Spermotrend Improves Semen Quality and Infertility in Men with Varicocele —Spermotrend and Male Infertility

Background: Infertility affects 8% - 12% of couples globally, with approximately half of the cases reported in males. Oxidative stress is a common factor increased in the varicocele condition and particularly affects spermatozoa, due to their sensitivity to oxidative signals and testicular hypotrophy. The objective of this clinical trial is to study the effectiveness of Spermotrend in the improvement of sperm parameters in male infertility. Methods: A total of 170 males aged > 18 years with a diagnosis of infertility and varicocele were consecutively enrolled in a Phase II, open-label clinical trial. Spermotrend was administered 1 capsule (450 mg) orally every 8 hours for 6 months and was evaluated through semen analysis at 4 and 6 months of follow-up. Results: The trial results show a significant improvement following the administration of Spermotrend over 6 months in sperm concentration (44.1% at baseline vs. 64.1% at 6 months), sperm survival (28.2% with sperm survival ≥ 2 hours vs.56.5%), normalization of sperm morphology (31.2% vs. 72.9%). Varicocele condition decreased in all patients and, by the end of the study, 55.3% of patients had normal venous flow and dilation. Only 5.9% of the patients showed grade 2 varicocele at the end of the study, while 38.8% showed grade 1 varicocele, with no patients showing grade 3 varicocele. Regarding testicular hypotrophy, 90.6% of the patients completed the study with normalized testicular volume by recovering normal venous flow. Conclusion: A short-term course of Spermotrend may significantly improve sperm parameters associated with male infertility. Clinical Trial Registration: The clinical trial protocol was registered in the international clinical trial registry, ClinicalTrials.gov, with the code: NCT05222841 on 15/06/2021.

Epidemiological and Clinical Aspects of Male Infertility in Patients Consulting at the Urology Department of the Yaounde Central Hospital

Introduction: About 10 to 15% of couples in the world and 20 to 30% in Cameroon consult for infertility problems. Infertility is of male origin in 40% of cases. Our objective was to evaluate the epidemiological and clinical aspects of male infertility in our setting. Methods: This was a cross-sectional and descriptive study, with retrospective data collection from the files of patients received for male infertility, over 5 years and 6 months (from January 1st, 2016 to April 30th, 2021) at the Urology Department of the Yaounde Central Hospital. Phone calls were made to patients with incomplete records for completion following a verbal consent. Data reported on data collection forms were entered into a data entry form designed on CSPro software version 7.2. The database was later exported for descriptive statistics using the IBM SPSS software version 23. Qualitative variables were summarized in frequencies and percentages while quantitative variables were summarized in means with their standard deviations for normally distributed data, or medians and interquartile ranges otherwise. Results: Out of 110 patients whose records were analyzed, the median age was 37.0 years, with an interquartile range of 8.3, with 55.5% in the age group 30 to 39 years. Of these 95 (86.4%) were married, 58 (52.7%) were from the West region, 76 (69.1%) were employed. Past history was dominated by mumps 40 (36.4%), varicocele surgery 25 (22.7%), alcoholism 87 (79.1%) and smoking 15 (13.6%). A disorder of spermatogenesis was found in all our patients: 37 (33.6%) azoospermia, 27 (24.6%) asthenospermia and 26 (23.7%) oligospermia patients. Paraclinical evidence of chlamydia and gonococcal infections were found respectively in 38 (34.5%) and 14 (12.7%) patients, varicocele and testicular dystrophy respectively in 95 (86.4%) and 38 (34.5%) patients. Infertility was primary in 67 (60.9%) patients. Conclusion: Most patients with infertility were in their thirties, had risky social habits and comorbidities. An early start of health promotion activities, comorbidities prevention and early detection of spermogram abnormalities would make it possible to reduce the frequency of male infertility.

Psychosocial Aspects of Male Infertility at the Service of Urology-Andrology of the Hospital of the Sino-Guinean Friendship

Objective: Describe the psychosocial aspects of male infertility at the hospital of the Sino-Guinean Friendship. Patients and method: It is a prospective study of a descriptive type covering a period of 6 months. The study covered 17 patients, all received for a desire to conceive after at least one year of regular sexual intercourse without contraception. The data were collected from patient interviews using a pre-established questionnaire. Results: The average age of the patients was 32.07 years with extremes of 23 years and 42 years. During this study, 64.70% of patients were no longer participating in community ceremonies. The patients’ relationships with their spouse and family deteriorated in 52.94% and 47.06%, respectively. Conversely, relations with the family of origin remained unchanged in 70.59 percent of cases. The reduction in economic activity was by 13 patients (76.48%). Conclusion: Male infertility causes a real psychic earthquake in men with its corollaries of negative feelings. The rather complex moral repercussions of male infertility affect not only the individual, his/her partner, and family, but also economic activity.

