Cambios morfofuncionales de los espermatozoides y factores de riesgo asociados a la infertilidad masculina

Introducción: En la actualidad muchos estudios han mostrado un declinar en la calidad del semen humano y un riesgo incrementado de subfertilidad masculina. Objetivo: Evaluar el grado de asociación de los cambios morfofuncionales de los espermatozoides con los factores de riesgo en la infertilidad masculina. Métodos: Se realizó un estudio descriptivo transversal a los 123 pacientes con alteraciones en el espermograma que acudieron al Centro Territorial de Atención a la Pareja Infértil de la provincia Holguín en el año 2021 que cumplían con los criterios de inclusión y exclusión establecidos. La información fue obtenida a partir de la revisión de las historias clínicas y la realización de un cuestionario. Se utilizó la prueba de correlación de Spearman para identificar la relación entre las variables estudiadas a un nivel de significancia (=0,05. Resultados: La teratozoospermia fue el cambio morfofuncional que predominó con 69 casos (56,09 %), al ser más frecuente en el grupo de edad de 30 a 39 años (22, 76 %), la exposición a temperaturas elevadas con 19,51 % y el varicocele con un 43,9 %. En la correlación de las variables estudiadas mostró una mayor asociación la malnutrición por exceso y la teratozoospermia en 44 pacientes. Conclusiones: La evaluación de los cambios morfofuncionales de los espermatozoides permitió́ conocer un predominio de los relacionados a la morfología. Factores de riesgo como la edad mayor de 30 años, la malnutrición por exceso, la exposición a altas temperaturas y el varicocele se asocian a la infertilidad masculina.

Introduction: As of the present moment many studies have evidenced a decline in the quality of the human semen and an incremented risk masculine sub-fertility. Objective: To evaluate the association's grade of the morphologic and functional changes of the spermatozoa with the risk factors in the masculine infertility. Methods: A descriptive transverse study was carried out in the 123 patients with alterations in the spermogram attended in the Territorial Center of Attention to the Infertile Couple in Holguín in the year 2021, and that fulfilled the established criteria of inclusion and exclusion. The information was gotten from the revision of the case histories and the realization of a questionnaire. Spearman's correlation to identify the relation between the studied variables was used. Results: The teratozoospermia was the morphofunctional change that predominated with 69 cases (56.09 %), being more frequent in the age bracket of 30 to 39 years (22 for a 76 %), the exposition to temperatures raised with 19.51 % and the varicocele with a 43.9 %. The malnutrition for excess and teratozoospermic in 44 patients evidenced a bigger association in the correlation of the studied variables. Conclusions: The evaluation of the changes allowed morphologic and functional of spermatozoa knowing a predominance of the related to the morphology. Risk factors like an age older than 30 years, the malnutrition for excess, the exposition to loud temperatures and the varicocele correlate to the masculine infertility.

Recombinant gonadotropin therapy to improve spermatogenesis in nonobstructive azoospermic patients - A proof of concept study

ABSTRACT Purpose: Nonobstructive azoospermia (NOA) associated with primary spermatogenic failure is a common cause of male infertility usually considered untreatable; however, some reports have suggested that hormonal stimulation to boost the intra-testicular testosterone level and spermatogenesis might increase the chance of achieving pregnancy using homologous sperm. Materials and Methods: We report a series of eight NOA males who received long-term treatment with recombinant human chorionic gonadotropin twice a week for spermatogenesis stimulation. Six males received additional recombinant follicle-stimulating hormone (FSH) supplementation 150-225 IU twice weekly. Results: After recombinant gonadotropin therapy, viable spermatozoa were retrieved from the ejaculate in two patients and by testicular sperm aspiration (TESA) in another two subjects. Singleton spermatozoon retrieved from testes were frozen by vitrification on Cell-Sleeper devices. Two live births were obtained after intracytoplasmic sperm injection with ejaculated spermatozoa and one live birth and an ongoing pregnancy using thawed spermatozoa from TESA. Conclusion: Our proof-of-concept study indicates that hormonal therapy with recombinant gonadotropins could be considered in infertile men with NOA as an alternative to sperm donation. Large-scale studies are needed to substantiate hormone stimulation therapy with recombinant gonadotropins in routine clinical practice for this severe form of male infertility.

