Idiopathic Infertility Research Articles

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.

IVF und ICSI – Von den Anfängen bis zur Gegenwart

In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are the most frequently utilized forms of assisted reproductive technologies (ART). They are indicated if the couple or the woman without a partner has proven infertility and a strong desire to have children. While the classical indications for IVF are tubal and idiopathic infertility, ICSI should only be used in cases of andrological subfertility. As a rule, controlled ovarian stimulation is performed to obtain multiple oocytes. This is followed by follicle puncture, fertilization of the oocyte, embryo culture and embryo transfer on days 2–5. The IVF and ICSI procedures differ only concerning the laboratory procedure. In IVF the sperm has to penetrate the zona pellucida of the oocyte independently in the reproductive medicine laboratory, whereas in the ICSI procedure it is actively injected into the oocyte. To date, over 8 million children have been conceived and born worldwide through IVF and ICSI. In Germany, more than 100,000 treatment cycles are carried out every year. The pregnancy rate per treatment is about 33% and the birth rate about 25%, they decrease with increasing maternal age.

Correlation of Single Nucleotide Polymorphisms of PRM1, PRM2, PYGO2, and DAZL Genes with Male Infertility in North West of Iran.

Almost half of infertility is related to male factors. Although the effect of genetic factors on male infertility is identified, about 30%-50% still has no proven cause and is classified as idiopathic infertility. This study was performed to investigate the correlation of some single nucleotide polymorphisms of PYGO2, DAZL, PRM1, and PRM2 genes with male infertility in idiopathic cases among the Iranian population. In this case-control study, 120 idiopathic azoospermia or severe oligospermia patients in the range of 25-45 years and 120 fertile men in the same age range were recruited as case and control groups, respectively. Eight different single nucleotide polymorphisms including PRM1 rs737008, PRM1 rs423668, PRM2 rs1646022, PRM2 rs11645592, PYGO2 rs141722381, PYGO2rs61758741, DAZL rs75931701, and DAZL rs188506466 were genotyped by using ampli ficat ion-r efrac tory mutation system polymerase chain reaction methods. Hardy-Weinberg was calculated by using online website. Statistical Package for Social Sciences software was applied for statistical analysis. P value <.05 was considered significant. Thirty percent of the samples were regenotyped to confirm the obtained results. The obtained results showed a significant correlation between PYGO2 rs141722381 in the heterozygote form (odds ratio: 2.803, 95% CI: 1.397-5.626). Heterozygote over-dominance was also observed in this variant (odds ratio: 2.637, 95%CI: 1.321-5.264). There was no significant association between other studied single nucleotide polymorphisms and male infertility. This study proposed a novel single nucleotide polymorphism as a predisposition of male infertility among the Iranian population, but more studies in larger populations are needed to confirm the results.

PREDICTORS OF A CLINICALLY SIGNIFICANT RESPONSE TO ANASTROZOLE THERAPY IN A MULTI-INSTITUTIONAL COHORT OF MEN WITH IDIOPATHIC INFERTILITY

Anastrozole is a selective aromatase inhibitor commonly prescribed as empiric medical therapy for men with idiopathic infertility and elevated estradiol levels. The goal of this study is to identify patient factors associated with a clinically significant improvement in semen parameters on anastrozole.

SPERM DNA METHYLATION PREDICTS HUMAN AGING IN FERTILE AND INFERTILE MEN

Epigenetics refers to heritable changes in gene expression that do not involve changes in the underlying DNA sequence. One of the most studied mechanisms of epigenetic change is DNA methylation. It is postulated that adverse outcomes related to advanced paternal age and assisted reproductive technologies (ART) are due to epigenetic changes. Prior studies have described accurate age estimation based on human somatic cell DNA methylation. We sought to evaluate the DNA methylation patterns of somatic cells and sperm from fertile men and men with idiopathic 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.

