Idiopathic Male Infertility Research Articles

PMON33 Non-Syndromic SRY Negative 46 XX Testicular Disorder of Sex Development (DSD): A Rare Cause of Infertility

Abstract Introduction Male infertility can be categorized as endocrine and systemic disorders, primary testicular defects in spermatogenesis, sperm transport disorders and idiopathic male infertility. Chromosomal abnormalities are one of the primary testicular defects. The overall incidence of chromosome abnormalities in infertile men is estimated to be around 5.8%. XX male is a rare sex chromosomal disorder in infertile men. We present case of a young patient with infertility, azoospermia, hypergonadotropic hypogonadism and classical (46, XX) karyotype with negative FISH and SRY gene. Case report: 28-Year-old gentleman was referred to adult endocrinology clinic as part of work up for infertility. Initial work up included 2 semen analyses which were consistent with azoospermia. Examination revealed height 180 cm, weight 77 kg, a body mass index 24 kg/m2, normal phenotypic male without gynecomastia and had normal male pattern hair distribution. Genital examination showed normal male phallus without hypospadias, a hypoplastic scrotum, bilateral firm testes, with no varicocele or hydrocele. Labs were suggestive of compensated primary hypogonadism (FSH 47.9 mIU/ml, LH 20.4 mIU/ml, total testosterone 397.9 ng/dl by LC/MS, free testosterone 15.76 ng/dl by equilibrium dialysis, Inhibin B < 10 pg/ml, and anti-Mullerian hormone 0.390 ng/ml. Given normal testosterone levels, he was not started on testosterone replacement. Karyotype analysis revealed 46 XX and FISH was negative for SRY gene. CT imaging of abdomen and pelvis did not reveal any Mullerian structures, prostrate and seminal vesicles reported as normal. Patient met with a Urologist and was informed that testicular sperm extraction will not be a possibility for him. Patient had a detailed consultation with a geneticist for genetic and family counseling. Chromosome microarray analysis was obtained and was normal. Invitae Disorders of sex development (DSD) panel obtained for genetic sequencing of 53 genes including SOX-9, DHH, WNT4, WT1, was found to be non-diagnostic. Conclusion and Discussion SRY negative 46 XX male is a DSD and a rare genetic cause of male factor infertility, with a discrepancy between genotype and phenotypic sex. In the case presented, genetic work up for potential etiologies has been unrevealing. Further studies are needed to identify the genetic causes of the SRY negative 46 XX male phenotype. Physicians involved in care of these patients should orient with clinical management and prognosis. For Classical 46 XX Males seeking fertility, the current options include invitro-fertilization with donor sperm or adoption only. Testosterone replacement should be considered to correct hypogonadism for physical and sexual well-being. Genetic consultation should be sought in all these cases. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

PMON33 Non-Syndromic SRY Negative 46 XX Testicular Disorder of Sex Development (DSD); A rare cause of Infertility

