Module on “Infertility (Part-3)” by Dr. Vishwesh BN

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THE INVESTIGATIONS OF MALE INFERTILITY

 A highly fertile couple practising coitus regularly take an average of 6–7 months to achieve a pregnancy, and four out of five women conceive within 1 year of commencing regular coitus without contraception. Failure to conceive during 12–18 months despite adequate opportunity is therefore always acceptable as justifying full investigation. A strong case can be made for investigating infertility of only 1 year’s duration—especially if the woman is aged over 30 years or the man is aged over 40 years. A clinical examination of both partners, and possibly semen analysis is indicated as soon as any couple becomes worried. An important preliminary to the investigation of infertility is to make certain that the woman is not suffering from a disability which might contraindicate pregnancy or make it undesirable. These conditions are present in 1% of women patients seeking advice and it is poor practice to encourage a pregnancy which has to be terminated

Clinical Assessment of Both Partners

History

The man and wife ideally should be questioned separately and then together, partly to have their evidence corroborated but mainly because either may have something to reveal confidentially. The special points on which information is required are as follows:

  • Ages, occupations, previous marriages
  • Duration of marriage and the period of time during which contraception has been practised
  • Are the partners separated for significant periods of time?
  • Previous illnesses and operations. Has the woman had appendicitis, peritonitis, tuberculosis  in any site, or any operation on or near the genital tract? Has the man had orchitis, renal    disease, bronchiectasis or any operation on or near the genital tract? Has either suffered   from gonorrhoea or Chlamydia infection or symptoms suggesting them? Severe head injury,  meningitis and encephalitis can affect the function of the hypothalamic-pituitary axis?
  • The family medical history of each, looking especially for tuberculosis on the woman’s side
  • Has the woman ever been pregnant by her husband or by another man?
  • Has the husband been responsible for pregnancy in another woman?
  • Is coitus normal and painless, how frequently is it practised and at what time in the cycle? Some couples have a wrong idea about the fertile period. More specific questions may be asked about their relationship and details regarding coitus, including erection, ejaculation and penetration.
  • Details of menstrual function including factors which favour an ovulatory cycle
  • Has the woman any other symptoms referred to the genital tract?
  • Drugs, e.g. mefenamic acid taken for mittelschmerz pain, may interfere with ovulation. Drugs used for treating hypertension (e.g. guanethidine) may cause impotence and salazopyrine (for ulcerative colitis), cytotoxic drugs, immunosuppressives and nitrofurantoin reduce the sperm count.
  • Alcohol intake may reduce the potency and frequency of coitus.

Examination:

  • This should cover all systems with particular attention to the reproductive systems where abnormalities of the penis; cryptorchidism; the size and consistency of the testes and epididymis; the presence of the vasa; a varicocele and any prostatic abnormality in the man. Clinical
  • Paternity is probably the best proof of male fertility, yet it can be misleading. The wide variation in results of semen analysis in fertile and infertile men at different times makes reassessment essential if a couple requests advice regarding their ability to conceive.
  • Responsibility for two or more pregnancies, however, usually means good fertility, provided the effects of advancing years and of intercurrent disease can be excluded. There are however, very few cases of infertile partnerships in which investigation of the male partner is not essential.
  • Careful inquiry into past illnesses and examination of the genitalia usually reveal some abnormal finding in approximately 20–30% of infertile men. In others it is disclosed only by semen analysis. Physical examination of the male is mandatory if semen analysis is abnormal.

