In Vitro (IVF) Evaluation of the Male

Understanding Infertility in the Male Partner
Infertility can affect both women and men. About 15 to 20% of married couples apply to an IVF department because of infertility, and a male infertility factor is present in approximately half of these cases. Infertile couples receiving treatment in our department are evaluated by a team which includes a gynecologist, a urology / andrology specialist, an embryologist and genetic experts. All are experts in their fields and work in close collaboration with each other. Thorough investigations are made and necessary examinations and treatments are planned and carried out by doctors in the fields of their expertise.

GENERAL INFORMATION
How does the male reproductive system function?
The follicle stimulating hormone (FSH) and the luteinizing hormone (LH) are secreted from the pituitary glands. LH regulates the production of testosterone in the testes. FSH stimulates the development of spermatozoa.

How are sperm produced?

• FSH and testosterone act on the germ cells located in the tubules of the testes.
• The daily sperm production in healthy men is around 123 million.
• The formation of a mature sperm cell takes from 42 to 76 days.

What are “sperm transmission channels”?
Sperm cells produced in the testes travel through a series of ducts: the epididymis, the ductus deference (vas deference), the seminal vesicle and the ejaculatory duct.

What is ejaculate?
Ejaculate is a whitish, mother of pearl-colored liquid containing sperm cells, called semen. The average volume of this fluid is 1.5 to 4 ml. Most of it is secreted from the testes, the prostate gland and the seminal vesicle.

This fluid includes substances which are important for sperm development and for keeping sperm alive until they reach the woman's egg (ovum). During sexual stimulation a little sticky liquid appears at the tip of the male sexual organ. This fluid is secreted from the gland around the urethra, and does not contain sperm. However, the first part of the ejaculate contains the greatest number of sperm cells.

What are “Azoospermia” and “Aspermia”
“Azoospermia” is the absence of sperm in the ejaculate. It occurs for two reasons:

1. Azoospermia may be due to impaired sperm production in the testes. This is termed Non-obstructive Azoospermia (NOA).
2. Azoospermia may be due to obstruction or congenital absence of, the sperm transmission channels. This is termed Obstructive Azoospermia (OA).

“Aspermia” is the absence of ejaculate. It may be due to obstructive azoospermia. It can also be caused by some systemic diseases, such as diabetes and diseases of the nervous system and by using certain medications.

What are “Hypospermia” and “Hemospermia”?
The term “Hypospermia” means that the volume of ejaculate is smaller than normal. It may be due to obstruction or to abstaining from sexual activity for only short periods.

“Hemospermia” is the term for the presence of blood in the ejaculate. It is not usually considered to be a cause for concern in young men, and may be due to long term sexual abstinence or to infection.

CAUSES OF MALE INFERTILITY
What can cause male infertility?

There is a range of causes of infertility in men, including:

1. Varicocele
2. Undescended testis (chriptorsidism)
3. Infectious disease
4. Genetic factors
5. Endocrine (hormonal) disorders
6. Surgery
7. Smoking, alcohol consumption
8. Toxic substances in the environment
9. Immunologic infertility
10. Chemotherapy and radiotherapy
11. Medications
12. Systemic diseases
13. Obstruction of sperm transmission channels or ejaculation problems (retrograde ejaculation)

Causes are not found in around 20 to 30% of cases. This phenomenon is termed idiopathic infertility.

VARICOCELE
What is Varicocele?
Varicocele is the varicous dilatation of testicular veins. It is the most common cause of male infertility, and is observed in around 20 to30% of infertile males. However, it can occur in 5 to10 % of the normal population.

What causes varicocele?
The causes of varicocele are not known. However, it is more common in tall men, in obese men, in men who have chronic constipation, lung disease or a chronic cough, in men who work in a standing position for a long time and in men who do strenuous sports, such as weightlifting.

For anatomic reasons, varicocele is more common on the left side (90%). In 8 to 9 % of cases, it is bilateral; and in only 1 to 2% it is found on the right.

What are the symptoms of varicocele?
Scrotal pain and swelling on testis are the most common symptoms of varicocele. Over the long term, the testes may decrease in size.

What effect does varicocele have on male fertility?
Increased intratesticular temperature, decreased testicular blood flow and increased levels of toxic substances due to varicocele result in decreased sperm production.

How can varicocele be diagnosed?
It is diagnosed by physical examination. Scrotal Doppler ultrasonography is helpful for diagnosis.

How can variocele be treated?
It is treated surgically. However, an operation is not recommended in all cases It is advised if the patient has any of the following:

1. Varicocele diagnosed during his teenage years as leading to testicular atrophy
2. Decreased semen analysis parameters
3. Repeated unsuccessful attempts at assisted reproduction.

UNDESCENDED TESTIS/TESTES (CRYPTORCHIDISM)
What is undescended testis (cryptorchidism)?
Testes develop in the abdomen of the unborn baby, just below the kidneys, and descend into the scrotum just before birth. In some babies they remain in a high position or outside the scrotum. This condition is called undescended testis/testes or cryptorchidism.

