Male Infertility Flashcards
Define infertility
It is the inability of a couple to conceive after 12 months of continuous unprotected sexual intercourse. Affects around 15% of couples worldwide.
Why is 12 months only a clinical reference?
Does not mean that a couple could not conceive naturally later on down the line.
Half of the couples which do not conceive during the first year will do so during the second year.
Male Infertility
Diagnosed when after testing both partners, reproductive problems have been found in the male. Implicated in 50% of infertility cases.
What is the first step in male infertility diganosis
Semen Analysis
Semen Analysis
Analysis of seminal fluid and sperm parameters as an indicator of male fertility potential.
Remains the gold standard.
WHO criteria for normal semen parameters.
There are two ways for conducting semen analysis:
Manual semen analysis
Computer-assisted semen analysis (CASA)
Why are there marginal changes between the WHO 2021 and WHO 2011 references?
The differences are due to the use of a much larger data set. Men in 2011 were mainly from europe and asia, 2021 men were from africa and south america too.
Define Normozoospermia (normal)
All sperm parameters within normal range
Define Azoospermia
No spermatozoa found in semen sample
Crytozoospermia
Virtually no spermatozoa present under microscope examination – only found after extensive search (centrifugation) and examination of pellet.
Oligozoospermia
Sperm count/conc. <15million/ml. (LESS)
Asthenozoospermia
(reduced) Sperm motility <42% (or progressive <30%).
Teratozoospermia
Normal morphology <4%. Reduced sperm morphology below 4%
Leucospermia
Leucocytes >1million/ml. Elevated presence of WBCs
Necrozoospermia
Proportion of dead spermatozoa outside normal range.
Oligoasthenoteratozoospermia
count, motility and morphology all below normal range.
Oligoasthenoteratozoospermia
count, motility and morphology all below normal range.
Oligoasthenoteratozoospermia
count, motility and morphology all below normal range.
Provide some causes of male infertility
Sperm production problems:
Chromosomal/genetic
HH
Cyrptorchisdism and varicocoele
Torsion and orchitis
Chemo and radiotherapy
Medicined and anabolic steroids
Sperm transport problems (obstruction):
CABVD and other obstructions.
Erectile and ejaculatory problems:
Retrograde ejaculation and other conditions.
Sperm antibodies
Sperm DNA fragmentation
Give examples of some sperm production problems- chromosomal/genetic
KLINEFELTER’S SYNDROME
JACOB’S SYNDROME
XX MALE SYNDROME
Y CHROMOSOME DELETIONS
KLINEFELTER’S SYNDROME (XXY) or variants
The presence of an additional X chromosome
Present with
Hypergonadotropic hypogonadism
FSH and LH levels are normal but due to the chromosomal abnormalities they have very small testes and reduced ability to synthesize testosterone when they receive the FSH and LH signal.
Azoospermia/severe oligospermia
Sexual dysfunction
Reduced presence of testosterone results in less pronounced male features: reduced chest hair, breast development, female pubic hair pattern, small testicular size, wider hips, poor beard growth.
JACOB’S SYNDROME (XXY or variants)
Presence of additional Y chromosome (more rare)
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)
Genetically XX but phenotypically male
In meiosis the 44 autosomes undergo crossover, however if there is a complete cross over in the sex chromosomes it is problematic as each gamete will have a mixture of X and Y in each sex chromosome. Each sex chromosome contains pseudo autosomal regions at the edges (PAR). The PAR regions are what undergo crossing over on the sex chromosomes.
So in the autosomes you have full crossing over but in the sex chromosomes its just the PAR regions.
In the Y chromosome the SRY region (male determining factor) is located just outside the PAR region.
Sometimes there is a fault in crossing over and the SRY region is captured in the crossing over. This results in an X chromosome that now contains the SRY region.
If a sperm cell with an X chromosome bearing the SRY fertilises an egg, it will result in an XX male.
1 in 20,000 – 30,000 males (rare)
Testosterone deficiency, impaired spermatogenesis
Azoospermia
Variation in phenotype:
Some have normal male secondary sexual characteristics, have intact SRY
Some have ambiguous secondary sexual characteristics, have fragment of SRY
Y CHROMOSOME DELETIONS
Deletions of genetic material in regions of the Y chromosome called azoospermia factor (AZF) A, B, or C
Responsible 5-10% of azoospermia or severe oligospermia cases.
How does Congential Hypogonadotrophic Hypogonadism effect sperm production?
Kallmann syndrome HH:
Mutation in the genes that coordinates the migration of GnRH neurons from the olfactory region, are anosmic:
KAL1, KAL2, PROK2/PROK2R, FGF8
Normosmic IHH
Spontaneous mutations occurring in the genes that are not associated with the migration:
GnRH1/GnRHR, KISS1/GPR54, TAC3/TAC3R
Prader-Willi syndrome:
Mutation in Chr 15
Isolated FSH or LH deficiency:
FSH/LH
Laurence-Moon-Bardet-Biedl Syndrome:
multiple BBS genes
