Treatment of Male Infertility

Treatment of male infertility has seen higher success rates in the last decade.

 I-Medical Treatment of Male Infertility

1-Hormones:

a-FSH  

FSH (Follicle Stimulating Hormone) is the hormone that directly stimulates the testis to produce sperm. It is secreted by the pituitary gland present in the brain. This hormone is present in both males and females. In the female, it stimulates the ovary to produce the follicle that contains the ovum.

The pituitary gland is sensitive to the activity of the testis. If activity is low, it raises the FSH level to stimulate the testis further. Therefore, an FSH level higher than normal is an indication of low activity of the testis, which is why the pituitary raised the FSH level. High FSH level is the reason for infertility or low testicular activity, it is only a result and a sign of the low activity of the testis. 

If FSH level drops below the lower normal limit, the testis stops producing sperm. This occurs in pituitary diseases 

 FSH is available as injections for the treatment of male infertility, that can be given is FSH level is below normal or if the testis is inactive despite a normal or slightly high level.

b-Androgens / Testosterone

Being responsible in part for spermatogenesis, and in full for the development of the testis and normal masculine characters, deficiency of testosterone may lead to infertility.

Treatment depends on the cause. If cause is failure of the testis to produce testosterone despite high LH level (the hormone produces by the pituitary to stimulate the testis to secrete testosterone), the patient is treated by testosterone preparations. If the cause is failure of the pituitary to secrete LH, LH injections can be administered for the treatment of male infertility.

Various forms of testosterone exist: tablets, injections and gel. An active form is also available (dihydrotestosterone). 

On the other hand, if testosterone level rises much above the normal level (abuse by athletes…etc) if leads to fall of FSH level and arrest of sperm production.

c-Anti-Estrogens 

Both males and females have the same set of hormones (FSH, LH, testosterone, estrogen and prolactin), though in different levels.

A rise in estrogen level may lead to infertility. Even in the presence of a normal estrogen level, it is the opinion of some physicians that neutralizing the normal estrogen will promote fertility in infertile patients.

Anti-estrogens can be used for the treatment of male infertility, to neutralize the excess estrogen by competing with it to its receptors at the cell surface.

d-Prolactin Lowering Drugs

As for estrogen, increased prolactin level can cause infertility. Some drugs can decrease prolactin level. However, it must be noted that a very high prolactin level may issue from a brain tumor (benign). It is therefore that brain CT is needed to exclude this possibility.

2-Medical Treatment for Varicocele

There is no medical treatment for varicocele. However, some drugs are claimed to increase the tone of veins and may temporarily and paritally neutralize the effect of varicocele, if the varicocele is of a minor grade.

3-Drugs that Enhance Sperm Motility

Carnitine

This is a compound that is concentrated in the epididymis where sperm acquires motility. It is used for the treatment of male infertility to enhance sperm motility.

Trental

Increases the energy source (ATP) in the neck and tail of the sperm, thereby increasing sperm motility

Anti-oxidants

Reactive oxygen species (ROS) are generated by pus cells (in case of infection) and by aging and dying cells. They damage the sperm external membrane leading to decreased motility and vitality. Anti-oxidants are used for the treatment of male infertility as they fight ROS and decrease their level.

Vitamins

The are general tonics that enhance general body functions. In particular, vitamin E acts as an anti-oxidant, and vitamin B12 enhances cell division and therefore sperm production.

4-Medical Treatment of Infection and Inflammation

 Infection and inflammation can result in infertility by damaging the testis, occluding the  vas deferens or by decreasing sperm quality and motility.

Antibiotics are necessary to treat infections, therefore may be a treatment of male infertility. In many instances, they should be given to both the man and woman, since infection is delivered from one partner to another at sexual intercourse.

Antibiotic treatment is preferably prescribed according to culture and sensitivity which determines the best antibiotic for the specific microbe an individual has.