How common is cryptorchidism?
It is one of the most common congenital abnormalities, and is present in 2% to 5% of full-term newborn baby boys. However, it is more common in premature baby boys (around 30%).

What effect does cryptorchidism have on male infertility?
Sperm production is negatively affected by the higher testicular temperature which results if the testes are undescended. While sperm production may be between 70% and 80% in cases of unilateral undescended testis, it is as low as 20%-30% in bilateral cases.

When should it be treated?
The testes may descend into the scrotum without medical intervention during the first year of life. If this does not happen naturally, it should be done surgically before the age of two. Sperm production is irreversibly affected after the age of 6.

INFECTIOUS DISEASES
What infectious diseases can cause male infertility?
Prostate infection (prostatitis) or sexually transmitted infections affect sperm function by increasing the number of white blood cells (leukocytes) in the ejaculate, and may result in male infertility.

Untreated gonorrhoea can lead to obstruction of sperm transmission channels. Tuberculosis affects the epididymis in the male reproductive system. Untreated tuberculosis can lead to obstruction.

Testicular infections, known as orchids, can lead to infertility by affecting the structure of the reproductive system and impairing sperm production. Mumps orchids developed after mumps infection are the most common cause of orchids. Before adolescence, mumps disease usually has no effect on sperm. However, after puberty, mumps orchids may develop in 40% of cases of unilateral or bilateral testicular infection.

GENETIC FACTORS
What are the genetic causes of male infertility?
The genetic structure of a normal male is 46, XY. This is made up of 22 pairs of autosomal chromosomes and one X and one Y sex chromosome.

There are several molecular mechanisms that affect sperm production, maturation and function. As yet, most of them have not been clearly identified.

Genetic disoders can cause male infertility by affecting sperm production in different ways:

1. Male sex chromosome disorders
2. number anomalies
3. structural abnormalities
4. Autosomal chromosome abnormalities in men
5. Abnormality in the genetic materials of the sperm

Disorders of the sex chromosome number
Klinefelter syndrome is the most common disorder of the sex chromosome number. It occurs in between 1 in 500 and 1 in1,000 of baby boys. These babies have one extra X chromosome, so their genetic structure is 47,XXY. Men with this syndrome are tall, with longer arms and legs than normal. They have poorly developed gender-specific characteristics, and small testicles (less than 5ml in volume). They have high levels of FSH and LH levels and their testosterone level is lower than normal. Generally, these patients have azoospermia.

In Klinefelter cases, sperm can be obtained by microscopic testicular sperm extraction (Micro TeSe). Using this method, our success rate is 53%.

Male sex chromosome structure abnormalities
Three different regions on the male Y chromosome control sperm production: AZF-a, AZF-b and AZF-c. Deficiencies in any of these areas affect sperm production in varying degrees. Deficiencies in the AZF-c region are the most common abnormality and are associated with decreased sperm count. Deficiencies in the AZF-a and AZF-b regions are associated with severe problems in sperm production and maturation.

Autosomal chromosome disorders
Some defects in the 22 pairs of chromosomes can cause male infertility.

Sperm genetic structure disorders
Defects in the genetic structure of sperm lead to functionally and morphologically impaired sperm. Infections, varicocele, smoking, environmental toxic agents and fever can all be causes.

ENDOCRINE (HORMONAL) DISORDERS
What endocrine disorders can cause male infertility?
Endocrine, or hormonal, disorders are present in around 3% to-5% of cases of male infertility. These problems are:

1. Lowered levels of f testosterone
2. Increased secretion of prolactin from the pituitary gland (blood prolactin level higher than 50 ng/mL)
3. Raised levels of serum estrogen, due, for example, to drug use or obesity..
4. Adrenal gland disorders
5. Thyroid gland disorders

What is hypogonadism?
Hypogonadism is a clinical condition resulting from decreased testosterone production. It leads to male infertility and sexual dysfunction. There are two types of hypogonadism: “primary” and” secondary”.

In primary hypogonadism, also known as “primary testicular failure”, the serum testosterone level is low and FSH and/or LH levels are high.

In secondary hypogonadism, both testosterone and FHS/LH levels are low. This condition is one of the most common treatable endocrine abnormalities found in male infertility.

SURGERY
What kind of operations can lead to male infertility?
Testicular operations or any kind of operation in the inguinal region, such as hernia repair, or surgery for varicocele, can cause damage or injury to testicular vessels or sperm transmission channels, and can lead to infertility.

Surgical operations for lymph nodes in the back of the abdomen for cancer (retroperitoneal lymph node surgery), aorta surgery, colon surgery and spinal cord surgery can damage the neural mechanisms, affecting sperm transport, and leading to sperm escaping back into the bladder. Some prostate or bladder surgery can lead to a similar situation.

SMOKING AND ALCOHOL CONSUMPTION
What effect do smoking and alcohol consumption have on sperm production and function?
Smoking is the one of the main causes of damage to the genetic material of sperm.DNA damage. Moreover, smoking can result in the failure of assisted reproductive methods.

