3.12 Infertility Flashcards
What are 2 other endocrine causes (rare) that aren’t related to the hypothalamic-pituitary gonadotrophic axis?
androgen receptor deficiency (rare)
hyper/hypothyroidism (reduced bioavailable testosterone)
What is infertility?
A disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months of regular unprotected sexual intercourse.
(every 2-3 days)
What is primary infertility?
Couple have not had a live birth previously (doesn’t count miscarriages)
What is secondary infertility?
when have had a liver birth more than >12 moths previously
How common is infertility?
~14% of couples (1 in7)
BUT half of these will conceive in next 12 months (at 24 months, 7%)
What is the most common cause of infertility in a couple?
combined male and female factor (30%) female factor (30%) male factor (30%)
How can we divide male factor infertility into 3 categories?
pre-testicular
testicular
post-testicular
What are some pre-testicular causes of infertility?
congenital and acquired endocrinopathies: Klinefelters Syndrome 47XXY Y chromosome deletion Hypothalamic-pituitary-gonadal axis Testosterone Prolactin
What are some testicular causes of infertility?
congenital - cryptorchidism infection (STDs) immunological (anti-sperm) vascular trauma/surgery toxins (chemo, drugs, smoking)
What are some post-testicular causes of infertility?
congenital (absence of vas deference is CF) obstructive azoospermia iatrogenic (vasectomy) ED caused by: - retrograde ejaculations - mechanical impairment - psychological
What is cryptorchidism?
undescended tested
90% in inguinal canal
How can we categorise infertility in females? (5)
Ovarian causes (40%) Tubal causes (30%) Uterine causes (10%) Cervical causes (5%) Pelvic causes (5%)
What are some ovarian causes of female infertility? (2)
anovulation
corpus luteum insufficiency
What are some tubual causes of female infertility? (3)
tubopathy due to :
- infection
- endometriosis
- trauma
What are some uterine causes of female infertility? (4)
Unfavourable endometrium due to:
- chronic endometritis (TB)
- fibroid
- adhesions
- congenital malformation
What are some cervical causes of female infertility? (2)
ineffective sperm penetration due to:
- chronic cervicitis
- immunological (antisperm Ab)
What are some pelvic causes of female infertility? (2)
endometriosis
adhesions
What is endometriosis?
presence of functioning endometrial tissue outside of the uterus 5% of women
Why does endometriosis cause problems?
endometrial tissue continues to respond to oestrogen as normal
What are some symptoms of endometriosis? (4)
inc. menstrual pain
menstrual irregularities
deep dyspareunia (pain during sexual intercourse)
infertility
What are some treatments for endometriosis? (4)
hormonal
laparoscopic ablation (destroy endometrial tissue outside of uterus)
hysterectomy
bilateral salpingo-oopherectomy (remove both ovaries and fallopian tubes)
What are fibroids?
benign tumours of myometrium (also causes problems as respond to oestrogen)
What is the incidence of fibroids in pre-menopausal women?
1-20%, incidence increases with age
What are some symptoms of fibroids? (5)
usually asymptomatic inc. menstrual pain menstrual irregularities deep dyspareunia infertility
What is the treatment for fibroids? (2)
hormonal (to reduce proliferation)
hysterectomy
What are two main non-endocrine causes of female infertility?
endometriosis
fibroids
Explain the hypothalamuic-pituitary-gonadal axis
In hypothalamus, kisspeptin neurones activate kisspeptin receptors on GnRH neurones.
GnRH neurones then secrete GnRH into hypophyseal-portal circulation.
GnRH acts on gonadotrophs in anterior pituitary causing them to secrete LH & FSH into the blood.
LH & FSH act on gonads to produce (testosterone and oestrogen)
Oestrogen (aromatised in men) and progesterone provide negative feedback to hypothalamus and anterior pituitary
What is the release pattern of GnRH?
Pulsatile
What is the release pattern of LH & FSH?
pulsatile (cyclical in women)
What is the release pattern of testosterone?
diurnal
What would LH, FSH, and testosterone be in hyperprolactinemia?
LH = low FSH = low Testosterone = low
What would LH, FSH, and testosterone be in primary testicular failure (e.g. Klinefelters syndrome)?
LH = high FSH = high Testosterone = low
What is Klinefelters syndrome an example of?
primary hypogonadism
What are causes of male infertility that affect the hypothalamus?
