Male infertility is the inability of a man to impregnate a fertile female partner, resulting in difficulty or inability to conceive a child. It is a significant health issue that affects a considerable number of couples worldwide. Male infertility is caused by various factors, including abnormalities in sperm production, sperm transport, and sperm function.

The prevalence of male infertility varies across populations and regions. However, it is estimated that male factor infertility contributes to about 40-50% of all infertility cases. Male infertility can occur at any age but becomes more prevalent with advancing age.

There are several factors that can contribute to male infertility. These include genetic abnormalities, hormonal imbalances, testicular disorders, structural abnormalities of the reproductive system, infections, exposure to certain environmental factors, lifestyle choices (such as smoking and excessive alcohol consumption), and certain medical conditions (such as diabetes and obesity).

Prevalence:

• Male infertility contributes to a significant proportion of infertility cases worldwide.
• The exact prevalence varies across different populations and geographic regions.

Global Estimates:

• According to the World Health Organization, approximately 13% to 15% of couples worldwide experience infertility, and male factors contribute to about 50% of these cases.
• The prevalence of male infertility is consistent across different regions, including North America, Europe, Asia, and Africa.

Population-Specific Estimates:

• Studies have reported varying prevalence rates of male infertility based on specific populations and study designs.
• Certain populations, such as those seeking fertility treatment, may have higher rates of male infertility compared to the general population.

Primary and Secondary Infertility:

• Male infertility can be classified as primary (no previous successful pregnancies) or secondary (previous successful pregnancies but currently unable to conceive).
• The prevalence of primary and secondary infertility may differ, but both contribute to the overall burden of male infertility.

Spermatogenesis Disorders:

• Spermatogenesis is the process of sperm production in the testes. Disorders affecting spermatogenesis can contribute to male infertility.
• Examples of spermatogenesis disorders include genetic abnormalities, testicular dysfunction, hormonal imbalances, varicocele, and exposure to toxins or radiation.

Semen Abnormalities:

• Semen abnormalities, such as low sperm count (oligospermia), poor sperm motility (asthenospermia), and abnormal sperm morphology (teratospermia), can lead to male infertility.
• These abnormalities may be caused by various factors, including hormonal imbalances, testicular dysfunction, genetic disorders, infections, and lifestyle factors.

Hormonal Imbalances:

• Hormonal imbalances, particularly involving reproductive hormones such as testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), can affect sperm production and function.
• Disorders such as hypogonadism, pituitary or hypothalamic dysfunction, and certain medications can disrupt hormonal balance and lead to male infertility.

Varicocele:

• Varicocele refers to the enlargement of veins within the scrotum, which can increase scrotal temperature and impair sperm production.
• Varicocele is a cause of male infertility and can be associated with impaired sperm quality and testicular dysfunction.

Genetic Factors:

• Genetic abnormalities, including chromosomal disorders and gene mutations, can contribute to male infertility.
• Conditions such as Klinefelter syndrome, Y chromosome microdeletions, and cystic fibrosis gene mutations are associated with impaired sperm production and function.

Hormonal Imbalances:

• Hormonal imbalances can affect male fertility by disrupting the production and regulation of reproductive hormones.
• Conditions such as hypogonadism, pituitary or hypothalamic dysfunction, and certain medications may lead to hormonal imbalances and infertility.

Testicular Factors:

• Testicular disorders can impair sperm production and function, leading to male infertility.
• Conditions such as cryptorchidism (undescended testicles), testicular trauma, testicular cancer, and testicular failure can contribute to infertility.

Obstruction of Reproductive Tract:

• Obstruction or blockage in male reproductive tract can prevent the normal transport of sperm.
• Conditions such as congenital abnormalities, infections, vasectomy, and ejaculatory duct obstructions can cause reproductive tract obstruction.

Environmental and Lifestyle Factors:

• Exposure to environmental toxins, pollutants, radiation, and certain medications can negatively impact sperm production and function.
• Lifestyle factors like smoking, excessive alcohol consumption, drug abuse, and obesity can also contribute to male infertility.

Semen Parameters:

• Semen analysis is a crucial diagnostic tool for assessing male fertility.
• Abnormal semen parameters, including low sperm count, poor motility, and abnormal morphology, are associated with reduced fertility potential.

Reproductive Hormones:

• Hormonal imbalances, such as low levels of testosterone or elevated levels of follicle-stimulating hormone (FSH), can impact fertility outcomes.
• Hormone levels, especially testosterone and FSH, can provide valuable prognostic information regarding the underlying cause and severity of male infertility.

Sperm DNA Integrity:

• The integrity of sperm DNA is important for successful fertilization and embryo development.
• High levels of sperm DNA fragmentation are associated with decreased fertility and lower pregnancy rates.