Research progress of genetic testing in male infertility / 中华检验医学杂志

About 15% of the world's population at child-bearing age suffer from infertility. After cancer and cardiovascular and cerebrovascular diseases, the infertility will become the third-largest intractable disease. Among the causes of infertility, male factors account for about half. As a main male factor, genetic factor has become the focus of reproductive research in recent years. Therefore, to formulate a corresponding diagnosis and treatment scheme for male infertility, accurate genetic testing is needed. It is an effective means to meet the demand of high fertility and solve the problem of population decline in current society.

Study on the correlation between male serum calcitonin gene-related peptide and the embryo culture outcome after in vitro fertilization / 中华检验医学杂志

Objective:To investigate the correlation between serum calcitonin gene-related peptide (CGRP) and the culture outcome of in vitro fertilization embryo in male patients with infertility.Methods:In this study, the randomized samples from 25 male patients who received in vitro fertilization-embryo transfer (IVF-ET) in the 1st Affiliated Hospital of Fujian Medical University from June 2019 to October 2019 were analyzed by multiple linear stepwise regression, with some important clinical outcomes, such as the logarithmic conversion index of serum CGRP, fertilization method, masturbation difficulty, age, infertility duration, and prolactin, as independent variables, while total fertilization rate, normal fertilization rate, high quality embryo rate at day 3, blastocyst formation rate as dependent variables.Results:The Pearson correlation analysis showed that the D3 high-quality embryo rate was related to the normal sperm morphology rate in the primary infertility group ( r=0.537, P=0.048), the blastocyst formation rate was correlated with sperm density ( r=0.760, P=0.002), the CGRP logarithm was correlated with the total fertilization rate ( r=0.693, P=0.006). The logarithmic conversion index of serum CGRP was related to the total fertilization rate and normal fertilization rate in the secondary infertility group ( r=0.614, P=0.042 and r=0.611, P=0.046). In the secondary infertility group, there was a linear relationship between normal fertilization rate and total sperm count, serum CGRP log conversion, and sperm normal morphology rate, with standardized regression coefficients of 0.2, -0.729, and 6.8, respectively. Conclusion:Serum CGRP level, together with total sperm count and normal sperm morphology rate may affects normal fertilization rate in male patients with infertility.

Oxidative origin of sperm DNA fragmentation in the adult varicocele

ABSTRACT Purpose: Sperm DNA fragmentation is a major cellular mechanism underlying varicocele-related male infertility. However, the type of DNA fragmentation - whether oxidative or of another nature - remains unknown. Thus, the aim of this study was to evaluate single- and double-stranded sperm DNA fragmentation, and oxidative-induced sperm DNA damage in men with varicocele. Materials and Methods: A cross-sectional study was performed, including 94 normozoospermic adults, of which 39 men without varicocele (controls) and 55 men with varicocele grades II or III, uni- or bilaterally. All men collected semen by masturbation. After semen analysis, the remaining volume was used for evaluation of three types of sperm DNA damage: (i) total DNA fragmentation, using an alkaline comet assay, (ii) double-stranded DNA fragmentation, using a neutral comet assay, and (iii) oxidative DNA damage, using an alkaline comet assay associated with the DNA glycosylase formamidopyrimidine enzyme. In each assay, percentage of sperm with any degree of DNA fragmentation, and with high DNA fragmentation were compared between the groups using an unpaired Student's t test or a Mann-Whitney test. Results: The varicocele group presented a higher rate of sperm with fragmented DNA (both any and high DNA fragmentation), considering single-stranded DNA fragmentation, double-stranded DNA fragmentation, or a combination of both, as well as oxidative- induced DNA fragmentation. Conclusions: Patients with varicocele have an increase in sperm DNA fragmentation levels, particularly in oxidative stress-induced sperm DNA damage.

