madman
Super Moderator
Male infertility due to testicular disorders
Aditi Sharma, Suks Minhas, Waljit S Dhillo, and Channa N Jayasena
Abstract
Context: Male infertility is defined as the inability to conceive following 1 year of regular unprotected intercourse. It is the causative factor in 50% of couples and a leading indication for assisted reproductive techniques (ART). Testicular failure is the most common cause of male infertility, yet the least studied to date.
Evidence Acquisition: The review is an evidence-based summary of male infertility due to testicular failure with a focus on etiology, clinical assessment, and current management approaches. PubMed-searched articles and relevant clinical guidelines were reviewed in detail.
Evidence Synthesis/Results: Spermatogenesis is under multiple levels of regulation and novel molecular diagnostic tests of sperm function (reactive oxidative species and DNA fragmentation) have since been developed, and albeit currently remain as research tools. Several genetic, environmental, and lifestyle factors provoking testicular failure have been elucidated during the last decade; nevertheless, 40% of cases are idiopathic, with novel monogenic genes linked in the etiopathogenesis. Microsurgical testicular sperm extraction (micro-TESE) and hormonal stimulation with gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors are recently developed therapeutic approaches for men with the most severe form of testicular failure, nonobstructive azoospermia. However, high-quality clinical trial data is currently lacking.
Conclusions: Male infertility due to testicular failure has traditionally been viewed as unmodifiable. In the absence of effective pharmacological therapies, the delivery of lifestyle advice is a potentially important treatment option. Future research efforts are needed to determine unidentified factors causative in “idiopathic” male infertility and long-term follow-up studies of babies conceived through ART.
Infertility is defined as being unable to conceive after 12 months of regular (at least twice weekly) unprotected intercourse (1, 2). Male infertility is due to abnormal sperm parameters in the male partner and contributes to 50% of all cases of infertility (3, 4). A recent systematic review reported a fall in total sperm counts by 59.3% since the 1970s, in North America, Europe, and Australasia (5); however, other studies have failed to observe such a change (6, 7). Furthermore, male infertility is increasingly observed as a “canary in the coal mine” for future male health conditions (8), with an association with cardiovascular disease, testicular cancer, quality of life, and increased all-cause mortality (9). Male infertility may be broadly subdivided into 3 categories: (1) hypothalamic-pituitary disease-causing secondary hypogonadism; (2) obstruction of seminal outflow (usually termed, obstructive azoospermia, OA), and testicular dysfunction (which may be associated with primary hypogonadism) (10–12).
Azoospermia is defined as the absence of sperm in the ejaculate. It affects approximately 1% of all men and is the most severe manifestation of testicular failure (13). Secondary hypogonadism has been extensively summarized in the literature and has established therapies, gonadotropin-releasing hormone (GnRH), and gonadotropin replacement (14, 15). By contrast, OA and testicular dysfunction are less well-studied but represent rapidly evolving conditions with emerging endocrine and surgical therapies for affected patients. Our review, therefore, focuses on primary testicular dysfunction as a cause of male infertility
*Physiology of spermatogenesis
*Sperm quality
*Oxidative stress and sperm DNA fragmentation
*Etiology of Male Infertility Due to Testicular Dysfunction
Genetic
Klinefelter’s syndrome
Robertsonian translocations and inversions
Y-chromosome microdeletions
46 XX male syndrome
Monogenic causes of male infertility
*Developmental
*Acquired
Genitourinary infections
Cancer and its treatment
Varicocele
Medications
*Obesity
*Endocrine-disrupting chemicals
*Lifestyle factors
Smoking
Alcohol
Recreational drug use
Caffeine
Physical activity
*Assessment of Male Infertility Due to Testicular Failure
History
Physical examination
Investigations
Testicular histology
*Principles of Management
Optimization of chances for a spontaneous pregnancy
Lifestyle changes
*Putative Hormonal Therapies for Testicular Failure
Gonadotropins
Antiestrogens
*Surgical sperm retrieval techniques
Sperm retrieval techniques
*Effects on offspring following ART for male infertility
Conclusion
Underlying genetic predisposition, exposure to environmental factors, and adverse lifestyle behaviors contribute to the etiopathogenesis of testicular dysfunction. However, 40% of cases of testicular failure remain classified as idiopathic. Future research is needed to determine unidentified factors causative in idiopathic male factor infertility. This would lead to novel individualized and targeted pharmacological therapies to complement ART, which is unaffordable to many couples worldwide.
