Materiały źródłowe

• #1 Male Infertility – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562258/

  Infertility is usually defined as the inability of a couple to conceive even after 1 year of unprotected, frequent sexual intercourse. The male is solely responsible in about 20% of cases and is a contributing factor in another 30% to 40% of all infertility cases. As male and female causes often co-exist, it is essential that both partners are investigated for infertility and managed together. Overall, the male factor substantially contributes to about 50% of all cases of infertility. […] The key purpose for evaluating a male for infertility is to identify the contributing factors, offer treatment for those that are reversible, determine if the patient is a candidate for assisted reproductive techniques, and offer counseling for irreversible and untreatable conditions. […] There are several reasons for male fertility, including both reversible and irreversible conditions. Other factors can influence each partner, including age, medications, surgical history, exposure to environmental toxins, genetic problems, and systemic diseases. Up to 6% of men evaluated for male infertility will be found to have more serious underlying pathology, such as cancer. This is an additional reason to do a comprehensive evaluation of the male partners of infertile couples so that any significant, underlying medical conditions can be identified and treated.

• #2 Male infertility: pathogenesis and clinical diagnosis – PubMed

  https://pubmed.ncbi.nlm.nih.gov/21397198/

  Infertility affects about 7% of all men. The etiology of impaired sperm production and function can be related to factors acting at pre-testicular, post-testicular or directly at the testicular level. Primary testicular failure accounts for about 75% of all male factor infertility. Genetic factors can be identified in about 15% of cases (congenital hypogonadotrophic hypogonadism, congenital absence of vas deferens, primitive testicular failure). Despite progresses, mainly in the field of genetics, the etiology is still unknown in about 50% cases and it is termed „idiopathic infertility”. […] A part from few exceptions, the only available therapy for male factor infertility is assisted reproduction which allows conception also in severe male factor, including azoospermia following testicular sperm extraction. The complete diagnostic workup is important for: i) the identification of treatable/reversible or health-threatening conditions; ii) selection of patients for assisted reproductive techniques; iii) for appropriate genetic counselling including preventive measures (preimplanatation or prenatal diagnosis) to safeguard the health of future offspring.

• #3 Male Infertility: Causes, Symptoms, Tests & Treatment

  https://my.clevelandclinic.org/health/diseases/17201-male-infertility

  Infertility can concern both male and female individuals. Specifically, male infertility is a condition that affects men. It interferes with the ability of their reproductive system to impregnate a female. […] Many biological and environmental factors can cause male infertility. These include: Sperm problems, including malformed sperm, low sperm count (oligospermia) and the absence of sperm in your semen (azoospermia). Genetic disorders, including Klinefelter syndrome and myotonic dystrophy. Some medical conditions, including diabetes, certain autoimmune diseases that attack your sperm and cystic fibrosis. Infections, including epididymitis, orchitis and sexually transmitted infections (STIs), including gonorrhea or HIV. Swollen veins in your testicles (varicoceles). Cancer treatments, including chemotherapy, radiation therapy or surgical removal of your testicles (orchiectomy). Testicular trauma. Hormonal disorders that affect your hypothalamus or pituitary glands. […] Yes, many different treatment options can reverse male infertility. Depending on the cause, your treatment may include: Lifestyle changes, medications, surgery, and assisted reproductive technology (ART) procedures.

• #4 Male Infertility – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562258/

  There are multiple causes for male infertility, which can be broadly classified due to their general underlying etiology. These include endocrine disorders (usually due to hypogonadism) estimated at 2% to 5% of cases, sperm transport disorders (such as vasectomy) at 5%, primary testicular defects (which include abnormal sperm parameters without any identifiable cause) at 65% to 80% and idiopathic (where an infertile male has normal sperm and semen parameters) at 10% to 20%. […] Acquired urogenital abnormalities – bilateral obstruction or ligation of the vas deferens, bilateral orchiectomy, epididymitis, TURP, varicoceles, and retrograde ejaculation. Congenital urogenital abnormalities – absent, dysfunctional, or obstructed epididymis, congenital abnormalities of the vas deferens, undescended testes, and ejaculatory duct disorders (cysts). Endocrinological causes – congenital GnRH Deficiency (Kallmann syndrome), Prader-Willi syndrome, Laurence-Moon-Beidl syndrome, iron overload syndrome, familial cerebellar ataxia, head trauma, intracranial radiation, testosterone supplementation, and hyperthyroidism. Environmental toxins – insecticides, fungicides, pesticides, smoking, excess alcohol, Agent Orange, and other chemical exposures. Genetic causes – mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, primary ciliary dyskinesia, Kallmann syndrome, Klinefelter syndrome, Young syndrome, Sertoli cell-only syndrome, Kal- 1, Kal -2, FSH, LH, FGFS, GnRH1/GNRHR PROK2/PROK2R gene deficiencies, chromosomal anomalies, Y chromosome microdeletion, AR mutations, and gr/gr deletion. Idiopathic causes – idiopathic male infertility (10% to 20%) where semen parameters are all normal, but the male remains infertile. Immunological causes – lymphocytic hypophysitis, hemosiderosis, hemochromatosis, sarcoidosis, histiocytosis, tuberculosis, and fungal infections. Malignancies – sellar masses, pituitary macroadenomas, craniopharyngiomas, and surgical or radiation treatment for these conditions, testicular tumors, and adrenal tumors leading to an excess of androgens.

• #5 Male Infertility | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/23503

  There are multiple causes for male infertility, which can be broadly classified due to their general underlying etiology. These include endocrine disorders (usually due to hypogonadism) estimated at 2% to 5% of cases, sperm transport disorders (such as vasectomy) at 5%, primary testicular defects (which include abnormal sperm parameters without any identifiable cause) at 65% to 80% and idiopathic (where an infertile male has normal sperm and semen parameters) at 10% to 20%.[12] […] Male infertility can also be classified based on the medical interventions that can potentially assist conception as follows: [13] Treatable causes of male infertility are found in 18% of cases – obstructive azoospermia, ejaculatory duct and prostatic midline cysts, gonadotropin deficiency, sexual function disorders, sperm autoimmunity, varicoceles, and reversible effects of toxins. Uncorrectable male infertility or subfertility is found in 70% of cases – oligozoospermia, asthenozoospermia, teratozoospermia, and normospermia with functional defects. ART will generally be necessary for reproduction. Untreatable male sterility is seen in 12% of cases – primary seminiferous tubular failure, Sertoli cell-only syndrome, and bilateral orchiectomy.

• #6 Male Infertility – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562258/

  Male infertility can also be classified based on the medical interventions that can potentially assist conception as follows: Treatable causes of male infertility are found in 18% of cases – obstructive azoospermia, ejaculatory duct and prostatic midline cysts, gonadotropin deficiency, sexual function disorders, sperm autoimmunity, varicoceles, and reversible effects of toxins. Uncorrectable male infertility or subfertility is found in 70% of cases – oligozoospermia, asthenozoospermia, teratozoospermia, and normospermia with functional defects. ART will generally be necessary for reproduction. Untreatable male sterility is seen in 12% of cases – primary seminiferous tubular failure, Sertoli cell-only syndrome, and bilateral orchiectomy. […] Male infertility can also be classified as follows: Pre-testicular causes include hypogonadotropic hypogonadism, erectile dysfunction, or coital disorders such as retrograde ejaculation, anejaculation, genetic factors, and chromosomal abnormalities. Testicular disorders include testicular tumors, orchiectomy, primitive testicular dysfunction, cryptorchidism, and atrophic testes. Varicoceles are associated with male infertility, most likely through impairment of testicular thermoregulation due to disruption of the pampiniform venous plexus heat regulation mechanism. Epididymal dysfunction can be caused by fetal intrauterine exposure to estrogens, various drugs and chemical toxins, epididymal cysts, spermatoceles with or without surgery, epididymitis, or may be idiopathic. Post-testicular etiologies include lesions of the seminal tract, inflammatory diseases, congenital absence of the vas deferens, post-vasectomy, erectile dysfunction, premature ejaculation, and the use of a condom or diaphragm.

• #7 Male Infertility | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/23503

  Male infertility can also be classified as follows: Pre-testicular causes include hypogonadotropic hypogonadism, erectile dysfunction, or coital disorders such as retrograde ejaculation, anejaculation, genetic factors, and chromosomal abnormalities. Testicular disorders include testicular tumors, orchiectomy, primitive testicular dysfunction, cryptorchidism, and atrophic testes. Varicoceles are associated with male infertility, most likely through impairment of testicular thermoregulation due to disruption of the pampiniform venous plexus heat regulation mechanism. Epididymal dysfunction can be caused by fetal intrauterine exposure to estrogens, various drugs and chemical toxins, epididymal cysts, spermatoceles with or without surgery, epididymitis, or may be idiopathic.[35][36] […] Any medication, tumor, disease, or disorder that affects the pituitary gland or hypothalamus can potentially cause male infertility by altering gonadotropic releasing hormone or causing gonadotropin deficiency such as idiopathic hypogonadotropic hypogonadism (IHH), Kallmann syndrome (IHH with anosmia), and combined pituitary hormone deficiency.

• #8 Male Infertility: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/436829-overview

  Infertility in men can result from deficiencies in sperm formation, concentration, or transportation. This general division allows an appropriate workup of potential underlying causes of infertility and helps define a course of action for treatment. […] Infertile men may have deficiencies in sperm formation, concentration (eg, oligospermia [too few sperm], azoospermia [no sperm in the ejaculate]), or transportation. The causes can be categorized as obstructive or nonobstructive. This general division allows an appropriate workup of potential underlying causes of infertility and helps define a course of action for treatment. […] Gonadal and sexual functions are mediated by the hypothalamic-pituitary-gonadal axis, a closed-loop system with feedback control from the testicles. The hypothalamus, the primary integration center, responds to various signals from the central nervous system (CNS), pituitary gland, and testicles to secrete gonadotropin-releasing hormone (GnRH) in a pulsatile pattern approximately every 70-90 minutes.