The association of seminal oxidation reduction potential with sperm parameters in patients with unexplained and male factor infertility

ABSTRACT Purpose: Understanding the effects of high oxidation reduction potential (ORP) levels on sperm parameters will help to identify patients with unexplained and male factor infertility who may have seminal oxidative stress and determine if ORP testing is needed. This study aimed to evaluate the association between seminal ORP and conventional sperm parameters. Materials and Methods: A total of 58 patients who provided a semen sample for simultaneous evaluation of sperm parameters and ORP between January and September 2019 were enrolled in this retrospective study. To identify normal and high ORP levels, a static ORP (sORP) cut-off value of 1.36mV/106sperm/mL was used. Sperm parameters were compared between infertile men with normal sORP (control group, n=23) and high sORP values (study group, n=35). Results: Men with sORP values >1.36mV/106sperm/mL had significantly lower total sperm count (TSC) (p <0.001), sperm concentration (p <0.001) and total motile sperm count (TMSC) (p <0.001). In addition, progressive motility (p=0.04) and fast forward progressive motility (p <0.001) were significantly lower in the study group. A negative correlation was found between sORP and TSC (r=-0.820, p <0.001), sperm concentration (r=-0.822, p <0.001), TMSC (r=-0.808, p <0.001) and progressive motility (r=-0.378, p=0.004). Non-progressive motility positively correlated with sORP (r=0.344, p=0.010). Conclusions: This study has shown that TSC, sperm concentration, progressive motility and TMSC are associated with seminal oxidative stress, indicated by a sORP cut-off of 1.36mV/106sperm/mL. Presence of oligozoospermia, reduced progressive motilty or low TMSC in sperm analysis should raise the suspicion of oxidative stress and warrants seminal ROS testing.

Protocolo para el manejo de la pareja infértil con implantación de catgut en puntos de acupuntura / Protocol for the management of infertile couples with catgut implantation in acupuncture points

RESUMEN Introducción: en la mujer, el hallazgo inmediato más importante en los estudios de infertilidad es la ausencia de ovulación y aunque en su tratamiento existen alternativas, aún son ineficaces debido a limitaciones diagnósticas y terapéuticas. En las causas masculinas, las alteraciones idiopáticas de la calidad del semen predominan, son más frecuentes la astenozoospermia y oligozoospermia, asociado al diagnóstico de varicocele. Las razones por las cuales el potencial de fertilidad no siempre se mejora después de tratamiento quirúrgico oportuno y adecuado del varicocele, están todavía en estudio, y los tratamientos convencionales propuestos son costosos y no siempre efectivos. Objetivo: elaborar un protocolo para el manejo de la pareja infértil con implantación de catgut en puntos de acupuntura. Desarrollo: se analizaron temáticas sobre la atención a la mujer con ciclos anovulatorios y a hombres infértiles después del tratamiento quirúrgico del varicocele y con infertilidad idiopática y los tratamientos tradicionales propuestos. Se generaron preguntas científicas para confeccionar el protocolo. Protocolo para el manejo de la pareja infértil con implantación de catgut en puntos de acupuntura que incluye: profesionales a quienes va dirigido, población diana, recursos necesarios, equipo de trabajo, papel de los miembros del equipo, secuencia de actuación, modo de realización, ventajas, desventajas y contraindicaciones de la implantación de catgut, diferenciación y tratamiento en cada caso según el diagnóstico tradicional chino e indicadores de evaluación. Conclusiones: la modalidad terapéutica propuesta, es una alternativa inocua y poco costosa que contribuye a mejorar la fecundidad y la natalidad de la pareja infértil.