Semen Analysis

The demonstration of spermatozoa in material removed from the vagina or cervix after coitus is inadequate for the purpose of assessing male fertility. Whatever be the findings on a postcoital test, full semen analysis is also essential. For this purpose, semen collected in a condom during coitus is unsatisfactory because the rubber and its preservative powder are spermicidal. The specimen is best collected after 3 days of abstinence, masturbating directly into a dry and clean wide-mouthed glass container. It is kept as close as possible to body temperature (by carrying it in a hip pocket), and its examination carried out as soon as possible after it has liquefied (this takes half an hour), preferably within 1 hour, as motility declines progressively with time. Collection under home conditions is generally preferred by the ‘patient’ but for optimal results it is best carried out near the laboratory. Semen analysis should be carried out on at least two different occasions if the first test suggests impaired fertility. Of all the characteristics of semen which can be studied, the essential ones are volume of fluid; number, motility and morphology of spermatozoa. There is no such thing as a “normal” semen because of the wide fluctuations present in any one individual, but according to the WHO criteria, the volume should be 2–6 mL; liquefaction should be complete in 30 minutes; the sperm count should be 20 million/mL or more; 60% should have forward progressive motility or 25% or more should show rapid progression within 60 minutes of ejaculation and 70% or more must be morphologically normal. Fewer than 1 million white blood cells/mL should be present. Computer assisted semen analysis (CASA) was introduced to remove inconsistencies in sperm counts with traditional methods. However, errors still occur especially with low counts when other cells can be miscounted as sperm. The CASA systems can also provide information on sperm velocity which is suggestive. Immature forms of spermatozoa are ranked as morphologically abnormal. Any one specimen is assessed by considering these features in relation to each other. For example, a low percentage of morphological abnormalities may compensate for a poor sperm count while a small volume detracts from a high sperm density. A very high volume with resulting dilution can be a disadvantage. Caution is necessary in interpreting the significance of motility of spermatozoa because this varies so much with the conditions of collection and storage of the specimen. When the number and morphology of spermatozoa are good, the finding of poor motility should be taken seriously for it may be due to antisperm antibodies. True absence of motility (necrospermia) in a fresh and otherwise normal specimen is an extremely rare finding. Usually 70–80% of spermatozoa are motile when the specimen is collected. The presence of pus cells indicates an inflammatory lesion, usually in the prostate, but is not necessarily significant so far as fertility is concerned. Semen culture should be done. Urethral swabs are required for chlamydial culture. Most men with pyospermia prove fertile without treatment; nevertheless pyospermia in an infertile man is best treated. Fructose is secreted by the seminal vesicles and is essential to the metabolism of spermatozoa as it provides energy for their movements. At the time of ejaculation, semen contains 200–300 mg/dL fructose but this falls to 100 mg/dL in 4–8 hours. When azoospermia is the result of an obstructive lesion, absence of both fructose and spermatozoa indicates that the block is at or below the level of the ejaculatory ducts. Infection of the seminal vesicles also decreases the ejaculate volume resulting in low fructose levels. Prostate infection can lead to obstructive oligozoospermia or azoospermia and a lowered zinc concentration. When semen is not emitted and retrograde ejaculation is suspected, the urine collected immediately after orgasm should be examined for spermatozoa. Low male fertility, as found on semen analysis, should be understated to the couple concerned because it is impossible to interpret the results except in very general terms.

Trial wash:

It is now found that all semen samples should have sperm wash done to evaluate the motile sperm counts and this is called as trial wash.

  • Performed during semen analysis
  • Evaluation of semen for various assisted conception procedures
  • Helps to select suitable sperm wash methods and helps to plan treatment.

Number of motile spermatozoa inseminated (NMSI) and morphology on the success of intrauterine insemination has been studied. When the NMSI was more than 5 million postwash with a normal morphology of more than 30% the pregnancy rate per cycle was 18.42%, whereas if NMSI was less than 5 million postwash and morphology of less than 30% the pregnancy rate per cycle was 5.43%. However, in those who yield less NMSI, if few cycles intrauterine insemination (IUI) fails should be considered for assisted reproductive techniques (ART).

Sperm Function Tests

The lack of correlation between the various aspects of the semen analysis and fertility outcomes led to the development of tests for sperm function. However, these are also of limited utility because each of them tests only one aspect of sperm function. With the development of intracytoplasmic sperm injection (ICSI) their importance in clinical practice is doubtful. Sperm function tests vary in their ability to detect defects in the complex processes leading to fertilisation, and are of limited use from a practical point of view.  Unless there is azoospermia, the predictive value of subnormal semen variables is limited. No functional test has yet been established that can unequivocally predict the fertilising capacity of spermatozoa.