Aditi Sharma, Suks Minhas, Waljit S Dhillo, and Channa N Jayasena
Abstract
Context: Male infertility is defined as the inability to conceive following 1 year of regular unprotected intercourse. It is the causative factor in 50% of couples and a leading indication for assisted reproductive techniques (ART). Testicular failure is the most common cause of male infertility, yet the least studied to date.
Evidence Acquisition: The review is an evidence-based summary of male infertility due to testicular failure with a focus on etiology, clinical assessment, and current management approaches. PubMed-searched articles and relevant clinical guidelines were reviewed in detail.
Evidence Synthesis/Results: Spermatogenesis is under multiple levels of regulation and novel molecular diagnostic tests of sperm function (reactive oxidative species and DNA fragmentation) have since been developed, and albeit currently remain as research tools. Several genetic, environmental, and lifestyle factors provoking testicular failure have been elucidated during the last decade; nevertheless, 40% of cases are idiopathic, with novel monogenic genes linked in the etiopathogenesis. Microsurgical testicular sperm extraction (micro-TESE) and hormonal stimulation with gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors are recently developed therapeutic approaches for men with the most severe form of testicular failure, nonobstructive azoospermia. However, high-quality clinical trial data is currently lacking.
Conclusions: Male infertility due to testicular failure has traditionally been viewed as unmodifiable. In the absence of effective pharmacological therapies, the delivery of lifestyle advice is a potentially important treatment option. Future research efforts are needed to determine unidentified factors causative in “idiopathic” male infertility and long-term follow-up studies of babies conceived through ART.
Infertility is defined as being unable to conceive after 12 months of regular (at least twice weekly) unprotected intercourse (1, 2). Male infertility is due to abnormal sperm parameters in the male partner and contributes to 50% of all cases of infertility (3, 4). A recent systematic review reported a fall in total sperm counts by 59.3% since the 1970s, in North America, Europe, and Australasia (5); however, other studies have failed to observe such a change (6, 7). Furthermore, male infertility is increasingly observed as a “canary in the coal mine” for future male health conditions (8), with an association with cardiovascular disease, testicular cancer, quality of life, and increased all-cause mortality (9). Male infertility may be broadly subdivided into 3 categories: (1) hypothalamic-pituitary disease-causing secondary hypogonadism; (2) obstruction of seminal outflow (usually termed, obstructive azoospermia, OA), and testicular dysfunction (which may be associated with primary hypogonadism) (10–12).
Azoospermia is defined as the absence of sperm in the ejaculate. It affects approximately 1% of all men and is the most severe manifestation of testicular failure (13). Secondary hypogonadism has been extensively summarized in the literature and has established therapies, gonadotropin-releasing hormone (GnRH), and gonadotropin replacement (14, 15). By contrast, OA and testicular dysfunction are less well-studied but represent rapidly evolving conditions with emerging endocrine and surgical therapies for affected patients. Our review, therefore, focuses on primary testicular dysfunction as a cause of male infertility
*Physiology of spermatogenesis
*Sperm quality
*Oxidative stress and sperm DNA fragmentation
*Etiology of Male Infertility Due to Testicular Dysfunction
Genetic
Klinefelter’s syndrome
Robertsonian translocations and inversions
Y-chromosome microdeletions
46 XX male syndrome
Monogenic causes of male infertility
*Developmental
*Acquired
Genitourinary infections
Cancer and its treatment
Varicocele
Medications
*Obesity
*Endocrine-disrupting chemicals
*Lifestyle factors
Smoking
Alcohol
Recreational drug use
Caffeine
Physical activity
*Assessment of Male Infertility Due to Testicular Failure
History
Physical examination
Investigations
Testicular histology
*Principles of Management
Optimization of chances for a spontaneous pregnancy
Lifestyle changes
*Putative Hormonal Therapies for Testicular Failure
Gonadotropins
Antiestrogens
*Surgical sperm retrieval techniques
Sperm retrieval techniques
*Effects on offspring following ART for male infertility
Conclusion
Underlying genetic predisposition, exposure to environmental factors, and adverse lifestyle behaviors contribute to the etiopathogenesis of testicular dysfunction. However, 40% of cases of testicular failure remain classified as idiopathic. Future research is needed to determine unidentified factors causative in idiopathic male factor infertility. This would lead to novel individualized and targeted pharmacological therapies to complement ART, which is unaffordable to many couples worldwide.
