Summary
Reactive oxygen species (ROS) have been extensively studied as a cause of male infertility. Excessive levels of ROS coupled with a deficiency in antioxidants can lead to oxidative stress ...(OS), which in turn can lead to nuclear and mitochondrial DNA damage, telomere shortening, epigenetic alterations and Y chromosomal microdeletions. In this review, we discuss how OS induces DNA damage and the types of DNA damage that can occur. We also briefly touch on the clinical consequences of OS‐induced DNA damage.
Lycopene and male infertility Durairajanayagam, Damayanthi; Agarwal, Ashok; Ong, Chloe ...
Asian journal of andrology,
05/2014, Volume:
16, Issue:
3
Journal Article
Peer reviewed
Open access
Excessive amounts of reactive oxygen species (ROS) cause a state of oxidative stress, which result in sperm membrane lipid peroxidation, DNA damage and apoptosis, leading to decreased sperm viability ...and motility. Elevated levels of ROS are a major cause of idiopathic male factor infertility, which is an increasingly common problem today. Lycopene, the most potent singlet oxygen quencher of all carotenoids, is a possible treatment option for male infertility because of its antioxidant properties. By reacting with and neutralizing free radicals, lycopene could reduce the incidence of oxidative stress and thus, lessen the damage that would otherwise be inflicted on spermatozoa. It is postulated that lycopene may have other beneficial effects via nonoxidative mechanisms in the testis, such as gap junction communication, modulation of gene expression, regulation of the cell cycle and immunoenhancement. Various lycopene supplementation studies conducted on both humans and animals have shown promising results in alleviating male infertility--lipid peroxidation and DNA damage were decreased, while sperm count and viability, and general immunity were increased. Improvement of these parameters indicates a reduction in oxidative stress, and thus the spermatozoa is less vulnerable to oxidative damage, which increases the chances of a normal sperm fertilizing the egg. Human trials have reported improvement in sperm parameters and pregnancy rates with supplementation of 4-8 mg of lycopene daily for 3-12 months. However, further detailed and extensive research is still required to determine the dosage and the usefulness of lycopene as a treatment for male infertility.
Abstract
STUDY QUESTION
Is there a temporal relationship between endometriosis and infertility?
SUMMARY ANSWER
Endometriosis is associated with a higher risk of subsequent infertility, but only among ...women age <35 years.
WHAT IS KNOWN ALREADY
Endometriosis is the most commonly observed gynecologic pathology among infertile women undergoing laparoscopic examination. Whether endometriosis is a cause of infertility or an incidental discovery during the infertility examination is unknown.
STUDY DESIGN, SIZE, DURATION
This study included data collected from 58 427 married premenopausal female nurses <40 years of age from 1989 to 2005, who are participants of the Nurses' Health Study II prospective cohort.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Our exposure was laparoscopically confirmed endometriosis. Multivariate Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for infertility risk (defined as attempting to conceive for >12 months) among women with and without endometriosis.
MAIN RESULTS AND THE ROLE OF CHANCE
We identified 4612 incident cases of infertility due to any cause over 362 219 person-years of follow-up. Compared with women without a history of endometriosis, women with endometriosis had an age-adjusted 2-fold increased risk of incident infertility (HR = 2.12, 95% CI = 1.76–2.56) that attenuated slightly after accounting for parity. The relationship with endometriosis was only observed among women <35 years of age (multivariate HR <35 years = 1.77, 95% CI = 1.46–2.14; multivariate HR 35–39 years = 1.20, 95% CI = 0.94–1.53; P-interaction = 0.008). Risk of primary versus secondary infertility was similar subsequent to endometriosis diagnosis. Among women with primary infertility, 50% became parous after the endometriosis diagnosis, and among all women with endometriosis, 83% were parous by age 40 years.
LIMITATIONS, REASONS FOR CAUTION
We did not have information on participants' intentions to conceive, but by restricting the analytic population to married women we increased the likelihood that pregnancies were planned (and therefore infertility would be recognized). Women in our cohort with undiagnosed asymptomatic endometriosis will be misclassified as unexposed. However, the small proportion of these women are diluted among the >50 000 women accurately classified as endometriosis-free, minimizing the impact of exposure misclassification on the effect estimates.