Alcohol consumption affects hormonal mechanisms, and can lead to a decrease in the production of testosterone over a long-term period.

TOXIC SUBSTANCES IN THE ENVIRONMENT
What environmental factors cause male infertility?
Heavy metals such as lead and mercury, pesticides, organic solvents, high ambient temperatures and electromagnetism have detrimental effects on sperm. Mobile phones, computer monitors and laptop computers affect sperm production through electromagnetic waves and the thermal effects. However, it is difficult to be precise about the length and intensity of exposure to environmental factors needed to bring about these adverse effects on human sperm.

Acidic fluids and lubricants are toxic to sperm.

Working in hot environments, such as furnaces or metallurgical plants, hot showers and frequent saunas can affect sperm quality.

IMMUNOLOGIC INFERTILITY
What is immunologic infertility?
Infectious diseases, scrotal trauma and surgery on the testes can result in disturbance of the testicular structure. This can lead to the human immune system being activated against sperm cells and a decrease in sperm motility. Reproductive techniques are recommended methods for immunologic infertility.

CHEMOTHERAPY AND RADIOTHERAPY
How do chemotherapy and radiotherapy affect sperm production?
The drugs used in cancer treatment are toxic to all cells that are rapidly growing in number. In particular, the drugs used for Hodgkin's lymphoma and leukemia are extremely toxic. As a result, within eight to twelve weeks of starting chemotherapy, the production of sperm is interrupted. Depending on the dose and the duration, it may restart in only 15% to 30% of patients in one to five years after discontinuation of the treatment.

Radiotherapy has a similar effect. With applications above 600 Rad, azoospermia develops in 10 weeks.

Sperm freezing is advisable for all men in their reproductive years before cancer treatment, radiotherapy and/or chemotherapy.

MEDICATIONS
Which drugs affect sperm production?
As well as cancer drugs, many other drugs can affect sperm production.

1. Antibiotics:Nitrofurantoine, gentamycin, erythromycin, and tetracycline have harmful effects on the testes.
2. Drugs that inhibit the production of testosterone:Sprinolactone, ketoconazole and cimetidine block the production of testosterone and affect the production of sperm.
3. Sulfasalazine affects sperm count and motility.
4. Alpha-blockers:Alpha-blockers used to treat prostate diseases and hypertension can cause ejaculate to escape back into the bladder.
5. 5-alpha reductase inhibitors:finasteride and dutasteride are used in the treatment of prostate disease. They prevent testosterone activation and can cause a decrease in the volume of the ejaculate.
6. Antidepressants:serotonin reuptake inhibitors, phenothiazines, and lithium affect the functions of the hypothalamus and pituitary.
7. Exogenous testosterone and steroids:These drugs cause hypogonadism and azoospermia. Sperm production can be achieved six months after stopping medication. However, azoospermia is irreversible if they are taken over a long period.

SYSTEMIC DISEASES
What illnesses can affect male fertility?
Diabetes, multiple sclerosis and spinal cord diseases can cause sperm transport problems, and lead to retrograde ejaculation, the ejaculation of semen backward towards the bladder instead of forward through the urethra.

Sperm production can be affected by hormonal imbalance in patients with liver and kidney failure. Immunosuppressive drugs taken after kidney or liver transplants may decrease sperm production.

Thyroid diseases can affect sperm production.

OBSTRUCTION OF SPERM TRANSMISSION CHANNELS
What is obstructive azoospermia?
If the volume of the ejaculate is less than 1.5 ml, the most likely cause of azoospermia is obstruction of the sperm transmission channels. In these cases, sperm production in the testes and testicular size are normal. However, the sperm cannot flow out because of anatomical or functional problems of the sperm transmission channels. Some causes of obstructive azoospermia can be treated surgically.

What is the congenital absence of sperm channels?
In some infertile men, the vas deferens is absent. This condition is associated with a genetic disorder called cystic fibrosis. Additional genetic tests should be performed in this condition.

What other congenital disorders cause obstruction?
Masses such as epididymal cysts, spermatocele or a cystic mass on the urethra can block the passage of sperm.

Are there other causes of obstruction?
Infections such as untreated gonorrhea and tuberculosis, surgery in the inguinal area, such ashernia repair or varicocele surgery, and some diagnostic techniques for male infertility such as vasography, can cause the obstruction of sperm channels. In some cases, reconstructive surgery is possible.

What is retrograde ejaculation?
During ejaculation, bladder muscles contract, pushing ejaculate through the urethra into the penis. If there are any defects in the structure of these muscles, they fail to contract, and ejaculate flows back into the bladder.

What causes retrograde ejaculation?
Retrograde ejaculation results from:

1. Diseases of the nervous system, such as diabetes, and spinal cord diseases.
2. Previous surgery, such as prostate or bladder neck surgery, some abdominal operations and oncologic operations.
3. Some medications, such as those prescribed for prostate disease or psychiatric disorders.

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