Underlying Cause:

• The specific cause of male infertility can significantly influence the prognosis.
• For example, genetic abnormalities, testicular disorders, and obstructive lesions may have varying degrees of impact on fertility outcomes.

Age Group:

• Male infertility can occur at any age, but certain age groups may be more commonly affected.
• Younger men may present with congenital abnormalities or genetic factors that contribute to infertility.
• Older men may experience age-related decline in fertility potential, such as decreased sperm quality and quantity.

Associated Comorbidity or Activity:

• Certain medical conditions or lifestyle factors can be associated with male infertility.
• Comorbidities such as diabetes, obesity, and hormonal disorders may contribute to infertility.
• Activities or exposures such as smoking, excessive alcohol consumption, drug use, and exposure to toxins or radiation can impact fertility.

Acuity of Presentation:

• Male infertility can present as primary infertility (no previous pregnancies) or secondary infertility (previous successful pregnancies followed by difficulty in conceiving again).
• The duration and severity of infertility symptoms can vary among individuals.
• Some men may experience acute symptoms related to an underlying condition or injury, while others may have a chronic and persistent issue with fertility.

Genital Examination:

• Inspection of the external genitalia is done to assess any abnormalities or structural abnormalities such as undescended testes, varicoceles, or penile abnormalities.
• Palpation of the scrotum and testes is performed to check for size, consistency, and presence of any masses or lumps.
• Examination of the vas deferens and epididymis may be done to identify any blockages or abnormalities.
• Assessment of the prostate gland through digital rectal examination (DRE) may be performed to check for signs of infection or prostate-related issues.

Semen Analysis:

• Semen analysis is a crucial part of the physical examination for male infertility.
• It involves collecting a semen sample for laboratory analysis to evaluate various parameters such as sperm count, motility, morphology, and volume.
• The analysis helps to assess the quality and quantity of sperm and can provide valuable insights into potential causes of infertility.

Hormonal Evaluation:

• Blood tests may be conducted to measure hormone levels, including testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin.
• Hormonal imbalances can affect sperm production and function, and the evaluation helps to identify any underlying endocrine disorders.

Additional Investigations:

• Depending on the clinical findings and suspected causes, further investigations may be recommended, such as genetic testing, imaging studies (e.g., ultrasound), or specialized tests to assess sperm function or DNA integrity.

Lifestyle modifications:

In some cases, simple lifestyle changes can improve fertility. These may include quitting smoking, reducing alcohol intake, maintaining a healthy weight, managing stress levels, and avoiding exposure to toxins and environmental hazards.

Hormone therapy:

If hormonal imbalances are causing infertility, hormone replacement therapy or medications such as clomiphene citrate or gonadotropins may be used to stimulate sperm production.

Antibiotics:

If an infection is the cause of infertility, antibiotics can be prescribed to treat the infection and potentially restore fertility.

Medications for erectile dysfunction:

Erectile dysfunction can sometimes contribute to male infertility. Medications like sildenafil (Viagra) or other phosphodiesterase type 5 inhibitors can help improve erectile function.

Surgical interventions:

Some cases of male infertility require surgical procedures to correct underlying issues. These may include:

Varicocele repair:

Varicoceles are enlarged veins in the scrotum that can impact sperm production. Surgical repair of varicoceles may improve sperm count and motility.

Vasectomy reversal:

If a man has previously undergone a vasectomy and wants to restore fertility, vasectomy reversal surgery can be considered.

Obstruction removal:

In cases where there is a blockage preventing the release of sperm, surgical interventions may be performed to remove or bypass the obstruction.

Assisted Reproductive Techniques (ART):

ART procedures, as mentioned earlier, can be used when other treatments are unsuccessful or not applicable. These techniques include in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and other advanced reproductive technologies.

Donor sperm:

In cases where the male partner has severe infertility issues that cannot be resolved through other means, the couple may consider using donor sperm for insemination or IVF.

Endocrinology, Reproductive/Infertility

OB/GYN and Women\'s Health

Urology

Avoid hot baths and saunas: Prolonged exposure to hot water, such as taking hot baths or spending extended periods in saunas, can raise scrotal temperature and potentially impair sperm production.

Limit tight-fitting underwear: Wearing tight underwear or clothing can increase scrotal temperature. Opt for loose-fitting underwear made of breathable fabrics to promote air circulation and reduce heat buildup.

Avoid prolonged sitting: Sitting for long periods, especially with legs crossed, can increase scrotal temperature. Take breaks, stand up, and move around periodically to allow for better air circulation.

Stay away from heat sources: Minimize exposure to direct heat sources such as laptops, heated car seats, and electric blankets, as they can elevate scrotal temperature.