WIDER IMPLICATIONS OF THE FINDINGS
This study supports a temporal association between endometriosis and infertility risk. Our prospective analysis indicates a possible detection bias in previous studies, with our findings suggesting that the infertility risk posed by endometriosis is about half the estimates observed in cross-sectional analyses.
STUDY FUNDING/COMPETING INTERESTS
This work was supported by the National Institutes of Health (grant numbers: UM1 CA176726, HD52473, HD57210, T32DK007703, T32HD060454, K01DK103720). We have no competing interests to declare.
Introduction
The
long interspersed nuclear element-1
(
LINE1
) gene is a retrotransposon whose methylation status appears to play a role in spermatogenesis, the outcome of assisted reproductive ...techniques (ART), and even in recurrent pregnancy loss (RPL). Advanced paternal age appears associated with altered sperm parameters, RPL, poor ART outcomes, and compromised offspring health. The methylation status of
LINE1
has been reported to be affected by age. The latest meta-analysis on the
LINE1
methylation pattern in spermatozoa found no significant differences in methylation levels between infertile patients and fertile controls. However, to the best of our knowledge, no updated meta-analysis on this topic has been published recently. Furthermore, no comprehensive meta-regression analysis was performed to investigate the association between sperm
LINE1
methylation pattern and age.
Objectives
To provide an updated and comprehensive systematic review and meta-analysis on sperm
LINE1
gene methylation degree in patients with abnormal sperm parameters compared to men with normal sperm parameters and to probe the association between sperm
LINE1
methylation status and age and/or sperm concentration.
Methods
This meta-analysis was registered in PROSPERO (registration n. CRD42023397056). It was performed according to the MOOSE guidelines for Meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Only original articles evaluating
LINE1
gene methylation in spermatozoa from patients with infertility or abnormalities in one or more sperm parameters compared to fertile or normozoospermic men were included.
Results
Of 192 abstracts evaluated for eligibility, only 5 studies were included in the quantitative synthesis, involving a total of 340 patients and 150 controls. Our analysis showed no significant difference in
LINE1
gene methylation degree in patients with infertility and/or abnormal sperm parameters compared to fertile controls and/or men with normal sperm parameters, although there was significant heterogeneity across studies. No significant evidence of publication bias was found, and no study was sensitive enough to alter the results. In meta-regression analysis, we found that the results were independent of both ages and sperm concentration. A sub-analysis examining patients and controls separately was also conducted and we found a trend for a positive correlation between
LINE1
methylation and sperm concentration in the control group only.
Conclusions
The results of this systematic review and meta-analysis do not suggest a determining role of sperm
LINE1
gene methylation degree in patients with infertility and/or abnormal sperm parameters. Therefore, we do not suggest including
LINE1
in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to be analyzed in couples undergoing ART cycles.
clinical infertility is failure to conceive within a year of regular sexual intercourse by a non contracepting couple. Infertility care is costly and result in investigations being incomplete and ...inconclusive. It is therefore important to streamline investigations offered to infertile couples such that only the most cost effective tests are done. This paper explores the adequacy of investigations and treatments offered to women presenting for infertility care.
the data used in this analysis was obtained from a cross sectional sample of 216 women who presented with infertility in public and private gynaecological clinics in Harare, Zimbabwe. Information on investigations and treatment offered to women presenting for care was extracted from hospital cards, case notes, laboratory and radiological reports. Data was analysed using STATA SE/15.
of the 178 (82.4%) who had ultrasound scan evaluation (USS) 50 (28.1%) had fibroids and 22 (12.4%) had polycystic ovaries. Tubal patency tests were done in 118 participants using (hystero-salpingogram) HSG alone in 62.7%, laparoscope and dye alone in 21.2% and both in 16.1% of them. Of the 97 (44.9%) men who had semen analysis 61 (62.9%) had abnormal parameters.
this study reveals that evaluation for tubal patency and USS to rule out reproductive organ pathology are not being offered to all women with a diagnosis of infertility. Likewise, male partner semen evaluation is not being done in all male partners. There is a high prevalence of abnormal semen parameters. Studies should be done to understand why some male partners are not forthcoming in providing semen for analysis. It is important for protocols to be produced by professional bodies which prescribe the minimum basic investigations in couples with infertility.