The role of small non-coding RNAs(sncRNAs)in male infertility:A scoping review

Objective:To give a brief overview of the field of epigenetics and the potential predictive power that small non-coding RNA(sncRNA)may hold in relation to improving the treatment and diagnosis of male infertility.Methods:PRISMA-ScR was used as the scoping review guideline for this investigation.All article data here have been accessed from MEDLINE–PubMed,Science Direct,EBSCO,Scopus,Sage Journals,and Google Scholar.The terms"small non coding RNA,male,infertility,miRNA,sperm"were used in the search between 2015 and 2023.Results:The study comprised 35 publications in total.Several sncRNAs,miR-155,miR-16,miR-196,miR-525-3p,miR-891 were found to be effective in regulating the mechanism of spermatozoa processing in the infertility of men.sncRNA can be used as a biomarker of male infertility.Conclusions:sncRNAs can act as biomarkers for the diagnosis of reproductive diseases.Actually,by recognizing sncRNAs and their mechanisms,a new way to treat infertile men would be paved.The functional annotation of sncRNAs in spermatogenesis is still in its infancy but has enormous potential.This is despite the fact that many potential sncRNAs have been found to date with the use of cutting-edge technology and publicly accessible sncRNA annotation tools.

Chromosomal disorders and male infertility

Infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family. Despite this, the molecular and genetic factors underlying the cause of infertility remain largely undiscovered. Nevertheless, more and more genetic factors associated with infertility are being identified. This review will focus on our current understanding of the chromosomal basis of male infertility specifically： chromosomal aneuploidy, structural and numerical karyotype abnormalities and Y chromosomal microdeletions. Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans. Aneuploidy is predominantly maternal in origin, but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts. Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm. Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed, as well as the application of preimplantation genetic diagnosis （PGD） in such cases. Clinical recommendations where possible will be made, as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility.

Lycopene and male infertility

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.

Human protamines and the developing spermatid: their structure, function, expression and relationshipwith male infertility

<abstract>During spermiogenesis, the protamine proteins play an integral role in spermatid chromatin compaction. Recent research has focused on many facets of protamine biology, including protamine gene and protein structure/ function relationships, mechanisms of protamine expression regulation and involvement of the protamines in male fertility. In this paper, we review our current understanding of the structure and function of the protamine-1 (P1) and protamine-2 (P2) proteins and genes, the expression and regulation of these genes and the relationship between the protamines and male fertility. In addition, we offer a brief outlook on future investigation into protamine proteins.

Prevalent false positives of azoospermia factor a （AZFa） microdeletions caused by single-nucleotide polymorphism rs72609647 in the sY84 screening of male infertility

Multiplex polymerase chain reaction （PCR） has been widely used to detect Y-chromosome micredeletions, which is one of the major causes of male infertility. Both the European Academy of Andrology （EAA） and the European Molecular Genetics Quality Network （EMQN） have recommended the use of sY84 and sY86 markers for the detection of azoospermia factor a （AZFa） microdeletion during DNA testing for male infertility. In this study, a large-scale analysis of AZF microdeletion in a total of 630 Chinese males, including healthy semen donors （n=200）, infertile males with normal sperm count （n=226） and patients with either nonobstructive azoospermia or severe oligozoospermia （n=204）, was performed. A series of nine sequence-tagged site （STS） markers from the AZF region of the Y chromosome was used to detect microdeletions. All primers were designed based on the recommendations of the National Center for Biotechnology Information. An unusually high incidence （73/630, 11.6%） of sY84-absent but sY86-present genotypes was observed in the AZFa microdeletion screening. Sequencing the sY84-flanking region revealed a total of 73 patients with sY84-absent but sY86-present genotypes have a T-to-G transversion at the fifth base from the 5＇ end of the reverse sY84 primer. These prevalent false positives, which were not only observed in infertile men, but also observed in donors, resulted from a single-nucleotide polymorphism （SNP） named rs72609647 in the targeting sequence of the reverse sY84 primer. Our study suggests that a pre-screening of existence of rs72609647 polymorphism can prevent the frequent false positive results of AZFa microdeletions detection in the infertile Chinese males. Given the SNP rs72609647 was recently found in a deep sequencing of a Chinese individual, the current EAA and EMQN standards may need to be scrutinized among different populations to avoid the potential genetic variations in the primer binding sequences.