Abstract Introduction Male infertility can be categorized as endocrine and systemic disorders, primary testicular defects in spermatogenesis, sperm transport disorders and idiopathic male infertility. Chromosomal abnormalities are one of the primary testicular defects. The overall incidence of chromosome abnormalities in infertile men is estimated to be around 5.8%. XX male is a rare sex chromosomal disorder in infertile men. We present case of a young patient with infertility, azoospermia, hypergonadotropic hypogonadism and classical (46, XX) karyotype with negative FISH and SRY gene. Case report: 28-Year-old gentleman was referred to adult endocrinology clinic as part of work up for infertility. Initial work up included 2 semen analyses which were consistent with azoospermia. Examination revealed height 180 cm, weight 77 kg, a body mass index 24 kg/m2, normal phenotypic male without gynecomastia and had normal male pattern hair distribution. Genital examination showed normal male phallus without hypospadias, a hypoplastic scrotum, bilateral firm testes, with no varicocele or hydrocele. Labs were suggestive of compensated primary hypogonadism (FSH 47.9 mIU/ml, LH 20.4 mIU/ml, total testosterone 397.9 ng/dl by LC/MS, free testosterone 15.76 ng/dl by equilibrium dialysis, Inhibin B < 10 pg/ml, and anti-Mullerian hormone 0.390 ng/ml. Given normal testosterone levels, he was not started on testosterone replacement. Karyotype analysis revealed 46 XX and FISH was negative for SRY gene. CT imaging of abdomen and pelvis did not reveal any Mullerian structures, prostrate and seminal vesicles reported as normal. Patient met with a Urologist and was informed that testicular sperm extraction will not be a possibility for him. Patient had a detailed consultation with a geneticist for genetic and family counseling. Chromosome microarray analysis was obtained and was normal. Invitae Disorders of sex development (DSD) panel obtained for genetic sequencing of 53 genes including SOX-9, DHH, WNT4, WT1, was found to be non-diagnostic. Conclusion and Discussion SRY negative 46 XX male is a DSD and a rare genetic cause of male factor infertility, with a discrepancy between genotype and phenotypic sex. In the case presented, genetic work up for potential etiologies has been unrevealing. Further studies are needed to identify the genetic causes of the SRY negative 46 XX male phenotype. Physicians involved in care of these patients should orient with clinical management and prognosis. For Classical 46 XX Males seeking fertility, the current options include invitro-fertilization with donor sperm or adoption only. Testosterone replacement should be considered to correct hypogonadism for physical and sexual well-being. Genetic consultation should be sought in all these cases. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Erkek İnfertilitesinin Cerrahi Dışı Tedavisi: Spesifik Olmayan Tedavi

In male infertility, all possible known causes should be carefully evaluated and if detected, targeted treatment options for the cause should be implemented. The known causes of male infertility such as hypogonadotropic hypogonadism, hyperprolactinemia, genital tract infections, disorders of ejaculation, thyroid hormone disorders and varicocele can be treated efficiently by targeted therapies or surgical corrections. Unfortunately, these known causes cover about 20% of male infertility and the rest remains idiopathic. On the other hand, management of idiopathic, unexplained male infertility, in which no etiological factors can be found, is a challenge for both the clinician and couples seeking solutions. In the era of assisted reproductive technology, few medical options in this regard are still available with limited benefits and low scientific foundation based on theoretical concepts but empirical medical therapy continues as a mostly off-label option for obtaining a natural pregnancy. Comprehending the hypothalamic-pituitary-gonadal axis and the regulation of hormones is crucial in this regard. Empirical therapies have the potential to overcome overtreatment with assisted reproductive technology yet clinicians and couples must be aware of the limitations of empirical therapies and should be counseled in this direction. In this review, non-specific medical treatment options for idiopathic male infertility were covered.

Testosterone Serum Levels Are Related to Sperm DNA Fragmentation Index Reduction after FSH Administration in Males with Idiopathic Infertility.

Purpose: Although a robust physiological rationale supports follicle stimulating hormone (FSH) use in male idiopathic infertility, useful biomarkers to evaluate its efficacy are not available. Thus, the primary aim of the study was to evaluate if testosterone serum levels are related to sperm DNA fragmentation (sDF) index change after FSH administration. The secondary aim was to confirm sDF index validity as a biomarker of FSH administration effectiveness in male idiopathic infertility. Methods: A retrospective, post-hoc re-analysis was performed on prospectively collected raw data of clinical trials in which idiopathic infertile men were treated with FSH and both testosterone serum levels and sDF were reported. Results: Three trials were included, accounting for 251 patients. The comprehensive analysis confirmed FSH’s beneficial effect on spermatogenesis detected in each trial. Indeed, an overall significant sDF decrease (p < 0.001) of 20.2% of baseline value was detected. Although sDF resulted to be unrelated to testosterone serum levels at baseline, a significant correlation was highlighted after three months of FSH treatment (p = 0.002). Moreover, testosterone serum levels and patients’ age significantly correlated with sDF (p = 0.006). Dividing the cohort into responders/not responders to FSH treatment according to sDF change, the FSH effectiveness in terms of sDF improvement was related to testosterone and male age (p = 0.003). Conclusion: Exogenous FSH administration in male idiopathic infertility is efficient in reducing sDF basal levels by about 20%. In terms of sDF reduction, 59.2% of the patients treated were FSH-responders. After three months of FSH administration, a significant inverse correlation between sDF and testosterone was detected, suggesting an association between the FSH-administration-related sDF improvement and testosterone serum levels increase. These observations lead to the hypothesis that FSH may promote communications or interactions between Sertoli cells and Leydig cells.