Sperm Penetration Assay

Healthy sperms penetrate most, specially processed hamster ova from which the zona has been removed, and produce a significant degree of polyspermy per egg. The unhealthy sperms penetrate a lower number of ova and produce less polyspermy. A minimum of 10–30% ova are normally penetrated. The results of the test vary from time to time in the same individual and do not correlate with eventual fertility. However, this helps in early identification of patients who may be better suited for ICSI or donor insemination, especially in cases of unexplained infertility. In Vitro Sperm Penetration Tests If the postcoital test is poor, an alternative test is to place a drop of sperm on a glass slide alongside commercially available bovine mucus and to microscopically study its invasion by the spermatozoa (sperm penetration test). A modification of this type of test is to use an in vitro crossover sperm-cervical mucus contact test (SCMCT), that is, to use mid-cycle mucus and semen of the couple under question and compare it with donor sperm and donor mucus (Kremer test). However, these are of little practical value as couples with poor postcoital tests or unexplained infertility will be treated with IUI.

Other Tests

The CASA systems can provide information on the number of spermatozoa in a hyperactivated motility state which is suggestive of capacitation and on the hypo-osmotic swelling test which assesses the tail membrane function. Nonmotile sperm with a positive hypo-osmotic test are reported to do better with ICSI than nonmotile and negative hypo-osmotic test sperm. The hemizona assay tests the ability of the sperm to pass through the zona of the human egg. This test is no longer done following the development of ICSI.

Sperm Antibodies

Semen is known to be highly antigenic and sperm antibodies are a known cause of infertility. Agglutination is the sticking together of sperm in variable patterns, e.g. head-to-head, tail-to-tail, mixed agglutination. It is caused by antisperm antibodies which are usually IgA or IgG. Further tests like the immunobead or mixed antiglobulin reaction (MAR) test can be done for the detection of these antibodies in semen. The immunobead test can also be used to detect antibodies in serum or cervical mucus. With this test, less than 20% of sperms should be covered with adherent particles or beads. These tests are indicated when the semen analysis shows oligozoospermia or azoospermia; spontaneous sperm agglutination or low motility; an abnormal postcoital test; in the presence of infection; if there is failure of conception after vasectomy and in cases of unexplained infertility.

Hormonal Assessment

Up to 10% of subfertile males have endocrine abnormalities. Routine testing for endocrine dysfunction is not indicated; but should be carried out in those men found to have oligospermia or azoospermia. Follicle stimulating hormone, LH, prolactin and testosterone levels are helpful in this assessment. A raised FSH level reflects failure of spermatogenesis. Low levels of FSH and LH are diagnostic of hypogonadotrophic hypogonadism. Normal FSH levels with normal testes but azoospermia suggest obstruction. Raised LH levels with low testosterone levels indicate Leydig cell dysfunction. A low testosterone level warrants replacement therapy. Prolactin levels are not done routinely. Rarely, in cases of impotence or decreased libido, hyperprolactinaemia is seen without evidence of hypogonadism. Thyroid dysfunction is so rarely a factor in men that it is not necessary to assess thyroid stimulating hormone (TSH) levels unless clinical features indicate it.

Testicular Biopsy

Testicular biopsy is generally not recommended as the disruption of the blood-testes barrier can lead to the development of autoimmunity against spermatozoa. It is indicated in cases of azoospermia with normal FSH and inconclusive seminal markers to distinguish between a failure in spermatogenesis and an obstruction to the outflow of spermatozoa. It also reveals whether the tubules are basically normal but unstimulated or whether they are incapable of function. Examination of the material obtained requires a histologist with special experience.

Varicocele-  Assessment and Significance

A varicocele is a collection of dilated veins in the spermatic cord and is a common physical anomaly. Varicoceles are found in 11.7% of men with normal semen and 25.4% of men with abnormal semen. The mechanism by which varicoceles might impair fertility and spermatogenesis is not clear. Varicoceles may be associated with decreased ipsilateral testicular volume, elevated scrotal temperature and pain, as well as impaired semen quality. Hence, if there are gross varicoceles in an individual who has fluctuating levels of sperm count and motility varicocele surgery may be worth a try. If there is an improvement in the count and motility following varicocele surgery then the couple may benefit by IUI in some cases rather than having the only option in vitro fertilisation (IVF) or ICSI.