Anti-inflammatories also help decrease pain, testicular damage and vas occlusion during inflammation.

5-Medical Treatment for High Semen Viscosity

If semen is too viscous, sperm motility is hindered. Some mucolytic drugs are used for the treatment of male infertility by dissolving semen and decreasing its viscosity. They are also prescribed in inflammation and obstruction of nasal sinuses. If these fail, assisted reproduction (specifically IUI) can bypass the problem.

6-Medical Treatment for seiminal track obstruction

Male infertility can result from narrowing or occlusion of the track of sperm, resulting in low sperm count. If seminal track obstruction is partial , it may still be treated medically, by treating the causative infection and inflammation (see before) and by medications that decrease formation of fibrous tissue (tissues that accumulate in the vas deferens and occlude it). 

7-Medical Treatment for Antisperm Antibodies

Steroids (cortisone) can be used in small doses as treatment of male infertility to inhibit body immunity  to a mild extent that may be enough to decrease Antisperm antibody formation. However, steroids have many side effects and can be dangerous. Above all, their dose must be gradually tapered rather than stopped suddenly, and must be taken under strict medical supervision. A safer alternative is assisted reproduction.

II- Surgical Treatment for Male Infertility

The decision for surgery as treatment of male infertility is taken when other measures fail, or if there is a situation that will damage the testis if left untreated such as varicocele or rupture of the testis.

Testicular Biopsy:

In case sperm concentration is too little ( low sperm count / oligozoospermia ) or if there is no sperm at all ( azoospermia ), it is necessary to determine whether this is due to weak activity of the testis ( functional azoospermia ), or whether activity is normal but there is obstruction of the vas deferens that segregates the sperm despite normal activity of the testis ( obstructive azoospermia ). Accordingly, treatment modality is decided.

Determination of testicular activity is done by taking a very small sample of the testicular tissue through a small incision and examining it for its activity: testicular biopsy.

Testicular biopsy is performed under local anesthesia (or general if required). A 3-5 mm incision is cut in the scrotum down to the testis. A 2mm incision is cut in the testis and a 1mm biopsy of tissue is extracted. The testis is closed by one suture, and the scrotum is closed by 1 or 2 sutures. The procedure takes about 10 minutes and the patient can get off the operating table and walk out of the operating room on his own since it is neither painful nor uncomfortable. Patient can return to daily activities at the same day. Testicular biopsy is a minor procedure. 

Testicular biopsy tissues are examined in the pathology laboratory and the report comes out in 1-2 days. The result is determined according to the number of sperm in each tubule (unit of testicular tissue), the architecture of cell arrangement (regular or disorganized), and the thickness of the basement membrane (outer wall of each tubule). 

It is possible to examine part of the Testicular biopsy for sperm content immediately following extraction and to freeze the sperm for future use in ICSI.

Testicular biopsy: Determination of testicular activity is done by taking a very small sample of the testicular tissue through a small incision and examining it for its activity.
Testicular Biopsy

Microsurgical Testicular Sperm Extraction ( microTESE )

In some cases of male infertility – azoospermia, a biopsy is taken from the testis and it shows no sperm. This biopsy is taken from one pole of the testis as shown in the picture, and only represents this pole, meaning that there may be sperm in other parts of the testis.

Absence of sperm in one pole means that this is a case of weak activity of the testis. If all modalities of  treatment fail and ICSI is decided, it is necessary to find a couple of sperm with which to perform ICSI. In this case, microTESE is performed. This is when we search for sperm in all poles of the testis, and wherever they are found, they are extracted and used for ICSI whether immediately or later, in which case they are  frozen.

This search for sperm should be performed micro surgically, under optical magnification ( microTESE ). The sperm tubules with sperm appear larger and with a more yellowish tinge than do empty tubules.

microTESE biopsies do not usually affect masculinity or sexual performance or even testicular size. They are small. microTESE can be performed with local or general anesthesia, through a 1-2cm incision in the scrotum through which both testes can be accessed.