"Micro-deletions" of the human Y chromosome and their relationship with male infertility

The Y chromosome evolves from an autochromosome and accumulates male-related genes including sex-determining region of Y-chromosome （SRY） and several spermatogenesis-related genes. The human Y chromosome （60 Mb long） is largely composed of repetitive sequences that give it a heterochromatic appearance, and it consists of pseudoautosomal, euchromatic, and heterochromatic regions. Located on the two extremities of the Y chromosome, pseudoautosomal regions 1 and 2 （PAR1 and PAR2, 2.6 Mb and 320 bp long, respectively） are homologs with the termini of the X chromosome. The euchromatic region and some of the repeat-rich heterochromatic parts of the Y chromosome are called ＂male-specific Y＂ （MSY）, which occupy more than 95% of the whole Y chromosome. After evolution, the Y chromosome becomes the smallest in size with the least number of genes but with the most number of copies of genes that are mostly spermatogenesis-related. The Y chromosome is characterized by highly repetitive sequences （including direct repeats, inverted repeats, and palindromes） and high polymorphism. Several gene rearrangements on the Y chromosome occur during evolution owing to its specific gene structure. The consequences of such rearrangements are not only loss but also gain of specific genes. One hundred and fifty three haplotypes have been discovered in the human Y chromosome. The structure of the Y chromosome in the GenBank belongs to haplotype R1. There are 220 genes （104 coding genes, 111 pseudogenes, and 5 other uncategorized genes） according to the most recent count. The 104 coding genes encode a total of about 48 proteins/protein families （including putative proteins/protein families）. Among them, 16 gene products have been discovered in the azoospermia factor region （AZF） and are related to spermatogenesis. It has been discovered that one subset of gene rearrangements on the Y chromosome, ＂micro-deletions＂, is a major cause of male infertility in some populations. However, controversies exist about different Y chromosome haplotypes. Six AZFs of the Y chromosome have been discovered including AZFa, AZFb, AZFc, and their combinations AZFbc, AZFabc, and partial AZFc called AZFc/gr/gr. Different deletions in AZF lead to different content spermatogenesis loss from teratozoospermia to infertility in different populations depending on their Y haplotypes. This article describes the structure of the human Y chromosome and investigates the causes of micro-deletions and their relationship with male infertility from the view of chromosome evolution. After analysis of the relationship between AZFc and male infertility, we concluded that spermatogenesis is controlled by a network of genes, which may locate on the Y chromosome, the autochromosomes, or even on the X chromosome. Further investigation of the molecular mechanisms underlying male fertility/infertility will facilitate our knowledge of functional genomics.

Correlation between HPV sperm infection and male infertility

Human papillomavirus （HPV） is one of the most common sexually transmitted diseases which comprises a group of small DNA viruses that infect both cutaneous and mucous squamous epithelia. Liquid bead microarray technology （LBMA） were used to evaluate 24 HPV genotypes in confirmed fertile and infertile males of North China so that the effects of HPV infection on semen parameters and relationship with male infertility could be discussed. A total of 1138 subjects were recruited in this study; 142 were HPV-positive （12.48%）. Among 523 confirmed fertile males, only 35 were HPV-positive （6.70%）, and two of them had multiple infections. Among 615 infertile males, 107 were HPV-positive （17.4%）, and 29 of them had multiple infections. Infertile males had a relatively high HPV infection rate compared with confirmed fertile males. Sperm progressive motility （PR） and the normal morphology rate were significantly decreased in HPV-positive subjects. HPV-45, HPV-52, HPV-18, HPV-59 and HPV-16 infections were more frequently in infertile males. Hence, HPV infection is closely related to male infertility which will decrease sperm PR and morphology. HPV-45, HPV-52, HPV-18, HPV-59 and HPV-16 infection seems to be major risk factors.

Male infertility microsurgical training

Microsurgical training is imperative for urologists and clinical andrologists specializing in male infertility. Success in male infertility microsurgery is heavily dependent on the surgeon＇s microsurgical skills. Laboratory-based practice to enhance microsurgical skills improves the surgeon＇s confidence, and reduces stress and operating time, benefiting both the patient and the surgeon. This review provides guidelines for setting up a microsurgical laboratory to develop and enhance microsurgical skills using synthetic and animal models. The role of emerginE techniaues, such as robotic-assisted microsureerv, is also discussed.