ABSTRACT Introduction: in women, the most important immediate finding in infertility studies is the nonexistence of ovulation and although there are alternatives in their treatment, they are still ineffective due to diagnostic and therapeutic limitations. In male causes, idiopathic alterations in semen quality predominate, the most frequent being asthenozoospermia and oligozoospermia associated with the diagnosis of varicocele. The reasons why fertility potential is not always improved after timely and adequate surgical treatment of varicocele are still under study, and the proposed conventional treatments are expensive and not always effective. Objective: to elaborate a protocol for the management of the infertile couples with catgut implantation in acupuncture points. Development: topics regarding this protocol were analyzed on the care of women with anovulatory cycles and infertile men after surgical treatment of varicocele along with idiopathic infertility as well as the proposed traditional treatments, generating scientific questions to draw up the protocol. The protocol for the management of infertile couples with implantation of catgut in acupuncture points includes: professionals to whom it is directed, target population, necessary resources, teamwork, role of team members, sequence of action, approach for its implementation, advantages, disadvantages and contraindications concerning the implantation of catgut, differentiation and treatment in each case according to the traditional Chinese diagnosis and assessment indicators. Conclusions: the proposed therapeutic modality is an innocuous and inexpensive alternative that contributes to the improvement of fertility and birth rate in the infertile couples.

Are specialized sperm function tests clinically useful in planning assisted reproductive technology?

CASE STUDY 40-year-old male patient and 32-year-old female partner, with a history of primary infertility of two years duration. The workup revealed idiopathic mild oligoasthenotheratozoospermia, and no apparent female infertility factors. The couple has failed three intrauterine insemination (IUI) cycles, planning more IUI cycles but also considering in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI).

Demographics, Usage Patterns, and Safety of Male Users of Clomiphene in the United States

PURPOSE: The aim of this study was to characterize the demographics, usage patterns and complication rates of clomiphene use in male patients.MATERIALS AND METHODS: We retrospectively analyzed male patients from ages 20 to 55 years old who were prescribed clomiphene citrate from 2001 to 2014 using the Truven Health MarketScan, a US claims database. We collected data regarding associated medical diagnoses, diagnostic testing, duration of use, and reported side effects including thrombotic events, vision problems, gynecomastia, mental disorders, liver disease, nausea, or skin problems.RESULTS: In total, 12,318 men took clomiphene and represented the primary study cohort, with a mean age of 37.8 years. The percentage of men prescribed clomiphene increased over the study period, as did the average age of clomiphene users. Associated diagnoses included male infertility (52.0%), testicular hypofunction (13.5%), erectile dysfunction (2.4%), and low libido (0.4%). Associated testing included semen analysis (43.7%), testosterone (23.5%), luteinizing hormone (19.3%), and follicle-stimulating hormone (21.1%) levels. The median time of clomiphene use was 3.6 months, with 63% of men stopping within 6 months. No increased risk of reported clomiphene side effects were apparent in men taking the medication.CONCLUSIONS: There is a rising prevalence of clomiphene usage without associated adverse side effects in the US. The variability in associated diagnoses, diagnostic testing, and duration of use suggest a need for greater awareness of the proper evaluation and treatment of the men who are prescribed clomiphene.

Research progress of imaging examination in male infertility / 国际外科学杂志

At present,male infertility has become a serious social and medical burden in all countries in the world,and reduce people's happy life index.Base on this,radiologists and clinicians are trying to find some new technologies of the medical image examination methods,including X-rays,B-ultrasound,magnetic resonance imaging,etc,attempt to obtain the exact etiology diagnosis of male infertility in order to get more effective treatments and benefits with more happy families.This article of reviews the application and research progress of the latest imaging techniques in the etiological diagnosis of male infertility in recent years.

Scrotal ultrasonography for treatment choice of obstructive azoospermia / 中国医学影像技术

Objective: To explore the value of scrotal ultrasonography for choice of treatment of obstructive azoospermia. Methods: Totally 93 obstructive azoospermia patients were prospectively collected for scrotal ultrasound to evaluate whether the epididymis and vas deferens were intact, dilated or calcified. The diameter of epididymal duct and vas deferens were measured. Then the patients were divided into sperm extraction group (n=27) or vasal reconstruction group (n=66) according to the treatment. The etiology and sonographic appearances were compared between groups. The cut-off values of ultrasonic parameters were evaluated by ROC curve, followed by the sensitivity, specificity, positive predicative value, negative predicative value and accuracy. Results: There were significant differences of epididymal morphology, vas deferens dysplasia, calcification, and the diameter of epididymal duct between 2 groups (all P<0.05). Taken 0.55 mm for the cut-off value of diameter of epididymal duct, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of correctly identifying the patients suitable for sperm extraction was 87.47%, 86.70%, 77.82%, 92.76% and 87.03%, respectively. Conclusion: Scrotal ultrasonography plays an important role in guiding treatment for patients with obstructive azoospermia.

