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Year 3 Clinical > Male Infertility > Flashcards

Male Infertility Flashcards

1
Q

Determinants of gender?

A
  1. Chromosomes
  2. Genital sex
  3. Gonadal sex
  4. Perceived gender (psychological)

NOTE - even if a patient has only one X chromosome, they are female

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2
Q

Development of the internal reproductive tract in males?

A

Y chromosome has the sex-determining region, which causes the development of testis from the bi-potential gland

The foetal testes secrete testosterone and Mullerian inhibiting factors, which inhibit Mullerian (go on to degenerate) duct development and allow development of the Wolffian duct, for the male genital tract

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3
Q

Briefly, how does the female genital tract develop?

A

With stimulus of the male testicular hormones, the foetus will develop the female internal genital tract

In females, the Wolffian ducts degenerate and the Mullerian ducts develop, to form the female reproductive tract

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4
Q

Explain differentiation of the external genitalia

A

Dihydrotestonerone stimulates development of the penis

In the absence of dihydrotestosterone, female genitalia develop

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5
Q

At what gestation can the gender be determined?

A

On USS, ~16 weeks

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6
Q

Explain all the steps in development of a male foetus, from fertilisation to development of external genitalia and reproductive tract

A
  1. Ovum with an X chromosome is fertilised by a sperm with a Y chromosome (embryo has XY chromosomes)
  2. Sex-determining region of the Y chromosome stimulates differentiation of gonads into testes
  3. Testes secrete testosterone and Mullerian-inhibiting factor:
    • Testosterone itself transforms the Wolffian ducts into the male reproductive tract
    • Testosterone is converted into dihydrotestosterone and this causes the undifferentiated external genitalia to develop along male lines, e.g: penis, scrotum
    • Mullerian-inhibiting factor causes degeneration of Mullerian ducts
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7
Q

Explain all the steps in development of a female foetus, from fertilisation to development of external genitalia and reproductive tract

A
  1. Ovum with an X chromosome is fertilised by a sperm with an X chromosome (embryo has XX chromosomes)
  2. No Y chromosome, so no sex-determining region of Y; undifferentiated gonads develop into ovaries
  3. No testosterone or Mullerian-inhibiting factor is secreted:
    • Absence of testosterone leads to degeneration of the Wolffian ducts and the undifferentiated external genitalia develop along female lines, e.g: clitoris and labia
    • Lack of Mullerian-inhibiting factor causes Mullerian ducts to develop into female reproductive tracts, e.g: oviducts, uterus
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8
Q

What is Androgen Insensitivity Syndrome (AIS)?

A

X-linked recessive disorder characterised by congenital insensitivity to androgens; karyotype is 46XY

Androgen induction of Wolffian duct does not occur but Mullerian inhibition does occur

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9
Q

PC of AIS?

A

Commonly present at puberty with primary amenorrhoea and a lack of pubic hair

As Wolffian duct does not develop and because Mullerian inhibition does occur:
• External genitalia female, i.e: patients are born PHENOTYPICALLY FEMALE:
• Absence of uterus and ovaries
• Short vagina

Testis develop but they do not descend

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10
Q

Risks assoc. with AIS?

A

Undescended testes have a higher risk of cancer, due to higher temperature

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11
Q

Importance of testicular temperature?

A

Lower temperature outside the body facilitated spermatogenesis; nervous reflexes trigger dartos muscle contraction in the scrotal sac, so the testes are lowered/raised according to external temp

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12
Q

Define cryptorchidism?

A

Undescended testes; patient has reached adulthood and testes have not descended

It is becoming more common and it reduces sperm count; if it is unilateral, patient is usually fertile

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13
Q

Treatment of crytorchidism?

A

Orchidopexy should be performed <14 years, to reduce the risk of testicular germ cell cancer

If undescended in an adult patient, consider orchidectomy (6x increased risk of cancer)

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14
Q

Production and storage of sperm?

A

Produced in the testes and stored in the epididymis

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15
Q

Function of testes?

A

Spermatogenesis (in the seminiferous tubules)

  1. Production of testosterone (by the Leydig cells)
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16
Q

Functions of the Sertoli cells?

A
  1. Form a blood testis barrier:
    • Protects sperm from antibody attack
    • Provides a suitable fluid composition, allowing later stages of sperm development
  2. Provide nutrients for developing cells
  3. Phagocytosis - remove surplus cytoplasm from packaging process and destroy defective cells
  4. Secrete seminiferous tubule fluid - used to carry cells to the epididymis
  5. Secrete androgen-binding globulin:
    • Binds testosterone so conc. remains high in the lumen
    • Essential for sperm production
  6. Secrete inhibin and activin hormones - regulate FSH secretion and thus control spermatogenesis
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17
Q

Functions of dihydrotestosterone?