Alternatively, sperm can be aspirated by a needle with or without opening the skin (Fine Needle Aspiration / FNA ) . This is easier for both the physician and the patient, but the sperm yield is less than in classic microTESE in cases where sperm production is low ( Non-obstructive azoospermia / NOA ). In both cases microTESE or FNA, patients can leave the hospital in 1-2 hours and can return to their daily activities the next day.

Varicocelectomy for the Treatment of Male Infertility

 Varicocele is abnormal dilatation and tortuosity of veins exiting the testis. It can hinder sperm production both in quality and quantity. Varicocelectomy is a minor surgical procedure for the treatment of male infertility.

Regardless its size, all grades of varicocele (mild, moderate or sever) can cause infertility, though to different extents. Treatment of varicocele is ONLY by surgery (varicocelectomy). 

There is a debate between physicians about the value of varicocelectomy in the treatment of male infertility. However, when it comes to large grades of varicocele (Grade 3), there is no debate. There is a consensus that it should be treated surgically, otherwise it will result in total death of the testis (atrophy). Mild and moderate varicocele (grade 1 and 2) may not cause atrophy of the testis but do cause infertility that increases by time as long as the varicocele is left untreated, which is why it should be surgically eliminated. This is the opinion of Andrologists (such as myself) and Urologists. It is the opinion of Gynecologists that varicocelectomy should be restricted to larger grades of varicocele.   

Varicocelectomy (surgical treatment of varicocele) for the treatment of male infertility is performed by interrupting the abnormal veins in which blood pools, leaving behind the normal veins through which blood flows normally, while not touching the artery, the vas deferens, the nerves and the lymphatics. It is very important to avoid the latter structures otherwise infertility will be worse. Interrupting the continuity of abnormal veins is performed by closing the vein at two close points by sutures, and cutting the vein in-between the two points. 

There are various approaches for varicocelectomy:

1-Open Microsurgical Varicocelectomy for the Treatment of Male Infertility:

The use of optical magnification (surgical microscope or surgical loupe) helps to avoid injuring the important structures: the artery and the vas deferens.

Microsurgical varicocelectomy
Microsurgical varicocelectomy

The incisions range in length from 2-5 cm. Operative time is usually 30-45 minutes, and the patient leaves the hospital 5 hours later and can return to daily activities in one day.

2-Laparoscopic Varicocelectomy for the Treatment of Male Infertility:

This is endoscopy of the abdomen, that is performed through three separate incision, 1 cm each. The virtue of endoscopy is that it provides access to the right and left varicocele through the same small incisions. However, it provides access to only one system of veins, and the other two systems cannot be accessed. It is therefore that laparoscopic varicocelectomy is reserved for lower grades of varicocele when present on both sides. 

Laparoscopic Varicocelectomy
Laparoscopic Varicocelectomy

Varicocele Embolization

A catheter is inserted through the femoral vein the the upper thigh or the jugular vein in the neck. Under radiologic screening (real-time Xray), the catheter is advanced until it reaches the testicular vein, where occlusive material is inserted to close the testicular vein and thus perform varicocelectomy / Varicocele Embolization.

Pros of Varicocele Embolization: Minimally invasive, no incision

Cons of Varicocele Embolization:

  • Common: Higher recurrence rate than microsurgical Varicocelectomy
  • Rare:
    • Systemic embolization: the injected material can migrate to occlude a blood vessel elsewhere.
    • Vein inflammation
    • Possible bleeding
    • Xray exposure can be harmful for fertility

Orchiopexy (Treatment of Undescended Testis):

Eentrapment of the testis inside the abdomen leads to ooverheating of the testis, resulting in infertility and possibly tumor formation. It is therefore that the testis MUST be taken out of the abdomen whether by bringing it down to its normal place if possible (orchiopexy) or by total removal of the testis (orchiectomy) to avoid the formation of tumors (if descent is not possible).

