Introduction, male sub-fertility, diagnosis and treatment

1. Unit VII: Sub-Fertility
By: Isha Thapa Magar
Master in Nursing (WHD)
TU, IOM

2. Introduction
• Infertility is defined as 1 year of unprotected
intercourse without pregnancy.
o Primary infertility →patients who have never conceived.
o Secondary infertility → had previous pregnancy but
failure to conceive subsequently
• Sterility is defined as inability to conceive a
pregnancy. A permanent state of infertility.

3. Contd..
• Subfertility is defined as women or couples who are not sterile but
exhibit decreased reproductive efficiency.
• Generally, it is any form of reduced fertility with prolonged time of
unwanted non-conception.
• Approximately 85–90% of healthy young couples conceive within 1
year, most within 6 months.
• Infertility affects approximately 10–15% of couples.
• Cycle fecundability is probability that a cycle will result in pregnancy
and fecundity is probability that a cycle will result in a live birth.

4. • Fecundability is ability to conceive in a single
menstrual cycle. It is highly age-related, with a
significant decrease beginning at approximately 32
years of age and more rapid decline after age 37
• Fecundity → probability of achieving a live birth in a
single cycle and, by definition, has a value lower than
fecundability.

5. Natural Conception
• A healthy couple having frequent intercourse have about an
18–20% chance of conceiving in a single menstrual cycle.
• There is of course a cumulative increase in pregnancy rates
over time as couples try for conception.
• Within 6 months 70% of couples will have conceived, after
12 months 80% and after 24 months 90% of couples will
achieve a pregnancy.

6. Natural Conception Rate over a 3 years Period

7. Contd..
• Most important factor affecting fertility is female age, which is
related to a decline in quality and quantity of eggs.
• Female fertility tends to fall sharply over age of 36, with a further
dip after age of 40. However, there is a considerable variation and
biological age (or ovarian reserve) does not always precisely
correlate with chronological age.
• Male age is also an important factor; semen quality tends to fall in
men over age of 50, while frequency of intercourse tends to fall in
men over age of 40.

8. Contd..
• Both frequency and timing of sexual intercourse impact strongly on
the chance of conceiving naturally. Couples having intercourse three
times a week are three times more likely to conceive than couples
having intercourse once a week. Maximum ‘efficiency’ is probably
intercourse at least every alternate day.
• Increased frequency of intercourse should be encouraged in the
periovulatory period. Eggs are thought to be fertilizable for about
12–24 hours postovulation, while sperm can survive in the female
reproductive tract for up to 72 hours.

9. Contd..
• Ovulation usually occurs about 14 days prior to
menstruation, with luteal phase being relatively stable
at this length.
• ‘Fertile window’ for women will, therefore, be
different depending on average length of their
menstrual cycle (e.g. for a woman with a 28-day
menstrual cycle, her optimal fertile window will be
between days 12 and 15).

10. Contd..
• External factors may influence the chance of conception. smoking
can decrease the quality and quantity of eggs and sperm.
• Body mass index (BMI) exerts a strong influence on fertility, with
male and female BMI at both the high and low extremes associated
with a reduced chance of conceiving.
• Stress can have a direct influence on the hypothalamic–pituitary–
ovarian (HPO) axis, interfering with regular ovulation, and may
indirectly reduce conception by reducing libido and frequency of
intercourse.

11. Fig. Stages of fertility decline with increasing age,
related to the no. & quality of follicle pool.

15. Etiology In Male Infertility
 Male factors of infertility
• Disorders of spermatogenesis—50%
• Obstruction of the efferent ducts—30%
• Disorders of sperm motility—15%
• Sexual dysfunction
• Unexplained—15%

16. Contd..
1. Genetic—abnormal Y chromosome & XXY in Klinefelter’s
syndrome. Mutation of short or long arm Y chromosome.
2. Disorders of spermatogenesis.
 Hormonal (pre-testicular)
o Hypothalamic disorder
o Pituitary secretion of FSH, LH
o Hyperprolactinaemia causing impotence or diminished libido
o Hypothyroidism, adrenal gland disorder and diabetes.

