperm concentration, progressive motility and morphology were not significantly different in these two groups. Moreover, the prevalence of high levels of sperm DNA damage (>30xa0% DFI) was significantly higher in older compared to younger normozoospermic men (17xa0% vs. 3xa0%, respectively, Pu2009<u20090.001).ConclusionThe data indicate that a conventional semen analysis can often fail to detect a defect in spermatogenesis (high %DFI) in older men and suggest that infertile couples with advanced paternal age, including those with normal semen parameters, should consider sperm DNA testing as part of the couple evaluation.

Influence of microsurgical varicocelectomy on human sperm mitochondrial DNA copy number: a pilot study

BackgroundThere is good evidence to show that varicocele repair can improve conventional sperm parameters, as well as, sperm DNA integrity, in infertile men with a clinical varicocele.ObjectiveTo examine the effect of varicocelectomy on sperm quality, specifically, sperm nuclear chromatin integrity and sperm mitochondrial DNA (mtDNA) copy number.Design, Setting, and ParticipantsA prospective study done between March 2007 and January 2008. We evaluated a consecutive series of infertile men (nu2009=u200914) presenting to Ovo clinic with one year or more history of infertility, a clinically palpable varicocele and poor motility (<25xa0% rapid progressive and <50xa0% progressive).Surgical ProcedureMicrosurgical sub-inguinal varicocelectomy.Outcome Measurements and Statistical AnalysisConventional sperm parameters, sperm mtDNA copy number (by real time PCR) and sperm chromatin structure assay (SCSA) parameters (%DFI,% HDS) before and 4xa0months after microsurgical varicocelectomy.Results and LimitationsSperm concentration and SCSA parameters (%DFI and %HDS) improved significantly after surgery (Pu2009<u20090.05). Sperm mitochondrial DNA copy number decreased significantly after surgery (27u2009±u200930 to 9u2009±u20096 copies per sperm, respectively, Pu2009=u20090.032). There was a significant negative correlation between mitochondrial DNA copy number and sperm motility (ru2009=u2009− 0.71, Pu2009=u20090.002).ConclusionThese findings support the concept that correction of a varicocele can improve spermatogenesis and sperm function, as mitochondrial DNA copy number has been suggested to reflect the efficiency of spermatogenesis and has been inversely related to sperm motility.

Sperm retrieval outcomes with microdissection testicular sperm extraction (micro‐TESE) in men with cryptozoospermia

Several studies support of the use of testicular rather than ejaculated spermatozoa for intracytoplasmic sperm injection (ICSI) in couples with virtual azoospermia or cryptozoospermia, although this approach remains controversial. We sought to evaluate sperm retrieval outcomes with microdissection testicular sperm extraction (micro‐TESE) in men with cryptozoospermia. We conducted a retrospective study of 24 consecutive micro‐TESEs in men with cryptozoospermia. We also evaluated the outcomes of seven consecutive TESAs (testicular sperm aspiration) in cryptozoospermic men during the same time period (January 2007 and September 2014). Micro‐TESE and TESA were performed on the day prior to ICSI. Final assessment of sperm recovery (reported on the day of ICSI) was recorded as (i) successful (available spermatozoa for ICSI) or (ii) unsuccessful (no spermatozoa for ICSI). The decision to perform a unilateral or bilateral micro‐TESE was guided by the intra‐operative evaluation of sperm recovery from the first testicle. A unilateral procedure was performed in 87.5% (21/24) and 57% (4/7) of the micro‐TESE and TESA cohorts, respectively. Sperm recovery was successful in 96% (23/24) of the men who underwent micro‐TESE and 43% (3/7) of the men who underwent TESA (p < 0.01). The ICSI pregnancy rates (per embryo transfer) in the micro‐TESE and TESA groups were comparable [33% (6/18) and 50% (1/2), respectively]. The data indicate that micro‐TESE is a highly successful sperm retrieval technique for men with cryptozoospermia and few of these men will require a bilateral procedure. Moreover, sperm retrieval rates are higher with micro‐TESE than TESA in this group of men.

Beneficial effects of microsurgical varicocoelectomy on sperm maturation, DNA fragmentation, and nuclear sulfhydryl groups: a prospective trial

