Prevalence of Infertility
About 15% of couples do not achieve pregnancy within one year and seek medical treatment. Infertility affects both men and women. In 50% of voluntarily childless couples, a male-infertility-associated factor is found together with abnormal semen parameters.
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Causes of male infertility
Causes of male infertility
Male infertility could be classified into
3 major groups
In 30-40% of cases, no male-infertility-associated factor is found (idiopathic male infertility).
60%
Non obstructive infertility
Inadequate sperm production by the testes
35%
Obstructive infertility
Normal sperm production but there is a blockage in the genital tract.
5%
Coital infertility
Normal sperm production and patent genital tract; however infertility is secondary to sexual dysfunction which impairs intromission or ejaculation.
The percentages are based on studies for men with complete absence of sperm in their ejaculate; azoospermia
Causes of
male infertility
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1. Non obstructive inferitlity
Hormonal abnormalities
Hypogonadotropic hypogonadism, which may be idiopathic, or in acquired conditions such as brain tumours, head injuries, and following radiotherapy. The main congenital type is Kallmann’s syndrome which occurs in 1 in every 10 000 males at birth. Other hormonal abnormalities such as thyroid gland disorders, elevated levels of prolactin, and low testosterone levels will also impair sperm production.
Genetic causes
Structural and numerical chromosomal abnormalities are found in approximately 5% of infertile males and the prevalence may increase in men with complete absence of sperm. Genetic abnormalities include: Y chromosome microdeletions, aneuploidy: Klinefelter syndrome (47 XXY), the most common example of a numerical abnormality and chromosomal translocations. There are numerous other genes not yet identified that regulate sperm production, hormone production and hormone receptors. Any defect in such genes will impair fertility.
Exposure to Gonadotoxins
Gonado-toxins include; chemicals, recreational drugs, tobacco, alcohol, insecticides, pesticides, heavy metals.
Iatrogenic
anti-androgens, steroids, radiotherapy, and chemotherapy.
Orchitis
A common form of orchitis which is associated with infertility is Mumps orchitis. However any form of orchitis will affect fertility.
Testicular Torsion
If the condition is not corrected within 6 hours, it leads to permanent damage and shrinking of the affected testis. More over, this may be followed by production of anti-sperm antibodies which affect the other healthy testis.
Testicular tumours
Testicular tumours lead to infertility by destroying and compressing the healthy testicular tissue. Testicular tumours are slightly more common in the infertile male population than in the general male population. Thus, it is important to screen for testicular tumours in men with infertility.
Others
Varicocele
Undescended testes
Testicular Trauma
2. Obstructive infertility
Congenital absence of the Vas deferens
Due to CFTR gene defects may be unilateral or bilateral.
Vasal obstruction
The most common cause of isolated vasal obstruction is post operative after surgeries in the region of the inguinal canal or pelvis, such as hernia repair.
Epididymal tail obstruction
Obstruction at this level may be post inflammatory as in sexually transmitted infections (STIs) such as chlamydia and gonorrhea or after urinary tract infections, where the microbes travel in a retrograde manner from the urethra causing inflammation of the epididymis followed by obstruction.
Ejaculatory duct obstruction
They can be obstructed by congenital prostatic cysts, stones, or post prostatitis. In addition to infertility, patients may have a variety of symptoms such as painful ejaculation, reduced force and volume of ejaculate, haemospermia, dysuria, pelvic pain, and scrotal pain.
Others
Vasectomy
3. Coital infertility
Erectile dysfunction
patients with severe erectile dysfunction will have difficulties in intromission and deposition of semen in the vagina.
Premature ejaculation
In severe cases, ejaculation occurs before penetration; outside of the vagina.
Penile deformities
Patients with penile curvature, as in Peyronie’s disease or congenital penile curvature and patients with abnormal position of the urethral meatus, as in hypospadias or epispadias will have problems in vaginal penetration and sperm deposition.
