Male infertility Flashcards
What is male infertility? (5)
Diagnosed when after testing both partners, reproductive problems have been found in the male. Implicated in 50% of infertility cases.
- 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.
Normozoospermia (Normal)
All sperm parameters within normal range.
Azoospermia
No spermatozoa found in semen sample.
Cryptozoozpermia
Virtually no spermatozoa present – only found after extensive search (centrifugation).
Oligozoospermia
Sperm count/conc. <15million/ml.
Asthenozoospermia
Sperm motility <42% (or progressive <30%).
Teratozoospermia
Normal morphology <4%.
Leucospermia
Leucocytes >1million/ml.
Necrozoospermia
Proportion of dead spermatozoa outside normal range.
Male infertility - Causes (5)
- Sperm production problems
2.Sperm transport problems (obstruction)
3.Erectile and ejaculatory problems
4.Sperm antibodies
5.Sperm DNA fragmentation
Sperm production - chromosomal/genetic (4)
Klinefelter’s syndrome XXY or variants:
-Hypergonadotrphic hypogonadism
-Azoospermia/severe oligospermia
-Sexual dysfunction
Jacob’s syndrome XYY or variants:
-1 in 1000 males.
-Most show normal sexual development.
-Increased incidence of chromosomally abnormal spermatozoa.
-Sperm ranging from normal to azoospermic.
XX male syndrome (SRY translocation):
-1 in 20,000 – 30,000 males
-Testosterone deficiency, impaired spermatogenesis
-Azoospermia
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.
Sperm production – Hypogonadotrophic Hypogonadism congenital vs acquired (2)
Hypogonadotrophic hypogonadism (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
Hypogonadotrophic hypogonadism (acquired):
- Brain tumours – Pituitary adenomas, hypothalamic gliomas, craniopharyngiomas
Sperm production – cryptorchidism | varicocoele (2)
Cryptorchidism (undescended testes):
- Unilateral or bilateral
- Higher testicular temperatures compromise sperm production/quality.
- Azoospermia/severe oligospermia (untreated)
Varicocele:
- Unilateral or bilateral
- Higher testicular temperatures compromise sperm production/quality.
_ 10-15% of general population; 30-40% of male infertility cases.
Sperm production – torsion | orchitis (2)
Testicular Torsion:
- 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.
Orchitis:
- 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.
Sperm production – radiation | chemical agents (2)
Radiotherapy:
- 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
Chemotherapy:
- Attacks cells in the seminiferous epithelium, temporarily or permanently
damaging sperm/germ cells.
- Return to normal fertility depends on type and duration of chemo
Sperm production – medicines | anabolic steroids (4)
Medicines
Salazopyrin®: used to treat IBS & rheumatoid arthritis. Causes ST infertility, but reversible after 2- 3 months of stopping treatment.
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
Anabolic steroids:
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
Sperm transport – CAVD | other obstructions (2)
Congenital absence of the Vas deferens:
- Mutations in the cystic fibrosis transmembrane regulator gene (CFTR).
or
- Abnormalities in the differentiation of the mesonephric duct.
- Up to 5% of azoospermic men.
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.
Erectile and ejaculatory – retrograde | premature | delayed (2)
Retrograde ejaculation:
- Semen makes its way into the bladder.
- Prostate gland surgery most common cause.
- Other causes: diabetes, multiple sclerosis, alpha blockers
Other conditions:
- Erectile dysfunction
- Premature ejaculation
- Delayed ejaculation
- 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
How do you get anti-sperm antibodies? (5)
- Breach in the blood-testis barrier and exposure of immunogenic sperm antigens to the immune system.
- Immune response, resulting in an inflammatory reaction and ASA formation.
- Rare cases: ASA present in female reproductive tract resulting from an allergic reaction.
- Variable incidence data as testing is not performed routinely.
Risk factors: Genital trauma, torsion, biopsy, vasectomy, cryptorchidism.
Explain the effects of anti-sperm antibodies (3)
- Impaired motility/cervical mucus penetration (tail bound)
- Impaired oocyte interaction (head bound)
- Immunologic infertility
How do you test for anti-sperm antibodies – Immunobead test? (3)
- 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
Sperm DNA fragmentation (4)
- 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
Sperm DNA fragmentation – risk factors (10)
Varicocoele
Increased testicular temperature
Male reproductive tract infection
Infrequent ejaculation
Aging
Toxins and radiation
Cancer
Increased BMI and poor diet
Recreational drugs & medications
Smoking
Sperm DNA fragmentation – Diagnostic tests (3)
Sperm chromatin structure assay: Cells stained with acridine orange
Red = DNA fragmentation
Green = Normal
DFI % = red/(red + green) Normal → 0-15%
TUNEL assay: Cells treated with TDT and fluorescent–labelled dNTP
normal vs fragmented
Detection via flow cytometry or fluorescence microscopy
dNTP=Deoxynucleotide triphosphate
TDT = Terminal deoxynucleotidyl transferase
Comet assay: Cells embedded on agarose-coated slides and lysed
↓
Electrophoresis and fluorescent labelling
↓
Microscopy
Summary (3)
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.
