Infertility Flashcards
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.
Defined by WHO
What is the difference between primary and secondary infertility?
Primary - when you have not had a live birth previously.
Secondary - when you have had a live birth >12 months previously
How many couples does infertility affect?
1 in 7 couples (=14% of couples)
But~ half of these will then conceive in the next 12 months (i.e. at 24 months ~7% of couples)
The following are causes of infertility: male factor female factor combined male and female factor unknown factor
List them in order from most to least common cause.
Male factor = female factor = combined male and female factor
Unknown only 10%
What impacts may infertility have on the couple?
Psychological distress to couple:
- No biological child
- Impact on couples wellbeing
- Impact on larger family
- Investigations
- Treatments (often fail)
How might infertility affect society?
Less births
Less tax income
Investigation costs
Treatment costs
Outline the causes of infertility in males. Split your answer up into 3 sections: pre-testicular, testicular and post-testicular.
Pre-testicular: Congenital and acquired endocrinopathies - Klinefelters 47XXY - Y chromosome deletion - HPG, T, PRL
Testicular: (Congenital) Cryptochordism Infection - STDs Immunological - antisperm Abs Vascular - Varicocoele Trauma/surgery Toxins - Chemo/DXT (deep X-ray therapy) /Drugs/Smoking
Post-testicular:
Congenital - absence of vas deferens in CF
Obstructive azoospermia
Erectile dysfunction - retrograde ejaculation, mechanical impairment, psychological
Iatrogenic - vasectomy
What is cryptorchidism?
A condition in which one or both of the testes fail to descend from the abdomen into the scrotum. Undescended testis (90% in inguinal canal) Normal path for testis descent through inguinal canal.
Outline the causes of fertility in females. Split the causes up into pelvic, tubal, ovarian, uterine and cervical causes.
Pelvic Causes (5%): Endometriosis and adhesions
Tubal Causes (30%): Tubopathy due to infection, endometriosis, trauma
Ovarian Causes (40%): Anovulation (Endo), corpus luteum insufficiency
Uterine Causes (10%): Unfavourable endometrium due to: Chronic endometriosis (TB), fibroid, adhesions (synechiae), congenital malformation
Cervical Causes (5%): ineffective sperm penetrations due to chronic cervicitis, immunological (antisperm Ab)
Unexplained (10%)
What is endometriosis?
A condition resulting from the appearance of endometrial tissue outside the uterus > Pelvic pain (associated with menstruation).
(Happens to 5% of women; functioning tissue responds to
oestrogen.)
What are the symptoms of endometriosis?
Increased menstrual pain
Menstrual irregularities
Deep dyspareunia (pain during sexual intercourse)
Infertility
What are the treatment options for endometriosis?
Hormonal (Continuous OCP, progesterone)
Laparoscopic ablation
Hysterectomy
Bilateral salpingo-oophorectomy - moves ovaries and tubes
What are fibroids?
Benign tumours of the myometrium (1- 20% of pre-menopausal women, the frequency of fibroids increases with age).
Responds to oestrogen (Functioning endometrium tissue)
What are the symptoms of fibroids?
Can be asymptomatic.
Increased menstrual pain
Deep dyspareunia
Infertility
What are the treatment options for fibroids?
Hormonal (e.g. continuous OCP, progesterone, continuous GnRH agonists)
Hysterectomy
Which neurones regulate the pulsatility of the hypothalamic-pituitary gonadal axis?
Kisspeptin neurones
• Inhibited by prolactin
Which hypothalamic regulatory hormone controls FSH & LH secretion?
Gonadotrophin releasing hormone (GnRH) released from parvocellular GnRH hypothalamic neurones secreted into the primary capillary plexus within the median eminence.
Which endocrine cells release FSH and LH?
Gonadotrophs located in the anterior pituitary gland secreted into the secondary capillary plexus.
What cells do LH bind on to initiate testosterone release?
Leydig Cells
What type of cell does FSH bind to support spermatogenesis?
Sertoli cells
Explain what happens in a patient with hyperprolactinaemia and what happens to the their testosterone, oestrogen, FSH and LH levels.
Prolactin released from lactotrophs exerts an inhibitory effect on kisspeptin neurones and thus downregulating the pulsatile action of GnRH secretion from hypothalamic neurones.
- Low testosterone/oestrogen
- Low FSH
- Low LH
What are the symptoms of hyperprolactinaemia?
