Although in the past infertility problems were attributed to the woman, we now know that a male factor plays a significant role. Medical practice and research over recent years indicate that in 30–40% of couples, a male factor is the only reason causing infertility. In another 10–15% of couples a combination of male and female factors contribute to infertility. An infertility investigation should therefore include a thorough assessment of both partners.
SEMEN PRODUCTION AND SPERM FUNCTION
The organs and structure of the male reproductive system are designed to produce and store sperm before it is delivered to the female reproductive system. In men, the urinary system overlaps to some extent with the reproductive system, as some of the structures are common to both.
Unlike the female eggs (ova) which are present from birth, sperm cells are not produced until a male reaches puberty. As sperm is ejaculated, the testicles continually create more to replace them. Sperm far outnumber the ova produced by a woman – whereas the adult female has fewer than half a million eggs in her ovaries, a fertile male may release hundreds of millions of sperm during a single ejaculate.
The male reproductive system comprises the following organs and structures:
- The testicles, or testes, are two small organs in which sperm cells are produced. They are located within the scrotum, a loose pouch of skin that hangs outside of the man’s body, behind the penis. The testes are outside of the body cavity which ensures the efficient production of the sperm, which can be produced only at a temperature which is slightly below normal body temperature.
- Sperm cells are many times smaller than ova. The mature sperm are shaped somewhat like a tiny tadpole. Inside the head is the nucleus, which contains the cell’s genetic material. Over part of the head is a cap-like covering of very specific substances designed to break down the outermost layer of the ovum to allow fertilisation. The long, whip-like tail of the sperm cell provides it with a means of locomotion.
- Covering part of each testicle is the epididymus, the site of continual sperm maturation and storage for mature sperm cells.
- The vas deferens is a long narrow tube, stretching from the epididymus to the prostate, through which sperm pass on their way out of the body during ejaculation.
- The seminal vesicles are small glands located just behind the bladder. They secrete the seminal fluid that helps to lubricate and nourish the sperm cells. This fluid makes up about 60% of the volume of ejaculated sperm.
- The prostate gland lies just below the bladder and secretes fluid as sperm passes through. The bulbo-urethral glands (also called Cowper’s glands), which lie below the prostate gland, produce additional fluid to aid the sperms passage out of the body during ejaculation.
- The male urethra serves the dual purpose of both transporting urine and semen. A nerve reflex closes the opening of the bladder and prevents urine from passing through the urethra during ejaculation.
- The penis is the male reproductive organ through which semen exits during ejaculation. It is made up of spongy tissue that is tightly packed with blood vessels. During sexual arousal, the blood vessels in the penis relax and dilate, causing it to stiffen and become erect.
Sperm production and maturation last 74 days. This process commences in a multitude of sperm producing tubules in the testes where immature precursor or germ cells are stimulated to grow and develop into mature sperm. The FSH hormone produced by the pituitary gland (a small gland at the base of the brain) and testosterone hormone produced by the testes stimulate this process. From these tubules the sperm enter the epididymis where they further mature and become progressively more motile. After 12 – 21 days the mature sperm enter the vas deferens where they are stored until ejaculation takes place.
During ejaculation, mature sperm are released along with fluid from the prostate and the other male accessory glands forming the ejaculate or semen that is deposited into the vagina during ejaculation. The released sperm are not yet capable of fertilisation but undergo further activation (capacitation) in the mucus of the mouth of the womb (cervix) and on route towards the Fallopian tubes in anticipation of fertilisation. After ovulation the egg is transported into the Fallopian tube. As the sperm approach the egg they undergo a chemical reaction at their head end (the acrosome reaction), with the release of enzymes, which increase their motility and help to penetrate the surface of the egg. Once one sperm has fertilised the egg, the surface of the egg becomes impenetrable to other sperm.
When sperm samples are used for infertility treatment, special processing techniques can induce the capacitation and acrosome reaction.
CAUSES OF MALE INFERTILITY
PRE TESTICULAR CAUSES:
Hormone deficiency of the hypothalamus (in the base of the brain) and/or pituitary gland can prevent the synthesis of testosterone and affect the production of sperm in the testes. Clinically these men tend to have underdeveloped male sexual characteristics. Excessive milk hormone (prolactin) production of the pituitary gland or under function of the thyroid gland can also compromise sperm production.