Congenital hypogonadotrophic hypogonadism (asnomic (Kallmann Syndrome), or normosmic)
Acquired hypogonadotrophic hypogonadism (low BMI, excess exercise, stress, anorexia)
Hyperprolactinaemia
What are causes of male infertility that affect the anterior pituitary?
hypopituitarism
- remember causes of hypopituitarism
What does male infertility affecting the hypothalamus and pituitary have in common?
Both known as hypogonadotrophic hypogonadism,
Male fertility problems in pituitary just hypogonadism
What are causes of male infertility that affect the gonads?
congenital primary hypogonadism (Klinefelters 47 XXY)
acquired primary hypogonadism (cryptorchidism, trauma, chemo, radiation)
What is Kalmann’s syndrome caused by?
failure of embryological migration of GnRh neurones with olfactory fibers
What are the symptoms of Kalmann’s syndrome?
anosmia
cryptorchidism
failure of puberty (lack of testicle development, micropenis, primary amenorrhea)
infertility
What would tests for Kalmann’s syndrome look like?
low GnRH (not measureable)
low FSH and LH
low T
How does hyperprolactinaemia cause infertility?
prolactin binds to prolactin receptors on kisspeptin neurones in hypothalamus
inhibits kisspeptin release
decreases downstream FSH LH , then T/O
=oligomenorrhorea, amenorrhea, low libido, infertility, osteoporosis
What is the treatment for hyperprolacinaemia
dopamine agonist (cabergoline)
What is Klinefelter’s?
XXY
What would test results of Klinefelter’s be?
high LSH, FH low T (as problem in the testicles)
What are the symptoms of Klinefelter’s?
tall stature decreased facial hair breast developemnt mildly impaired IQ narrow shoulders reduced chest hair female type pubic hair pattern wide hips low bone density small penis and testes infertility
What are the main investigations for male infertlity?
semen analysis blood test: morning fasting T, LH, FSH, PRL, Karyotyping scrotal US/doppler MRI pituitary Chlamydia swab
What to look for in semen analysis?
sperm conc: 15 million/ml
total motility: 40%
What are the general lifestyle treatments for male infertility?
optimise BMI
smoking cessation
alcohol reduction/cessation
What would we see in premature ovarian insufficiency?
LH& FSH: high
Oestrogen: low
What would we see anorexia induced amenorrhoea?
all down (LH FSH Oestodiol)
What is premature ovarian insufficiency?
same symptoms as menopause
conception still in 20%
high FSH
What are some causes of premature ovarian insufficency?
autoimmune
genetic - fragile X/Turners syndrome
cancer therapy in past
What are some causes of hypergonadotropic hypogonadism in women?
premature ovarian insufficiency (aquired and congenital)
Turners (45X0) (congenital)
What is the most common endocrine disorder in women?
PCOS
What is the most common cause of infertility in women?
PCOS
How do we diagnose PCOS?
Rotterdam PCOS criteria (2 out of 3
Oligo or anovulation
Clinical +/- biochemical hyperandrogenism
polycystic ovaries (on ultrasound)
How is oligo or anovulation measured?
<21 or >35 day cycles
<8 or 9 cycles a year
>90 days for any cycle
How is clinical hyperandrogenism measured?
acne
hirsutism
alopecia
How is biochemical hyperandrogenism measured?
raised androgens (testosterone)
How is polycystic ovaries measured?
> 20 follicles or >10 per ovary
do not use US until 8 years post-menarche due to high incidence of multi-follicular ovaries at this stage
Which 2 factors of the Rotterdam PCOS gives the highest risk for impaired metabolism?
oligo or anovulation
and
clinical/biochemical hyperandrogenism
What are the treatments for PCOS?
what is being treated?
irregular menses - oral contraceptive pill
increased endometrial cancer risk - progesterone courses
amenorrhoea and T2D - metformin
infertility - clomiphene, letrozole
What is Turners syndrome?
45X0
What are the symptoms of Turners syndrome?
short stature low hairlines shield chest wide spaced nipples short 4th metacarpal small fingernails characteristic faces webbed neck coarctation of aorta poor breast development elbow deformity underdeveloped reproductive tract amenorrhoea
What are some tests for female fertility?
follicular phase 17-OHP
mid-luteal progesterone = successful ovulation