Oligomenorrhoea (>35d menses) or amenorrhoea (3-6 months with no menses)/low libido (and other hypogonadal symptoms)/ infertility/osteoporosis.
List the causes of hyperprolactinaemia.
Prolactinoma is a common cause (Secondary hypogonadism)
Pituitary stalk compression
Pregnancy & breastfeeding (Increased physiological release of prolactin)
Medications (Dopamine antagonists (anti-emetics and antipsychotics, oestrogens e.g. OCP).
Rare causes: PCOS and hypothyroiditis
What is the treatment for a hyperprolactinaemia?
Dopamine (D2) agonists – cabergoline > Dopamine inhibits prolactin secretion from lactotrophs within the anterior pituitary gland.
If D2 agonist ineffective > Surgery (Transsphenoidal)/DXT
What is Klinefelter’s syndrome?
A pre-testicular congenital defect concerned with a chromosomal disorder of 47XXY, interfering with the development of the testes.
The pituitary gland retains normal gonadotropic function, however the deficiency in testosterone leads to hypergonadotropic hypogonadism.
What happens to a patients FSH, LH and testosterone levels in Klinefelter’s syndrome?
High FSH
High LH
Low testosterone.
List the symptoms of a male patient with Klinefelter’s syndrome.
Micropenis and small testes Female-type pubic hair pattern Infertility (accounts for up to 3% of cases) Gynecomastia Decreased facial hair Tall stature Mildly impaired IQ Wide hips, narrow shoulders, reduced chest hair and low bone density.
What is Kallman Syndrome?
Refers to the failure of GnRH hypothalamic neurone migration with olfactory bundles, therefore a typical clinical feature also includes anosmia.
Reduced GnRH releases causes a downstream reduction in gonadotropin secretion. Hypogonadotropic hypogonadism (Low FSH, LH & Testosterone).
List the reproductive symptoms a patient with Kallmans syndrome would present with.
Lack of testicle development
Micropenis
Primary amenorrhoea
Infertility
List the causes of congenital hypogonadotrophic hypogonadism (secondary hypogonadism).
Kallmans Syndrome (Anosmia) or normosmic
List the acquired causes of hypogonadotrophic hypogonadism.
Low BMI, excess exercise, stress
List the causes of hypopituitarism (potentially lead to hypogonadism).
Pituitary tumour Infiltration Pituitary apoplexy Pituitary surgery Radiation
What is the name of the condition that gives rise to congenital primary hypogonadism?
Klinefelters (47XXY)
List the causes of acquired primary hypogonadism.
Cryptochirdism, trauma, chemo, radiation
Does hyperprolactinaemia cause hypogonadotrophic hypogonadism or hypergonadotrophic hypogonadism?
Hypogonadotrophic hypogonadism
What would the initial history for a male being considered for infertility involve?
Duration, previous children, pubertal milestones, associated symptoms (Testosterone deficiency, PRL symptoms, CHH symptoms), medical & surgical history, family and social history, medications/drugs.
What should an examination of a patient being considered for infertility include?
BMI Epididymal hardness Sexual characteristics Testicular volume Presence of vas deferens Other endocrine signs, Syndromic features Anosmia
List the investigations involved in determining whether or not a male patient is infertile.
Semen analysis
Blood tests: LH, FSH, PRL; morning fasting testosterone; sex-hormone binging globulin (SHBG); albumin, iron studies; also pituitary/thyroid profile; karyotyping > for sex chromosome abnormalities
Microbiology: Urine test, chlamydia swab
Imaging: Scrotal US/doppler (for varicocele/ obstruction, testicular volume), MRI pituitary (If low LH/FSH or high PRL)
What general lifestyle changes would you suggest to a infertile male?
Optimise BMI
Smoking cessation
Alcohol reduction/ cessation
What specific treatment would there be for male infertility?
Dopamine agonist (Cabergoline) for hyperprolactinaemia
Gonadotrophin treatment for fertility (Will also increase testosterone)
Testosterone (If no fertility is required)
Surgery (Micro testicular sperm extraction)
How long does the menstrual cycle last?
28 day cycle (24-35 days)
± 2 days each month
What is primary amenorrhoea?
Later than 16 years is regarded as abnormal.
What is secondary amenorrhoea?
Common for periods to be irregular/ anovulatory for first 18 months.
Periods start but then stop for at least 3-6 months.
Define amenorrhoea.