TESTICULAR CAUSES:
Genetic abnormalities, whether chromosomal or single gene defects, can lead to no or deficient sperm production. The most common genetic condition to be excluded is the Klinefelter Syndrome (XXY).
Prenatal exposure to DES (diethylstilboestrol), a medication that was given to some pregnant women in the 1950s to prevent miscarriage.
An undescended testis at birth is a common cause of male infertility even if only one testis is involved. Direct testicular injury or torsion (twisting) of the testes can also cause irreversible testicular damage. Post pubertal mumps causes inflammation of the testes, which also leads to irreversible functional damage in many of these patients.
Chemical substances like drugs and environmental toxins (like exposure to lead or mercury), as well as toxic radiation, damage the precursor cells of the sperm and also inhibit the rapid cell division involved in the sperm production.
Dilated (varicose) veins in the scrotum may interfere with the temperature regulating mechanism of the testes, leading to constant raised temperatures in the scrotum, which impair the sperm production process.
POST TESTICULAR CAUSES:
- Disorders of sperm transport: Congenital absence of the vas deferens occurs in 2% of infertile men and leads to the total absence of sperm in the ejaculate. Various genital infections can cause inflammation of the epididymis and the vas deferens resulting in scar formation and obstruction of these pathways for sperm transport. Damage to the pelvic nervous system due to uncontrolled diabetes or cancer surgery of the pelvis, can lead to abnormal function of the bladder neck with retrograde ejaculation into the bladder.
- Disorders of sperm motility or function: The absence of certain proteins in the tail of the sperm leads to totally immotile sperm. After infections, scrotal trauma or surgery, the immune system sometimes produces antibodies against sperm. These antibodies are not an all-or-none-phenomenon, but they may inhibit the motility of sperm and thereby contribute to infertility.
- Sexual dysfunction: Decreased libido, erectile dysfunction and premature ejaculation can all contribute to infertility. The problem of infertility leads to more anxiety resulting in the aggravation of the sexual dysfunction.
ASSESSMENT OF THE INFERTILE MALE
HISTORY:
A detailed medical history focused on the potential causes of male infertility should be taken meticulously as follows: A history of undescended testes, genital surgery or other scrotal trauma is essential. Exposure to occupational and environmental toxins, excessive heat or radiation should be excluded. Infections of the genital tract especially mumps with testicular involvement should be asked for during history taking. The drug history should be reviewed for previous chemotherapy, use of anabolic steroids and other medication known to interfere with sperm production or function. The use of illicit drugs and excessive alcohol consumption should be excluded because it can lead to decreased sperm count and quality. Medical history should exclude illnesses like diabetes and severe renal and liver disease. Recent illnesses can compromise sperm production especially if it was associated with generalised fever. This can have an effect on sperm production for the following three months. Careful and sensitive inquiry of sexual dysfunction should focus on the lack of libido, erectile dysfunction and ejaculatory dysfunction.
PHYSICAL EXAMINATION:
The physical examination should pay specific attention to male sexual characteristics like the male body habitus, male pattern hair growth and properly developed male genitalia. Subtle breast development and milky secretions should not be overlooked. Palpation of the thyroid and exclusion of other medical illnesses forms part of the physical examination.
A careful inspection and palpation of the male genitalia is the most important aspect of the male examination. The scrotal contents should be palpated to determine the size and consistency of the testes and the presence and characteristics of the epididymis and vas deferens. The penis should be inspected for anatomic abnormalities. In patients with ejaculatory dysfunction or symptoms suggestive of prostatitis or bladder neck dysfunction, a digital palpation of the prostate and seminal vesicles is indicated.
SPECIAL INVESTIGATIONS:
A carefully performed semen analysis is not a guarantee for fertility, but it is a highly predictive indicator of the functional status of the male reproductive system as well as the patency of the male reproductive tract. Achieving a pregnancy and not a normal semen analysis is however the ultimate proof of fertility, because this is clearly a couple related phenomenon.
During a semen analysis various parameters are assessed and documented. The World Health Organisation Laboratory Manual for human semen analysis sets specific testing criteria and parameters of normality. Semen analysis should therefore only be performed by accredited laboratories with well-trained laboratory personnel. The parameters of normal levels are not absolute and do not exclude the chance of spontaneous conception.