Anejaculation
Primary anejaculation may occur due to psychosexual factors or neurological causes such as decreased sensitivity of the genital organs or high threshold of the ejaculatory reflex. Secondary anejaculation may occur following surgeries in the pelvis or abdomen that cause injury of the sympathetic chain as in retro-peritoneal lymph node dissection and pan procto-colectomy. It may also occur in diabetic autonomic neuropathy, and in other causes of autonomic neuropathy. Some drugs such as alpha blockers and antidepressants may also lead to anejaculation.
Retrograde ejaculation
It occurs due to similar causes as for anejaculation and represents a milder degree. It is common after prostate surgery for BPH.
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Treatment of male infertility
History & examination of the male partner of an infertile couple
Detailed medical history is taken from the male partner to detect any predisposing factors for infertility. A general examination is performed to evaluate the secondary sexual characters; such as body hair, fat distribution and the presence of gynecomastia. A local examination of the genitalia is then performed to assess testicular size, consistency and absence of testicular lumps.
The epididymis is then examined to detect swellings and nodules which indicate obstruction, the vasa are palpated to confirm their presence and exclude dilatation which indicates blockage, and the cord is palpated to exclude the presence of a varicocele or a lump.
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Investigations for Male Infertility
Semen analysis
At least 2 tests are performed a couple of weeks apart. This is the base line investigation for male infertility. The results of semen analysis provide a guide to whether other investigations are needed or not. Although simple, yet it is a subjective test. Therefore it is best performed in specialist centres such as fertility units.
Semen culture
Is indicated in the presence of chronic infections of the genital tract. This is indicated by genital pain, painful ejaculation, or the presence of white blood cells in semen >5/HPF.
Sperm Function tests
These tests assess the fertilizing ability of the sperms.
Semen analysisMale reproductive genetic profile
this includes Karyotype, Y chromosome microdeletions, and Cystic fibrosis gene mutations. However there are numerous other genes involved in male fertility that have not yet been identified.
Hormonal profiles
The basic hormones that are tested are FSH, LH, Prolactin, and Testosterone. Other hormones may be tested for if there is a clinical indication.
Imaging “scrotal ultrasound and colour Doppler” is done to assess the testes and epididymi to detect their dimensions and exclude the presence of tumors or varicocele. A trans-rectal ultrasound scan (TRUS) may be performed if there is a suspicion of distal genital tract blockage or abnormality.
Other imaging tests may be performed based on other findings including:
MRI pelvis may help in diagnosing obstructions and abnormalities in the distal genital tract. It may also help in locating the testes in cases of undescended testes.
MRI Brain is performed in patients with abnormalities in the pituitary gland hormones e.g. elevated levels of prolactin, to exclude any problems in this area such as microadenomas.
TRUS guided seminal vesicle aspiration is done to confirm ejaculatory duct obstruction by detecting sperm in fluid aspirated from the seminal vesicles under ultrasound guidance.
TRUS guided seminal vesiculography is done to confirm ejaculatory duct obstruction where a contrast medium is injected into the seminal vesicle under ultrasound guidance. An X-ray is then taken and failure to see the contrast in the bladder denotes blockage.
Vasography involves injection of a contrast medium in the vas deferens followed by an X-ray to detect any blockage of the genital tract. Usually, it is done intra-operatively during testicular exploration surgery.
Treatment of male infertility
Once the cause is known a treatment could be provided directed to treating the actual cause of the problem leading to a cure. If treatment fails or no cause is identified (idiopathic cases), the couples are advised to try assisted reproductive techniques: artificial insemination, IVF, or ICSI based on the quality of sperm. In patients with non-obstructive azoospermia or patients with obstructive azoospermia not amenable to surgical reconstruction, treatment involves surgical sperm retrieval followed by intracytoplasmic sperm injection.
Medical treatment
Medical treatment may be effective in the following cases:
Patients with actual or relative hormonal imbalance, correction of such imbalance will improve sperm production as in patients with hypo-gonadotropic hypogonadism.