• #9 Male Infertility: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/436829-overview

  Release of GnRH is stimulated by melatonin from the pineal gland and inhibited by testosterone, inhibin, corticotropin-releasing hormone, opiates, illness, and stress. GnRH travels down the portal system to the anterior pituitary, located on a stalk in the sella turcica, to stimulate the release of the gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). […] The pulsatile nature of GnRH is essential to normal gonadotropin release; a continuous stimulation inhibits their secretion. […] Prolactin inhibits the production of GnRH from the hypothalamus and LH and FSH from the pituitary. Gonadotropin release is modulated by various other signals, such as estradiol (a potent inhibitor of both LH and FSH release), and inhibin from the Sertoli cell, which causes a selective decrease in FSH release.

• #10 Clomid for Men – Comprehensive Urology

  https://comprehensive-urology.com/urologist-desk/clomid-for-men/

  Clomiphene citrate is used by men to address specific health conditions, such as infertility and low testosterone. It has notable benefits like hormone stimulation and off-label potential but also comes with important considerations. […] The mechanism of clomiphene involves blocking estrogen receptors in the hypothalamus. This deactivation leads to an increase in the release of gonadotropin-releasing hormone (GnRH). Consequently, the pituitary gland boosts the production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones are vital for sperm production and testosterone synthesis in males. By enhancing these hormones, clomiphene helps improve both sperm count and quality. This can contribute significantly to addressing fertility issues. Maintaining ideal hormonal balance is crucial for optimal reproductive health in men taking clomiphene.

• #11 Male Infertility: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/436829-overview

  Sertoli cells also secrete inhibin, which provides negative feedback on the hypothalamus, and androgen-binding protein, which helps modulate androgen activity in the seminiferous tubules. […] The entire process of development from spermatogonium to spermatid takes 74 days and is described in 14 steps; as they mature, the developing spermatids progress closer to the lumen of the seminiferous tubule. […] The acrosome, a derivative of the Golgi process, surrounds the nucleus anteriorly and contains enzymes necessary to penetrate the ovum. […] The epididymis additionally secretes substances for sperm nutrition and protection such as glycerophosphorylcholine, carnitine, and sialic acid. […] Varicoceles may lead to impaired testicular spermatogenesis and steroidogenesis, potentially due to an increased intratesticular temperature, reflux of toxic metabolites, and/or germ cell hypoxia; this appears to be progressive over time.

• #12 Male Infertility – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562258/

  Any medication, tumor, disease, or disorder that affects the pituitary gland or hypothalamus can potentially cause male infertility by altering gonadotropic releasing hormone or causing gonadotropin deficiency such as idiopathic hypogonadotropic hypogonadism (IHH), Kallmann syndrome (IHH with anosmia), and combined pituitary hormone deficiency. Pituitary neoplasms such as sellar tumors, macroadenomas, and prolactinomas will also result in male infertility due to alterations in gonadotropin production as well as various genetic causes such as Prader-Willi, Young, and Laurence-Moon-Biedl syndromes. Various acquired disorders, such as primary androgen overproduction and exogenous testosterone supplementation, will also directly decrease gonadotropic secretion, causing reduced sperm counts and infertility.

• #13 Male infertility – The other side of the equation

  https://www.racgp.org.au/afp/2017/september/male-infertility

  Male infertility can result from anatomical or genetic abnormalities, systemic or neurological diseases, infections, trauma, iatrogenic injury, gonadotoxins and development of sperm antibodies. […] Male infertility can be caused by a wide range of conditions, encompassing anatomical or genetic abnormalities, systemic or neurological diseases, infections, trauma, iatrogenic injury, gonadotoxins and development of sperm antibodies. […] In 30-40% of male infertility cases, no cause is identified (idiopathic male infertility). […] The minimal assessment includes measurement of serum follicle stimulating hormone (FSH) and morning testosterone levels. […] Hypogonadotropic hypogonadism, also known as secondary hypogonadism, results from failure of the hypothalamic-pituitary axis to stimulate normal gonadal function.

• #14 Male Infertility | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/23503

  Various acquired disorders, such as primary androgen overproduction and exogenous testosterone supplementation, will also directly decrease gonadotropic secretion, causing reduced sperm counts and infertility. […] Testosterone supplementation has no role in male infertility patients trying to conceive.[61] Patients who need testosterone supplementation can preserve their fertility by taking clomiphene, which helps maintain FSH and LH levels.[62] Most patients who become infertile on testosterone therapy will eventually regain their sperm counts and fertility, but it will take time, and there are no guarantees. The best available data indicate that two-thirds of testosterone-treated men can expect the recovery of sperm production in 6 months, 90% after 1 year, and almost 100% after 2 years.[58]

• #15 Male Infertility: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/436829-overview

  Varicoceles lead to an increased incidence of sperm immaturity, apoptosis, and necrosis with severe disturbances in meiotic segregation compared with fertile men without varicoceles. These parameters generally improve after repair. […] The most common cause of acquired testicular failure in adults is viral orchitis, such as that caused by the mumps virus, echovirus, or group B arbovirus. […] The virus may either directly damage the seminiferous tubules or indirectly cause ischemic damage as the intense swelling leads to compression against the tough tunica albuginea. […] Causes of testicular failure also include granulomatous disease, sickle cell disease, and excessive use of alcohol, cigarettes, caffeine, or marijuana. […] Sexually transmitted infections, such as with Chlamydia trachomatis, Neisseria gonorrhoeae, genital mycoplasma, Trichomonas vaginalis, and human papillomavirus (HPV) have been reported to reduce sperm count and motility. Chronic prostatitis and epididymitis caused by bacterial or viral infection can also lead to male infertility.

• #16 Male Infertility – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562258/

  Prolactin levels in men usually are quite low. When elevated, they suggest a possible prolactin-secreting pituitary tumor. Such tumors may cause infertility, hypogonadism (low testosterone), gynecomastia, galactorrhea, and possibly a reduction of the peripheral visual fields due to compression of the optic chiasm. […] Anabolic steroid abuse and testosterone supplementation therapy are growing worldwide. At least 25% or more of physicians who prescribe testosterone to patients are unaware that it will cause significant, possibly long-term fertility and sterility problems in their patients. […] Mumps and several similar viruses constitute the most common cause of acquired testicular failure, and their incidence is increasing. This is probably due to a reduction in the usage of the MMR vaccine in children during the early 1990s. About one-quarter of the adults who get mumps will develop orchitis. Of these, one-third will have bilateral disease.

• #17 Correlation between viral infections in male semen and infertility: a literature review | Virology Journal | Full Text

  https://virologyj.biomedcentral.com/articles/10.1186/s12985-024-02431-w

  Infertility affects approximately one-sixth of couples globally, with the incidence of male infertility steadily increasing. […] This review consolidates findings from previous studies, outlining 40 viruses identified in human semen and summarizing their key characteristics, modes of transmission, and their effects on both the reproductive and endocrine systems. Furthermore, it elucidates potential pathogenic mechanisms and treatment prospects of viruses strongly associated with male infertility. […] The reasons for decreased male fertility vary but may be linked to congenital, acquired, or idiopathic factors affecting sperm production, among which reproductive tract infections are considered to be one of the most influential. […] Previous research has compiled a list of 38 viruses detected in the male reproductive tract and semen, many of which exhibit a strong affinity for the male reproductive organs, particularly the testes.

• #18 Male Infertility – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562258/

  Men with a history of undescended testicles tend to have lower fertility than men without that history, even if the cryptorchid testicle was surgically repaired at an early age. This is thought to be due to an inherent testicular defect. Men with cryptorchid testicles will typically have poorer quality sperm (lower motility, high abnormal morphology) and lower sperm counts. […] This is a genetic mutation where the male has XXY instead of the usual XY chromosomes. Patients are typically infertile with hypogonadism. There is a spectrum of symptoms, but the most typical are bilateral atrophic or hypertrophic testes, reduced muscle mass, scant body and facial hair, and gynecomastia. Often, the diagnosis is not made until adulthood, and infertility with azoospermia or severe oligozoospermia is a common presenting symptom.

• #19 Male Infertility and Oxidative Stress: A Focus on the Underlying Mechanisms

  https://www.mdpi.com/2076-3921/11/2/306

  Reactive oxygen species (ROS) play a critical role in defining the functional competence of human spermatozoa. When generated in moderate amounts, ROS promote sperm capacitation by facilitating cholesterol efflux from the plasma membrane, enhancing cAMP generation, inducing cytoplasmic alkalinization, increasing intracellular calcium levels, and stimulating the protein phosphorylation events that drive the attainment of a capacitated state. However, when ROS generation is excessive and/or the antioxidant defences of the reproductive system are compromised, a state of oxidative stress may be induced that disrupts the fertilizing capacity of the spermatozoa and the structural integrity of their DNA. […] The notion that oxidative stress is a major factor in the aetiology of male infertility has a long history stretching back to studies performed in the 1920s, when the impact of vitamin E deficiency on normal testicular function became apparent.

• #20 Male Infertility and Oxidative Stress: A Focus on the Underlying Mechanisms

  https://www.mdpi.com/2076-3921/11/2/306

  Oxidative stress in the male germ line has become an extensive field of investigation covering the promotion and suppression of sperm production and function, as well as the genetic and epigenetic changes in the germ line that impact the health and wellbeing of the offspring. […] The one consistent factor linking leukocytospermia and defective sperm function is oxidative stress. The infiltration of leukocytes into the male tract has been associated with increases in biomarkers of peroxidative damage such as malondialdehyde and the augmented generation of seminal ROS, as well as indicators of oxidative stress in spermatozoa including DNA fragmentation, 8OHdG formation in the sperm nucleus, and reduced sperm motility. […] The second source of ROS in the ejaculate is the spermatozoa themselves. It has been known since 1946 that spermatozoa are capable of generating ROS, although the underlying mechanisms still have to be resolved in detail.