18. Contd..
 Primary testicular disorders (testicular)
• Idiopathic
• Varicocele
• Absent germ cells.
• Chromosomal defect, i.e. Klinefelter’s syndrome.
• Cryptorchidism
• Orchitis (traumatic, mumps, TB, gonorrhoea)
• Chronic illness
• Immunological disorders (5%)
• Immotility

19. Contd..
3. Duct obstruction (post-testicular).
• Congenital absence
• Inflammatory block (gonococcal, tubercular),
• Surgical trauma
• E. coli, staphylococci, chlamydial infection
• DNA fragmentation of sperm
• Decreased motility and apoptosis

20. Contd..
4. Accessory gland disorders:
o Prostatitis
o Vesiculitis
o Congenital absence of vas
5. Disorders of sperms and vesicular fluid:
• Sperm antibodies and low fructose in seminal plasma.
• Sperm acrosome defect.
• Zona pellucida binding defect.
• Zona pellucida penetration defect.

23. Contd..
6. Sexual dysfunctions:
• Low-frequency coitus—wrong time, low libido.
• Impotence
• Hypospadias.
• Premature ejaculation
• Retrograde ejaculation

26. Contd..
7. Psychological and environmental factors
• Smoking,
• Alcohol consumption,
• Tobacco chewing,
• Diabetes
• Drugs—antihypertensive, antipsychotics, sex steroids, chemotherapy.
8. Obesity increases peripheral conversion of androgen to
oestrogen & affects fertility.
9.Chronic illness.

27. Diagnosis
1. History Taking. History includes age of man,
previous children, duration of infertility, and any
contraception practiced and for how long.
• coital frequency and timing related to ovulation.
• occupation—a frequent traveller or working in a hot
place.
• Habit of smoking, alcohol, tobacco and drugs.

28. Contd..
• History of tuberculosis, sexually transmitted infection, diabetes
and chronic illness. Diabetic neuropathy can cause impotence
and retrograde ejaculation. Fever of any cause can suppress
spermatogenesis for as long as 6 months. Chronic respiratory
disease.
• Operation on hernia or scrotum, undescended testis.
• Any coital problem such as premature and retrograde
ejaculation, failure to ejaculate.

29. Contd..
2.General Physical examination
• General height
• Weight and obesity may be hormonal defects.
• Secondary sex characters are abnormal in Klinefelter’s
syndrome, i.e. gynaecomastia
• Thyroid enlargement, enlarged breasts and hirsutism are
noted.
• Blood pressure should be checked.

30. Contd..
• Local physical examination
• examination of penis and scrotum, and surgical scar.
• normal scrotal volume is 15–35 mL (average 18 mL). Testicular
volume of less than 6 mL is seen in atropic testes and in Klinefelter’s
syndrome.
• testes well placed in scrotum.
• epididymis palpated for enlargement and thickness.
• vas feels thickened in inflamed conditions.
• Rectal examination concludes prostate examination.
• Presence of varicocele

31. Special Investigations
o Semen analysis
o Hormonal assays
o Testicular biopsy
o Immunological tests
o Patency of vas
o Chromosomal study
o Hemizona Assays
o DNA Fragmentation
o Sperm Penetration Assay
o Acrosomal Reaction

33. Semen Analysis

34. Terminologies
• Oligozoospermia→ Reduced sperm numbers
– Mild to moderate: 5–20 million/mL
– Severe: <5 million/mL
• Azoospermia→ No sperm in semen
– Azoospermia may be due to obstruction in outflow tract,
termed obstructive azoospermia, such as congenital
absence of vas deferens, severe infection, or vasectomy.
– Azoospermia may also follow testicular failure
(nonobstructive azoospermia)

35. Contd..
• Asthenozoospermia→ Reduced sperm motility→prolonged
abstinence, antisperm antibodies, genital tract infections, or
varicocele.
• Teratozoospermia →Abnormal sperm morphology

36. Types of Abnormal Sperm

38. Contd..
• Aspermia (anejaculation) →No ejaculate (ejaculation
failure)
• Leucocytospermia → Increased white cells in semen
• Necrozoospermia→ All sperm are nonviable or
nonmotile
• Polyzoospermia→ Count is more than 350 million/ ml.

39. Contd…
• Hypospermia→ low volume, less than 1.5 mL. →
due to improper collection or retrograde ejaculation.
• Hyperspermia → more than 5.5 mL → due to
prolonged abstinence or inflammation of seminal
vesicle.