Study the relationship between polymorphisms of pre-miRNA regions and expression of mature miRNA in samples of Iraqi infertile men

Polymorphisms that increase risk factor for male infertility is one of the most studied infertility genetic factor however polymorphisms within pre- miRNA sequences have not extensively documented. This study aimed to highlighted association between idiopathic male infertility and, hsa-mir-196a-2 rs11614913Polymorphism genotyping and expression level of mature miRNA were done in semen samples of Iraqi fertile and infertile male in order to study impact of polymorphism on expression level of mature miRNA andstudy correlationbetween both of polymorphism genotype and mature miRNA expression level with quality of semen parameters. Results of this study demonstrated that homozygous mutant (TT) and heterozygous mutant (CT) genotypes of pre-miRNA regions (hsa-miRNA-196a-2, rs11614913) were significantly (P ≤ 0.01) higher in patients group when compared with control and associated with idiopathic Asthenozoospermia, Oligoasthenozoospermia and specifically Azoospermia.Correlation between polymorphism genotype and semen parameters exhibits that genotype obviously impacts semen parameters. Analyzing correlation between polymorphism genotype and expression elucidated that mutant homozygous (TT) genotype increasing expression level of mature miRNA. Elevated level of miRNA-196a-5p exhibitednegative correlation with semen parameter.

Glutathione S-transferase genetic polymorphisms and fluoride-induced reproductive toxicity in men with idiopathic infertility.

Male infertility caused by idiopathic oligoasthenospermia (OAT) is known as idiopathic male infertility. Glutathione S-transferase (GST) and fluoride may play important roles in idiopathic male infertility, but their effects are still unknown. Our study examined the relationship between GST polymorphisms and fluoride-induced toxicity in idiopathic male infertility and determined the underlying mechanism. Sperm, blood, and urine samples were collected from 560 males. Fluoride levels were measured by a highly selective electrode method, and GST genotypes were identified using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Semen parameters, DNA fragmentation index (DFI), mitochondrial membrane potential (MMP), and oxidative stress (OS) biomarkers were statistically assessed at the P < 0.05 level. Compared with healthy fertile group, semen parameters, fluoride levels, OS biomarkers, sex hormone levels, and MMP and DFI levels were lower in the idiopathic male infertility group. For glutathione S-transferase M1 (GSTM1[-]) and glutathione S-transferase T1 (GSTT1[-]) or glutathione S-transferase P1 (GSTP1) mutant genotypes, levels of semen fluoride, OS, MMP, and DFI were considerably higher, and the mean levels of sperm parameters and testosterone were statistically significant in GSTM1(+), GSTT1(+), and GSTP1 wild-type genotypes. Both semen and blood fluoride levels were associated with oxidative stress in idiopathic male infertility patients. Elevated fluoride in semen with the genotypes listed above was linked to reproductive quality in idiopathic male infertility patients. In conclusion, GST polymorphisms and fluorine may have an indicative relationship between reproductive quality and sex hormone levels, and OS participates in the development of idiopathic male infertility.