• #21 Male Infertility and Oxidative Stress: A Focus on the Underlying Mechanisms

  https://www.mdpi.com/2076-3921/11/2/306

  In our own species, the spermatozoa rely heavily on glycolysis to meet their energy needs, and ROS generation by the mitochondria is a pathological change associated with a loss of sperm motility and the induction of sperm apoptosis. […] The ability of 4-HNE to adduct these proteins and stimulate mitochondrial ROS generation is also reinforced by the tendency of this aldehyde to form adducts with aldehyde dehydrogenase (ALDH), a key enzyme in the protection of spermatozoa against oxidative stress. […] Another class of enzymes thought to be involved in the production of ROS by human spermatozoa are the NADPH oxidases (NOX). […] The physiological purpose of this oxidase appears to be related to the redox regulation of sperm capacitation. Stimulation of L-amino acid oxidase activity in human spermatozoa results in the induction of several hallmarks of capacitation, including tyrosine phosphorylation of the sperm flagellum and the concomitant activation of phospho-SRC expression.

• #22 Male Infertility and Oxidative Stress: A Focus on the Underlying Mechanisms

  https://www.mdpi.com/2076-3921/11/2/306

  In addition to the excessive generation of ROS, oxidative stress may also be driven by a deficiency in available antioxidant protection. While it is generally appreciated that defective semen quality is commonly associated with low levels of antioxidant protection in semen, it is always difficult to differentiate the cause and effect in such circumstances. […] In summary, there is little doubt that oxidative stress is a major contributor to male and female infertility. Moreover, such stress can have a major impact on the health and wellbeing of future generations as a result of both epigenetic and genetic damage to the germ line that is oxidatively induced.

• #23

  https://journals.lww.com/cmj/fulltext/9900/mechanism_of_mitochondrial_oxidative.1098.aspx

  Male infertility has become a global concern, accounting for 20-70% of infertility. Dysfunctional spermatogenesis is the most common cause of male infertility; thus, treating abnormal spermatogenesis may improve male infertility and has attracted the attention of the medical community. Mitochondria are essential organelles that maintain cell homeostasis and normal physiological functions in various ways, such as mitochondrial oxidative phosphorylation (OXPHOS). Mitochondrial OXPHOS transmits electrons through the respiratory chain, synthesizes adenosine triphosphate (ATP), and produces reactive oxygen species (ROS). […] The disruption of mitochondrial OXPHOS caused by external factors can result in inadequate cellular energy supply, oxidative stress, apoptosis, or ferroptosis, all inhibiting spermatogenesis and damaging the male reproductive system, leading to male infertility. This article summarizes the latest pathological mechanism of mitochondrial OXPHOS disorder in testicular Sertoli cells and germ cells, which disrupts spermatogenesis and results in male infertility.

• #24

  https://journals.lww.com/cmj/fulltext/9900/mechanism_of_mitochondrial_oxidative.1098.aspx

  OXPHOS is the key to maintaining the energy demand and nutrient supply of Sertoli and germ cells during spermatogenesis. Studies have shown that male infertility factors account for 20-70% of infertile couples, and male sperm quality is gradually declining. The interruption of OXPHOS may induce energy metabolism disorders, increased oxidative stress, and the occurrence of apoptosis and ferroptosis in Sertoli cells or germ cells, thus interfering with the normal progression of spermatogenesis and resulting in male infertility issues such as decreased sperm motility and asthenospermia. […] Damage to mitochondrial OXPHOS in Sertoli cells causes energy metabolism disorders, oxidative stress, apoptosis, and ferroptosis, which are key factors in spermatogenesis disorders and male infertility. […] Impaired mitochondrial OXPHOS in Sertoli cells leads to insufficient ATP production and excessive production of ROS, which are mainly derived from complexes I and III in the respiratory chain. Excessive ROS production leads to depolarization of the mitochondrial inner membrane, further increasing ROS production. High ROS levels that exceed antioxidant capacity cause oxidative stress.

• #25

  https://journals.lww.com/cmj/fulltext/9900/mechanism_of_mitochondrial_oxidative.1098.aspx

  Apoptosis of Sertoli cells interferes with the proliferation of spermatogonia and meiosis of spermatocytes, resulting in spermatogenesis disorders and decreased male fertility. […] Dysfunction of mitochondrial OXPHOS in Sertoli cells leads to insufficient ATP synthesis and increased ROS production, impairing cell function and preventing cells from providing sufficient energy and nutrients to germ cells. […] The mechanisms supporting disruption of OXPHOS in Sertoli cells leading to apoptosis are shown in Figure 1B. […] Ferroptosis is a novel cell death mode that differs from apoptosis. Its morphological manifestations are mainly mitochondrial changes, including mitochondrial shrinkage, mitochondrial crest reduction, and mitochondrial outer membrane rupture. […] The mechanisms supporting disruption of OXPHOS in Sertoli cells leading to cell ferroptosis.

• #26

  https://journals.lww.com/cmj/fulltext/2025/02200/mechanism_of_mitochondrial_oxidative.1.aspx

  Apoptosis of Sertoli cells interferes with the proliferation of spermatogonia and meiosis of spermatocytes, resulting in spermatogenesis disorders and decreased male fertility. […] Ferroptosis is a novel cell death mode that differs from apoptosis. […] The mechanisms supporting disruption of OXPHOS in Sertoli cells leading to cell ferroptosis. […] The mechanisms by which mitochondria are involved in spermatogenesis are diverse and complex. […] This study explored the mechanisms of OXPHOS disorders and spermatogenesis abnormalities, providing ideas for future therapies targeting oxidative stress, apoptosis, and ferroptosis downstream of mitochondrial OXPHOS.

• #27

  https://journals.lww.com/cmj/fulltext/2025/02200/mechanism_of_mitochondrial_oxidative.1.aspx

  Damage to mitochondrial OXPHOS in Sertoli cells causes energy metabolism disorders, oxidative stress, apoptosis, and ferroptosis, which are key factors in spermatogenesis disorders and male infertility. […] Impaired mitochondrial OXPHOS in Sertoli cells leads to insufficient ATP production and excessive production of ROS, which are mainly derived from complexes I and III in the respiratory chain. […] Dysfunction of mitochondrial OXPHOS in Sertoli cells leads to insufficient ATP synthesis and increased ROS production, impairing cell function and preventing cells from providing sufficient energy and nutrients to germ cells. […] Sertoli cell dysfunction ultimately impairs testicular energy metabolism and spermatogenesis, leading to a decrease in male fertility. […] A decrease in mitochondrial membrane potential (MMP) in mouse spermatogonia and Sertoli cells, which leads to apoptosis, is one of the molecular mechanisms underlying the development of decreased male fertility.

• #28

  https://journals.lww.com/cmj/fulltext/9900/mechanism_of_mitochondrial_oxidative.1098.aspx

  Mitochondrial ATP synthase catalyzes ATP synthesis to energy storage and is essential for germ cell survival and maturation during spermatogenesis. […] Sufficient mitochondrial OXPHOS in germ cells is essential for the maintenance of male fertility. […] The mechanism supporting testicular torsion, resulting in a significant decrease in semen quality, is shown in Figure 2A. […] Apoptosis is an important cause of male infertility. Mitochondrial signal-mediated intrinsic apoptosis has been shown to play a key role in regulating the apoptosis of primordial germ cells. […] The mechanism by which high levels of ROS lead to germ cell apoptosis is shown in Figure 3. […] The mechanism of the mitochondrial-dependent pathway involved in germ cell apoptosis is shown in Figure 3. […] Abnormal mitochondrial OXPHOS is closely associated with ferroptosis.

• #29

  https://journals.lww.com/cmj/fulltext/9900/mechanism_of_mitochondrial_oxidative.1098.aspx

  The mechanism of germ cell death in the testes of scrotal mice may be like that in cryptorchidism patients. High temperatures cause OXPHOS disorder in testicular tissue. […] This review explored how abnormal mitochondrial OXPHOS affects spermatogenesis and leads to impaired fertility. We also discussed the mechanism of mitochondrial OXPHOS dysfunction in testicular Sertoli and germ cells, leading to abnormal spermatogenesis regarding energy metabolism disturbance, oxidative stress, cell apoptosis, and ferroptosis.

• #30 Genetics of male infertility: from research to clinic in: Reproduction Volume 150 Issue 5 (2015)

  https://rep.bioscientifica.com/view/journals/rep/150/5/R159.xml

  Male infertility is a multifactorial complex disease with highly heterogeneous phenotypic representation and in at least 15% of cases, this condition is related to known genetic disorders, including both chromosomal and single-gene alterations. […] In about 40% of primary testicular failure, the etiology remains unknown and a portion of them is likely to be caused by not yet identified genetic anomalies. […] The armamentarium of diagnostic tests has been implemented only by the screening for Y chromosome-linked gr/gr deletion in those populations for which consistent data with risk estimate are available. […] On the other hand, it is clearly demonstrated by both single nucleotide polymorphisms and comparative genomic hybridization arrays, that there is a rare variant burden (especially relevant concerning deletions) in men with impaired spermatogenesis.

• #31 Klinefelter syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Klinefelter_syndrome

  The term „hypogonadism” in XXY symptoms is often misinterpreted to mean „small testicles”, when it instead means decreased testicular hormone/endocrine function. Because of (primary) hypogonadism, individuals often have a low serum testosterone level, but high serum follicle-stimulating hormone and luteinizing hormone levels, hypergonadotropic hypogonadism. Despite this misunderstanding of the term, testicular growth is arrested. […] Destruction and hyalinization of the seminiferous tubules cause a reduction in the function of Sertoli cells and Leydig cells, leading to decreased production of FSH and testosterone. This results in impaired spermatogenesis and further endocrine dysfunction.