Combined conventional/antioxidant“Astaxanthin”treatment for male infertility:a double blind,randomized trial

Aim： To evaluate the treatment of male infertility with a strong natural antioxidant, in addition to conventional treatment. Methods： Using a double blind, randomized trial design, 30 men with infertility of ≥12 months and female partners with no demonstrable cause of infertility received conventional treatment according to the guidelines of the World Health Organization （WHO）, and either a strong antioxidant Astaxanthin 16 rag/day （AstaCarox, AstaReal AB, Gustavsberg, Sweden） or placebo for 3 months. The effects of treatment on semen parameters, reactive oxygen species （ROS）, zona-free hamster oocyte test, serum hormones including testosterone, luteinizing hormone （LH）, follicle stimulating hormone （FSH） and Inhibin B, and spontaneous or intrauterine insemination （IUI）-induced pregnancies were evaluated. Results： ROS and Inhibin B decreased significantly and sperm linear velocity increased in the Astaxanthin group （n = 11）, but not in the placebo group （n = 19）. The results of the zona-free hamster oocyte test tended to improve in the Astaxanthin group in contrast with the placebo group, though not reaching statistical significance. The total and per cycle pregnancy rates among the placebo cases （10.5 % and 3.6 %） were lower compared with 54.5 % and 23. 1% respectively in the Astaxanthin group （P=0.028; P=0.036）. Conclusion： Although the present study suggests a positive effect of Astaxanthin on sperm parameters and fertility, the results need to be confirmed in a larger trial before recommending Astaxanthin for the complementary treatment of infertile men. （Asian J Androl 2005 Sep; 7： 257-262）

The role of antioxidant therapy in the treatment of male infertility： an overview

In recent years, many studies have focused on the effect of oxidative stress, reactive oxygen species （ROS） and antioxidants on the male eproductive system. Under physiological conditions, sperm produces small amounts of ROS, which are needed for fertilisation, acrosome reaction and capacitation. However, if an increased production of ROS is not associated with a similar increase in scavenging systems, peroxidative damage of the sperm plasma membrane and loss of DNA integrity typically occur, which leads to cell death and reduced fertility. Furthermore, since there is no linear correlation between sperm quality and pregnancy rates, an improvement in semen parameters should not be the sole outcome considered in studies of antioxidant therapies. A definitive conclusion regarding the benefit of these therapies is difficult to obtain, as most of the previous studies lacked control groups, considered different antioxidants in different combinations and doses, or did not evaluate pregnancy rates in previously infertile couples. Even if beneficial effects were reported in a few cases of male infertility, more multicentre, double-blind studies performed with the same criteria are necessarv for an increased understanding of the effects of various antioxidants on fertility,

Vleiotic recombination and male infertility： from basic science to clinical reality？

Infertility is a common problem that affects approximately 15% of the population. Although many advances have been made in the treatment of infertility, the molecular and genetic causes of male infertility remain largely elusive. This review will present a summary of our current knowledge on the genetic origin of male infertility and the key events of male meiosis. It focuses on chromosome synapsis and meiotic recombination and the problems that arise when errors in these processes occur, specifically meiotic arrest and chromosome aneuploidy, the leading cause of pregnancy loss in humans. In addition, meiosis-specific candidate genes will be discussed, including a discussion on why we have been largely unsuccessful at identifying disease-causing mutations in infertile men. Finally clinical applications of sperm aneuploidy screening will be touched upon along with future prospective clinical tests to better characterize male infertility in a move towards personalized medicine.

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.

Male infertility: risk factors in Mongolian men

Aim: To determine the most common risk factors of male infertility in Mongolian men attending an infertility clinic. Methods: A prospective, case-control study was conducted in which 430 men were enrolled. All the men had sought their first infertility evaluation between 1998-2002 in the State Research Center on Maternal Child Health, Ulaanbaatar, Mongolia. They were divided into two groups depending on the results of their semen analysis: 191 with abnormal semen and 239 with normal semen profile. Univariate and multivariate analyses were performed to determine any association between risk factors and semen abnormality. Results: Logistic regression analysis demonstrated that the testicular volume, a history of sexually transmitted infections (STI), epididymitis and testicular damage all have statistically significant associations with semen abnormality, when controlled for multiple risk factors. Adjusted odds ratios of 3.4 for mumps orchitis, 2.3 for other orchitis and 3.9 for testicular injury were found. Gonorrhoea, the most commonly reported STIs in this study, gave an adjusted odds ratio of 1.0 for having one or more sperm abnormality. An adjusted odds ratio for subjects with a history of other STIs was 2.7. However, as a predictor of azoospermia, STIs had very high odds ratio, being 5.6 in patients with gonorrhoea and 7.6 in patients with other STIs. Conclusion: A history of pathology involving testicular damage appeared to have the strongest impact on male infertility in Mongolia. STIs have less impact on semen quality except when complicated by orchitis, epididymitis and vasal obstruction.

