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reproduction > male infertility > Flashcards

male infertility Flashcards

1
Q

Infertility

A

inability of a couple to conceive after 12 months of continuous unprotected
sexual intercourse. Affects around 15% of couples worldwide.
=> Does not mean that a couple could not conceive naturally later on down
the line.

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2
Q

Male infertility diagnosed when …

A

Diagnosed when after testing both partners, and reproductive problems have been found in the male. Implicated in 50% of infertility cases.

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3
Q

What is the first test done in diagnostics of male infertility?

A

Semen analysis :
*Usually the first diagnostic step in male fertility investigations.
* Analysis of seminal fluid and sperm parameters as an indicator of male fertility potential.
* Remains the gold standard.
* WHO criteria for normal semen parameters.

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4
Q

What is the WHO reference values (2021)

A
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5
Q

The two methods of Semen analysis….

A
  • Manual semen analysis
    -CASA
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6
Q

What are different morphology of sperms in semen analysis?

A
  1. Normozoospermia - all sperm parameters within normal range
  2. Azoospermia - No spermatozoa found in semen sample.
  3. Cryptozoozpermia – Virtually no spermatozoa present – only found after extensive
    search (centrifugation).
  4. Oligozoospermia – Sperm count/conc. <15million/ml.
  5. Asthenozoospermia – Sperm motility <42% (or progressive <30%).
  6. Teratozoospermia – Normal morphology <4%.
  7. Leucospermia – Leucocytes >1million/ml.
  8. ecrozoospermia – Proportion of dead spermatozoa outside normal range.
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7
Q

What are causes of male infertility?

A
  1. Sperm production problems
    2.Sperm transport problems (obstruction)
    3.Erectile and ejaculatory problems
    4.Sperm antibodies
    5.Sperm DNA fragmentation
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8
Q

Sperm production problems:

A
  • Chromosomal/genetic
  • HH
  • Cyrptorchisdism and varicocoele
  • Torsion and orchitis
  • Chemo and radiotherapy
  • Medicined and anabolic steroids
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9
Q

Sperm transport problems (obstruction)

A
  1. congenital absence of Vas deferens (CABVD)
    -Mutations in the cystic fibrosis
    transmembrane regulator gene (CFTR).
    -Abnormalities in the differentiation of the mesonephric duct.
    Up to 5% of azoospermic men.
  2. other obstructions:
    Obstruction of the vas deferens,
    epididymis or ejaculatory duct.
    Caused by infections, hernias or
    scarring from corrective surgeries
    around the male reproductive tract
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10
Q

Erectile and ejaculatory problems

A
  1. Retrograde ejaculation
    Semen makes its way into the bladder.
    Prostate gland surgery most common cause.
    Other causes: diabetes, multiple sclerosis, alpha blockers.

2.Other conditions:
Erectile dysfunction
Premature ejaculation
Delayed ejaculation

Physical and psychological causes
Physical – diabetes, spinal cord injuries, multiple
sclerosis, prostate/bladder surgery, thyroid
(overactive or underactive), anti-depressants,
beta-blockers, antipsychotics, muscle relaxants,
recreational drugs.

Psychological – depression, stress

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11
Q

Sperm production problem - Chromosomal/genetic

A
  1. Kinefelter’s syndrome XXY or variants
    - hypergonadotrophic hypogonadism
    -Azoospermia/severe oligospermia
    -sexual dysfunction
  2. Jacob’s syndrome XXY or variants
    - 1 in 1000 males
    - most show normal sexual development
    -increased incidence of chromosomally abnormal spermatozoa
    - sperm ranging from normal to azoospermic
  3. XX male syndrome (SRY translocation)
    -1 in 20,000 – 30,000 males
    -Testosterone deficiency, impaired
    -spermatogenesis
    -Azoospermia
  4. Y chromosome deletions
    -Deletions of genetic material in regions
    of the Y chromosome called azoospermia
    factor (AZF) A, B, or C
    -5-10% of azoospermia or severe
    oligospermia cases.
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12
Q

Sperm production – Hypogonadotrophic Hypogonadism

A

congenital:
Kallmann syndrome HH – KAL1, KAL2,
PROK2/PROK2R, FGF8
Normosmic IHH – GnRH1/GnRHR,
KISS1/GPR54, TAC3/TAC3R
Prader-Willi syndrome – Chr 15
Isolated FSH or LH deficiency – FSH/LR
Laurence-Moon-Bardet-Biedl Syndrome –
multiple BBS genes

accquired:
Brain tumours – Pituitary adenomas,
hypothalamic gliomas, craniopharyngiomas

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13
Q

Sperm production – cryptorchidism

A

Unilateral or bilateral - one or both testicles absent from scrotum - descending of testicle error seen in 3% of normal birth as and 30% of premature births
Higher testicular temperatures
compromise sperm production/quality.
Azoospermia/severe oligospermia
(untreated)

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14
Q

Sperm production - varicocoele

A

Unilateral or bilateral
Enlarging of testicular vein within the scrotum, which affects temperatures of the scrotum and
Higher testicular temperatures
compromise sperm production/quality.
10-15% of general population; 30-40%
of male infertility cases.