To assess fertility counseling and preservation practices among children, adolescents, and young adults with rheumatic diseases undergoing cyclophosphamide (CTX) treatment.
Retrospective chart review ...(2006-2016).
Academic pediatric center.
Male and female patients with systemic lupus erythematosus, Wegener's granulomatosis/granulomatosis with polyangiitis, or other vaculitides, receiving CTX treatment.
None.
Documentation of fertility counseling and fertility preservation.
A total of 58 subjects met the inclusion criteria; 5 were excluded due to incomplete records, thus N = 53. Of these 75% were female (N = 40). Median age was 14 years at diagnosis and 15 years at first CTX treatment. A total of 51% of subjects (69% of males and 45% of females) had no documentation about potential fertility loss before CTX treatment. Among females where fertility counseling was documented, the only fertility preservation option discussed was leuprolide acetate (LA), which was pursued in all of these cases. Of 13 males (77% postpubertal), 3 were offered sperm banking, of whom 2 declined and the other attempted after treatment began and was azoospermic. Of 53 patients, 1 was referred to a fertility specialist. Mean cumulative CTX dose was 9.2 g in males and 8 g in females.
Based on these findings, increasing awareness about infertility risk, fertility preservation options, and referral to fertility specialists is needed among pediatric rheumatologists. Prospective studies are needed to assess fertility outcomes in this patient population (including effectiveness of LA with regard to pregnancy rates PRs), as well as barriers/facilitators to fertility counseling and fertility preservation.
Semen abnormality (SA) male infertility has become a worldwide reproductive health problem. The invasive tests (e.g., testicular biopsy) and labor-intensive methods of semen collection severely ...inhibit diagnosis of male infertility. In addition, the pathogenesis and biological interpretation of male infertility are still obscure. In this report, a total of 84 semen abnormality (SA) patients, diagnosed as teratozoospermia (TE, n = 21), asthenozoospermia (AS, n = 23), oligozoospermia (OL, n = 20), azoospermia (AZ, n = 20), and age-matched healthy controls (HC, n = 29) were analyzed by GC-MS for discrimination analysis and discovery of potential biomarkers. Twenty-three biomarkers were obtained by multivariate statistical method (partial least squares-discriminant analysis, PLS-DA) and univariate statistical method (analysis of variance, ANOVA) with comparisons of TE versus HC, AS versus HC, OL versus HC and AZ versus HC. Based on those biomarkers, the most relevant pathways were mainly associated with the metabolism of carbohydrates, amino acids, and lipids. The principal metabolic alternations in SA male infertility included increased levels of energy-related metabolisms, such as tricarboxylic acid cycle, pyruvate metabolism, glyoxylate and dicarboxylate metabolism, glycine, serine, threonine metabolism and saturated fatty acid metabolism. Furthermore, increased levels of glutathione metabolism were related to oxidative stress. Finally, decreased levels of arginine and proline metabolism and inositol phosphate metabolism were observed. In conclusion, blood plasma metabolomics is powerful for characterizing metabolic disturbances in SA male infertility. From metabolic pathway analysis, energy production, oxidation stress and the released enzyme during spermatogenesis take the primary responsibilities for SA male infertility.
Varicocele is a common medical condition entangled with many controversies. Though it is highly prevalent in men with infertility, still it marks its presence in males who do have normal fertility. ...Determining which patients are negatively affected by varicocele would enable clinicians to better select those men who benefitted the most from surgery. Since conventional semen analysis has been limited in its ability to evaluate the negative effects of varicocele on fertility, a multitude of specialized laboratory tests have emerged. In this review, we examine the role and significance of specialized sperm function tests with regards to varicocele. Among the various tests, analysis of sperm DNA fragmentation and measurements of oxidative stress markers provide an independent measure of fertility in men with varicocele. These diagnostic modalities have both diagnostic and prognostic information complementary to, but distinct from conventional sperm parameters. Test results can guide management and aid in monitoring intervention outcomes. Proteomics, metabolomics, and genomics are areas; though still developing, holding promise to revolutionize our understanding of reproductive physiology, including varicocele.