• #32 New hope for male infertility: Researchers discover key mechanism in Klinefelter syndrome

  https://medicalxpress.com/news/2024-11-male-infertility-key-mechanism-klinefelter.html

  How does an extra X chromosome lead to infertility in men? Professor Qiao Jie and her team at Peking University Third Hospital revealed why Klinefelter syndrome, a common genetic condition affecting one in every 600 men, often leads to infertility—and they’ve identified a potential way to treat it. […] Their research, titled „How the extra X chromosome impairs the development of male fetal germ cells,” published in Nature provides new insights into the molecular mechanisms at play and even offers potential treatment avenues. […] The team studied fetal germ cells (FGCs) from Klinefelter patients, which develop early in life before disappearing. They found that the presence of the extra X chromosome causes both X chromosomes to remain active in fetal germ cells, causing an overload of certain genes. This gene surge disrupts important biological pathways and prevents the cells from maturing properly.

• #33 New hope for male infertility: PKU researchers discover key mechanism in Klinefelter syndrome | EurekAlert!

  https://www.eurekalert.org/news-releases/1069173

  Men with Klinefelter syndrome have an extra X chromosome, meaning their genetic makeup is 47, XXY instead of the usual 46, XY. They usually lose large amounts of key reproductive cells before puberty. This means they produce very few or no sperm and, until now, have no reliable treatment options. […] The team found that using TGF- inhibitors could help these fetal germ cells mature normally, pointing to possible treatments for infertility in men with Klinefelter syndrome.

• #34 New hope for male infertility: PKU researchers discover key mechanism in Klinefelter syndrome

  https://newsen.pku.edu.cn/news_events/news/research/14552.html

  Abnormal development of fetal germ cells in Klinefleter patients […] For those with Klinefelter syndrome, this painful reality is a constant struggle. […] How does an extra X chromosome lead to infertility in men? […] Their research, titled How the extra X chromosome impairs the development of male fetal germ cells, published in Nature Cells (DOI: 10.1038/s41586-024-08104-6) provides new insights into the molecular mechanisms at play and even offers potential treatment avenues. […] Men with Klinefelter syndrome have an extra X chromosome, meaning their genetic makeup is 47, XXY instead of the usual 46, XY. […] They found that the presence of the extra X chromosome causes both X chromosomes to remain active in fetal germ cells, causing an overload of certain genes. […] This gene surge disrupts important biological pathways and prevents the cells from maturing properly.

• #35 New hope for male infertility: PKU researchers discover key mechanism in Klinefelter syndrome

  https://newsen.pku.edu.cn/news_events/news/research/14552.html

  Additionally, these cells could not move to the right location in the testes, which is necessary for them to grow into mature, sperm-producing cells. […] With abnormal gene activity and disrupted movement, these cells are lost early, well before they can develop into functional sperm. […] The team found that using TGF- inhibitors could help these fetal germ cells mature normally, pointing to possible treatments for infertility in men with Klinefelter syndrome.

• #36 New hope for male infertility: Researchers discover key mechanism in Klinefelter syndrome

  https://medicalxpress.com/news/2024-11-male-infertility-key-mechanism-klinefelter.html

  Additionally, these cells could not move to the right location in the testes, which is necessary for them to grow into mature, sperm-producing cells. With abnormal gene activity and disrupted movement, these cells are lost early, well before they can develop into functional sperm. […] The team found that using TGF-β inhibitors could help these fetal germ cells mature normally, pointing to possible treatments for infertility in men with Klinefelter syndrome.

• #37 A new genetic mechanism for severe forms of male infertility

  https://frontlinegenomics.com/a-new-genetic-mechanism-for-severe-forms-of-male-infertility/

  Newcastle University scientists have identified a new genetic mechanism that can cause severe forms of male infertility. This breakthrough could help develop better treatment options for patients in the future. Approximately half of all cases of infertility are the result of male infertility. It affects around 7% of the male population. In most cases, the cause is unknown. While genetics is known to play a role in male infertility, there currently is a lack of diagnostically relevant genes. In addition, at least 40% of cases are classed as idiopathic. […] De novo mutations (DNMs) have been found in previous studies to play a role in other conditions with reproductive lethality, such as neurodevelopmental disorders. […] In a recent study, published in Nature Communications, researchers analysed exome sequencing data of 185 infertile males and their unaffected parents to explore the role of DNMs in severe male infertility. From their analysis, the team found 145 rare protein-altering mutations that were likely to negatively impact male infertility. […] Overall, this study provides evidence for the role of DNMs in severe male infertility and highlights potential new candidate genes affecting fertility.

• #38 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20220110/New-genetic-mechanism-that-can-cause-severe-male-infertility-identified.aspx

  Scientists at Newcastle University have identified a new genetic mechanism that can cause severe forms of male infertility. […] The study, published today in Nature Communications, shows that new mutations, not inherited from father or mother, play a major role in this medical condition. […] Experts have found that mutations occurring during the reproduction process, when the DNA of both parents is replicated, can result in infertility in men later in life. […] However, our research has found that mutations which occur when the DNA is replicated during reproduction in parents plays a significant role in the infertility in their sons. […] Scientists collected and studied DNA from a global cohort of 185 infertile men and their parents. They identified 145 rare protein-altering mutations that are likely to negatively impact male fertility.

• #39 New Genetic Mechanism Can Cause Severe Forms of Male Infertility | Technology Networks

  https://www.technologynetworks.com/genomics/news/new-genetic-mechanism-can-cause-severe-forms-of-male-infertility-357377

  Scientists at Newcastle University have identified a new genetic mechanism that can cause severe forms of male infertility. […] The study, published today in Nature Communications, shows that new mutations, not inherited from father or mother, play a major role in this medical condition. […] Experts have found that mutations occurring during the reproduction process, when the DNA of both parents is replicated, can result in infertility in men later in life. […] However, our research has found that mutations which occur when the DNA is replicated during reproduction in parents plays a significant role in the infertility in their sons. […] Scientists collected and studied DNA from a global cohort of 185 infertile men and their parents. They identified 145 rare protein-altering mutations that are likely to negatively impact male fertility.

• #40 New Genetic Mechanism Can Cause Severe Forms of Male Infertility | Technology Networks

  https://www.technologynetworks.com/genomics/news/new-genetic-mechanism-can-cause-severe-forms-of-male-infertility-357377

  As many as 29 of the mutations affect genes directly involved in processes related to spermatogenesis the process of sperm cell development – or other cellular processes related to reproduction. […] Experts identified mutations in the gene RBM5 in multiple infertile men. […] Importantly, these mutations mostly cause a dominant form of infertility, where only one mutated gene is required. […] This research indicates a significant proportion of these children may inherit infertility from their father. […] Professor Veltman said: If we are able to obtain a genetic diagnosis, then we can start understanding better male infertility problems and why some infertile men still produce sperm that can be used successfully for assisted reproduction. […] Moving forwards, the scientists want to expand their work by studying thousands of patients and their parents in a large international consortium. […] They will follow-up their research by conducting further studies into the role these newly identified mutated genes have on the impact of spermatogenesis and on the overall fertility in humans.

• #41 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20220110/New-genetic-mechanism-that-can-cause-severe-male-infertility-identified.aspx

  As many as 29 of the mutations affect genes directly involved in processes related to spermatogenesis the process of sperm cell development – or other cellular processes related to reproduction. […] Experts identified mutations in the gene RBM5 in multiple infertile men. Previous research carried out in mice has shown that this gene plays a role in male infertility. […] Importantly, these mutations mostly cause a dominant form of infertility, where only one mutated gene is required. […] This research indicates a significant proportion of these children may inherit infertility from their father. […] Moving forwards, the scientists want to expand their work by studying thousands of patients and their parents in a large international consortium. […] They will follow-up their research by conducting further studies into the role these newly identified mutated genes have on the impact of spermatogenesis and on the overall fertility in humans.

• #42 Genetics of male infertility: from research to clinic in: Reproduction Volume 150 Issue 5 (2015)

  https://rep.bioscientifica.com/view/journals/rep/150/5/R159.xml

  In the era of next generation sequencing (NGS), we expect to expand our diagnostic skills, since mutations in several hundred genes can potentially lead to infertility and each of them is likely responsible for only a small fraction of cases. […] Although these novel approaches will certainly help in discovering hidden genetic factors, a more comprehensive picture of the etiopathogenesis of idiopathic male infertility will only be achieved by a parallel investigation of the complex world of gene environmental interaction and epigenetics. […] The search for hidden genetic factors, especially focusing on polymorphisms, in idiopathic infertile patients were intensified in the late 1990s, since this approach turned out to be successful in some other complex multifactorial diseases. […] Starting from 2009, novel approaches such as single nucleotide polymorphism (SNP) array, comparative genomic hybridization-array (array-CGH) and next generation sequencing (NGS) provided important data also on rare variants.

• #43 Genetics of male infertility: from research to clinic in: Reproduction Volume 150 Issue 5 (2015)

  https://rep.bioscientifica.com/view/journals/rep/150/5/R159.xml

  The results obtained up to 2007 have been summarized in the meta-analysis by Tttelmann et al. (2007), who reported significant association with impaired spermatogenesis only for two genetic factors: a partial AZFc deletion (gr/gr deletion) and the rs1801133 (c.677CT) variant in the MTHFR gene. […] Although reliability of the presently available meta-analyses is largely limited by the heterogeneous inclusion criteria used for patients and controls selection, in this review we attempt to provide a short description of those SNPs that according to the latest meta-analyses result significantly associated with spermatogenic failure. […] The conclusion presented by Tttelmann et al. (2007) stimulated further studies, which led to controversial results and to novel meta-analyses. […] The last meta-analysis (Gong et al. 2015), which included 26 published studies (5575 cases and 5447 controls from Asian, African and Caucasian populations), indicated that the MTFHR variant is associated with AZ (AZ) (OR=1.36, 95% CI: 1.181.55, P=0.000) and oligoasthenoteratozoospermia (OAT) (OR=1.35, 95% CI: 1.111.64, P=0.003), but not with oligozoospermia.