SINGLE COMPOUND ANTIOXIDANTS ARE SIMILARLY EFFECTIVE AS MULTI-COMPOUND ANTIOXIDANTS OVER A 3-MONTH PERIOD IN MEN WITH IDIOPATHIC INFERTILITY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Meta-analytic evidence supports the use of antioxidants (AOXs) for the treatment of idiopathic male infertility (IMI). However, many questions remain unanswered, including what the most effective AOX formulation and duration of therapy is. This systematic review and meta-analysis (SRMA) was conducted to assess the impact of single versus combination AOX formulations and durations of therapy on clinical pregnancy rate, conventional semen parameters, sperm DNA fragmentation (SDF), and seminal indices of oxidative stress (OS) in IMI.

The cost of the circadian desynchrony on the Leydig cell function

The increased frequency of different lifestyles that disrupts circadian rhythms, together with a trend in the accretion of male idiopathic infertility, imposes the necessity to understand the contribution of circadian rhythms disruption to fertility regulation. In this study, the effects of circadian desynchrony (CD) on the steroidogenic capacity of adult Leydig cells were studied. Adult rats were housed under a disturbing light regime (2 days of constant light, 2 days of continual dark, and 3 days of 12:12 h light:dark schedule) designed to mimic shiftwork in humans. CD was characterized by changed and decreased rhythmic locomotor activity and reduced blood testosterone. In the Leydig cells changed transcription of the clock genes (Bmal1, Clock, Cry1 and Reverba/b increased while Per1/2 reversed phase) was detected. This was followed by reduced transcription of genes (Star, Cyp11a1, and Hsd3b1/2) primarily involved in mitosteroidogenesis. In parallel, mitochondrial membrane potential (Δψi) and ATP production declined losing their characteristic oscillatory pattern. Also, the main markers of mitochondrial biogenesis (Ppargc1a, Nrf1, Tfam, Cytc), fusion (Mfn2), and mitophagy (Pink1 and Tfeb) were disturbed. Collectively, CD targets mitochondria in Leydig cells by reducing mitosteroidogenesis, mitoenergetics, and disturbing mitochondrial dynamics. These changes contribute to testosterone decline compromising androgen-dependent functions, including reproduction.

Lipophilic phthalic acid esters impair human sperm acrosomal reaction through the likely inhibition of phospholipase A2-signaling pathway

Phthalic acid esters (PAEs) are recognized endocrine disruptors. Detection of PAEs in semen from idiopathic infertile males suggests possible direct mechanisms of sperm toxicity. In this study we aimed to correlate sperm function with semen levels of PAEs. Semen samples were obtained from 100 male patients attending the Unit of Andrology and Reproductive Medicine, University Hospital of Padova, (Italy), 22 of which having a recognized history of idiopathic infertility. Compared to fertile subjects, infertile patients showed reduced levels of acrosome reaction (AR), evaluated by CD46 staining upon progesterone (P4) triggering (p < 0.001). Subjects showing positive detection of PAEs in semen, evaluated by liquid chromatography-mass spectrometry (LC-MS), were significantly more represented in those reporting an history of infertility (13 out of 22), compared to fertile subjects (25 out of 78, P = 0.0266). In vitro sperm exposure to PAEs showed that lipophilic PAE representative Di-n-octyl phthalate (DNOP) had higher cell accumulation and inhibition of P4-induced AR than less lipophilic PAE representative Dibutyl phthalate (DBP). Computer-based binding analysis and fluorimetric inhibition assay, showed that both DNOP and DBP had similar Phospholipase-A2 (PLA2) inhibitory activity (respectively: 3.98 nM and 5.52 nM). However, only DNOP showed a significant inhibition of PLA2-mediated AR, triggered by A23187 calcium ionophore. Incubation with PLA2-related product arachidonic acid restored AR. Our data are suggestive of a novel mechanistic model of PAEs interference on sperm function, through the inhibition of PLA2-mediated signaling. According to this hypothesis, the inhibitory efficacy of the specific PAE is possibly linked to the corresponding cell accumulation.