Myo-inositol in the treatment of male factor infertility

About 187 million couples worldwide suffer from infertility, with the male factor being diagnosed in 2070% of cases. The main cause of idiopathic infertility has been recognized as the adverse effects of reactive oxygen species. On the one hand, the cellular antioxidant defense is a highly efficient multilevel system; therefore, the pharmacological targets may vary. On the other hand, antioxidant enzymes (superoxide dismutase, catalase, peroxidase) have high activity and specificity, which limits the pharmacological capabilities of direct antioxidants. Indirect methods, such as the normalization of mitochondrial function, are more promising. Mitochondria play a key role in providing energy for sperm motility (one of the main factors of male fertility). Myo-inositol (MI) derivatives involved in cell signaling regulate intracellular Ca2+ ion levels affecting mitochondrial oxidative metabolism and adenosine triphosphate production. Thus, mitochondrial antioxidants are of particular interest for therapeutic strategies. Currently, various routes and regimens of MI use in the treatment of males with oligo-astheno-teratozoospermia (OAT) are being considered in clinical practice. MI-based oral nutraceutical complexes for the treatment of male factor infertility contain both direct and indirect antioxidants. In vitro studies revealed damage to mitochondrial cristae in the sperm intermediate tract in patients with OAT. Experimental studies have demonstrated that mitochondrial structure is restored when sperm are incubated in an MI-containing medium. Clinical studies confirmed that sperm incubation in such an environment leads to increased sperm motility and viability in patients with OAT. Intravaginal administration of MI showed increased total sperm motility and an increased proportion of progressively motile sperm. It is the progressive motility that is considered the best marker for identifying quality and healthy sperm. This type of sperm is usually used for in vitro fertilization techniques. In addition, intravaginal MI administration improved the quality of cervical mucus and reduced its viscosity and crystallization. The effect of intravaginal MI on cervical mucus can be considered as an additional independent factor in increasing fertility.

TRPV1 channel in spermatozoa is a molecular target for ROS-mediated sperm dysfunction and differentially expressed in both natural and ART pregnancy failure.

Bi-directional crosstalk between Ca2+ signaling and ROS modulates physiological processes as a part of a regulatory circuit including sperm function. The role of transient receptor potential vanilloid 1 (TRPV1) in this regard cannot be undermined. This is the first report demonstrating the Ca2+-sensitive TRPV1 channel to be under-expressed in spermatozoa of subfertile men, idiopathic infertile men, and normozoospermic infertile males with high ROS (idiopathic infertility and unilateral varicocele). To study the effect of TRPV1 in determining the fertility outcome, we compared the expression profile of TRPV1 in spermatozoa of male partners who achieved pregnancy by natural conception (NC+, n = 10), IVF (IVF+, n = 23), or ICSI (ICSI +, n = 9) and their respective counterparts with failed pregnancy NC (n = 7), IVF (n = 23), or ICSI (n = 10), by both immunocytochemistry and flow-cytometry. Reduced expression of TRPV1 in sperm of IVF ± and ICSI ± men with respect to that NC+ men imply its role in mediating successful fertilization. Unsuccessful pregnancy outcome with an underexpression of TRPV1 in sperm of NC-/IVF-/ICSI-men suggests its role in conception and maintenance of pregnancy. Since ROS is regarded as one of the major contributors to sperm dysfunction, the effect of H2O2 +/- TRPV1 modulators (RTX/iRTX) on acrosomal reaction and calcium influx was evaluated to confirm TRPV1 as a redox sensor in human sperm. A significant increment in the percentage of acrosome reacted spermatozoa along with augmented Ca2+-influx was observed after H2O2 treatment, both in the presence or absence of TRPV1 agonist resiniferatoxin (RTX). The effect was attenuated by the TRPV1 antagonist iodoresiniferatoxin (iRTX), indicating the involvement of TRPV1 in mediating H2O2 response. Enhancement of motility and triggering of acrosomal reaction post TRPV1 activation suggested that disruption of these signaling cascades in vivo, possibly due to down-regulation of TRPV1 in these subfertile males. Bioinformatic analysis of the crosstalk between TRPV1 with fertility candidate proteins (reported to influence IVF outcome) revealed cell death and survival, cellular compromise, and embryonic development to be the primary networks affected by anomalous TRPV1 expression. We therefore postulate that TRPV1 can act as a redox sensor, and its expression in spermatozoa may serve as a fertility marker.

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.

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.

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.