Most specialists recommend 2 – 3 semen analyses to establish a baseline for semen quality. The semen should best be obtained by masturbation after a 2 – 3 day period of abstinence. The semen should be produced into a sterile bottle and should be assessed within 1 –2 hours of collection.
Besides the physical characteristics of the semen sample like the volume, pH, viscosity and liquefaction, the following are the most important parameters tested:
- Sperm count: normal = ³ 20 million sperm/ml
- Sperm motility: normal if 40–50% of the sperm are motile with proper forward progression. Microscopic evaluation can detect agglutination of sperm, which might indicate an inflammatory or immunological process.
- Sperm morphology: during the assessment of morphology, the appearance of the sperm on a special stained slide is assessed. Under very strict criteria of normal appearance, most men have ³ 14 % normal appearing sperm. A strict morphology of £ 4 % might be a poor prognostic factor, especially in the presence of a low sperm count and motility. The WHO criteria are a less strict.
In the event of a very poor sperm count or quality, blood tests should be performed to assess the hormonal function of the pituitary gland, the thyroid gland as well as the testes. In these patients it is also recommended that the male undergoes a blood test for genetic abnormalities. In these men a scrotal ultrasound should also be performed to exclude a very early testicular tumour, which can occur in 1 % of these patients. A scrotal ultrasound should also be performed in patients where a varicocoele could be palpated. The diameter of these varicous veins as well as reversed blood flow in them can then be determined.
TREATMENT OF MALE INFERTILITY
In the majority of patients with an abnormal semen analysis, no specific cause can be identified after a thorough assessment as mentioned above. Only some of the identified causes of male infertility can be treated successfully as shown by an improvement in the semen analysis and by spontaneous conception. In the other patients, assisted reproduction techniques will have to be used to achieve a pregnancy in these infertile couples.
GENERAL MEASURES:
These general measures should be introduced in all patients wanting to achieve a pregnancy. Even in patients that have to undergo assisted reproductive techniques, these measures can help to improve the function and thus the fertilisation potential of the sperm.
Life style adjustments: Avoid smoking, which can cause a lower sperm count and motility. The toxic substances in cigarette smoke can also interfere with fertilisation and early pregnancy development. Alcohol, and recreational drug – abuse should be avoided for the same reasons. Stay clear of environmental and occupational poisons and hazards. Keep the scrotum cool: avoid tight-fitting underwear or jogging pants and avoid hot baths, saunas and working environments. Ease up on intense exercise because aggressive exercise can also build up heat around the testes resulting in compromised sperm quality. Prolonged periods of sexual abstinence result in higher volume semen with older sperm, which exhibit decreased motility. Sexual intercourse every 3–5 days maintains the best volume and potency of the semen. Excessive stress has been shown to interfere with hormonal function and should therefore also be targeted in the life style adjustments.
Dietary observance and supplementation: A balanced diet with adequate intake of fresh fruits and vegetables is a basic requirement of a healthy life style. Dietary supplementation of selenium and vitamin C may improve fertility potential by their antioxidant effect. Zinc plays an important role in the prostatic fluid with an antioxidant and “fuelling” effect on the sperm.
MEDICAL THERAPY:
In patients with deficient or absent hormone production of the pituitary gland, treatment with specific hormone injections over a prolonged period of time can normalise the sperm count and quality. This rare clinical phenomenon is the only place where medical therapy has been shown to be effective. The use of clomiphene citrate in unexplained male infertility has not been shown to improve the sperm quality and spontaneous conception.
The use of testosterone tablets or injections should be discouraged because it can potentially decrease the sperm quality even further.
The use of corticosteroids for antisperm antibodies has not been shown to be effective.
Medication to strengthen the bladder neck in patients with retrogade ejaculation should be considered.
SURGICAL TREATMENT:
Surgical treatment for a varicocele may improve the sperm parameters. Traditionally the spermatic vein was ligated by a surgical procedure. Now, radiographic embolisation of the spermatic veins is the preferred method because of its accuracy and minimal invasive approach. This method does not require a general anaesthetic and the patient can leave the hospital within hours and return to work the following day.
