Reproductive Flashcards
What are the conception rates at: - 6 months - 12 months - 2 years What is the shape of a graph with conception rate against time?
Cumulative conception rates: 6 months - 75%; 12 months - 90%; and 2 years 95%. Each month of trying, the number of people who can conceive goes up.
Initially, very steep cure, then at around two months tails off
What is the definition of infertility?
What is primary and secondary infertility?
Infertility = failure to achieve a clinical pregnancy after 12 months of more of regular unprotected sexual intercourse (in absence of known reason) in a couple who have never had a child (WHO definition). Either primary (couple never conceived) or secondary (couple previously conceived, although pregnancy may not have been successful e.g. miscarriage or ectopic pregnancy).
Give 7 factors which increase your chance of conception, related to:
- Age
- PMHx
- Duration of trying to conceive
- Timing of intercourse
- BMI
- Smoking
- Caffeine
- Woman aged under 30 years
- Previous pregnancy - if you’ve previously been pregnant, your changes of achieving pregnancy again goes up
- Less than three years trying to conceive
- Intercourse occurring during the six days before ovulation, particularly two days before ovulation
- Woman’s body mass index (BMI) 20-30
- Both partners non-smokers
- Caffeine intake less than two cups of coffee daily
At what age does fertility start to decline?
20
What are the four groups of causes of infertility?
Unexplained
Tubal
Ovulation
Male
Give some causes of anovulatory infertility
- Physiological
- Hypothalamic
- Pituitary
- Ovarian
- Others
Physiological - puberty, pregnancy, lactation, menopause
Hypothalamic - anorexia nervosa, bulimia, excessive exercise
Pituitary - hyperprolactinaemia, tumours
Ovarian - PCOS, premature oviarian failure
Others - chronic renal failure, drugs, endocrine disorders
In anorexia nervosa, what will be the values of:
- FSH
- LH
- Oestradiol
All three will be low
In PCOS, what will the following be like?
Free androgens
LH
Glucose tolerance test
High free androgens
High LH
Impaired glucose tolerance
Premature ovarian failure - Give some possible causes - Clinical features? - FSH, LH, oestradiol? When should you measure LH and FSH?
Causes - idiopathic, genetic (Turner’s syndrome, fragile X), chemotherapy, radiotherapy, oophorectomy.
Clinical Features: hot flushes, night sweats, atrophic vaginitis.
High FSH
High LH
Low oestradiol
Give some infective and non-infective causes of tubal disease in infertility
Infective
- Pelvic inflammatory disease* (chlamydia, gonorrhoea, other: anaerobes, syphilis, TB)
- Transperitoneal spread: appendicitis, intra-abdominal abscess
- Following procedure: IUCD insertion, hysteroscopy, HSG
Non-infective
- Endometriosis
- Surgical (sterilisation, ectopic pregnancies)
- Fibroids
- Polyps
- Congenital
What is hydrosalpinx?
What might cause it?
Clinical features?
A hydrosalpinx is a distally blocked fallopian tube filled with serous or clear fluid. The blocked tube may become substantially distended giving the tube a characteristic sausage-like or retort-like shape. It can be caused by PID Clinical features - Abdominal/pelvic pain febrile - Vaginal discharge dyspareunia - Cervical excitation menorrhagia - Dysmenorrhoea - Infertility - Ectopic pregnancy
What is the ultrasound appearance of endometriosis?
“chocolate” cyst
Name five groups of causes of male infertility and their incidence?
Hypothalamic/pituitary - 1-2% Testicular disease - 30-40% Obstruction/transport - 10-20% Unexplained - 40-50% Others - 5-10%
Give six endocrine causes of male infertility
- Hypogonadotropic hypogonadism (e.g. Kallmann syndrome, anorexia)
- Testicular failure (Klinefelter’s syndrome: 47 XXY, chemotherapy, radiotherapy, undescended testes, idiopathic)
- Hyperprolactinaemia (macro or microadenoma) – treated very easily with dopamine agonists
- Acromegaly
- Cushing’s disease
- Hyper or hypothyroidism
Obstructive male infertility
- Examples?
- Clinical features?
- LH, FSH, testosterone?
E.g. congenital absence (cystic fibrosis), infection, vasectomy.
Clinical features
- Normal testicular volume
- Normal secondary sexual characteristics
- Vas deferens may be absent
Normal LH, FSH and testosterone
Non-obstructive causes of male infertility
- Examples?
- Clinical features?
- LH, FSH, testosterone?
E.g. 47 XXY, chemotherapy, radiotherapy, undescended testes, idiopathic.
Clinical features
- Low testicular volume
- Reduced secondary sexual characteristics
- Vas deferens present
Endocrine features
High LH, FSH and low testosterone
When investigating a woman with infertility, when in the menstrual cycle do you measure progesterone, and why do you measure this?
Midluteal progesterone level (day 21 of 28 day cycle or 7 days prior to expected period in prolonged cycles), progesterone > 30nmol/l suggestive ovulation.
What two investigations can you do to check tubal patency in a woman?
Hysterosalpingiogram or laparoscopy
When should you do a hysterosalpingiogram?
If positive, what should you follow it up with?
What is one disadvantage?
Do it if nil known risk factors tubal/ pelvic pathology
Do it if laparoscopy contraindicated
If this is abnormal then follow up with laparoscopy.
