Male Infertility

The term subfertility may be preferable to infertility as many of the bars to conception are relative rather than absolute and in about 30% of cases no cause is found.
When couples try to conceive:

• 16% will still be unsuccessful at the end of 1 year¹
• 8% after 2 years
• 7% at the end of 3 years

Subfertility may be due to problems with one or both partners.

• Advancing age is not as important in the male as in the female and there are well documented anecdotes of men fathering children late in life, but advancing male age does impair fertility.^2,3
• The relationship between parental age and risk of congenital abnormalities is less well known for men than for women but it does exist.⁴

The search for the cause of infertility or subfertility should be systematic and led by clinical features, not a blind screening process for everything.

• Coitus must be satisfactory and occurring on a frequent basis, preferably at least 3 times a week.
  • Perhaps he is away much of the time of there may be physical or emotional problems.
  • Is penetration adequate?
  • Erectile dysfunction can occasionally present as a complaint of infertility.
• Ejaculatory problems
  • Premature ejaculation is unsatisfactory and worthy of attention, but unlikely to cause infertility unless it tends to occur before adequate penetration has been achieved.
  • Retrograde ejaculation can be a problem, but usually occurs in older men who have had a transurethral resection of prostate for benign prostatic hyperplasia.
• Systemic disease may well impair fertility, probably by interference with the hypothalamic-pituitary axis.
  • Although this tends to be less marked than with female infertility it still exists.
  • Undiagnosed coeliac disease is a poorly recognised problem in female infertility, but it can also impair male reproductive function.⁵
• Past medical history may reveal a cause for infertility.
• Mumps after the age of puberty may have caused orchitis.
• Note previous treatment for malignancy.⁶
  • Chemotherapeutic agents, such as those used in childhood leukaemia, may result in subsequent sterility.
  • Surgery and radiotherapy may be relevant if they involved the region.
  • In men about to receive chemotherapy the question of sperm banking needs to be considered,⁷ but the retention of fertility for prepubertal boys with malignancy remains a problem.⁸
  • Preserving pre-pubertal gonadal tissue for future use is the next stage but for the future.⁹
• Bilateral cryptorchidism is a cause for concern.
  • Operation tends to be performed in the first few years of life.
  • In previous years some surgeons would await puberty to see if spontaneous descent occurred but this is totally unsatisfactory.
• Torsion of the testis may be relevant as failure to reduce it swiftly can compromise blood supply and cause lasting damage.
• Sexually transmitted diseases can cause infertility.
• Drug and medication history.
  Legal drugs taken for legitimate purposes may cause problems.
  • Phenothiazines and the older typical antipsychotics as well as metoclopramide increase levels of prolactin.¹⁰
  • Sulphasalazine impairs spermatogenesis.
  • He may be taking e.g. immunosuppressants for autoimmune disease or after transplantation.

• The basis of investigation of male infertility is a semen analysis - see Infertility - assessment and management in primary care.
• A diagnostic testicular biopsy is indicated in patients with normal FSH and normal testicular volume, to differentiate between obstructive and non-obstructive azoospermia (NOA).
  • Testicular biopsy can also be performed as part of a therapeutic process in patients with clinical evidence of NOA who decide to undergo intracytoplasmic sperm injection (ICSI).
  • About 50-60% of men with NOA have some seminiferous tubules with spermatozoa that can be used for ICSI.

General health

Even in the absence of systemic illness, poor general health will impair fertility.

• Aim for an ideal BMI.
  • In those who are overweight (BMI 25 to 30) and obese (BMI>30) there is a relationship between the degree of excessive weight and poor quality and quantity of sperm.¹¹
• The adverse effects of smoking on male fertility are inadequately appreciated.^12,13
• Excessive alcohol consumption also impairs fertility.¹⁴
  • The effect of lower levels of consumption does not seem to have been adequately researched.
• Male exposure to recreational drugs, toxic substances in the workplace and ionising radiation do not seem to have a significant effect on fertility, but may cause an increase in congenital malformations, spontaneous abortions, fetal resorption, low birth weight infants, increase in childhood cancers, developmental and behavioural abnormalities.¹⁵
• Past abuse of anabolic steroids may cause infertility.¹⁶
  • It is reasonable to suggest that anyone intent on embarking on the rigours of fatherhood should show responsibility with regard to alcohol, drugs and other aspects of lifestyle.

Disorders of the testis and spermatogenesis

These may be structural or hormonal.