• #44 Genetics of male infertility: from research to clinic in: Reproduction Volume 150 Issue 5 (2015)

  https://rep.bioscientifica.com/view/journals/rep/150/5/R159.xml

  Overall, for both SNPs the conferred susceptibility to AZ and OAT is modest, implying a marginal biological role for this SNP in infertility. […] Controversies might depend on different ethnic origin (variant frequency does differ among different populations), and the penetrance of this mutation is likely to be affected by diet, e.g., subjects carrying the variant may have a major risk for male infertility in cases of low folate intake. […] The best candidate genes are those with specific expression in germ cells or those that have specific spermatogenic function or play important roles in meiosis or endocrine regulation of the testis. […] The search for hidden genetic factors was largely unsuccessful in identifying recurrent genetic factors with potential clinical application. […] In this regard, system biology, which allows revealing possible gene interactions and common biological pathways, will provide an informative tool for NGS data interpretation.

• #45

  https://link.springer.com/article/10.1007/s11934-001-0035-7

  Varicocele is the most commonly identifiable, surgically correctable lesion associated with male-factor infertility. Surgical correction of a varicocele, whether unilateral or bilateral, results in improvement not only in semen parameters but also in spontaneous and assisted pregnancy rates. Varicoceles seem to induce a number of changes in the testicular microenvironment. These alterations in temperature, hemodynamics, and reactive oxidative species and antioxidant concentrations have been demonstrated to produce deleterious effects on spermatogenesis. However, despite current knowledge in the pathophysiology of varicocele-associated male infertility, the exact mechanism or mechanisms by which varicoceles impair fertility remains elusive. This review examines scientific evidence regarding the pathophysiology of varicocele-associated male infertility. […] Varicocele is associated with elevated spermatozoal reactive oxygen species production and diminished seminal plasma antioxidant capacity. […] Correction of varicoceles improves ROS and TAC levels. […] Varicocelectomy benefits even men with severe oligospermia and azoospermia.

• #46 :: WJMH :: World Journal of Men’s Health

  https://wjmh.org/DOIx.php?id=10.5534/wjmh.190018

  Male infertility is a rising problem and the etiology at the molecular level is unclear. […] Varicocele is characterized by the enlargement of the pampiniform plexus, which may be due to the presence of malfunctioning valves. In these patients, testicular function is affected due to the retrograde flow of blood. Thus, varicocele has a detrimental effect on spermatogenesis by inducing a state of testicular hyperthermia, hypoxia and oxidative stress. […] The mechanisms associated with the pathophysiology of varicocele have been reviewed in detail by Agarwal et al and Cho et al. Furthermore, varicocele drastically alters semen parameters and these patients exhibit compromised fertility. […] Advancement in the current omics techniques, especially proteomics have revolutionized the field of sperm molecular biology. Proteomics, a high throughput platform, is used to identify and select non-invasive biomarkers for the diagnosis of male infertility.

• #47 Pathogenesis of Autoimmune Male Infertility: Juxtacrine, Paracrine, and Endocrine Dysregulation

  https://www.mdpi.com/1873-149X/28/4/30

  Immunopathological factors are leading in the pathogenesis of male infertility, essential for its cases regardless of different etiology. […] The presence of ASAs in the blood and semen of infertile men was first reported by Philip R’mke in the Netherlands and Leo Wilson in the USA back in 1954, and since then, researchers have focused on them. […] Nowadays, ASAs production is considered one of the main mechanisms of male infertility. […] The presence of ASAs in varicocele is accompanied by a deterioration in sperm parameters. […] Varicocele causes congestion of local blood circulation. Hypoxic damage of the testicular parenchyma, relative scrotal hyperthermia, venous hypertension, and passive hyperemia reflux of metabolites and bioregulators (catecholamines) from the kidneys and adrenal glands, as well as hypoandrogenism are considered as the main mechanisms resulting in damage to the blood–testis barrier.

• #48 Pathophysiology | Center for Male Reproductive Medicine & Microsurgery

  https://maleinfertility.org/procedures/microsurgical-varicocelectomy/pathophysiology

  Despite a large number of animal and human studies, the exact mechanism whereby varicoceles cause impaired testicular function remains uncertain. Theories include abnormally high scrotal temperature, hypoxia due to venous stasis, dilution of intratesticular substrates (e.g. testosterone), imbalances of the hypotalamic-pituitary-gonadal axis, and reflux of renal and adrenal metabolites down the spermatic vein. […] In addition, nitric oxide, reactive oxygen species, and regulators of apoptosis have all recently been implicated in the pathophysiology of varicoceles. […] The most vigorously studied pathophysiologic theory is that of increased testicular temperature. It has long been observed that even minor fluctuation in temperature can affect spermatogenesis and sperm function. It has been suggested that varicoceles impair testicular thermoregulation by disrupting the countercurrent heat exchange mechanism in the pampiniform venous plexus.

• #49 Pathophysiology | Center for Male Reproductive Medicine & Microsurgery

  https://maleinfertility.org/procedures/microsurgical-varicocelectomy/pathophysiology

  Recently, Wright and colleagues showed in humans that scrotal skin surface temperatures were elevated in men with varicoceles compared to control patients. Following varicocele ligation, scrotal temperatures returned to a level nearly identical to those of controls. Previous studies have demonstrated that scrotal skin surface temperatures reliably reflect intratesticular temperatures. The pathophysiology of varicocele is probably multi-factorial.

• #50 :: WJMH :: World Journal of Men’s Health

  https://wjmh.org/DOIx.php?id=10.5534/wjmh.190018

  Altered expression of sperm proteins in infertile patients indicate compromised spermatogenesis or defects in vital sperm functions, such as capacitation, hyperactivation and acrosome reaction, which are essential for the fertilization process. […] In varicocele condition, these sperm functions are compromised, and sperm/seminal plasma proteomic analysis have reported altered expression of sperm and seminal plasma proteins. […] Varicocele associated male infertility manifests as a consequence of a high state of oxidative stress and mitochondrial dysfunction. […] The sperm proteomic profile of varicocele patients revealed that 87% of DEPs involved in sperm function and energy metabolism were downregulated in both unilateral and bilateral varicocele patients. […] Other ETC and testis-specific protein PDH have been suggested as potential non-invasive biomarkers of mitochondrial dysfunction in varicocele patients.

• #51 :: WJMH :: World Journal of Men’s Health

  https://wjmh.org/DOIx.php?id=10.5534/wjmh.190018

  The majority of these DEPs were involved in important cellular molecular functions including ion binding, and oxidoreductase activity; as well as biological processes such as small molecule metabolic process, response to stress, signal transduction, and cellular protein modification process. […] Dysregulation of sperm functions (capacitation, hyperactivation, and acrosome reaction) and reproductive functions (zona pellucida binding and fertilization) in bilateral varicocele patients were more pronounced due to differential expression of proteins. […] The list of potential sperm biomarkers in varicocele patients based on fertilization, motility and morphology, DNA damage, oxidative stress, and mitochondrial dysfunction are presented in Table 1. […] The first report on seminal plasma proteomics in adult varicocele patients using the 2D gel electrophoresis technique was published in 2012.

• #52 Male Infertility – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562258/

  The use of gonadotropin therapy in most men with idiopathic infertility is controversial. A meta-analysis of 6 randomized trials of gonadotropic therapy in male infertility patients reported higher pregnancy rates than the placebo group. […] Overall, varicocelectomy is expected to ultimately improve semen parameters in at least 60% to 70% of patients with clinically significant varicoceles. […] Patients with ejaculatory duct obstructions, usually found on transrectal ultrasonography, are likely to benefit from transurethral resection of the ejaculatory ducts. […] These are advanced microsurgical procedures performed on men with obstructive azoospermia due to bilateral epididymal or vasal obstruction. […] Intrauterine insemination is a form of assisted reproduction where semen and sperm are collected from the male partner (or a donor) and artificially instilled into the fertile female uterus.

• #53 Pathogenesis of Autoimmune Male Infertility: Juxtacrine, Paracrine, and Endocrine Dysregulation

  https://www.mdpi.com/1873-149X/28/4/30

  Pathogenesis of male infertility is often associated with autoimmunity towards sperm antigens essential for fertilization. Antisperm autoantibodies (ASAs) have immobilizing and cytotoxic properties, impairing spermatogenesis, causing sperm agglutination, altering spermatozoa motility and acrosomal reaction, and thus preventing ovum fertilization. […] The etiology of male infertility includes both autoimmune and non-autoimmune diseases but equally develops through autoimmune links of pathogenesis. Varicocele commonly leads to infertility due to testicular ischemic damage, venous stasis, local hyperthermia, and hypoandrogenism. […] The assessment of the autoimmunity role in the pathogenesis of male infertility is ambiguous, so the purpose of this review is to show the effects of ASAs on the pathogenesis of male infertility.