Chronic uro-genital infections
Coital infertility
Surgical treatment
Surgery for male infertility includes:
Microsurgical vasectomy reversal
Vasectomy is a popular and very effective form of contraception being performed in approximately 50,000 men per year in the UK. Historically, it was always considered to be a permanent procedure. However with the high divorce rate in western societies, vasectomy reversal is now becoming a common request. In the absence of a female factor for infertility, vasectomy reversal should be offered as a first-line therapy to couples who seek conception after vasectomy. Multiple studies have demonstrated the superior cost effectiveness of vasectomy reversal over IVF. Micro-surgical Vasectomy reversal patency rates exceed 80% and pregnancy rates exceed 50%.
Microsurgical epididymo-vasostomy
This is performed to bypass an obstruction at the level of the epididymis, or if vasectomy reversal by connecting both vasal ends could not be performed due to technical reasons. The patency and pregnancy rates after this procedure exceed 60% and 40% respectively which makes it superior to IVF.
Microsurgical vaso-vasostomy
This is performed to bypass a blockage in the vas deferens. It is similar to microsurgical vasectomy reversal, but the level at which the surgery is performed varies according to the level of obstruction which is usually inguinal commonly following hernia repair.
Transurethral resection of the ejaculatory ducts or de-roofing of prostatic cysts to treat ejaculatory duct obstruction
Patients achieve significant improvement of the semen parameters in 65% to 95% of cases, and a pregnancy rate of 20% to 30% of patients. Long-term relief of post-coital and perineal pain occurs in 60% of patients.
Microsurgical varicocelectomy
The surgical microscope is used to selectively identify the dilated veins which are ligated, sparing the arteries and lymphatic vessels. This significantly improves the outcome and reduces the complications. Varicocelectomy is of benefit if there are semen abnormalities and the varicocele is clinically palpable in the absence of female factor of infertility. Varicocele repair surgery improves sperm motility, density, morphology, and sperm functions tests. It also reduces the levels of free oxygen radicals (ROS) which impair sperm production and reduces sperm DNA fragmentation. The levels of FSH and Testosterone will usually improve. Varicocele repair can improve seminal parameters enough to allow patients to downgrade the method of assisted reproduction or to bypass assisted reproduction altogether. The treatment of male infertility with varicocelectomy followed by intrauterine insemination has been shown to be more cost-effective than in vitro fertilization and intracytoplasmic sperm injection. The average spontaneous pregnancy rate after varicocelectomy is 39%.
Surgical sperm retrieval and assisted reproduction
Indications
- Non obstructive azoospermia (NOA):
- Obstructive azoospermia not amenable to reconstruction as in CBAVD
- Coital infertility due to anejaculation
Methods
Testicular sperm extraction (TESE & Microdissection TESE)
This is performed in patients with non-obstructive azoospermia (NOA). For patients with non obstructive azoospermia Micro-TESE done by a specialist offers the highest chance of finding sperm and the least complication rate. This makes it more superior to other methods of sperm retrieval performed by non specialists.
Percutaneous epididymal sperm extraction (PESA)
This is performed in patients with an obstructive azoospermia that is not amenable to surgical correction, as in cases of congenital absence of the vas deferens
Microsurgical epididymal sperm extraction (MESA)
This is usually performed as a backup in patients with obstructive azoospermia, who are having microsurgery to bypass the blockage.
For patients with obstructive azoospermia the sperm retrieval rate is almost 100% unless the blockage is associated with other causes of infertility. The sperm retrieval rate for patients with non obstructive azoospermia (NOA) varies from 20% to 60%, depending on the cause, clinical findings, and the results of the investigations.
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Conclusion
Management of the infertile male requires specialist care in order to allow for the identification and treatment of the cause and thus for spontaneous pregnancy to occur. In patients with non-obstructive azoospermia micro-surgical testicular sperm extraction (Micro-TESE) by a specialist followed by intra-cytoplasmic sperm injection (ICSI) offers the best chances of fatherhood to these patients.