Microtubular Dysfunction and Male Infertility

Research progress of imaging examination in male infertility / 国际外科学杂志

At present, male infertility has become a serious social and medical burden in all countries in the world, and reduce people′s happy life index. Base on this, radiologists and clinicians are trying to find some new technologies of the medical image examination methods, including X-rays, B-ultrasound, magnetic resonance imaging, etc, attempt to obtain the exact etiology diagnosis of male infertility in order to get more effective treatments and benefits with more happy families. This article of reviews the application and research progress of the latest imaging techniques in the etiological diagnosis of male infertility in recent years.

Testicular Fine-Needle Aspiration for Sperm Retrieval in Azoospermia: A Small Step toward the Technical Standardization

PURPOSE: The aim was to describe our preliminary experience performing testicular fine-needle aspiration (TEFNA) with a larger needle in infertile patients with obstructive azoospermia, and to provide a systematic literature review of the different testicular sperm aspiration techniques, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. MATERIALS AND METHODS: We prospectively collected data between March 2017 and June 2018. All men underwent bilateral TEFNA under analgo-sedation, using a larger disposable 18-gauge butterfly needle with 60 mL Luer-Lock syringe attached to it. RESULTS: Thirty consecutive patients were enrolled. Median operative time was 16 minutes (interquartile range [IQR]: 12–30 minutes). No intraoperative complications occurred. Two/thirty patients (6.7%) reported postoperative adverse events: 1 patient had prolonged orchialgia, 1 patient presented scrotal hematoma. Successful sperm retrieval was found in 28/30 cases (93.3%). Median sperm concentration was 0.05 ×106/mL (IQR: 0.001–0.1 ×106/mL). Median total sperm motility was 10% (IQR: 0%–15%). In 20/30 men (66.7%) sperm retrieved was used for fresh intracytoplasmic sperm injection cycle, in 8/30 (26.7%) sperm cryopreservation was necessary, because on the day of sperm retrieval the female resulted not responder to ovarian stimulation. In this cases mean number of 3 (IQR: 1–4) bio system straws was cryopreserved. CONCLUSIONS: TEFNA with 18-gauge needle proved to be a feasible, safe and effective treatment, even if future prospective studies will be addressed to clarify what type of azoospermia benefits from this procedure, and if a larger needle permits to improve Assisted Reproductive Technologies (ART) outcomes.

Metabolic Syndrome and Male Fertility

Metabolic syndrome (MetS) represents a cluster of conditions that have a negative impact on human health overall. Its prevalence has been rapidly increasing worldwide and has coincided with a global decrease in birth rates and fertility potential. This review aims to address this observation through studying the relationship between MetS and male reproductive health. The effects of obesity, dyslipidemia, hypertension, and insulin resistance on male fertility were examined and supporting evidence explaining the pathophysiology of sperm dysfunction with each MetS component were described. Adopting a healthy lifestyle appears to be the single most important intervention to prevent the unwanted effects of MetS on men's health and fertility. Further studies addressing the components of MetS and their impact on male reproduction are required to enhance our understanding of the underlying pathophysiology and to propose new methods for therapeutic intervention.