A
  1. Enlargement of male sex organs
  2. Secondary sexual characteristics
  3. Anabolism
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18
Q

What is Gonadotrophin Releasing Hormone (GnRH)?

A

A decapeptide that is released from the hypothalamus in pulsatile bursts, every 2-3 hours from the age of 8-12 years

It stimulates the anterior pituitary to produce LH and FSH

Testosterone feeds back to suppress release of GnRH and LH, i.e: GnRH is under -ve feedback control of testosterone

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19
Q

What are LH and FSH?

A

Glycoproteins secreted by the anterior pituitary; their release is stimulated by GnRH and under -ve feedback control from testosterone

Their production is non-cyclical in males, unlike in females

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20
Q

Function of LH?

A

Acts on Leydig cells to stimulate testosterone secretion

It is regulated by -ve feedback from testosterone

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21
Q

Function of FSH?

A

Acts on Sertoli cells to enhance spermatogenesis

It is regulated by -ve feedback from inhibin

22
Q

What is testosterone?

A

Steroid hormone derived from cholesterol; it is secreted into the blood and seminiferous tubules for sperm production

Exerts -ve feedback on hypothalamus and pituitary gland

23
Q

Effects of testosterone in males on different stages of development?

A

Before birth:
• Masculinises reproductive tract
• Promotes descent of testes

Puberty:
• Promotes puberty and development of male characteristics

Adult:
• Controls spermatogenesis
• Secondary sexual characteristics (male body shape, deep voice, thickened skin)
• Libido
• May influence penile erection and aggressive behaviour

24
Q

What are inhibin and activin?

A

Closely related peptides that are secreted by Sertoli cells

They feedback to affect FSH production:
• Inhibin inhibits FSH production
• Activin stimulates FSH production

25
Q

What happens to the spermatozoa after ejaculation?

A
  1. Liquefied by enzymes from the prostate gland; chemoattraction allows the sperm to find the oocyte and bind to the zona pellucida (likelihood of union is increased by hyperactivity of sperm, via biochemical and electrical events called capacitation)
  2. Docking of the sperm on to the ovum
  3. Acrosomal exocytosis
  4. Hyperactivated motility (increased likelihood of sperm entering the ovum)
  5. Penetration of egg coat and fusion with the oocyte membrane
  6. Zonal reaction (hardens zona pellucida to prevent sperm other than a single one from getting in)
26
Q

Where does fertilisation typically occur?

A

In the ampullary region of the Fallopian tube

27
Q

Accessory tissues of the male reproductive tract and their functions?

A

Epididymis and vas deferens:
• Exit route from testes to urethra
• Conc. and store sperm
• Site for sperm maturation

Seminal vesicles:
• Produce semen into ejaculatory duct 
• Supply fructose
• Secrete prostaglandins (stimulate motility)
• Secrete fibrinogen (clot precursor)

Prostate gland:
• Produces alkaline fluid (neutralises vaginal acidity)
• Produces clotting enzymes to clot semen within the female

Bulbourethral glands:
• Secrete mucous to act as a lubricant

28
Q

Route of sperm?

A

From testes to epididymis to vas deferences to ejaculatory duct to urethra

  1. Erection
  2. Emission
  3. Ejaculation
29
Q

Control and purpose of erection?

A

Under parasympathetic control (point and shoot)

30
Q

Purpose of emission?

A

Contraction of accessory sex glands and vas deferens, so semen is expelled to the urethra

31
Q

Control and purpose of ejaculation?

A

Contraction of smooth muscle of urethra and erectile muscles

Under sympathetic control (point and shoot)

32
Q

Issues that can cause premature OR retrograde ejaculation?

A

Premature ejaculation (before penetrative sexual intercourse)

Retorgrade ejaculation (backwards into bladder)

Causes inc. neuropathy, prostate surgery or anti-cholinergic drugs

33
Q

Define male infertility?

A

Infertility resulting from failure of the sperm to normally fertilise the egg; usually assoc. with abnormalities in semen analysis

34
Q

Occurrence of male infertility?

A

Common cause of infertility

Evidence that male infertility is increasing possibly related to environmental oestrogens

35
Q

Causes of male infertility?