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15
Q

Sperm production - torsion

A

Rare condition - Twisting of the testis
inside the scrotum. This cuts off blood
supply to the testis.
Most common in teenagers and young
men.
Torsion is a medical emergency and
intervention (orchidopexy) within 6hrs
gives best chance of avoiding
permanent damage.

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16
Q

Sperm production - orchitis

A

Inflammation of one or both testes
resulting from an infection (bacterial
or viral).
Risk of damage to seminiferous
tubules.
1 in 10 males experience drop in sperm
counts but rarely large enough to
cause infertility.
Mumps orchitis used to be the most
common cause of orchitis but now less
common due to vaccination.

17
Q

Sperm production - radiotherapy

A

Uses high energy X-rays to kill cancer
cells in a specific area while limiting
damage to normal cells.
Testicular cancers: Potential damage to
the testis, problems with
spermatogenesis.
Brain/rest of the body: Could affect
glands that produce reproductive
hormones e.g. anterior pituitary

18
Q

Sperm production - chemotherapy

A

Attacks cells in the seminiferous
epithelium, temporarily or permanently
damaging sperm/germ cells.
Return to normal fertility depends on
type and duration of chemo.

19
Q

Sperm production - medicines

A
  1. Salazopyrin®: used to treat inflammatory
    bowel disease & rheumatoid arthritis. Causes
    short-term infertility, but reversible after 2-
    3 months of stopping treatment.
  2. Testosterone (tablets/injections): used to
    treat androgen deficiency. Can result in a
    sustained decline in sperm production via –ve
    feedback on the hypothalamus and anterior
    pituitary
20
Q

Sperm production - anabolic steroids

A

Drug formulations that contain natural
androgens like testosterone or synthetic
androgens that are similar in chemical
structure.
Side effects: testicular shrinkage, sustained
decline in sperm production via –ve feedback
on the hypothalamus and anterior pituitary

21
Q

Sperm antibodies

A

-Breach in the blood-testis barrier and exposure of immunogenic sperm antigens to the immune system.
- Immune response, sees it as non self cell and fights it, resulting in an inflammatory reaction and anti sperm antibodies formation.
-Rare cases: ASA present in female reproductive tract resulting from an allergic reaction.
-Variable incidence data as testing is not performed routinely.

22
Q

Risk factors for anti - sperm antibodies

A

Genital trauma, torsion, biopsy, vasectomy, cryptorchidism.

23
Q

Anti-sperm antibody lead to …

A
  • Impaired motility/cervical mucus penetration (tail bound)
  • Impaired oocyte interaction (head bound)
  • Immunologic infertility
24
Q

Test for anti-sperm antibodies - immunobead test

A
  • Performed by mixing sample with latex particles that have been coated with human IgA/G.
  • To this mixture, a monospecific antihuman IgA/G antiserum is added.
  • The formation of agglutinates between particles and motile spermatozoa indicates the presence of
    IgA/G antibodies on the spermatozoa
24
Q

Sperm DNA fragmentation

A
  • Major cause = oxidative stress.
  • Free radicals (ROS) attack the DNA molecule causing breaks in the sperm DNA strands.
  • Can be present in men with both abnormal and normal semen parameters.
  • Variable incidence data as testing is not performed routinely.
    ↑sperm DNA fragmentation leads to higher miscarriage rates (ESHRE Recurrent
    Pregnancy Loss Guideline, 2017).
25
Q

Sperm DNA fragmentation – risk factors

A
  1. Varicocoele
    -Increased testicular temperature
    -Male reproductive tract infection
    -Infrequent ejaculation
    -Aging
  2. Toxins and radiation
    -Cancer
    -Increased BMI and poor diet
    -Recreational drugs & medications
    -Smoking
26
Q

Sperm DNA fragmentation – Diagnostic tests

A
  1. Sperm chromatin structure assay
    Cells stained with acridine orange
    Red = DNA fragmentation
    Green = Normal
    DFI % = red/(red + green)
    Normal → 0-15%
  2. TUNEL assay
    Cells treated with TDT and
    fluorescent–labelled dNTP
    Detection via flow cytometry or
    fluorescence microscopy
    dNTP=Deoxynucleotide triphosphate
    TDT = Terminal deoxynucleotidyl
    transferase
  3. Comet assay
    Cells embedded on agarose-coated slides
    and lysed
    ↓
    Electrophoresis and fluorescent labelling
    ↓
    Microscopy
27
Q

Summary

A

Male infertility is implicated in 50% of infertility cases and the first diagnostic step is a
semen analysis test using the WHO (2021) criteria.
Male infertility could result from conditions that impair sperm production, sperm
transport, as well as erectile and ejaculatory function.
Anti-sperm antibodies and sperm DNA fragmentation are known to impair sperm function
and are also implicated in infertility.

reproduction (29 decks)

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