Heat affects the sensitive sperm-producing cells and not the sturdy hormone-producing cells. Therefore infertility occurs but impotence and low virility do not occur. Even if both testes have to be removes, impotence and decreased masculinity will not occur (provided testosterone injections are used every 4 months)

Ususally the undescended testis produces absolutely no sperm. Bringing down the testis to its normal place(orchiopexy) in early childhood may help resuming sperm production. Orchiopexy at adulthood is absolutely necessary for avoiding tumors, and may rarely help with sperm production.

Diagnosis: the position of the testis can sometimes be determined  by ultrasonography, CT or MRI. If they fail to demonstrate the testis, laparoscopy is necessary to confirm its presence or absence. Laparoscopy is also the way by which the testis is brought down or removed. 

Bringing down the testis or its removal is best performed by laparoscopy because it involves only three small incisions, 1 cm each, contrary to open surgery which usually involves a long incision 10cm long at least.  

Upon laparoscopy, the whole abdomen is explored until the testis is found. The bands of tissue that trap the testis are cut. This allows the testis to move downwards. If this is not enough for the testis to reach the exterior of the abdomen, its main blood vessels (that  go upwards) are cut to allow it to descend further. The testis takes blood from alternative blood vessels. If this still is not enough and the testis is still in the abdomen, it has to excised and totally removed as mentioned before.

If the testis is removed, it can be analyzed and if sperm are found, they can be frozen for future conception by ICSI.

The ideal result is bringing the testis down to the scrotum. If this is not possible, the second best result is to bring the testis out underneath the skin of the abdomen. If this is achieved, a biopsy is usually taken from the testis to check for activity and for tumors, and it is followed up thereafter every 6 months.

Commonly, a hernia accompanies the undescended testis. This must be treated in the same operation. 

Hormonal treatment for undescended testis can only be used in young age, in mild grades of testicular undescent where the testis is already out of the abdominal wall but not in the scrotum, and if there is no hernia alongside the testicular undescent.

Retractile Testis:

Is a condition where the testis is trapped in a position higher than normal, but can occasionally settle down to its normal position. That is, it moves up and down. This condition does not affect fertility unless the testis is pressed or hit at its higher position.

Surgical correction may be indicated for cosmetic reasons. Hormonal treatment for this condition is controversial.

Hormonal treatment is based on the assumption that the hormones will increase the size and weight of the testis, and thus being heavy it will not go up. This is possible only in childhood, but has the disadvantages of possible mild masculinization and shorter height of the child. Moreover, some adults have a large and heavy testis that still goes up and down (retractile) despite its weight.

Surgical Treatment of Torsion of the Testis:

 Torsion of the testis is an emergency. Surgical treatment should preferably be within 6 hours following the start of the condition. The scrotum is opened and both testes are delivered. The testis that suffers torsion is usually black and surrounded by bloody fluid.

The torted testis is rotated in the opposite direction to undo torsion. Hot towels are applied to the testis to increase the blood flow to it. If the testis comes back to life and its color turns white (more or less) again, it is preserved and fixed in the scrotum such that it does not rotate again. If it is dead, it is removed.

The other testis is fixed as well because it is known that if a testis undergoes torsion, the other one is liable to the same condition.

Hydrocelectomy:

A hydrocele is a collection of fluid that occupies the space between two of the layers that surround the testis. This fluid may be watery (serous), or may be blood or pus. Collection of watery fluid may occur without a known cause or following surgical treatment for varicocele if not performed properly. Pus collects due to infection. Blood collects due to trauma (accidental blows), tumors, as a complication of surgery or following torsion.

Hydrocele causes enlargement of the scrotum which may in some cases be painful. This condition requires surgical treatment if it is very large, or if it is very tense causing pressure on the testis, or if it is enlarging progressively.