When should you perform hysteroscopy?
Hysteroscopy - only performed in cases where suspected or known endometrial pathology: i.e. uterine septum, adhesions, polyp.
Which endocrine tests should you do in an infertile female?
If anovulatory cycle or infrequent periods: - Urine HCG - Prolactin - TSH - Testosterone and SHBG - LH, FSH and oestradiol If hirsute - testosterone and SHBG. If amenorrhoea: - Endocrine profile (as in anovulatory cycle) - Chromosome analysis
Gonadotrophin releasing hormone
- Where is it synthesized?
- Pattern of release?
- Function?
Synthesised by neurons in hypothalamus
Pulsatile release
Stimulates FSH (low frequency pulses) and LH (high frequency pulses) synthesis / release
Follicular stimulating hormone
- Where is it secreted?
- Two functions?
Secreted by anterior pituitary
Stimulates follicular development
Thickens endometrium
Luteinising hormone
- Secreted where?
- What does the peak do?
- Two functions?
Secreted by anterior pituitary
Peak stimulates ovulation
Stimulates corpus luteum development
Thickens endometrium
What triggers ovulation?
The LH surge triggers ovulation.
What do ovulation prediction kits test?
Ovulation predictor kits work by detecting the LH surge (36h before ovulation).
When in the menstrual cycle does oestradiol peak
Just before ovulation
When in the menstrual cycle does progesterone peak?
What produces progesterone here?
Following ovulation
The corpus luteum
Estrogen
- Secreted in which two places?
- What does it stimulate?
- What else is it responsible for?
- What happens if it is high in concentration?
Secreted primarily by the ovaries (follicles) and adrenal cortex (and placenta in pregnancy)
Stimulates thickening of the endometrium
Responsible for the fertile cervical mucus
High estrogen concentration inhibits secretion of FSH and prolactin (-ve feedback) / stimulates secretion of LH (+ve feedback)
Progesterone
- What secretes it?
- What does it inhibit?
- What else is it responsible for?
- Function?
- What does it do to body temperature and smooth muscle?
Secreted by corpus luteum to maintain early pregnancy (placenta during pregnancy)
Inhibits secretion of LH
Responsible for infertile (thick) cervical mucus
Maintain thickness of endometrium
Has thermogenic effect (increases basal body temperature)
Relaxes smooth muscles
Which hormone is responsible for fertile cervical mucus and which for thick (infertile) mucus?
Fertile = estrogen
Infertile (thick) = progesterone
What test can you do to confirm ovulation?
Confirm by midluteal (D21) serum progesterone (>30 nmol/L) X 2 samples
What three groups does the WHO classify ovulation disorders into?
Group I - hypothalamic pituitary failure
Group II - hypothalamic pituitary dysfunction
Group III - ovarian failure
What is the main cause of hypothalamic pituitary failure in ovulatory disorders?
What are the levels of FSH and LH?
What will progesterone challenge test show?
What are some possible causes of this?
Treatment?
Hypogonadotrophic hypogonadism FSH and LH are low Oestrogen deficiency - negative progesterone challenge test - Stress - Anorexia / low BMI - Brain / pituitary tumours - Head trauma - Kallman’s syndrome - Drugs (steroids, opiates) Treatment - pulsatile GnRH either SC or IV
Hypothalamic pituitary dysfunction - what will the levels of gonadotrophins and estrogen be like?
Normal gonadotrophins / excess LH
Normal oestrogen levels
What is the most common condition in hypothalamic pituitary dysfunction in infertility?
What is commonly seen in this condition, relating to endocrinology?
PCOS
Insulin resistance
How should you pre-treat a patient with PCOS?
Weight loss to optimise results - BMI >30 poor treatment outcome
Life style modification: smoking, alcohol
Folic acid 400 mcg / 5mg daily
Check prescribed drugs
Rubella immune
Normal semen analysis
(Patent fallopian tube)
What are the three options for ovulation induction in PCOS?
Briefly describe each
- Medication
- Clomifene citrate:
50-100-150 mg tab, days 2-6
- 70% ovulate, 40-60% conceive
- Alternatively tamoxifen, letrozole - Gonadotrophin therapy: daily injections
- Recombinant FSH
- 80% ovulate, 60-70% conceive
- Risks: multiple pregnancy, overstimulation - Laparoscopic ovarian diathermy:
- 80% ovulate, risk ovarian destruction
- Mainly singleton pregnancies
What % of patients do not ovulate on Clomid?
What are the treatment options for these patients?
15 –20% of patients do not ovulate on Clomifene - options for these patients include:
- Metformin
- Gonadotrophin therapy (FSH injections)
- Laparoscopic ovarian drilling
- Assisted conception treatment
What role does metformin play in ovulation induction?
Improves insulin resistance, reduction in androgen production (and increase in SHBG)
Restoration of menstruation and ovulation
Does not help in weight loss
May increase in pregnancy rate
What are the three main risks in ovulation induction?
- Ovarian hyperstimulation
- Multiple pregnancy
- ?risk ovarian cancer?
Ovarian failure
What will the levels of FSH, LH and oestrogen be like?
High levels gonadotrophins - raised FSH>30IU/L x 2 samples
Low oestrogen levels
What is the progesterone challenge test?
Progesterone challenge test (menstrual bleed in response to a five day course of progesterone: indicates estrogen levels normal).