A

Idiopathic - most common cause (fit, healthy male who has abnormal semen analysis but no reason can be found)

Obstructive, e.g: CF (absence of vas), vasectomy, infection

Non-obstructive:
• Congenital, e.g: cryoptorchadism
• Infection, e.g: mumps, orchitis
• Iatrogenic, e.g: chemo/radiotherapy
• Pathological, e.g: testicular tumour
• Genetic, e.g: chromosomal (Klinefelter's syndrome, microdeletions of Y chromosome, Robertsonian translocation)
• Specific semen abnormality, e.g: globozoospermia 
• Systemic disorder
• Endocrine
36
Q

Endocrine causes of male infertility?

A

Pituitary tumours, e.g: acromegaly, Cushing’s disease, hyperprolactinaemia

Hypothalamic causes - idiopathic, tumours, Kallman’s syndrome, anorexia (decreased LH, FSH and testosterone)

Thyroid disorders - hyper / hypothyroidism (decreased LH, FSH and testosterone)

Diabetes (decreases sexual function and decreased testosterone)

CAH (increased testosterone)

Androgen insensitivity (normal / raised LH and testosterone)

Steroid abuse (decreased LH, FSH and testosterone)

37
Q

Examination of male infertility?

A

General exam (secondary sexual characteristics, presence of gynaecomastia)

Genital exams (testicular volume with orchidometer, presence of vas deferens and epididymis, penis (urethral orifice), presence of any varicocoele / other scrotal swellings)

38
Q

Normal testicular volume?

A

Pre-pubertal 1-3 mls

Adults 12-25 mls

If below 5mls, patient is unlikely to be fertile

39
Q

Measurements from semen analysis?

A

Volume, density, motility (what proportion are moving), progression (how well they move) and morphology

40
Q

Extrinsic factors that may cause abnormalities in semen analysis, i.e: other than infertility?

A

Completeness of sample

Period of abstinence

Condition during transport

Time between production and assessment

Natural variations between samples

Health of man 3 months before production, e.g: general health, surgery

41
Q

Further assessment of male infertility?

A

Repeat semen analysis (6 weeks later)

Endocrine profile (LH, FSH, testosterone, PRL, TSH)

Chromosome analysis, inc. Y-chromosome microdeletions

CF screening

Depending on results:
• Testicular biopsy
• Scrotal scan

42
Q

Clinical features of obstructive male infertility?

A

Normal testicular volume

Normal secondary sexual characteristics

Vas deferens may be absent

43
Q

Endocrine features of obstructive male infertility?

A

Normal LH, FSH and testosterone

44
Q

Clinical features of non-obstructive male infertility?

A

Low testicular volume

Reduced secondary sexual characteristics

Vas deferens present

45
Q

Endocrine features of non-obstructive male infertility?

A

High LH, FSH and low testosterone

46
Q

Lifestyle changes that can be used to treat male infertility?

A

Frequency of sexual intercourse (2-3x per week) and avoid lubricants that are toxic to sperm

Alcohol <4 units / day

Smoking (assoc. decrease semen quality and decreased health)

Caffeine (no evidence)

BMI <30 likely to improve fertility and health

Avoid tight-fitting underwear and prolonged hot baths/sauna may improve

Certain occupations (overheating / exposure to chemicals)

Benefits of anti-oxidants (vitamin C or zinc)

47
Q

Treatment of male infertility with IUI?

A

Indication is mildly reduced sperm count

Procedure is semen sample prepared to produce conc. sperm sample; this is inseminated into uterine cavity around time ovulation

Pregnancy rate is 15% per treatment cycle

48
Q

Treatment of male infertility with ICSI?

A

Indication is very low sperm count

Sperm is injected into stripped oocyte obtained during IVF

Pregnancy rate is 30% per treatment cycle

49
Q

Treatment of male infertility with surgical sperm aspiration?

A

Indication is azoospermia

Sperm is aspirated surgically (as a diagnostic procedure or at the time of oocyte recovery); sperm is then injected into the oocyte

Success rate of obtaining sperm:
• 95% in obstructive azoospermia
• 50% in non-obstructive azoospermia

50
Q

Treatment of male infertility with donor sperm insemination?

A

Indications are:
• Azoospermia or very low sperm count
• Genetic conditions
• Infective conditions

Sperm donors are matched for recipient characteristics and screened for genetic conditions and STIs; sperm is quarantined by cryopreservation and rescreened
Prepared, thawed semen sample is inserted intrauterine at the time of ovulation

Pregnancy rate is 15% per treatment cycle

Year 3 Clinical (100 decks)

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