• Persistent azoospermia is incompatible with fertility.
  • Whilst a low sperm count is a poor prognostic feature, and the lower the count the worse the prognosis, it is not totally incompatible with fertility.
• Klinefelter's syndrome with karyotype XXY is associated with hypogonadism and disorders of spermatogenesis.
• Failure of descent of the testes has already been mentioned.
  • Early orchidopexy is required to permit normal development.
• Testicular feminisation is when there is resistance to the virilising effects of androgens and a child with an XY karyotype appears as a girl.
  • This can be much less complete and more limited resistance to androgens can lead to poor development of the testes.¹⁷
• Testicular tumours are usually treated by orchidectomy, possibly followed by radiotherapy.
  • In men presenting with infertility and abnormal semen analysis there is a 20-fold increase in the risk of testicular cancer.¹⁸
  • Treatment of testicular cancer reduces fertility by 30%, but this is most marked in those who have received radiotherapy.¹⁹
• Traditional teaching has been that varicocele results in a warmer environment for the testis and that this impairs spermatogenesis and fertility.
  • There has been much dispute over the years about the significance of varicocele, but an interesting recent observation is that varicocele is more associated with secondary than primary infertility and so it may be responsible for a premature decline in sperm count.²⁰
• Trauma can cause testicular damage.
• Pituitary tumours will displace or destroy normal tissue and the production of FSH and LH is often the first to be affected.
  • Panhypopituitarism is also called Simmond's disease.
• Hyperprolactinaemia rarely present with galactorrhoea in men.
  • In one study it caused gynaecomastia in 8% of men but impotence in 30%.²¹
  • The control of prolactin is unlike the other releasing factors in that it is controlled by an inhibiting rather than a releasing factor from the hypothalamus into the hypothalamic-pituitary portal circulation.
  • It is also released in response to thyrotrophin releasing factor, as is TSH, and so it is elevated if thyroxine is low.
• The pituitary gland may be responsible for other disorders such as Cushing's syndrome.
• Low levels of testosterone are found in 20 to 30% of infertile men, but giving testosterone does not improve fertility.¹⁶

Disorders of the genital tract

• Failure of adequate differentiation of the embryonic testis can cause failure of proper development of the spermatic ducts.
• In vasectomy the objective is to interrupt the vas deferens and it may be possible to reunite this in an attempt to reverse the procedure but the success rate as measured by successful pregnancy is poor.
• Congenital urogenital abnormalities such as hypospadias can cause problems. It tends to deposit the semen in the acid environment of the vagina rather than near the friendlier environment of the cervix.
• Does the possession of just one testis impair fertility?
  • In theory it should reduce the sperm count by 50% that would have no significant effect on fertility.
  • However, the loss of the testis may have been associated with other problems that may have had an adverse effect on the other one such as chemotherapy or radiotherapy for cancer.
  • Where a single testis has been lost or failed to develop in the absence of other problems, the presence of just one testis does not have an adverse effect on fertility.²²

Disorders of the testis and spermatogenesis

Persistent azoospermia is incompatible with fertility. The couple may wish to consider donor sperm.

• Whilst a low sperm count is a poor prognostic feature, and the lower the count the worse the prognosis, it is not totally incompatible with fertility.
• Treatment of testicular cancer reduces fertility by 30%, but this is most marked in those who have received radiotherapy.
• Testicular sperm extraction (TESE) and ICSI were introduced in 1993 for treatment of obstructive azoospermia. This technique can also be used for azoospermic men who appear to have disturbed spermatogenesis. If sperm are detected in the testicular biopsy, ICSI with either cryopreserved or fresh sperm can be proposed to the couple.
• Traditional teaching has been that varicocele results in a warmer environment for the testis and that this impairs spermatogenesis and fertility.
• Varicocele treatment is recommended for adolescents who have progressive failure of testicular development documented by serial clinical examination.
• Reviews of randomized clinical trials have raised doubts about the benefit of varicocele treatment in subfertile men.²⁴
• Varicocele treatment for infertility should not be done unless there has been full
• discussion with the infertile couple about the uncertainties of treatment benefit.

Disorders of the genital tract

• Failure of adequate differentiation of the embryonic testis can cause failure of proper development of the spermatic ducts.
• Primary or secondary hypogonadism should be treated with testosterone substitution therapy. This has been shown to achieve fertility in men with hypogonadotropic hypogonadism.
• Congenital urogenital abnormalities such as hypospadias can cause problems. It tends to deposit the semen in the acid environment of the vagina rather than near the friendlier environment of the cervix.
• In men with unilateral cryptorchidism fertility is almost equal to that of men without cryptorchidism. However, bilateral cryptorchidism means the likelihood of achieving a pregnancy is significantly reduced.
• Obstructive lesions of the seminal tract should be suspected in azoospermic or severely oligo-azoospermic patients with normal-sized testes and normal endocrine results. Results of reconstructive microsurgery depend on the cause and location of the obstruction and the expertise of the surgeon.