The Effect of the Time Interval From Sperm Processing to Intrauterine Insemination on the Pregnancy Outcomes of Infertile Women.

Objective: Intrauterine insemination (IUI) is the first-line treatment in couples suffering from various causes of subfertility and infertility. Considering the relatively low rate of pregnancy achieved with each cycle in this method, optimizing various steps in the process including the time interval from sperm collection to IUI may result in an increased rate of success. The goal of this study was to assess the impact of time intervals from the end of sperm processing to IUI (SP-IUI) on the pregnancy rate in IUI. Materials and methods: This single-center prospective cohort study evaluated couples with normal male partner sperm analysis and idiopathic female infertility undergoing IUI from 2018 to 2021. Cycles were stimulated using subcutaneous recombinant FSH and oral Letrozole. Ovulation was triggered using GnRH antagonist when the leading follicle's size reached greater than 14mm. The participants were placed in one of the three groups based on SP-IUI: group 1 (0-60 min), group II (60-90 min), and Group III: (>90 min). Results: 269 couples were included in the study. Sperm processing expectedly resulted in an increased concentration of total sperm count and sperm motility (P<0.001). The rate of chemical or clinical pregnancy, abortion, IUFD, multigestation, pregnancy, term birth, and ectopic pregnancy was not significantly different across study groups (P>0.05). Conclusion: The results of this study suggest that SP-IUI intervals evaluated in this study do not vary in terms of pregnancy rate or adverse pregnancy outcomes in IUI with normal male partner semen analysis. Hence, infertile couples can be flexible in the collection of semen specimens without time and site (at home or hospital) limitations.

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.

Молекулярные механизмы мужского бесплодия: основные направления научного поиска

This review provides up-to-date information on the molecular basis of the pathogenesis of male infertility at the cellular and subcellular levels. The emphasis is on the importance of new next-generation sequencing technologies as a high-performance tool for studying the genome and epigenomic mechanisms, transcriptome, proteome and metabolome of ejaculate, and organs of the reproductive system. This methodology made it possible to identify differentially expressed metabolic and signaling pathways in fertile and infertile men that combine the genotype and phenotype of a particular individual into a single whole. The current ideas about the relationship between oxidative stress and imbalance of redox systems with DNA damage in spermatozoa as the leading mechanism for the development of idiopathic infertility are summarized. The role of miRNAs, methyloma aberrations, deficiency of phospholipase C zeta in spermatozoa in the pathology of fertility is given. Deciphering the molecular profile and molecular phenotypes of infertility as a result of the interaction of genetic and environmental factors is a necessary condition for screening the most informative biomarkers, assessing their stratification potential, and validating new molecules as potential targets for targeted therapy.

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.

FMR1 alleles in women with idiopathic infertility

Introduction: The frequency of the premutated alleles of the FMR1 gene varies from 1: 100 to 1: 260 Israeli, Canadian, Finnish and American women, but it is unknown in Brazil. Premutation carriers may have reduced reproductive age and are at risk of transmitting the expanded allele to their offspring, and consequently fragile X syndrome. Objective: To observe the distribution range of the FMR1 gene alleles in a population of women with idiopathic infertility, without symptoms of premature ovarian insufficiency. Methods: The presence of premutation in FMR1 was assessed by conventional PCR, agarose and acrylamide gel and analysis of fragments in capillary electrophoresis. From the lymphocyte DNA obtained from 283 women undergoing infertility treatment. Results: It was observed that 169 patients had the normal heterozygous allele (59.7%), 114 had the normal homozygous allele (40.6%) and no patient had the premutation. Premature ovarian insufficiency is seen in 20 to 30% of women with the premutated allele. Thus, the condition can be asymptomatic in a large part of the premutation carriers. Brazil has a diverse population and, therefore, the allele frequencies of many gene variants are unknown. Previous Brazilian studies have shown a low frequency of the premutated allele in different patient cohorts. Corroborating these articles, the results demonstrated that the frequency of the premutated allele is low in the infertile women population studied. Conclusion: Tracking the size of the FMR1 gene alleles allows the expansion of knowledge about the frequency of risk alleles associated to genetic diseases in the Brazilian population.