Be cautious with hot tubs and heated car seats: Avoid prolonged exposure to hot tubs or heated car seats, as they can raise scrotal temperature. If using them, limit the duration of exposure and take breaks to cool down.

Keep testicles cool: Some men find relief by placing a cool pack or ice pack on the scrotum for short periods. However, it is important not to apply ice directly to the skin, as it can cause injury. Use a cloth or towel as a barrier.

Endocrinology, Reproductive/Infertility

Urology

Impact on sperm quality: Smoking has been linked to decreased sperm count, motility, and morphology, which can contribute to male infertility.

DNA damage: Smoking can cause DNA damage to sperm, leading to genetic abnormalities and reduced fertility.

Hormonal disruption: Tobacco smoking can disrupt hormonal balance, affecting testosterone levels and other hormonal factors involved in sperm production.

Oxidative stress: Smoking increases the production of reactive oxygen species (ROS) in the body, leading to oxidative stress. This can damage sperm cells and impair fertility.

Erectile dysfunction: Smoking is a known risk factor for erectile dysfunction, which can further contribute to difficulties in achieving pregnancy.

Second hand smoke: Exposure to second hand smoke can also have adverse effects on male fertility. It is important to avoid or minimize exposure to tobacco smoke in the environment.

Endocrinology, Reproductive/Infertility

Urology

Effects of Alcohol on Sperm Quality:

• Alcohol and sperm production: Alcohol consumption can disrupt the production of healthy sperm, leading to decreased sperm count, motility, and morphology.
• Alcohol and sperm DNA integrity: Excessive alcohol intake may increase oxidative stress and DNA damage in sperm, potentially affecting fertility.

Alcohol and Hormonal Imbalances:

• Testosterone levels: Alcohol can interfere with testosterone production and regulation, leading to hormonal imbalances that may contribute to infertility.
• Hormonal disruption: Alcohol can disrupt the balance of other reproductive hormones involved in sperm production and function.

Alcohol and Sexual Dysfunction:

• Erectile dysfunction: Heavy alcohol consumption can contribute to erectile dysfunction, making it difficult to achieve or maintain an erection needed for successful intercourse.
• Decreased libido: Alcohol can reduce sexual desire and impair sexual performance, potentially affecting fertility.

Alcohol and Semen Analysis:

• Semen parameters: Excessive alcohol intake may negatively impact semen parameters, including sperm concentration, motility, and morphology.
• Semen volume: Alcohol can lead to dehydration, resulting in reduced semen volume.

Strategies to Limit Alcohol Intake:

• Moderate alcohol consumption: Advising men to limit alcohol intake to moderate levels, defined as up to one to two drinks per day.
• Alcohol cessation: Encouraging individuals with heavy alcohol consumption to quit or significantly reduce their alcohol intake.

Endocrinology, Reproductive/Infertility

Urology

Obesity and Male Fertility:

• Impact on hormone levels: Obesity can disrupt hormonal balance, leading to reduced testosterone levels and increased estrogen levels, which can negatively affect sperm production and quality.
• Sperm parameters: Obesity is associated with decreased sperm concentration, motility, and normal morphology, leading to impaired fertility.
• Inflammatory factors: Adipose tissue in obese individuals produces inflammatory factors that can interfere with sperm function and fertility.

Weight Loss and Fertility Improvement:

• Improving hormone levels: Losing excess weight can help restore hormonal balance, including testosterone levels, and improve fertility potential.
• Enhancement of sperm parameters: Weight loss has been shown to improve sperm count leading to enhanced fertility outcomes.
• Reduction of inflammation: Weight loss can reduce inflammation in the body, which can positively impact sperm quality and function.

Strategies for Weight Management:

• Balanced diet: Following a balanced and nutritious diet that includes whole foods, fruits, vegetables, lean proteins, and healthy fats.
• Calorie control: Consuming the appropriate number of calories to achieve a healthy weight, while avoiding excessive calorie intake.
• Regular physical activity: Engaging in regular exercise and physical activity to support the weight loss and overall health.
• Behavioural changes: Adopting healthy lifestyle habits, such as portion control, mindful eating, and stress management.

Endocrinology, Reproductive/Infertility

Urology

Continued attempts at conception through vaginal intercourse:

If there are sperm present in the ejaculate, couples can continue trying to conceive naturally through regular sexual intercourse.

Assisted Reproductive Techniques (ART):

ART procedures like in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) can be considered. These techniques involve retrieving eggs from the female partner, fertilizing them with sperm in a laboratory, and transferring resulting embryos to the woman’s uterus.

ART may improve the chances of conception for couples with male factor infertility, but evidence regarding its effectiveness in improving live birth rates is limited.