There is evidence to show that varicocele repair can improve conventional sperm parameters but the effects on sperm chromatin integrity have not been fully elucidated. We sought to examine the effects of varicocelectomy on sperm maturation, nuclear chromatin integrity and nuclear sulfhydryl groups. We conducted a prospective study of consecutive infertile men (n=29) that underwent a microsurgical sub‐inguinal varicocelectomy for treatment of a clinically palpable varicocele and abnormal semen parameters. Six healthy sperm donors served as controls. We evaluated conventional sperm parameters and markers of sperm chromatin and DNA integrity (aniline blue (AB) staining, iodoacetamide fluorescein (IAF) fluorescence and, % DNA fragmentation index (%DFI) and percent high DNA stainability (%HDS) by sperm chromatin structure assay) before and 6 months after surgery. The sperm %DFI, %HDS, % 5‐IAF staining (diffuse head staining) and % AB staining (dark blue) were all significantly lower in the control group compared to infertile men with varicocele (8 vs. 20%, 4.0 vs. 9.6%, 1.7 vs. 16.3%, and 2.5 vs. 13.5% respectively). The %HDS and %DFI decreased significantly after surgery (from 10% to 6% and from 20% to 13%, respectively). Similarly, the %5‐IAF and %AB staining also decreased significantly after surgery (from 16.3% to 5.4%, and from 13.5% to 5.4%, respectively). We observed significant inversely relationships between sperm progressive motility and both %IAF staining and %DFI (r=−0.44 and −0.43, respectively). The data show that varicocelectomy is associated with an improvement in sperm DNA integrity and chromatin compaction using three different assays of sperm chromatin integrity.

Can the rapid identification of mature spermatozoa during microdissection testicular sperm extraction guide operative planning

The minimum sperm count and quality that must be identified during microdissection testicular sperm extraction (micro‐TESE) to deem the procedure successful remains to be established. We conducted a retrospective study of 81 consecutive men with non‐obstructive azoospermia who underwent a primary (first) micro‐TESE between March 2007 and October 2013. Final assessment of sperm recovery [reported on the day of (intracytoplasmic sperm injection) ICSI] was recorded as (i) successful (available spermatozoa for ICSI) or (ii) unsuccessful (no spermatozoa for ICSI). The decision to perform a unilateral (with limited or complete microdissection) or bilateral micro‐TESE was guided by the intra‐operative identification of sperm recovery (≥5 motile or non‐motile sperm) from the first testicle. Overall, sperm recovery was successful in 56% (45/81) of the men. A unilateral micro‐TESE was performed in 47% (38/81) of the men (based on intra‐operative identification of sperm) and in 100% (38/38) of these men, spermatozoa was found on final assessment. In 42% (16/38) of the unilateral cases, a limited microdissection was performed (owing to the rapid intra‐operative identification of sperm). The remaining 43 men underwent a bilateral micro‐TESE and 16% (7/43) of these men had sperm identified on final assessment. The cumulative ICSI pregnancy rates (per cycle started and per embryo transfer) were 47% (21/45) and 60% (21/35), respectively, with a mean (±SD) of 1.9 ± 1.0 embryos transferred. The data demonstrate that intra‐operative assessment of sperm recovery can correctly identify those men that require a unilateral micro‐TESE. Moreover, the rapid identification of sperm recovery can allow some men to undergo a limited unilateral micro‐TESE and avoid the need for complete testicular microdissection.

Evaluation of Chromatin and DNA Integrity in Testicular Sperm

There is a universal agreement that the examination of conventional semen parameters alone only provides the clinician with a general sense of male reproductive health. Recently, sperm DNA fragmentation/damage has been studied extensively in an attempt to improve the diagnostic accuracy of the male evaluation, particularly, in couples with idiopathic infertility. However, the pathophysiology and etiology of sperm DNA damage (DD) in humans are incompletely understood, and to date, there are very few data on the treatment options for infertile men with this sperm defect. There are several tests used to assess chromatin and/or DD in ejaculated spermatozoa. Using these assays, attempts have been made toward establishing threshold values for the percentage of sperm with DD, the values above which fertility would be affected. Nonetheless, these assays need to be standardized, as there is wide variation among the various tests of sperm DD and these assays have not been tailored to evaluate testicular sperm DD. An alternative approach to improve assisted reproductive technology (ART) outcomes in men with high levels of sperm DD is to obtain testicular spermatozoa. This approach is based on the assumption that testicular spermatozoa generally have lower levels of DD than ejaculated spermatozoa because sperm DD may in part be caused by a posttesticular insult.

Routine cardiac assessment is not necessary for all patients with erectile dysfunction

Erectile dysfunction (ED) is defined as the persistent inability to achieve and/or maintain an erection sufficient for satisfactory sexual performance. The combined prevalence of minimal, moderate and complete ED was reported as high as 52% from the Massachusetts Male Aging Study.1 At age 40, there is an about a 40% prevalence rate, increasing to almost 70% in men at age 70.1 In Canada, a similar overall prevalence of ED was reported (49.4%).2 In addition, ED been shown to have a negative impact on a patient’s quality of life, sexual relationships and overall well-being.3 The etiology of ED fits in one of 3 categories: organic, psychogenic or, most commonly, a combination of both. n nPhophodiesterase-5 (PDE) inhibitors revolutionized ED treatment and is the first-line treatment. These agents have been shown to be effective with good safety profiles in a comorbid population of men with ED, including patients with vascular disease, coronary artery disease (CAD), hypertension and diabetes.4–6 Treatment options for patients not responding to oral drugs (or contraindicated) include intracavernous injections, intraurethral alprostadil, vacuum-constriction devices and penile prosthesis.7