Surgical reversal of a vasectomy (male sterilisation) leads to patency of the vas deferens in 80% of patients and a spontaneous pregnancy in 52% of patients. The success of this procedure is, however, inversely related to the time period since the vasectomy was performed. After a vasectomy, antisperm antibodies progressively occur with duration of time. High levels of antisperm antibodies before reversal of the vasectomy decreases the prospects of spontaneous conception because of the immobilising effect of the antibodies.
ASSISTED REPRODUCTION:
Artificial insemination: This procedure may be considered in patients with a marginally compromised semen analysis. It is also indicated in patients where the mucus of the mouth of the womb has been found to be unfavourable for the penetration of the sperm. In this procedure the ovulation of the women is often augmented and timed. When ovulation is expected to occur, the semen sample is processed resulting in a small volume of semen with high concentration of very active sperm. With a thin catheter, this sample is then transferred into the cavity of the womb. This procedure bypasses the mouth of the womb and results in a high concentration of very motile sperm in the Fallopian tubes in anticipation of the egg.
In patients with total absence of sperm due to testicular failure, processed donor sperm can be used for artificial insemination. Before undergoing this procedure, these couples must undergo thorough psychological and social assessment by a social worker or a psychologist.
Donor sperm is obtainable from sperm banks, which are responsible to screen the donor for medical, infective and genetic risks. The sperm sample is being kept frozen and only released after six months if follow up infective testing was still negative. Special questionnaires are used to match the physical characteristics of the male partner with those of the anonymous sperm donor.
In vitro fertilisation (IVF): In patients with moderate male factor infertility or additional female causes of infertility, this procedure offers the best chance of conception. It should also be considered in patients where 4–6 artificial inseminations have not led to a conception. During this procedure, the woman receives hormonal treatment to induce the growth of many eggs. This process is monitored very carefully and when the eggs are deemed to be mature, transvaginal aspiration of the eggs is performed under ultrasound guidance. Each egg is then placed in a droplet of very special culture medium in a very strictly controlled laboratory environment. To each egg is added a specific concentration of processed sperm. If the sperm quality is compromised, the concentration of sperm per egg is increased. Under these circumstances, spontaneous fertilisation of the egg takes place. The fertilised eggs then continue to grow and develop as embryos. Between three to five days after the eggs were fertilised, three or less of the best embryos are then transferred into the womb with a very thin and soft catheter.
Intra cytoplasmic sperm injection (ICSI): In patients where the sperm count and quality is so poor that spontaneous fertilisation of the eggs is not possible, assisted fertilisation is performed by the ICSI procedure. The eggs are obtained as during the IVF procedure. Each egg is then cleaned and assessed for maturity. A single motile and normal looking sperm is then injected into each mature egg, using a very special glass needle. Fertilisation and further embryo development is then assessed and the embryo transfer performed are discussed under the IVF procedure.
In patients with no sperm in the ejaculate, sperm can be retrieved from the epididymis or the testes and then used for the ICSI procedure. If no sperm can be retrieved in these cases, an incision and biopsy of the testes is sometimes indicated to find sperm and to confirm the exact tissue status and diagnosis. These needle aspiration procedures are most successful in men with a failed reversal of a vasectomy.
Electro ejaculation: In men with severe sexual dysfunction or patients with spinal cord injuries where sexual function and ejaculation is severely compromised, electro ejaculation can be used to obtain a semen sample for assisted reproduction. Under general anaesthesia, a special probe placed in the rectum of the patient generates specific controlled voltages, which stimulate the pelvic nerves of the patient. This then leads to ejaculation and the sample is then collected in a clean glass jar for use in assisted reproduction.
CONCLUSION
Male infertility is a common finding in the couple presenting with infertility. It is therefore essential to always assess the male thoroughly in order to identify organic disease and potential causes of infertility. Unfortunately in most cases no treatable causes of the male infertility can be identified. General measures to improve the sperm quality should be employed and individualised and focused use of assisted reproduction should lead to a pregnancy in most of these couples. The emotional and psychological impact of infertility in the male is often underestimated. Counselling and appropriate support of these couples by an experienced infertility team can help to limit this emotional impact.
– with thanks to Dr Merwyn Jacobson, Vitalab
(To learn more about Vitalab and their services, contact them at +27 (11) 911 4700, or by e-mailing them at info@vitalab.com)
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