Current and promising methods of idiopathic male infertility treatment

For a significant number of couples around the world, male infertility is a serious ordeal. The truth is that this is also a major clinical challenge for the andrologist – up to 50 % of men with infertility have no identifiable etiology and there is no effective, available evidence-based treatment. For a long time, antioxidant supplements have been used as empiric therapy, but there is still no conclusive evidence that fertility and live birth rates actually improve after this approach has been used. This review is an attempt to summarize current and prospective treatments for idiopathic male infertility. Particular attention is paid to regulatory peptides as promising candidates for improving male fertility.

Effect of Bisphenol S on testicular tissue after low-dose lactation exposure

Exposure to endocrine disruptors such as bisphenols, can lead to and be the explanation for idiopathic infertility. In our study, we assessed the effect of exposure to bisphenol S (BPS) via breast milk on the testicular tissue health of adult male mice. Lactating dams were exposed to BPS through drinking water (0.216 ng g bw/day and 21.6 ng g bw/day) from post-natal day 0–15. Although there was no significant difference in testicular histopathology between the control and experimental groups, we observed an increase in the number of tight and gap junctions in the blood-testis barrier (BTB) of adult mice after lactation BPS exposure. Moreover, there was an increase in oxidative stress markers in adult testicular tissue of mice exposed via breast milk. Our lactation model indicates that breast milk is a route of exposure to an endocrine disruptor that can be responsible for idiopathic male infertility through the damage of the BTB and weakening of oxidative stress resistance in adulthood.

The association of testis-specific hTAF7L gene variants with idiopathic azoospermic and severe oligozoospermic male infertility.

Spermatogenesis is regulated by complex tissue specific gene expression in the testis to achieve normal male fertility. X-chromosome specific TATA binding protein (TBP)-associated factor 7L (hTAF7L) is one of the transcriptional regulator genes considered essential for spermatogenesis. The aim of this study was to evaluate the role of variants/mutations in the testis-specific hTAF7L gene in non-obstructive azoospermia and severe oligozoospermia male infertility. We studied 156 idiopathic non-obstructive azoospermic, severe oligozoospermic infertile males and 50 fertile proven controls. Infertile males and control subjects were genotyped for variants of the hTAF7L gene using polymerase chain reaction and a direct Sanger sequencing approach. The odds ratio evaluated the association of hTAF7L gene variants with idiopathic male infertility. The variants found in the hTAF7L gene were subjected to an in-silico analysis study. In infertile study subjects, we observed 11 single base pair nucleotide changes at various exons and three frameshift variants at exon 10 in the hTAF7L gene. We also found more than one variant in some non-obstructive azoospermia and severe oligozoospermia infertile males along with control subjects. All these variants changed the amino acid sequences in the hTAF7L gene. However, similar changes were also seen in fertile subjects, and the differences were not statistically significant. In-silico tools also predicted that the variants were likely to be benign. The variants in cDNA of the hTAF7L gene were typical SNPs. It is found that the hTAF7L gene is highly polymorphic and these missense variants are not directly associated with male infertility. However, we feel that more studies are needed to elucidate the role of multiple variants of the hTAF7L gene in the process of normal spermatogenesis.

Effects of Medicines and Supplements on Spontaneous Pregnancy and Semen Parameters in Male Infertility: A Systematic Review Update and Network Meta-Analysis