Review of Guidelines for the Evaluation and Treatment of Leukocytospermia in Male Infertility

Leukocytospermia is an ill-defined and poorly understood condition affecting up to 30% of male factor infertility. Current guidelines on leukocytospermia vary significantly, although it has been linked to increased rates of infertility, uncertainty about its clinical significance, diagnosis, and treatment remains. The guidelines are conflicting with sparse data scattered across different specialties and continents. This study aims to compare and contrast available international guidelines and recommendations. In addition to these guidelines, we sought to consolidate the findings of trials over the last several decades. English language articles on human observational studies, retrospective, prospective, clinical trials and randomized control trials were searched for using the following terms: “leukocytospermia, pyospermia, and male infertility.” Articles about treatment and management of leukocytospermia that were published between January 2010 and April 2018 were included, as well as four articles referenced in best practice and guideline statements from urological and andrological associations. Disagreements on this topic are highlighted as some guidelines describe no correlation between leukocytospermia and infertility while others show that treatment leads to improvement of sperm quality by many measures including improved pregnancy rate. Various treatments have been suggested including antibiotics, anti-inflammatory medications, and frequent ejaculation. There is a need for definitive characterization of Leukocytospermia as an infectious or inflammatory marker and a re-evaluation of the leukocyte concentration threshold. Additional studies investigating rates of conception as a measure of outcome are needed, to provide greater level of evidence and generalizability of leukocytopsermia management.

Epigenetics of Male Fertility: Effects on Assisted Reproductive Techniques

During the last decades the study of male infertility and the introduction of the assisted reproductive techniques (ARTs) has allowed to understand that normal sperm parameters do not always predict fertilization. Sperm genetic components could play an important role in the early stages of embryonic development. Based on these acquisitions, several epigenetic investigations have been developed on spermatozoa, with the aim of understanding the multifactorial etiology of male infertility and of showing whether embryonic development may be influenced by sperm epigenetic abnormalities. This article reviews the possible epigenetic modifications of spermatozoa and their effects on male fertility, embryonic development and ART outcome. It focuses mainly on sperm DNA methylation, chromatin remodeling, histone modifications and RNAs.

Recovery of Spermatogenesis Following Cancer Treatment with Cytotoxic Chemotherapy and Radiotherapy

The survival rates of boys and men with cancer have increased due to advances in cancer treatments; however, maintenance of quality of life, including fertility preservation, remains a major issue. Fertile male patients who receive radiation and/or chemotherapy face temporary, long-term, or permanent gonadal damage, particularly with exposure to alkylating agents and whole-body irradiation, which sometimes induce critical germ cell damage. These cytotoxic treatments have a significant impact on a patient's ability to have their own biological offspring, which is of particular concern to cancer patients of reproductive age. Therefore, various strategies are needed in order to preserve male fertility. Sperm cryopreservation is an effective method for preserving spermatozoa. Advances have also been achieved in pre-pubertal germ cell storage and research to generate differentiated male germ cells from various types of stem cells, including embryonic stem cells, induced pluripotent stem cells, and spermatogonial stem cells. These approaches offer hope to many patients in whom germ cell loss is associated with sterility, but are still experimental and preliminary. This review examines the current understanding of the effects of chemotherapy and radiation on male fertility.

Traditional Chinese Medicine as a Remedy for Male Infertility: A Review

Male infertility (MI) is a complex multifactorial disease, and idiopathic infertility accounts for 30% of cases of MI. At present, the evidence for the effectiveness of empirical drugs is limited, and in vitro fertilization is costly and may increase the risk of birth defects and childhood cancers. Therefore, affected individuals may feel obliged to pursue natural remedies. Traditional Chinese medicine (TCM) may represent a useful option for infertile men. It has been demonstrated that TCM can regulate the hypothalamic-pituitary-testicular axis and boost the function of Sertoli cells and Leydig cells. TCM can also alleviate inflammation, prevent oxidative stress, reduce the DNA fragmentation index, and modulate the proliferation and apoptosis of germ cells. Furthermore, TCM can supply trace elements and vitamins, ameliorate the microcirculation of the testis, decrease the levels of serum anti-sperm antibody, and modify epigenetic markers. However, the evidence in favor of TCM is not compelling, which has hindered the development of TCM. This review attempts to elucidate the underlying therapeutic mechanisms of TCM. We also explore the advantages of TCM, differences between TCM and Western medicine, and problems in existing studies. Subsequently, we propose solutions to these problems and present perspectives for the future development of TCM.

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.