In cases where spermatozoa or spermatids are seen only in testicular biopsies, ART can be effective:

Surgical retrieval of sperm:

In some cases, men with primary (hypergonadotropic) hypogonadism and azoospermia on semen analysis may have spermatids or mature spermatozoa present in testicular biopsies. These can be surgically retrieved and used for fertilization through ART techniques such as IVF or ICSI. It is important to note that genetic implications may exist for using sperm from men with certain conditions or severe oligozoospermia.

However, if no sperm is seen in testicular biopsies due to a primary testicular defect in spermatogenesis (azoospermia), there is currently no therapy available to enable conception.

Surgical repair of varicocele:

Varicocele repair may be considered in infertile men with abnormal semen analyses and large, grade 3 varicoceles. However, its efficacy in improving fertility has conflicting evidence, and the quality of the evidence is generally low. Varicocele surgery is not recommended for men with small, nonpalpable varicoceles or severe oligozoospermia or azoospermia, as they may have severe germ cell damage.

Treatment of leukospermia:

Antibiotic treatment for leukospermia is not recommended, as specific organisms are rarely identified in these cases. There is insufficient evidence to support the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in improving male fertility, and they may have potential adverse effects.

Medical therapies to increase circulating gonadotropin concentrations:

The use of clomiphene, aromatase inhibitors, or gonadotropin therapy for idiopathic dysspermatogenesis or idiopathic male infertility is not recommended. The evidence for these treatments is limited, and larger trials are needed to determine their efficacy.

• clomiphene citrate:

clomiphene citrate is a medication commonly used in the treatment of female infertility. It works by blocking estrogen receptors in the hypothalamus, leading to increased production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which stimulate the testes to produce testosterone and sperm. In some cases, clomiphene citrate may be prescribed “off-label” for men with idiopathic male infertility or idiopathic dysspermatogenesis. However, the evidence supporting its use in men is limited, and larger trials are needed to determine its efficacy and safety.

• Aromatase inhibitors:

Aromatase inhibitors, such as letrozole or anastrozole, are medications commonly used to treat estrogen-sensitive breast cancer in women. They work by blocking the conversion of androgens (such as testosterone) into estrogen. In men, aromatase inhibitors may be used off-label to increase testosterone levels and potentially improve sperm production. However, the evidence for their use in male infertility is limited to case reports and small studies, and further research is needed to establish their effectiveness.

• Recombinant human follicle-stimulating hormone (rhFSH):

Recombinant human follicle-stimulating hormone (rhFSH) is a medication that directly stimulates the production of sperm in the testes. It is used in assisted reproductive techniques such as in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) to increase sperm production in men with severe male factor infertility. However, the use of rhFSH as a standalone treatment for male infertility is still being investigated, and more research is needed to determine its efficacy and safety outside of assisted reproductive techniques.

Lifestyle changes:

Adopting healthy lifestyle practices, such as avoiding tobacco, marijuana, excessive alcohol intake, and obesity, may be beneficial for optimizing spermatogenesis. There is limited evidence to support the avoidance of tight-fitting underwear, saunas, or hot baths as necessary measures.

Dietary supplements:

Fish oil supplements, containing omega-3 fatty acids DHA and EPA, have shown inconsistent results in improving sperm parameters in infertile men in placebo-controlled studies. Based on available evidence, the use of fish oil as a therapy for male infertility is not recommended.

Endocrinology, Reproductive/Infertility

Urology

Medications to Stimulate Sperm Production:

Human Chorionic Gonadotropin (hCG):

• hCG is a hormone that mimics the action of LH in the body.
• It can be used to stimulate testosterone production in men with secondary hypogonadism, where there is insufficient LH production.
• By boosting testosterone levels, hCG can improve sperm production and fertility in some cases.

Gonadotropin-Releasing Hormone (GnRH) Analogs:

• GnRH analogs, such as leuprolide or triptorelin, can be used to suppress the production of testosterone in certain cases.
• They are sometimes used in the treatment of male infertility associated with hormone-sensitive conditions, such as pituitary disorders or excessive androgen production.

Endocrinology, Reproductive/Infertility

Y chromosome microdeletions: In men with Y chromosome microdeletions, hormone therapy may be used to address hormonal imbalances or deficiencies. Testosterone replacement therapy or medications to stimulate sperm production, such as clomiphene citrate or human chorionic gonadotropin, may be prescribed.

Klinefelter syndrome: Men with Klinefelter syndrome may benefit from testosterone replacement therapy to address hormonal imbalances and improve sperm production.

Cystic fibrosis: For men with cystic fibrosis, treatment may involve medications to manage symptoms and improve overall health. In some cases, assisted reproductive techniques, such as in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI), may be used to achieve pregnancy.