Module on “Infertility: (Part-1)” by Dr. Vishwesh BN

INFERTILITY

Infertility is defined as the inability of a couple to achieve conception after 1 year of unprotected coitus. Sterility is an absolute state of inability to conceive. Secondary infertility or sterility are the same states developing after an initial phase of fertility. All these conditions can affect either the male or female partner of a marriage.

CONCEPT OF FERTILITY

Fertility is a relative rather than an absolute state, and comparatively few individuals are fully sterile or fully fertile. The majority fall somewhere in between these two extremes and the fertility of a marriage is a sum of the fertilities of the two partners. Low fertility in one can to some extent be balanced by high fertility in the other, whereas low fertility in both partners may result in infertility. This explains why some couples fail to reproduce yet, when they separate and each takes a new mate, they both proceed to have children.

Fertility also varies from time to time in the same individual. In the male these are not obvious except during childhood and, less absolutely, in old age, but in the female, physiological infertility is seen before puberty, after puberty and before maturation. Although menstruation may be occurring regularly, fertility is usually low until the age of 16–17 years. The explanation of this is unknown although it is sometimes assumed that it is because a higher percentage of menstrual cycles are anovular in the earlier years, during pregnancy, when ovulation is suppressed, during lactation, before the menopause. After the age of 34 years, fertility falls; there is a gradual decline in conception rates with age, after the menopause.

Factors Essential for Conception

Healthy spermatozoa should be deposited high in the vagina at or near the cervix (male factor). The spermatozoa should undergo changes (capacitation, acrosome reaction)and acquire motility (cervical factor). The motile spermatozoa should ascend through the cervix into the uterine cavity and the fallopian tubes. There should be ovulation(ovarian factor).™ The fallopian tubes should be patent and the oocyte should be picked up by the fimbriated end of the tube (tubal factor). The spermatozoa should fertilize the oocyte at the ampulla of the tube.The embryo should reach the uterine cavity after 3–4 days of fertilization. The endometrium should be receptive (by estrogen, progesterone, IGF-l, cytokines, integrins) for implantation, and the corpus luteum should function adequately.

CAUSES OF MALE INFERTILITY
There are still some cases of unexplained infertility, despite the increased sophistication of tests now available. In any series of infertile marriages, the main aetiological factor is found in the female in about 40% of cases; about 35% of the husbands concerned have some degree of infertility. In 10–20% of cases, a combination of factors operates and the rest have unexplained infertility. Failure to produce spermatozoa in sufficient numbers and with the capacity to fertilise in most cases of azoospermia and oligospermia the underlying cause is not clear, although it is now accepted that motility and abnormal forms are at least as important as the number of spermatozoa. Established and postulated causes include the following:

Testicular causes-

• Incomplete development of the testes. The frequency of sex chromosomal aberrations among men with aplastic testes and azoospermia is probably high.
• Late descent, or non-descent, of the testes which may or may not be the result of the former cause. In either case, the spermatogenetic function of the testis depends on its extra-abdominal site, probably because of the ill-effect of heat on the seminiferous tubules. The tissue temperature of the scrotal testis is 2°C lower than that of the rest of the body.
• Previous orchitis due to mumps or other severe infectious fevers (including influenza), or chlamydial infection occurring after the age of 14 years. Orchitis complicates 25–50% of cases of adult mumps.
• Damage to the testes resulting from operation, accident or exposure to X-rays. The injury may be to its blood supply rather than to the gonad itself. Exposure of the testes to heat impairs spermatogenesis, at least temporarily; frequent hot baths or the wearing of non-porous nylon underwear and suspensory garments may have this effect. Varicocele is not uncommonly found in infertile men; if its association is causal it may be because it raises the scrotal temperature or leads to anoxia of the testicular tissues. Workers in foundries or welders may similarly be exposed to high temperature.
• Diseases of the testes such as tumours, tuberculosis and syphilis.
• Depression of testicular activity by disease of other endocrine glands (especially the hypothalamic-pituitary system, e.g. hypogonadism as in the Laurence-MoonBiedl or Frohlich syndrome, thyrotoxicosis, diabetes mellitus), by general ill health and by drugs and poisons.
• Steroids in high doses, antiandrogens, e.g. cyproterone, spironolactone, cimetidine and cannabis, depress the hypothalamopituitary-testicular axis. Methotrexate, colchicine, nitrofurantoin, sulfasalazine, cocaine and alcohol act directly on the testis. Nifedipine, allopurinol and nicotine impair the fertilising capacity of the sperm, while sperm motility is impaired by lignocaine, procaine, propranolol, quinine, chlorpromazine, minocycline and tetracycline.
• Age: Male fertility tends to diminish after the age of 40 years although spermatogenesis usually continues to some extent until old age. Octogenarian fathers are by no means rare.
• Sperm agglutinins and antibodies: In some infertile men, or following operations for reversal of vasectomy, sperm agglutinins are demonstrable in circulation, which may damage seminiferous tubules as well as cause spermatozoa to agglutinate after ejaculation. Other local and circulatory antibodies to testes as well as to spermatozoa are described in the male.
• Bilateral obstruction of the epididymis, the Vas or the ejaculatory ducts-
• These may be caused by the following:
• Accident or operation, especially herniorrhaphy.
• Infections, of which gonorrhoea and tuberculosis are the most important; the lesion is usually an epididymitis.
• Congenital absence or gross hypoplasia of the vas Congenital or developmental obstruction of the epididymis which is usually associated with congenital cystic disease of the lungs to form a definite syndrome. Failure to Deposit Spermatozoa in the Vagina.
• Impotence (including the type in which erection and penetration take place but there is no emission)
• Premature ejaculation
• Abnormalities of the penis such as hypospadias and phimosis
• Retrograde ejaculation into the bladder. This happens after prostatectomy and certain nerve resection operations. It can also occur in apparently normal men.
• Drugs which affect ejaculation include α-blockers, ganglion blockers, the tricyclic antidepressants, monoamine oxidase inhibitors, phenothiazines, β-blockers and thiazides.