• #54 Pathogenesis of Autoimmune Male Infertility: Juxtacrine, Paracrine, and Endocrine Dysregulation

  https://ouci.dntb.gov.ua/en/works/7ABOZz84/

  According to global data, there is a male reproductive potential decrease. Pathogenesis of male infertility is often associated with autoimmunity towards sperm antigens essential for fertilization. Antisperm autoantibodies (ASAs) have immobilizing and cytotoxic properties, impairing spermatogenesis, causing sperm agglutination, altering spermatozoa motility and acrosomal reaction, and thus preventing ovum fertilization. […] The assessment of the autoimmunity role in the pathogenesis of male infertility is ambiguous, so the purpose of this review is to show the effects of ASAs on the pathogenesis of male infertility. […] Varicocele commonly leads to infertility due to testicular ischemic damage, venous stasis, local hyperthermia, and hypoandrogenism. However, varicocelectomy can alter the blood–testis barrier, facilitating ASAs production as well. There are contradictory data on the role of ASAs in the pathogenesis of varicocele-related infertility. Infection and inflammation both promote ASAs production due to “danger concept” mechanisms and because of antigen mimicry. Systemic pro-autoimmune influences like hyperprolactinemia, hypoandrogenism, and hypothyroidism also facilitate ASAs production.

• #55 Pathogenesis of Autoimmune Male Infertility: Juxtacrine, Paracrine, and Endocrine Dysregulation

  https://www.mdpi.com/1873-149X/28/4/30

  The pathogenesis of varicocele is multifactorial. […] The combined effects of various ASAs on different components of spermatozoa can also lead to immunological infertility. […] The effect of ASAs on reproductive function can be realized in various ways: impaired spermatogenesis, sperm agglutination, decreased motility, impaired penetration of spermatozoa into cervical mucus, impaired acrosomal reaction, obstruction of ovum fertilization, impaired embryo implantation, and deranged early development of zygote. […] ASAs-mediated infertility should be suspected if sperm agglutination and motility impairment are diagnosed by semen analysis in the absence of leukocytospermia and infection. […] The current pandemic of the new coronavirus infection COVID-19 may also alter male fertility, addressing autoimmune mechanisms.

• #56 New mechanism for male infertility discovered | EurekAlert!

  https://www.eurekalert.org/news-releases/898862

  A new study led from Karolinska Institutet in Sweden links male infertility to autoimmune prostatic inflammation. […] In the present study, the researchers have discovered a reason for reduced fertility in people with autoimmune polyendocrine syndrome type 1 (APS1), which increases the risk of developing autoimmune disease (caused by the immune system attacking and damaging healthy cells) and which is often used as a model for autoimmune disease in general. […] While infertility in women with APS1 is caused by autoimmune action against the ovaries, what gives rise to the corresponding infertility in men has never been ascertained. […] „We found that the immune system in a large group of patients reacted to a protein formed only in the prostate, namely the enzyme transglutaminase 4,” says lead investigator Dr Nils Landegren at Karolinska Institutet’s Department of Medicine in Solna.

• #57

  https://www.uu.se/en/news/2015/2015-06-18-new-mechanism-for-male-infertility-discovered

  A new Swedish study links male infertility to autoimmune prostatic inflammation. […] In the present study, the researchers have discovered a reason for reduced fertility in people with autoimmune polyendocrine syndrome type 1 (APS1), which increases the risk of developing autoimmune disease (caused by the immune system attacking and damaging healthy cells) and which is often used as a model for autoimmune disease in general. […] While infertility in women with APS1 is caused by autoimmune action against the ovaries, what gives rise to the corresponding infertility in men has never been ascertained. […] We found that the immune system in a large group of patients reacted to a protein formed only in the prostate, namely the enzyme transglutaminase 4, says lead investigator Dr Nils Landegren at Karolinska Institutets Department of Medicine in Solna and Uppsala University.

• #58 New mechanism for male infertility discovered | EurekAlert!

  https://www.eurekalert.org/news-releases/898862

  Interestingly, previous studies on mice have shown that transglutaminase 4 plays an important part in male fertility. […] „The finds are important as they point to a new disease mechanism for male infertility, but more work needs to be done to understand the significance of autoimmune prostatitis to infertility in the male population at large,” says Dr Landegren.

• #59

  https://www.uu.se/en/news/2015/2015-06-18-new-mechanism-for-male-infertility-discovered

  What we found was that it was only men who reacted to transglutaminase 4 and that the immune reaction first appeared at the onset of puberty once the prostate gland had matured. […] Interestingly, previous studies on mice have shown that transglutaminase 4 plays an important part in male fertility. […] The finds are important as they point to a new disease mechanism for male infertility, but more work needs to be done to understand the significance of autoimmune prostatitis to infertility in the male population at large, says Dr Landegren.

• #60 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20210819/Study-reveals-mechanism-behind-male-infertility-caused-by-autoimmune-disease.aspx

  Investigators have found that the absence of autoimmune regulator (Aire) in mice results in fertility problems similar to those affecting men with autoimmune polyendocrine syndrome type I (APS-1). Aire-dependent central tolerance plays a critical role in maintaining male fertility by preventing autoimmune attack against multiple reproductive targets, they report in The American Journal of Pathology. […] Male factors account for a large portion of infertility in couples, and the mechanisms underlying male infertility are poorly understood. This study is important because it represents a previously underexplored mechanism by which fertility can be impacted through autoimmune disease. […] Aire-deficient males exhibited dramatically reduced mating frequency and fertility; those able to mate took up to two weeks to do so, and their sperm quality was poor. Sperm from the Aire-deficient males were rarely able to produce litters, and even when they were used for in vitro fertilization, could not produce viable embryos.

• #61 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20210819/Study-reveals-mechanism-behind-male-infertility-caused-by-autoimmune-disease.aspx

  Aire-deficient males were found to produce low levels of testosterone and develop autoimmune disease against many components of the male reproductive tract, especially in the epididymis. […] The correlation between impaired central immune tolerance and fertility has potential implications not only for male APS-1 patients but may also provide important insights into both male autoimmune and unexplained cases of infertility. […] „By knowing more detail about what causes infertility in men, we can develop treatments and prophylactics to curb degenerative processes that affect fertility,” commented Dr. Petroff. „It may be possible to use general immunosuppressive treatments. Even better, it might be possible to design highly specific therapies that target particular immune cells, preventing these cells from causing damage to reproductive organs.”

• #62

  https://benthamscience.com/public/ebook_volume/3854

  Male reproductive tract infections (MRTIs) are a notable yet frequently overlooked contributor to male infertility. The complex interplay between infections and the male reproductive capacity stems from both direct and indirect effects these infections exert on sperm functionality, quality, and the seminal milieu.

• #63

  https://benthamscience.com/public/ebook_volume/3854

  An intricate relationship exists between inflammation and oxidative stress, a connection that has profound implications for male infertility. The objective of this chapter is to delineate the molecular and cellular mechanisms underpinning the loop between inflammation and oxidative stress (OS), emphasizing its crucial role in the pathophysiology of male reproductive dysfunction. […] Bacterial infections in the male reproductive system, such as prostatitis, epididymitis, orchitis, urethritis, and balanitis, represent critical health issues contributing to male infertility. […] The interaction between viral infections and male reproductive health has significant implications for fertility and warrants a comprehensive understanding. […] The impact of fungal or mycotic infections on male reproductive health, while significant, remains largely underinvestigated compared to other types of infections in the male reproductive tract.

• #64 Correlation between viral infections in male semen and infertility: a literature review | Virology Journal | Full Text

  https://virologyj.biomedcentral.com/articles/10.1186/s12985-024-02431-w

  This resurgence of concern highlights the potential impact of viral infections on male fertility. […] Within semen, viruses may infect sperm or precursor cells, attaching to molecules on the sperm surface as free viral particles or residing within immune cells, leading to pathology in the reproductive system, abnormalities in semen parameters, and declined sperm quality. […] Despite recent advancements in the study of semen viruses, a definitive correlation between viral infections and fertility remains unclear. […] The mechanisms by which sperm function may be impaired after HPV infection are still poorly understood. […] Research indicates that the presence of glycosaminoglycans or other soluble substances on the surface of sperm facilitates HPV attachment to the equatorial region of the sperm head.

• #65 Correlation between viral infections in male semen and infertility: a literature review | Virology Journal | Full Text

  https://virologyj.biomedcentral.com/articles/10.1186/s12985-024-02431-w

  Certain HPV genotypes are associated with sperm DNA fragmentation, decreased motility and fertilization potential, abnormal sperm quality, and the formation of antisperm antibodies. […] Viral genes may be transmitted to oocytes and embryo cells, causing DNA fragmentation and apoptosis, ultimately resulting in pregnancy loss. […] The guidelines issued by the European Society of Human Reproduction and Embryology (ESHRE) state that HPV in semen is a viral factor highly associated with assisted reproduction outcomes. […] For couples with fertility problems, if they have unexplained infertility, a history of HPV infection, show related clinical manifestations, or if there is the presence of ASA and asthenospermia, HPV DNA testing and genotyping are recommended for the male partner. […] The presence of CMV in semen ranges approximately between 6% and 56.9%, and it has been associated with decreased sperm count and motility, as well as an increased failure rate in assisted reproduction.

• #66 Correlation between viral infections in male semen and infertility: a literature review | Virology Journal | Full Text

  https://virologyj.biomedcentral.com/articles/10.1186/s12985-024-02431-w

  The prevalence of EBV in semen ranges from 0.4% to 45% and may be associated with leukocytospermia. […] Studies have confirmed severe damage to the testes following SARS-CoV-2 infection, including testicular atrophy, inflammatory cell infiltration, germ cell apoptosis, and microthrombosis in testicular blood vessels. […] ZIKV infection can also cause local inflammation and tissue damage in the reproductive organs, resulting in symptoms such as hematospermia, ejaculatory pain, reduced sperm count, and abnormal secretion of reproductive hormones. […] ZIKV exhibits tropism for various cell types in the reproductive tract, and experimental studies have confirmed that ZIKV exhibits a preference for infecting cells within the testes, resulting in cell death and disruption of the seminiferous tubules, ultimately leading to severe testicular damage and infertility. […] The mechanisms collectively explain the multifaceted impact of viral infections on male fertility, demonstrating how local and systemic effects lead to significant changes in sperm and semen parameters.