In this study, we used a network meta-analysis (NMA) to compare the effectiveness of medicines and supplements for idiopathic male infertility and to identify the best treatment. Medline, Excerpta Medica Database (EMBASE), Ovid, and China National Knowledge Infrastructure (CNKI), were searched for the period from January 1990 to June 2021 using the keywords “male infertility,” “medical therapy,” “supplement/nutrient therapy,” and related terms. Randomized controlled trials (RCTs) investigating medicines (mainly follicle-stimulating hormone (FSH), androgen, and clomiphene/tamoxifen) or supplements (mainly zinc, selenium, vitamin C or E, carnitine, coenzyme Q10 (CoQ10), or combined treatment) for idiopathic infertile men were selected for meta-analysis. Preferred reporting items for systematic reviews and meta-analysis (PRISMA) was used for data extraction, and a risk-of-bias tool and grades of recommendation, assessment, development, and evaluation (GRADE) system adapted to the NMA were employed to assess the quality of the evidence. The primary outcomes were live birth and spontaneous pregnancy rate (SPR). The secondary outcomes were sperm parameters (including concentration, progressive motility, and morphology) and side effects. In total, 65 RCTs involving 7541 men with sperm abnormalities but normal hormone levels were included. A total of 36 studies reported SPR but only three reported live birth rates. The quality of the included studies was found to be moderate to high. Compared with a placebo or being untreated, carnitine plus vitamins significantly improved SPR (relative risk (RR) = 3.7, 95% confidence interval (95%CI), 1.6–8.5); fatty acids significantly increased sperm concentrations (mean difference (MD) = 12.5 × 10 6 mL −1 , 95%CI, 3.1 × 10 6 –22.0 × 10 6 ); and selective estrogen receptor modulator (SERM) plus CoQ10 significantly improved sperm progressive motility (MD = 11.0%, 95%CI, 0.1%–21.9%) and normal sperm morphology (MD = 11.0%, 95%CI, 4.6%–17.4%). The most optimal intervention was carnitine plus vitamins and fatty acids for SPR and sperm concentrations, respectively, even after excluding trials at a high risk of bias. Compared with a placebo or being untreated, FSH (RR = 4.9, 95%CI, 1.1–21.3) significantly increased SPR, whereas SERM plus kallikrein increased sperm concentration (MD = 16.5 × 10 6 mL −1 , 95%CI, 1.6 × 10 6 –31.4 × 10 6 ), and SERM plus CoQ10 significantly improved sperm progressive motility (MD = 11.3%, 95%CI, 7.3%–15.4%) and normal morphology (MD = 11.2%, 95%CI, 5.4%–16.9%) in men with oligoasthenozoospermia (OA). In terms of side effects, fatty acids and pentoxifylline were associated with foul breath and/or a bad taste (RR = 8.1, 95%CI, 1.0–63.5) and vomiting (RR = 8.0, 95%CI, 1.0–63.0), respectively. In conclusion, the optimal treatment for male infertility for live birth is still unknown. Carnitine plus vitamins and FSH are likely to be better than other therapies in achieving successful spontaneous pregnancy in couples overall and in couples with men with OA, respectively. The efficacy of other treatments on pregnancy outcomes warrants further verification.

Opportunities and Challenges Arising from the Australian Male Infertility Exposure (AMIE) Study

Background: A four-stream research program, Men and Infertility over the Lifecourse, is funded by the MRFF to address the medical, personal and social cost of idiopathic male infertility. This program includes a national case control study: AMIE. Designing and implementing AMIE poses both opportunities and challenges.

Novel Potency Assay for MSC Secretome-Based Treatment of Idiopathic Male Infertility Employed Leydig Cells and Revealed Vascular Endothelial Growth Factor as a Promising Potency Marker.