No periods for at least 3-6 months OR up to 3 periods per year.
Define oligo-menorrhoea (few periods).
Irregular or infrequent periods >35 day cycles
OR
4-9 cycles per year
Does the Premature Ovarian Insufficiency have the same symptoms as menopause?
Yes
What is POI?
Premature ovarian failure is the cessation of menses for more than a year in an individual less than the age of 40 secondary to loss of ovarian function.
In how many cases of POI can conception still occur?
20%
How can you diagnose if a patient has POI?
Diagnosis High FSH >25iU/L (x2 at least 4 weeks apart). Serum oestradiol is
low, thus there is a loss of negative feedback.
List the causes of POI
Autoimmune
Genetic (Fragile X syndrome/ Turner’s Syndrome (Monosomy X)
Cancer therapy (Radio-/chemotherapy)
What is PCOS?
In PCOS, there are polycystic ovaries where the follicles are undeveloped sacs, in which the eggs develop. These eggs cannot release the egg hence no ovulation or maturation – leading to infertility if untreated.
What % of women of reproductive age does PCOS affect?
5-15%
Outline the diagnosis of PCOS using the Rotterdam PCOS Diagnostic Criteria (2 out of 3)
Oligomenorrhoea or anovulation (amenorrhoea):
- Normally assessed by menstrual frequency.
- <21 days or >35 days
- <8-9 cycles/year
- >90 days for any cycle
If necessary anovulation can be proven by: lack of progesterone rise OR US (ultrasonogram)
Clinical +/- Biochemical hyperandrogenism:
Clinical - Acne, hirsutism (Ferriman-Gallwey score), alopecia (Ludwig score)
Biochemical - Raised androgens (e.g. testosterone)
Polycystic ovaries (US): greater than or equal to 20 follicles OR greater than or equal to 10ml either ovary on TVUS (8MHz) Don't use US until 8 year post-menarche due to high incidence of multi-follicular ovaries at this stage.
List and explain the treatments for PCOS.
Taking metformin and the OCP will lead to irregular menses/amenorrhoea >infertility. Can treat using clomiphene, letrozole and/or IVF.
For hirsutism > creams, waxing, laser and/or anti-androgens e.g. spironolactone.
(Progesterone can be taken to decrease the risk of endometrial cancer.
How does letrozole?
Works via inhibiting the aromatase-mediated conversion of testosterone to oestradiol. This means levels of oestradiol drop, hence there is less negative feedback exerted on GnRH secretion.
Greater GnRH pulsatile release > Increases FSH and LH levels. FSH is required to stimulate ovaries to grow a follicle.
Outline the mechanism of clomiphene.
An oestradiol receptor antagonist prevents negative feedback being exerted on hypothalamic-pituitary axis leading to a marked response with increased GnRH and FSH/LH.
What is Turner’s syndrome?
Turner’s syndrome is a chromosomal abnormality with the karyotype 45X0.
What are the symptoms/characteristic features of Turner’s syndrome?
Short stature Shield crest with widely spaced nipples High arched palate Webbed feet Gonadal dysgenesis Aortic coarctation Short fourth metacarpal and elbow deformity. There is primary amenorrhoea and delayed puberty due to hypergonadotropic hypogonadism
Describe the LH, FSH and androgen levels in a patient with Turner’s syndrome.
LH and FSH are elevated
Androgens reduced
What aspects may the history of a patient with female infertility include?
Duration, previous children, pubertal milestones, breastfeeding
Menstrual history: oligomenorrhoea or 1/20 amenorrhoea, associated symptoms (e.g. Oestrogen deficiency, PRL symptoms, CHH features), medical & surgical history, family history, social history, medications/drugs
What may the examination of a female patient who could potentially have infertility involve?
Including BMI, sexual characteristics, hyperandrogenism signs, pelvic examination, other endocrine signs, syndromic features, anosmia.
List the investigations that would be involved to determine whether or not a patient has infertility.
Blood tests: LH, FSH, PRL Oestradiol, androgens Follicular phase 17-OHP, Mid-Luteal Prog Sex hormone binding globulin (SHBG) Albumin, Iron studies Pituitary/thyroid profile Karyotyping
Always conduct pregnancy test (urine or serum beta-HCG)
Microbiology:
Urine test
Chlamydia swab
Imaging:
US (Transvaginal)
Hysterosalpingogram
MRI pituitary (If low FSH/LH or high PRL)