• #67 Male Infertility | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/23503

  COVID-19 appears to cause somewhat reduced fertility and even infertility in some recovered males, especially if the infection is severe. The virus appears to affect the testis by direct cellular infection via a cytokine storm and through the side effects of the various antiviral and immunological therapies used in its treatment.[34] Further investigations are needed to better elucidate both the mechanisms of damage and possible remedies specific to COVID-19 infection-related infertility.[34]

• #68 Gonorrhea – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/gonorrhea/symptoms-causes/syc-20351774

  Infertility in men. Gonorrhea can cause inflammation in epididymis, the coiled tube above and behind the testicles that stores and transports sperm. This inflammation is known as epididymitis and without treatment it can lead to infertility.

• #69 Sulphasalazine and male infertility: reversibility and possible mechanism. | Gut

  https://gut.bmj.com/content/22/6/445

  Earlier observations on infertility related to sulphasalazine treatment were extended and semen samples obtained from 28 patients with inflammatory bowel disease on treatment with sulphasalazine at 2-4 g per day. […] Gross semen abnormalities were seen in 18 patients on this drug for more than two months. […] The time course of the drug’s effect on semen quality is consistent with the hypothesis that sulphasalazine or a metabolite, possibly sulphapyridine, is directly toxic to developing spermatozoa. […] These studies confirmed the preliminary report and suggest that prolonged treatment with sulphasalazine may universally depress semen quality and cause reversible infertility.

• #70 Male infertility – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/male-infertility/symptoms-causes/syc-20374773

  Defects of tubules that transport sperm. Many different tubes carry sperm. They can be blocked due to various causes, including inadvertent injury from surgery, prior infections, trauma or abnormal development, such as with cystic fibrosis or similar inherited conditions. […] Chromosome defects. Inherited disorders such as Klinefelter’s syndrome in which a male is born with two X chromosomes and one Y chromosome (instead of one X and one Y) cause abnormal development of the male reproductive organs. Other genetic syndromes associated with infertility include cystic fibrosis and Kallmann’s syndrome. […] Overexposure to certain environmental elements such as heat, toxins and chemicals can reduce sperm production or sperm function. […] Some other causes of male infertility include: Drug use. Anabolic steroids taken to stimulate muscle strength and growth can cause the testicles to shrink and sperm production to decrease. Use of cocaine or marijuana may temporarily reduce the number and quality of your sperm as well. […] Male infertility isn’t always preventable. However, you can try to avoid some known causes of male infertility.

• #71 Clomid for Men – Comprehensive Urology

  https://comprehensive-urology.com/urologist-desk/clomid-for-men/

  Clomiphene citrate can effectively increase testosterone levels in men with hypogonadism. It stimulates the pituitary gland to produce more luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which in turn boost testosterone production. […] Research has shown that Clomiphene citrate is beneficial for improving fertility in men. It increases the production of testosterone, which is crucial for spermatogenesis. A study suggests that a daily dose of 25 mg is effective in stimulating endogenous testosterone production. This enhances the pathway necessary for sperm production, making Clomiphene a promising option for men experiencing fertility issues. […] Clomiphene works by stimulating the pituitary gland, leading to an increase in the production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This boost in hormones supports the testes in producing more testosterone, aiding in counteracting low testosterone issues.

• #72 Impact of environmental factors on human semen quality and male fertility: a narrative review | Environmental Sciences Europe | Full Text

  https://enveurope.springeropen.com/articles/10.1186/s12302-021-00585-w

  Worldwide rising trend in infertility has been observed in the past few years with male infertility arising as a major problem. One main reason for the rise in male infertility cases is declining semen quality. It was found that any factor that affects semen quality can affect male fertility. […] Adverse environmental factors have a significant impact on semen quality, leading to decreased sperm concentration, total sperm count, motility, viability, and increased abnormal sperm morphology, sperm DNA fragmentation, ultimately causing male infertility. […] Semen quality is the major predictor of male fertility outcome. It was observed that environmental pollution unfavorably affects semen quality by impairing the process of spermatogenesis, steroidogenesis, Sertoli cell, and sperm functions, thereby leading to decreased male fertility.

• #73 Impact of environmental factors on human semen quality and male fertility: a narrative review | Environmental Sciences Europe | Full Text

  https://enveurope.springeropen.com/articles/10.1186/s12302-021-00585-w

  The exact mechanism by which air pollutants result in male infertility is not clear, but it can be explained to some extent by the facts that air pollution leads to: a). Hormonal disruption: The heavy metals such as lead, zinc, copper, and PAH present in the exhaust of automobiles have estrogenic, antiestrogenic, and antiandrogenic actions, which in turn can result in abnormal gonadal steroidogenesis and gametogenesis, thereby leading to infertility. […] Heavy metals affect male fertility by inducing reactive oxygen species generation, which in turn cause lipid peroxidation, sperm DNA damage, leading to infertility. […] Another major factor that may contribute to male infertility is exposure to excessive heat at the workplace or due to climate change. Temperature plays a crucial role in maintaining normal spermatogenesis in testes. […] Hence, exposure to high temperatures both due to occupation or environmental factors has a deleterious impact on overall semen quality and can cause male infertility.

• #74 Male Reproduction: From Pathophysiology to Clinical Assessment | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-031-11701-5_12

  The pathophysiology and the clinical assessment, including treatment strategies, of these situations will be discussed in the next chapters of this book. […] Exposure to high levels of PFOS, and of PFOA and PFOS combined, are associated with a reduction in the concentration of morphologically normal spermatozoa in adult men. […] A testicular toxicity of PFOS has been demonstrated in rats. […] In humans, in utero exposure to PFOA was associated later in adult life with lower sperm concentration and total sperm count and with higher levels of luteinizing hormone and follicle-stimulating hormone. […] In infertile male patients, PFOS levels were higher than fertile subjects. […] These findings clearly suggest an antiandrogenic potential of PFAS. […] Several studies have underlined the possible role of HPV in causing male infertility.

• #75 Where do obesity and male infertility collide? | BMC Medical Genomics | Full Text

  https://bmcmedgenomics.biomedcentral.com/articles/10.1186/s12920-024-01897-5

  The parallel rise in obesity and male infertility in modern societies necessitates the identification of susceptibility genes underlying these interconnected health issues. […] Obesity exacerbates infertility through various mechanisms. Metabolic dysregulation caused by increased adipose tissue affects testosterone secretion levels necessary for spermatogenesis. […] Mitochondrial dysfunction and oxidative stress in sperm lead to DNA damage and apoptosis which is associated with reduced pregnancy rates. […] Understanding the complex interplay between obesity and male infertility is crucial for effective management and treatment. […] The study identified a significant association between the AA (P value=0.001) genotype and A allele (P value=0.003) of the APOB rs13306194 variant and infertility in obese men.

• #76 Where do obesity and male infertility collide? | BMC Medical Genomics | Full Text

  https://bmcmedgenomics.biomedcentral.com/articles/10.1186/s12920-024-01897-5

  Moreover, the AA genotype of rs13306194 APOB was associated with a significant decrease in APOB gene expression in obese infertile men (p=0.05). […] Our findings reveal a novel association between differential APOB expression and male infertility. […] The observed association between APOB expression and the AA genotype of rs13306194 suggests that this genetic alteration may influence APOB gene expression and function. […] These findings underscore the critical role of lipid metabolism in male fertility, as lipids are essential components of the sperm cell membrane and liquid content. […] The STRING algorithm analysis identified several genes closely related to APOB that may actively contribute to male infertility. […] Our study identified a potential association between the APOB rs13306194 variant and male infertility in obese patients.

• #77 Male Reproduction: From Pathophysiology to Clinical Assessment | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-031-11701-5_12

  These data, combined with the higher prevalence of sperm HPV-infection in infertile subjects compared to general population, suggested a role for HPV as a cause of sperm damage and, consequently, of male infertility. […] HPV infection in semen represents moreover a risk factor for the development of anti-sperm antibodies (ASAs). […] In detail, more than 40% of HPV infected infertile patients had ASAs on the sperm surface. […] Several mechanisms have been hypothesized to explain obesity-induced sperm damage. […] A pivotal role is played by heat-induced damage. […] Furthermore, several hormonal alterations have been described and contribute to impairing spermatogenesis in obese patients. […] In conclusion, exposure to environmental risk factors, such as pollutants or infections, or adverse lifestyle, i.e., causing obesity, may interfere at different levels with male fertility, and might play a major role in situations of idiopathic infertility.

• #78 New mechanism underlying male infertility | ScienceDaily

  https://www.sciencedaily.com/releases/2021/01/210107164756.htm

  One essential component of each eukaryotic cell is the cytoskeleton. […] The flagellum has to beat in a very precise and coordinated manner to allow progressive swimming of the sperm. Failure to do so can lead to male infertility. […] These findings imply that a perturbation of this modification could underlie some forms of male infertility in humans. […] Sperm flagella are essential for male fertility and thus for sexual reproduction. […] Failure to do so can lead to male infertility. […] To keep sperm swimming in a straight line, the modification of the protein tubulin by enzymes is essential. […] In the absence of glycylation, they became uncoordinated, and as a result, we suddenly saw sperm swimming in circles. […] „We observed functional defects on sperm from mice lacking glycylation, which resulted in a reduction of fertility. Since mice as a model system are known to have robust fertility, a similar defect in humans, could lead to male sterility” says Carsten Janke.