Surgical techniques for the management of male infertility

Evaluation and surgical treatment of male infertility has evolved and expanded, now leading to more precise diagnoses and tailored treatments with diminished morbidity and greater success. Surgeries for male infertility are divided into four major categories： （i） diagnostic surgery; （ii） surgery to improve sperm production; （iii） surgery to improve sperm delivery; and （iv） surgery to retrieve sperm for use with in vitrofertilization and intracytoplasmic sperm injection （IVF-ICSI）. While today we are more successful than ever in treating male infertility, pregnancy is still not always achieved likely due to factors that remain poorly understood. Clinicians treating infertility should advocate for couple-based therapy, and require that both partners have a thorough evaluation and an informed discussion before undergoing specific surgical therapies.

Genetic variants in TP53 and MDM2 associated with male infertility in Chinese population

The TP53, a transcriptional regulator and tumor suppressor, is functionally important in spermatogenesis. MDM2 is a key regulator of the p53 pathway and modulates p53 activity. Both proteins have been functionally linked to germ cell apoptosis, which may affect human infertility, but very little is known on how common polymorphisms in these genes may influence germ cell apoptosis and the risk of male infertility. Thus, this study was designed to test whether three previously described polymorphisms 72Arg〉Pro （rs1042522） and the Ex2＋ 19C〉T （rs2287498） in TP53, and the 5＇ untranslated region （5＇ UTR） 309T〉G （rs937283） in MDM2, are associated with idiopathic male infertility in a Chinese population. The three polymorphisms were genotyped using OpenArray assay in a hospital-based case-control study, including 580 infertile patients and 580 fertile controls. Our analyses revealed that TP53 Ex2-1-19C〉T and MDM2 309T〉G polymorphisms are associated with male infertility. Furthermore, we detected a nearly statistically significant additive interaction between TP53 rs2287498 and MDM2 rs937283 for the development of male infertility （Pinteraction--O-055）- In summary, this study found preliminary evidence, demonstrating that genetic variants in genes of the TP53 pathway are risk factors for male infertility.

Eurycoma longifolia Jack in managing idiopathic male infertility

This study investigated the effect of treatment with the proprietary standardized, water-soluble extract of the root of the Malaysian plant, Eurycoma longifolia Jack, which is thought to enhance male fertility with regard to higher semen volumes, sperm concentrations, the percentage of normal sperm morphology and sperm motility in male partners of sub-fertile couples with idiopathic infertility. A total of 350 patients were given 200 mg of the extract daily and follow-up semen analyses were performed every 3 months for 9 months. Of these 350 patients, 75 patients completed one full cycle of 3 months. Follow-up semen analyses in these patients showed significant improvement in all semen parameters. The proprietary extract of Eurycoma longifolia Jack significantly improved the sperm quality in these patients, allowing for 11 （14.7%） spontaneous pregnancies.

The genetic variation in Monocarboxylic acid transporter 2 （MCT2） has functional and clinical relevance with male infertility

Monocarboxylic acid transporter 2 （MCT2） transports pyruvate and lactate outside and inside of sperms, mainly as energy sources and plays roles in the regulation of spermatogenesis. We investigated the association among genetic variations in the MCT2 gene, male infertility and MCT2 expression levels in sperm. The functional and genetic significance of the intron 2 （＋28201A 〉 G, rs10506398） and 3＇ untranslated region （UTR） single nucleotide polymorphism （SNP） （＋2626G 〉 A, rs10506399） of MCT2 variants were investigated. Two MCT2 polymorphisms were associated with male infertility （n = 471, P 〈 0.05）. In particular, the MCT2-3＇ UTR SNP （＋2626 G 〉 A） had a strong association with the oligoasthenoteratozoospermia （OAT） group. The ＋2626GG type had an almost 2.4-fold higher sperm count than that of the ＋2626AA type （＋2626GG; 66 x 106 vs ＋2626AA; 27 x 106, P 〈 0.0001）. The MCT2-3＇ UTR SNP may be important for expression, as it is located at the MCT2 3＇ UTR. The average MCT2 protein amount in sperm of the ＋2626GG type was about two times higher than that of the ＋2626AA type. The results suggest that genetic variation in MCT2 has functional and clinical relevance with male infertility.