40. Introduction
• Semen analysis is the most important part of male
investigation
• It measures semen volume, sperm concentration, sperm
motility, and sperm morphology
• Any significant deviations from reference limits are
generally classified as male factor infertility
• This should be first step in investigation because, if some
gross abnormalities are detected (example being absence of
sperm).

41. Contd..
• Collection
o Collection is best done by masturbation failing which by
coitus interruptus.
o Semen is collected in a clean container.
o If masturbation into a container is not possible, condoms
specially designed for semen analysis should be used rather
than latex condoms, which are toxic to sperm.

43. Contd..
• Intercourse to collect sample is discouraged because
of risk of contamination.
• Sample should be sent to laboratory within 30
minutes to 1 hour of collection to prevent dehydration
and degradation.
• Coitus should be avoided for 2–3 days prior to test
(abstinence).

44. Semen Analysis WHO-2010 (1992)

45. Testicular Biopsy
• Testicular biopsy is indicated in azoospermia to
distinguish between testicular failure and obstruction in
vas deferens.
• It also reveals whether seminiferous tubules are normal
but unstimulated by anterior pituitary gland, or
whether they are incapable of function due to primary
gonadal failure.
• 1 to 2%males have endocrine dysfunction.

46. Hormonal Assays
• FSH
• High FSH level denotes primary gonadal failure.
• Normal level in azoospermia →suggests obstructive lesion in vas or
epididymis.
• Low FSH level → indicates pituitary or hypothalamic failure and a
need for FSH/LH/GnRH treatment.
• Prolactin level >30 ng/mL → indicates hyperprolactinaemia
requiring treatment.
• Low testosterone level → indicates low LH or Leydig cell
dysfunction.
• No response to GnRH suggests pituitary failure.

47. Chromosomal Study
• Karyotyping should be undertaken in azoospermic
men, as 15–20% of them have chromosomal
disorders.
• The most common disorder is Klinefelter’s syndrome
with 47 XXY karyotype.

49. Immunological Tests
• Antibodies IgG or IgA, bound to sperm head or midpiece, causing
sperm agglutinating and sperm immobilizing; leading to infertility.
• Antibodies are produced following infection (orchitis), trauma or
vasectomy.
• Most commonly employed assay contains immunobeads, which are
mixed with sperm preparation.
• These beads will bind to antibodies present in a sperm sample. This
mixture can be visualized under a standard microscope.
• With affected individuals, beads bind to antibodies that have bound to
sperm.

50. Fig. Immunoreactive beads bind to antibodies that are bound to sperm

51. Transrectal ultrasound (TRUS)
• It is done to visualize seminal vesicles, prostate and
ejaculatory ducts obstruction.
• Indications of TRUS
o Azoospermia or severe oligospermia with a normal testicular
volume,
o Abnormal digital rectal examination,
o Ejaculatory duct abnormality (cysts, dilatation or calcification),
o Genital abnormality (hypospadias).

52. Contd..
• DNA Fragmentation
– Increased levels of DNA damage are associated with
advanced paternal age and external factors such as cigarette
smoking, chemotherapy, radiation, environmental toxins,
varicocele, and genital tract infections.
• Vasogram
– Is a radiographic study done to evaluate ejaculatory duct
obstruction. It is mostly replaced by TRUS.

53. Hemizona Assays (HZA)
• This test analysis sperm’s ability to bind to zona pellucida.
• Human oocytes are bisected (to prevent fertilization) and
are mixed either with partner’s sperm or with fertile donor
sperm.
• Hemizona index is calculated as (bound sperm from
subfertile male) divided by (bound sperm from fertile male)
X 100.
• It may be a useful diagnostic tool in male infertility
evaluation

55. Sperm Penetration Assay
• Sperm penetration assay is done by mixing capacitated
human sperm with hamster oocytes.
• Zona pellucida typically prevents cross-species sperm
binding and must first be removed from these test oocytes
(zona-free hamster oocyte)
• No of oocytes that are penetrated by sperm is calculated.
• Conclusion: More oocytes will be penetrated by sperm from
fertile men than by sperm from infertile men.

57. Acrosomal Reaction
• Penetration of an oocyte requires that sperm undergo an
acrosomal reaction, during which enzymatic contents of
acrosome are released on interaction with oocyte
membrane.
• Various methods can be used to induce acrosomal
reaction in a patient’s sperm sample.
• Percentage of sperm that undergoes reaction is
compared with that of a fertile male’s control sample.