Surgical treatment is termed “hydrocelectomy”. It consists of evacuation of the fluid and removal of a large part of the layers that surround the testis underneath the skin of the scrotum. These layers are the ones that produce the watery fluid.


 
Surgical Correction of Obstructive Azoospermia:  

In cases of infertility due to obstruction of the sperm track (Obstructive Azoospermia), options are medical treatment, surgical treatment and ICSI . ICSI is performed using sperm that is surgically extracted from the testis. Accordingly, since surgical intervention is performed anyway, it is advisable to perform surgical correction together with ICSI or on its own. 

If performed in the hands of an expert, success rate of surgical correction of obstruction for treatment of male infertility ranges from 60% to 90% depending on the method of correction, whether conventional (60%) or microsurgical (90%).

Microsurgery is the performance of correction using very small instruments that match the diameter of the sperm track (0.1-2mm), under visualization with the surgical microscope. This also involves the use of ultra thin sutures. This achieves a higher success rate (90%) in comparison to conventional surgery that is performed with the regular instruments and sutures without magnification. 

 All surgeries for obstruction are one-day surgeries. Patients leave the hospital in the same day and can return to daily activities in one day. The results appear somewhere between 3 to 12 months after surgery.

There is a number of  surgical techniques to chose from according to the exact site (or sites) of obstruction. For example, if the site of obstruction is at the junction of the vas and epididymis, we resort to epididymovasostomy (see later), and if the site is along the vas, we use vasovasostomy (see later)..etc. The site (or sites of obstruction can be estimated before surgery by chemical markers of obstruction and Ultrasonography.

During surgery, the site or sites of obstruction are pointed out very accurately by vasography or by inserting a fine probe along the track to see where it stops. Commonly, there are multiple sites of obstruction rather than a single site.

It has to be noted that following obstruction for long periods, Antisperm antibodies become abundant in semen and decrease sperm motility. Thus, following surgical correction and re-appearance of sperm in semen, its motility may be slow. Accordingly, natural pregnancy may or may not occur. If it does not occur, intrauterine insemination may be resorted to, and not necessarily ICSI.

Epididympvasostomy (EV):

If there is zero sperm due to obstructive azoospermia, the lower most part of the vas  (where it joins the tail of the epididymis) may be occluded. This is when we perform an Epididympvasostomy / EV. Epididympvasostomy is when we connect the body of the epididymis  to a higher part of the vas deferens beyond its lowermost part to bypass obstruction (see the illustration).

Thus, sperm leave the testis, enter the head of the epididymis, proceed to its body and out to the vas without having to pass through the tail of the epididymis or the lowermost part of the vas where the occlusion is present. 

Vasovasostomy / Vasectomy Reversal

  This is the technique used whenever the vas is occluded far from the epididymis so as epididymovasostomy is not possible. This can be due to prior vasectomy. Vasovasostomy / Vasectomy reversal consists of cutting the occluded segment of the vas and reconnecting the cut ends. Again, this can be done in the conventional way or the microsurgical way. Vasovasostomy is also performed when reversal of vasectomy is desired. Microsurgical vasectomy reversal or vasovasostomy carries around 90% success rate in terms of re-appearance of sperm in semen.

Shaeer’s Vasovasostomy 

  This is a technique designed by the author of this website; Prof.Shaeer, and is published and applied internationally. It aims at correction of obstruction resulting from previous surgeries such as hernia repair, by connecting the part of vas deferens present inside the pelvis with the one in the scrotum, bypassing the occluded segment of the vas. Shaeer’s Vasovasostomy is performed by laparoscopy (abdominal endoscope) through very tiny incisions

Trans Urethral Resection of the Ejaculatory Ducts (TURED) for the Treatment of Male Infertility

If obstruction is in the ejaculatory ducts, the obstructing tissue can be cut by inserting a narrow endoscope into the urethra (under anesthesia) up to the ejaculatory ducts and cutting under vision