Other Tests

Vasography is used in cases of proximal vas deferens obstruction before microsurgical repair. Transrectal ultrasonography is combined with seminal vesiculography to demonstrate ejaculatory duct obstruction. Chromosomal analysis is indicated in men with eunuchoid features and oliogzoospermia, who may have the 47, XXY complement of Klinefelter’s syndrome. A high prevalance of Y chromosome submicroscopic deletions is also reported in oligozoospermic men.

1. What is the first test done for infertility in a man?
a) FSH test
b) Semen Analysis
c) Blood test
d) HIV test

2. What is the normal volume of semen for a man?
a) 1-2 ml
b) 6-10 ml
c) 2-6 ml
d) 11-15 ml

3. What is a normal sperm count?
a) 5 million sperm per ml
b) 20 million sperm per ml
c) 10 million sperm per ml
d) 30 million per ml

4. What is the best sperm motility
a) Grade a (fast progressive)
b) Grade b (slow progressive)
c) Grade c (nonprogressive)
d) Grade d (immotile )

5. What does Azoospermia signify
a) Very low sperm count
b) Low sperm count
c) Normal sperm count
d) Zero sperm count

6. What does a Testicular Biopsy do?
a) Checks for sperm production
b) Checks for cancer in the testicles
c) Checks the diameter of the testicle
d) Checks for injury to testicle

7. For a semen analysis, semen is collected from:
a) Vagina or cervix after coitus
b) Semen collected in a condom during coitus
c) Masturbating directly into a container.
d) Any of the above

8. The different patterns of sperm agglutination are:
a) Head-to-head
b) Tail-to-tail
c) Mixed agglutination
d) All of the above

9. This is the most common sex chromosome disorder with karyotype XXY associated with male infertility.
a) True hermaphrodites.
b) Klinefelter’s syndrome
c) Turner syndrome
d) Androgen Insensitivity Syndrome

10. Transrectal Ultrasonography is suggested in case of:
a) Oliogzoospermia
b) Varicocele
c) To demonstrate ejaculatory duct obstruction.
d) To demonstrate proximal vas deferens obstruction

Answers:
1. b
2. c
3. b
4. a
5. d
6. a
7. c
8. d
9. b
10. c

References:

1. Hiralal Konar Editor: Textbook of DC Dutta’s obstetrics. 8th Edition. New Delhi: Jaypee Brothers Medical Publishers; 2015.
2. Narendra Malhotra, Pratap Kumar, Jaideep Malhotra, Neharika Malhotra Bora and Parul Mittal M. Revised and updated. Jeffcoate’s Principles Of Gynaecology. Eighth Edition New Delhi: Jaypee Brothers Medical Publishers; 2014.
3. Cecilia Bottomley and Janice Rymer. 100 cases in Obstetrics and Gynaecology. 2nd edition. Series editor: Janice Rymer. CRC Press: Taylor & Francis Group; 2015.
4. Andrew T. Raftery, Michael S. Delbridge, Marcus J.D. Wagstaff and Katherine I. Bridge, Editors: Churchill’s Pocketbooks Surgery. 5th edition. Elsevier; 2017
5. Hiralal Konar Editor: Dutta’s Bedside Clinics and Viva-Voce in Obstetrics and Gynecology. Sixth Edition. New Delhi: Jaypee Brothers Medical Publishers; 2016.
6. Sakshi Arora. Pre Neet Obstetrics and Gynaecology. First Edition. New Delhi: Jaypee Brothers Medical Publishers; 2013.
7. Sarala Gopalan, S.Rathnakumar and Vanita Jain editors. Mudaliar and Menons Clinical Obstetrics. 7th Revised Edition. Orient Longman, Bombay.
8. Cunningham, Leveno, Bloom, Spong, Dashe, Hoffman, Casey, Sheffield. Williams Obstetrics. 24th edition. McGraw Hill Education; 2014.
9. D. Keith Edmonds. Editor .Dewhurst’s Textbook of Obstetrics & Gynaecology. Seventh edition, Blackwell Publishing; 2007.
10. World Health Organization. Infertility. 2013.

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