59. Management of Male Infertility

60. Contd…
 Health Education.
• Sexual counselling—coital frequency and timing,
• Coital position
• masturbation leading to sperm dilution.
 Substance abuse.
– Advice on avoidance of tobacco (smoking, chewing), moderation in
consumption of alcohol and avoidance of drug abuse.
– Antioxidants, vitamin E improve semen parameters. Pentoxifylline 400
mg t.i.d improves sperm motility.

61. Contd..
 Reduce heat around scrotum.
• Avoid hot baths, wear loose cotton underwear (cotton
clothing to encourage ventilation), avoid strenuous activities
and occupation in hot environment and control obesity.
 Retrograde Ejaculation
• Phenylephrie is used to improve tone of internal urethral
splincter.
• If this fails reconstruction of bladder neck is recommended.

62. Contd..
 Surgical.
• Surgical correction of varicocele helps to improve sperm
motility.
• Orchidopexy in undescended testes should be done
between 2-3 years of age to have adequate
spermatogenesis.
• Obstruction in vas by Vasovasostomy (VV) and
vasoepididymostomy (VE) anastomosis will restore
patency.

63. Contd..
 Leukocytospermia
o Genital tract infection needs prolonged course of antibiotics.
o Doxycycline or erythromycin is given for a period of 4–6 weeks
depending on the response.
 Antioxidants
o vitamin E 100 mg, vitamin C 500–1000 mg, N-acetylcysteine 200–500
mg t.i.d., carnitine 3 g daily, selenium 225 mg, pentoxyfilline 400 mg
t.i.d.
o Lycopene 2 mg daily for 6 months to improve quality of sperms and
prevent sperm DNA damage.

64. Contd..
 Premature ejaculation.
• Dapoxetine works within 1 h; 30–60 mg is taken 1 h
before intercourse.
Hormonal Therapy.
• Testosterone, pituitary hormones and GnRH have all been
tried to improve spermatogenesis with variable results.
• Bromocriptine is useful in hyperprolactinaemia.

65. Hormonal Therapy
 Human chorionic gonadotropin (HCG)
o Is recommended in hypogonadotropic-hypogonadism.
o hCG 5000 IU IM once or twice weekly given to stimulate endogenous
testosterone production.
o Human menopausal gonadotropin (hMG) or pure FSH (75–150 IU) is added
to hCG when there is no sperm in the ejaculate with hCG alone.
o Follow-up with testosterone level and semen analysis.
o It takes 6–9 months to produce normal semen counts.
o Stop FSH, but continue with HCG.

66. Contd..
 Clomiphene
o 25 mg daily for 25 days followed by rest for 5 days is given cyclically
for 3–6 cycles.
o Is recommended in hypogonadal infertility
o It increases serum level of FSH, LH and testosterone.
 Testosterone
o 25–50 mg daily orally improves testicular function.
o A larger dose of 100–150 mg daily suppresses spermatogenesis.
o After a 3 month course of treatment, rebound phenomena occur with
improved spermatogenesis.

67. Contd..
 GnRH
o Is indicated in hypothalamic failure.
o GnRH 5–20 mcg subcutaneously 2 hourly for 1–2 years.
Dexamethasone
o For spermal antibodies 0.5 mg daily or 50 mg prednisone daily
for 10 days in each cycle for 3–6 months is recommended.

68. Erectile dysfunction & Impotency
o Psychosexual treatment may be of help.
o Recommendation of Sildenafil (Viagra)—25–100 mg 1 h
before intercourse, effect lasts for 1–2 h for erectile
dysfunction.
o Is used only in erectile function, and does not improve
libido.

69. Contd..
o Penile vascular surgery and penile prosthesis
implantation rods are also available for erectile
dysfunction.
o Penile implant AMS 700 is 3-piece inflatable
penile prosthesis which is now available.

70. AMS 700 Penile Implant

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73. Contd..
Assisted reproductive technology
• Following ART are used for male infertility
o Intrauterine insemination (IUI)
o Testicular sperm extraction (TESE)
o Microsurgical epididymal sperm aspiration (MESA)
o Percutaneous Epididymal Sperm Aspiration (PESA)
o Intracytoplasmic sperm injection (ICSl)