Idiopathic male infertility is a highly prevalent diagnosis in developed countries with no specific treatment options. Although empirical medical treatment is widely used to restore male fertility, its efficacy remains limited and inconclusively proven. Therefore, the development of novel therapeutic approaches in this field is a high-priority task. Since the failure of testicular microenvironment components might be involved in the pathogenesis of idiopathic male infertility, application of mesenchymal stromal cells (MSCs) as well as the MSC secretome is worth considering. Previously, we showed that the intratesticular injection of MSCs or the MSC secretome led to the recovery of spermatogenesis at least through replenishing the testicular microenvironment and its maintenance by MSC-secreted paracrine factors. However, the clinical use of such products has been limited to single trials to date. This may be due to the lack of relevant potency tests reflecting mechanisms of action of the MSC secretome in male infertility models. Based on the presumptive MSC secretome mode of action on the testicular microenvironment, we suggest a novel approach to test the potential efficacy of the MSC secretome for idiopathic male infertility treatment. It represents a potency assay based on evaluation of testosterone production by isolated Leydig cells. We demonstrated that the MSC secretome stimulated testosterone secretion by Leydig cells in vitro. We then hypothesized that among the major factors of the MSC secretome, vascular endothelial growth factor (VEGF) could be responsible for the observed effects, which we confirmed by the revealed correlation between the extent of stimulated testosterone production and VEGF concentration in the MSC secretome. The pilot results obtained from the doxorubicin-induced male infertility murine model also indicate the important impact of VEGF in the MSC secretome’s regenerative effects. Utilizing VEGF as a surrogate factor, a novel approach to study the potency of MSC secretome-based products for idiopathic male infertility treatment is suggested. Further validation is required for its implementation into the biopharmaceutical manufacturing process.

Evaluation of sperm integrin α5β1 as a potential marker of fertility in humans.

Sperm selection for assisted reproduction techniques is generally based on basic parameters, while key aspects of sperm competence and its journey from the deposition site to the fertilization site are overlooked. Consequently, identifying molecular markers in spermatozoa that can efficiently predict the fertility of a semen sample could be of great interest, particularly in cases of idiopathic male infertility. When spermatozoa reach the female reproductive tract, it provides to them the cellular and molecular microenvironment needed to acquire fertilizing ability. In this sense, considering the role that integrin α5β1 of spermatozoa plays in reproduction-related events, we investigated the correlation between the subcellular localization of sperm integrin α5β1 and early embryo development outcome after in vitro fertilization (IVF) procedures in human. Twenty-four semen samples from normozoospermic men and metaphase II (MII) oocytes from healthy women aged under 38 years, from couples who underwent IVF cycles, were used in this work. Sperm α5β1 localization was evaluated by immunofluorescence assay using an antibody against integrin α5 subunit. Integrin α5β1 was mainly localized in the sperm acrosomal region (45.33±7.89%) or the equatorial segment (30.12±7.43%). The early embryo development rate (data obtained from the Fertility Center) correlated positively with the localization of α5β1 in the acrosomal region (number of usable embryos / inseminated oocytes: ρ = 0.75; p<0.01 and number of usable embryos/total number of two pronuclear zygotes: ρ = 0.80; p<0.01). However, this correlation was not significant when the equatorial segment mark was evaluated. In addition, human sperm released from co-culture with bovine oviductal epithelial cells (BOEC) showed a significant enrichment in the acrosomal localization pattern of α5β1 compared to those sperm that were not co-cultured with BOEC (85.20±5.35% vs 35.00±17.09%, respectively, p<0.05). In conclusion, the evaluation of sperm integrin α5β1 immunolocalization could be a useful tool to select sperm with fertilizing ability from human semen samples before IVF procedures.

Male fertility: summary overview of the publications January – March 2022

The article presents an overview of the most significant publications on the topic of male infertility. The main selection criteria were the practical significance of the article, as well as the impact factor of the journal in which it was published, according to the SCImago Journal Rank (SJR). As a result, a list of 10 papers published in the first quarter (January – March) of 2022 was compiled. The review includes articles on the following issues: the role of coronavirus infection in male infertility, the effectiveness of aromatase inhibitors in infertile men, the effect of assisted reproductive technologies on the reproductive health of descendants, recurrent miscarriage, the effect of antibiotic therapy on the DNA fragmentation index, the role of antisperm antibodies in male infertility, the incidence of idiopathic male infertility, the Sixth Edition WHO guidelines for the ejaculate processing, as well as the relationship of depression with male infertility.