Abnormal Semen Quality

• An unusually high or small volume of ejaculation
• Other physicochemical anomalies which may or may not be significant are low fructose or high prostaglandin content, and undue viscosity
• Oligozoospermia: Less than 20 million sperm/mL
• Asthenozoospermia: Less than 50% sperm with forward progression or less than 25% with rapid progression
• Teratozoospermia: Less than 30% morphologically normal forms
  • Asthenoterato-oligozoospermia: Combinations of the above
  • Azoospermia: Absence of sperm in the seminal fluid; aspermia is the absence of ejaculate.

The common causes of male infertility are summarised as follows:

 

Pre-testicular	Testicular	Post-testicular
Endocrine • Gonadotropin deficiency • Obesity • Thyroid dysfunction •Hyperprolactinemia	• • Immotile cilia (kartagener) syndrome • Cryptorchidism • Infection (mumps orchitis) • Toxins: Drugs, smoking,radiation • Varicocele • Immunologic • Sertoli-cell-only syndrome • Primary testicular failure • Oligoastheno-teratozoospermia	• Obstruction of efferent duct • Congenital – Absence of Vas deferens (cystic fibrosis) –young’s syndrome • Acquired Infection: Tuberculosis, Gonorrhea • Surgical – Herniorrhaphy • Vasectomy
Psychosexual • Erectile dysfunction • Impotence		Others • Ejaculatory failure • Retrograde ejaculation • Hypospadias • Bladder neck surgery
Drugs • Antihypertensives • Antipsychotics
Genetic • 47 xxy(p. 229) • Y chromosome deletions • Single gene mutations

 

Assessment Questions

1. Define infertility.

Infertility is defined as the inability of a couple to achieve conception after 1 year of unprotected coitus.

2. Define sterility

Sterility is an absolute state of inability to conceive.

3. What is the difference between Primary and Secondary infertility.

Primary infertility denotes those patients who have never conceived whereas secondary infertility indicates previous pregnancy but failure to conceive subsequently.

4. Name some physiological conditions leading to infertility in females

Physiological infertility is seen before puberty, after puberty and before maturation. Although menstruation may be occurring regularly, fertility is usually low until the age of 16–17 years because a higher percentage of menstrual cycles are anovular in the earlier years, during pregnancy, when ovulation is suppressed, during lactation, before the menopause. After the age of 34 years, fertility falls; there is a gradual decline in conception rates with age, after the menopause.

5. What are the factors essential for conception?

Healthy spermatozoa should be deposited high in the vagina at or near the cervix, the spermatozoa should undergo changes (capacitation, acrosome reaction)and acquire motility (cervical factor). The motile spermatozoa should ascend through the cervix into the uterine cavity and the fallopian tubes, there should be ovulation(ovarian factor), the fallopian tubes should be patent and the oocyte should be picked up by the fimbriated end of the tube (tubal factor), the spermatozoa should fertilize the oocyte at the ampulla of the tube, the embryo should reach the uterine cavity after 3–4 days of fertilization, the endometrium should be receptive (by estrogen, progesterone, IGF-l, cytokines, integrins) for implantation, and the corpus luteum should function adequately.

6. Name some endocrine causes of male infertility.

Gonadotropin deficiency, obesity, thyroid dysfunction and hyperprolactinemia are some endocrine causes of male infertility.

7. Name some testicular causes of male infertility.

Immotile cilia (kartagener) syndrome, cryptorchidism, Infection (mumps orchitis), toxins including  drugs, smoking, radiation , Varicocele, Immunologic causes, sertoli-cell-only syndrome, primary testicular failure and oligoastheno-teratozoospermia are some of the endocrine causes of male infertility.

8. Name some Post-testicular causes of male infertility.

Obstruction of efferent duct, congenital absence of vas deferens, young’s syndrome ,

acquired infections like tuberculosis, gonorrhoea etc, Surgical procedures like herniorrhaphy, vasectomy, ejaculatory failure, retrograde ejaculation, hypospadias, bladder neck surgery etc are some Post-testicular causes of male infertility.

9. Describe some conditions of abnormal semen quality.

An unusually high or small volume of ejaculation , other physicochemical anomalies like low fructose or high prostaglandin content, and undue viscosity , oligozoospermia,   asthenozoospermia, teratozoospermia, asthenoterato-oligozoospermia and azoospermia are some conditions of abnormal semen quality

10. What is the difference between oligozoospermia, asthenozoospermia, teratozoospermia,  asthenoterato-oligozoospermia and azoospermia.

Oligozoospermia: Less than 20 million sperm/mL

Asthenozoospermia: Less than 50% sperm with forward progression or less than 25% with rapid progression

Teratozoospermia: Less than 30% morphologically normal forms

Asthenoterato-oligozoospermia: Combinations of the above

Azoospermia: Absence of sperm in the seminal fluid; aspermia is the absence of ejaculate.

References:

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