• #79 Study Points to a New Mechanism Underlying Male Infertility | Technology Networks

  https://www.technologynetworks.com/cell-science/news/study-points-to-a-new-mechanism-underlying-male-infertility-344406

  One essential component of each eukaryotic cell is the cytoskeleton. […] The flagellum has to beat in a very precise and coordinated manner to allow progressive swimming of the sperm. Failure to do so can lead to male infertility. […] These findings imply that a perturbation of this modification could underlie some forms of male infertility in humans. […] Sperm flagella are essential for male fertility and thus for sexual reproduction. […] To keep sperm swimming in a straight line, the modification of the protein tubulin by enzymes is essential. […] In the absence of glycylation, they became uncoordinated, and as a result, we suddenly saw sperm swimming in circles. […] Since mice as a model system are known to have robust fertility, a similar defect in humans, could lead to male sterility.

• #80 New mechanism underlying male infertility | ScienceDaily

  https://www.sciencedaily.com/releases/2021/01/210107164756.htm

  This explains why the swimming of the sperm cells is perturbed. […] Our findings provide direct evidence that microtubules have an active role in regulating fundamental biological processes via a code of tubulin modifications. Further, this study points to a new mechanism underlying male infertility.

• #81 Study Points to a New Mechanism Underlying Male Infertility | Technology Networks

  https://www.technologynetworks.com/cell-science/news/study-points-to-a-new-mechanism-underlying-male-infertility-344406

  This explains why the swimming of the sperm cells is perturbed. […] Our findings provide direct evidence that microtubules have an active role in regulating fundamental biological processes via a code of tubulin modifications. Further, this study points to a new mechanism underlying male infertility.

• #82 Protamines and their role in pathogenesis of male infertility – Bisht – Translational Cancer Research

  https://tcr.amegroups.org/article/view/8230/7282

  Sperm DNA damage is the single largest cause of defective sperm function and may be the underlying cause of idiopathic male infertility. […] Male infertility is defined as a multifactorial syndrome affecting 1 out of every 20 men in the reproductive age group. […] Although extensive research has been done in the context of male infertility but the exact cause is still unknown (idiopathic) and is mainly attributed to genetic reasons. […] Decline in sperm function is believed to be the primary, single, and defined cause of male infertility, resulting in failed fertilization. […] Haploinsufficiency of either PRM1 or PRM2 or abnormal PRM1/PRM2 protein ratio is associated with an increased risk of male factor infertility as this may result in improper compaction of sperm nuclear DNA and leaving the DNA highly vulnerable to environmental insults.

• #83 Protamines and their role in pathogenesis of male infertility – Bisht – Translational Cancer Research

  https://tcr.amegroups.org/article/view/8230/7282

  A noticeable number of case-control studies have been done which have shown that polymorphisms or mutations in protamine encoded genes results in conformational changes in the encoded proteins, changes in sperm chromatin structure and hence impaired spermatogenesis. […] An increase in sperm histone:protamine ratio is associated with poor chromatin compaction and thus, male factor infertility. […] Altered relative ratio of PRM1:PRM2 at the level of mRNA and protein also leads to male factor infertility. […] Perturbation in PRM1:PRM2 is associated with poor chromatin and hence an increased risk of male infertility as sperm requires a full complement of both the protamines to convey the male genome to the next generation. […] DNA damage in sperm is only partially repaired due to highly truncated DNA damage detection and repair mechanism. […] Thus, for maintenance of sperm DNA integrity optimal PRM1 and PRM2 ratios should be maintained as DNA repair mechanism are deficient in sperm and this is vital for birth of healthy offspring.

• #84 A homozygous FANCM frameshift pathogenic variant causes male infertility | Genetics in Medicine

  https://www.nature.com/articles/s41436-018-0015-7

  A homozygous PV in FANCM (c.1946_1958del, p.P648Lfs*16) was found cosegregating with male infertility. […] These findings revealed male infertility to be a novel phenotype of human patients with a biallelic FANCM PV. […] The loss-of-function FANCM PV increased ICL sensitivity in lymphocytes of patients and Fancm C/C spermatogonia. […] Adult Fancm C/C mice showed spermatogenic failure, with germ cell loss in 50.2% of testicular tubules and round-spermatid maturation arrest in 43.5% of tubules. […] Hypogonadism and reduced fertility have been noted in both male and female mice with homozygous Fancm PV, mainly due to defective proliferation of primordial germ cells (PGCs). […] Biallelic FANCM PV may be associated with impaired fertility in human females, but whether they could cause infertility in men, particularly spermatogenic failure, is yet unknown.

• #85 A homozygous FANCM frameshift pathogenic variant causes male infertility | Genetics in Medicine

  https://www.nature.com/articles/s41436-018-0015-7

  This PV causes lymphocytic ICL sensitivity in patients, thus showing a loss-of-function effect. […] Altogether, these findings revealed that male infertility is a novel phenotype of the biallelic FANCM PV in humans. […] The truncated FANCM (p.P648Lfs*16) is predicted to lose the domains required for its interaction with the FA core complex, and thus it should not activate FANCD2 monoubiquitination. […] These results indicated that the truncating FANCM PV impairs FA pathway, demonstrating a loss-of-function effect. […] In fertility tests, adult Fancm C/C males were generally subfertile and produced significantly smaller litters than WT and Fancm +/C mice. […] Hence, Fancm C/C mice phenocopied the clinical phenotypes in our patients. […] The homozygous FANCM PV disrupted testicular integrity. […] Our findings that a homozygous loss-of-function FANCM PV impaired spermatogenesis and caused male infertility provide novel insights into genotype-phenotype correlations for biallelic FANCM PV.

• #86 Fertility in Men With CF | Cystic Fibrosis Foundation

  https://www.cff.org/managing-cf/fertility-men-cf

  Most men with cystic fibrosis (9798%) are infertile but not sterile because they produce sperm. […] Infertility in men with CF occurs because of an absence of the sperm canal. […] Most men with CF (9798%) are infertile because of an absence of the sperm canal, known as congenital bilateral absence of the vas deferens (CBAVD). The sperm never make it into the semen, making it impossible for them to reach and fertilize an egg through intercourse. […] Although the cause of CBAVD is not conclusively known, it is thought to be associated with cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations that also cause problems in the pancreas and lungs. […] Even though most men with CF are infertile, some do still have sperm present in their ejaculate.

• #87 Ejaculatory physiology and pathophysiology: assessment and treatment in male infertility – Revenig – Translational Andrology and Urology

  https://tau.amegroups.org/article/view/3515/html

  Azoospermia is a heterogeneous condition with multiple etiologies and a variety of treatments. Retrograde ejaculation and failure of emission are in a spectrum of ejaculatory disorders which impair male fertility. Retrograde ejaculation and failure of emission are the two disorders of ejaculatory function which result in anejaculation and infertility. While all three have a common pathway of anejaculation, the disorders leading to these conditions comprise a heterogeneous group of conditions with differing etiologies and therapies. Retrograde ejaculation is the flow of semen into the bladder due to an incompletely closed bladder neck. Retrograde ejaculation was the observed cause in 18%, although as a source of infertility it was only implicated in 0.7%. Additionally, it has been noted the incidence is likely rising as a consequence increasing rates of diabetes, use of -receptor antagonists, and bladder neck surgery for malignancies. A variety of mechanical, neurologic, and pharmacologic etiologies are responsible for retrograde ejaculation. Failure of emission is when there is complete disruption of emission during sexual activity. Orgasm and the expulsive phase of ejaculation occur, but there is failure of deposition of the reproductive glands to deposit the necessary fluid into the prostatic urethra during stimulation. It is clinically characterized simply as anejaculation, but on investigation for retrograde ejaculation, there will be no evidence of retrograde ejaculation in post-orgasm urine. Failure of emission is defined as the lack of sperm on antegrade and retrograde semen analysis. This can be caused by peripheral neuropathy caused by diabetes as well as any spinal cord injury (SCI). Basically, we view failure of emission and retrograde ejaculation as a spectrum of ejaculatory dysfunction with failure of emission being the ultimate failure of the ejaculatory system.

• #88 Male Infertility – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562258/

  The purpose of evaluating the male partner of a couple suffering from infertility is as follows: To determine if the male factor is contributing to the couple’s infertility issue, to identify the small percentage of cases (about 20%) that can be normalized with treatment, to determine if ART would ultimately benefit the couple, to identify significant underlying pathology or associated medical comorbidities, and to determine if there are age, health, lifestyle, or genetic factors that could affect the outcome or success rate if ART is required. […] The semen analysis is the cornerstone of laboratory evaluation of male infertility. At least 2 separate samples should be collected, separated by at least 1 week but optimally by a month. […] The semen is evaluated for volume, pH, leukocytes, immature germ cells, and liquefaction, while the sperm is assessed for count, concentration, vitality, motility, progression, debris, and morphology.

• #89 Male Infertility – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562258/

  IVF can be used in couples when IUI with ovarian stimulation has failed, in women over 40 years of age, or when there are known conditions precluding the use of simpler techniques, such as bilateral tubal disorders. […] Overall, IVF with ICSI is preferred when there are very significant male factors that cannot be overcome by other means, but at least a few viable sperm can still be retrieved.

• #90 Male infertility – The other side of the equation

  https://www.racgp.org.au/afp/2017/september/male-infertility

  Even if hypogonadism is identified, exogenous testosterone use is contraindicated in patients seeking fertility treatment. […] Antibodies against sperm can form when there is disruption in the blood-testis barrier and sperm antigens prime the immune system. […] Greater sperm DNA fragmentation is seen in patients who are infertile, and is associated with worse pregnancy outcomes. […] Genetic testing is indicated for patients with severe oligospermia (5 million/mL). […] A specific region, named AZF (azoospermia factor), in the long arm of the Y chromosome is critical to normal spermatogenesis. […] Karyotype testing is indicated in patients with severe oligospermia (5 million/mL), because the prevalence of karyotype abnormalities is inversely proportional to sperm count: 1% with normal sperm count, 5% with severe oligospermia (5 million/mL) and 10-15% with azoospermia. […] The most common abnormality is Klinefelter syndrome (47, XXY), which accounts for approximately two-thirds of abnormalities in men who are infertile.

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