Role of Antioxidant Supplements in Idiopathic Male Infertility in Erbil City

Background: Fertil Aid for Men is a non-prescription dietary supplement, it’s a mixture of multiple antioxidants,vitamins, a blend of herbal ingredients, and amino acid, as L-Carnitine. This research aims to appraise theeffectiveness of a mixture of vitamins and antioxidants on seminal fluid parameters in males with idiopathicinfertility.Method: Thirty-three men with idiopathic infertility were involved inthis prospective clinical study. The baselinesemen specimens were taken from the subjects following three to seven days’ abstinence. Semen parametersincluding (volume, pH, concentration, and motility) were measured. Abnormal sperm sample subjects were givena FertilAid capsule three times daily for 90 days then final semen analysis was estimated.The outcomes of this study demonstrated consumption of fertilAid has significantly improved sperm count/ml (p&lt; 0.05), also significant amelioration in the sperm motility including progressive and non-progressive motility (p&lt; 0.05). The rate of total sperm motility was significantly improved (p &lt; 0.05).The concentration of immotile spermhas considerablyreduced (p &lt; 0.05).Conclusion: The administration of a combination of L-Carnitine, Zinc, Maca Root, Asian Ginseng, Vitamin C, E,Beta Carotene, and Selenium PLUS CoQ10 in idiopathic male infertility has notably improved sperm parameters.

Sperm DNA Fragmentation in Reproductive Medicine: A Review.

Approximately 15% of the world's couples suffer from infertility during their reproductive period of which the male factor is responsible for 50% of cases. Male factor infertility is multifactorial in origin, and sperm DNA fragmentation (SDF) has also been linked to male infertility including idiopathic male infertility. Some degree of controlled DNA nicking is essential for adequate DNA compaction, but excessive SDF is usually associated with reduced male fertility potential, reduced fertilisation, poor embryo quality, recurrent pregnancy loss and poor assisted reproductive techniques (ARTs) outcomes. Although semen analysis remains the gold standard for diagnosis of male factor infertility worldwide, its limitations motivated the search and the development of complementary tests of sperm function and integrity. SDF assay is an emerging diagnostic tool in infertile men, and several indications for SDF testing in infertile couples have also been proposed. The use of SDF in routine male infertility assessment is, however, still controversial. Furthermore, both direct and indirect SDF tests are now available. Hence, the present review was conducted to summarise the recent evidence of SDF, underlying mechanisms, clinical indications, diagnostic tests, as well as the role of SDF in male factor infertility, pregnancy and ART outcomes.

Comparison of L-Carnitine vs. Coq10 and Vitamin E for idiopathic male infertility: a randomized controlled trial.

This study aimed at comparing sperm parameters and hormonal levels with L-carnitine vs. CoQ10 and Vitamin E therapy for patients with asthenozoospermia and teratozoospermia. A single-blind randomized controlled trial (RCT) was designed wherein patients were randomly allocated to receive L-carnitine complex nutrient treatment (study group - 15 g/bag, orally one bag at a time, twice a day) or CoQ10 (control group - 10 mg tablet orally, thrice daily) with Vitamin E (100 mg tablet orally, thrice daily) for three months. Outcome variables were sperm concentration, progressive sperm motility, normal sperm morphology, testosterone, follicle-stimulating hormone, luteinizing hormone (LH), and prolactin levels. 143 patients were analyzed (73 in study and 70 in control group). Compared to baseline, sperm count, progressive sperm motility, and morphology improved significantly in the study group, but only progressive sperm motility and morphology improved in the control group. Serum testosterone levels significantly increased both in the study and control groups, while LH increased only in the study but not in the control group. All sperm parameters showed significantly better improvement in the study group, compared to the control group. Testosterone and LH levels were also higher in the study group compared to the control group. L-carnitine significantly improves sperm motility, morphology, and concentration, while also improving testosterone and LH levels. Use of CoQ10 and Vitamin E resulted in improvement of only sperm motility, morphology, and testosterone levels. L-carnitine was found to be superior to the combination of CoQ10 and Vitamin E in improving sperm parameters. Further studies examining clinical pregnancy rates are needed to strengthen the evidence.