Fertility and reproduction Flashcards
What is FSH ?
Follicle stimulating hormone
What is LH ?
Luteinizing hormone
What is the role of FSH in females?
Causes the growth of ovarian follicles (oogenesis) and causes the ovary to secrete oestrogen
What is the role of FSH in males?
Causes the testes to produce sperm (spermatogenesis)
What is the role of LH in females?
Causes ovulation and causes progesterone production by the Corpus Luteum
What is the role of LH in males?
Causes the testes to secrete testosterone
What secretes FSH and LH ?
Anterior pituitary gland
What are the two ‘gonadotropic’ hormones?
FSH and LH
What is GnRH ?
Gonadotropin releasing hormone
What is the role of gonadotropin releasing hormone (GnRH) ?
It is responsible for the release of FSH and LH from the anterior pituitary
How does GnRH released?
In a pulsatile manner
What is GnRH pulsatility regulated by?
Oestrogen and Progesterone
How long is the follicular phase on average?
Typically 14 days (+/- 7 days)
How long is the luteal phase on average?
14 days - more constant than the follicular phase
Where is GnRH released from?
Hypothalamus
When does the LH surge occur?
24-36 hours before ovulation occurs
What hormone peaks before ovulation?
Estradiol
What hormone peaks after ovulation?
Progesterone
What does oestrogen do?
Responsible for fertile cervical mucus and stimulates thickening of the endometrium
What type of feedback does oestrogen have on the pituitary and hypothalamus?
Mostly -ve
What does progesterone do?
Inhibits LH secretion and is responsible for infertile cervical mucus and maintains thickness of the endometrium
Which hormone has a thermogenic effect?
Progesterone - increases basal body temperature
What does spinnbarkeit mean?
A property of cervical mucus in response to high levels of oestrogen around the time of ovulation - becomes thin, slippery and stretchy
When does menopause commonly occur?
What is a follicle made up of?
What happens when it grows?
An oocyte surrounded by follicular cells
Increased follicular cells
Name the hormones produced by the adenohypophysis?
Reminder: FLAT PEG
FSH
LH
ACTH
TSH
Prolactin
Endorphins
Growth hormone
Where is testosterone produced?
By Leydig cells under the control of LH
What is testosterone converted to?
Dihydrotestosterone and oestradiol
What is oligomenorrhoea?
Cycles > 42 days in length
Less than 8 periods a year
What is amenorrhoea?
Absent menstruation
What is a Group I ovulatory disorder ?
Hypothalamic pituitary failure - issue is with hormones higher up
What is a Group II ovulatory disorder ?
Hypothalamic pituitary dysfunction (most common)
What is a Group III ovulatory disorder ?
Ovarian insufficiency - menopause, ovarian failure
What is the GAIN FIT PIE pneumonic?
Aetiology of ovulation disorders
Genetic
Autoimmune
Iatrogenic
Neoplasm
Functional
Infectious / inflammatory
Trauma + vascular
Physiological
Idiopathic
Endocrine
Signs of hypothalamic ovulation disorder?
Amenorrhoea, low levels of FSH / LH / Oestrogen
What is a progesterone challenge test?
Administration of progesterone to induce a period (provera)
What is suggested if progesterone challenge test does not induce bleeding ?
Low oestrogen levels, uterine / endometrial abnormality or cervical stenosis
Management options of hypothalamic ovulation disorders?
Pulsatile GnRH - SC or IV pump worn continuously with pulsatile administration every 90 minutes
Gonadotrophin daily injections - cause higher multiple pregnancy rates
Signs of a pituitary issue ovulatory disorder?
Amenorrhoea, low levels of FSH / LH / Oestrogen, possible co-existent abnormalities in other anterior pituitary hormones
What is hyperprolactinaemia ?
Raise in prolactin causing leakage of milky substance from nipples
How do we treat hyperprolactinaemia ?
Dopamine agonist - cabergoline
How do we diagnose hyperprolactinaemia ?
Raised serum prolactin, low/normal FSH/LH, low oestrogen
MRI to find prolactinoma
Signs of ovarian ovulatory disorders?
Characterised by high levels of gonadotrophins (FSH / LH) and low oestrogen levels
Amenorrhoea, menopausal
Premature ovarian insufficiency treatment options?
Hormone replacement therapy, egg / embryo donation or cryopreservation
What is PCOS ?
A diagnosis based on 2/3 criteria:
- Oligo/amenorrhoea
- Polycystic ovaries on USS
- Clinical / biochemical signs of hyperandrogenism (acne, hirsutism)
What is a common endocrine complication of PCOS ?
Insulin resistance - PCOS patients more likely to have T2DM
Management of PCOS ?
Subfertility - ovulation induction
General management of associated acne / hirsutism / obesity
Medical management of PCOS ?
Clomiphene citrate (anti-oestrogen) tablets for 2-6 days to begin with - monitored with scans
Gonadotrophin therapy daily injections - highly successful but more risk
What diabetic medication is commonly given in PCOS ?
Metformin - in combination with other lifestyle factors can restore menstruation and ovulation
What is the surgical management of PCOS ?
Laparoscopic ovarian diathermy - keyhole surgery and needle delivery of heat to the ovary
What is the rule of 4 in relation to PCOS surgery ?
40W current, 4 seconds, 4 punctures for the laparoscopic ovarian diathermy
Last line treatment of PCOS ?
IVF
The 3 main risks of ovulation induction?
- Ovarian hyperstimulation
- Multiple pregnancy
- Ovarian cancer risk
Give 3 reasons for premature ovarian failure?
Genetic (Turner’s, fragile X)
Chemo / radiotherapy
Idiopathic
Give the common clinical features of premature ovarian failure?
Hot flushes, night sweats
Atrophic vaginitis
Amenorrhoea
Infertility
Give the endocrine features of premature ovarian failure?
High FSH
High LH
Low oestradiol
What is male hypogonadism in simple terms?
A low / reduced gonadal function
What is primary hypogonadism?
The testes are primarily affected
Spermatogenesis is more affected than testosterone production
What happens in primary hypogonadism that leads to an increase in LH / FSH levels?
Hypergonadotropic hypogonadism
A decrease in testosterone means there is less -ve feedback to the pituitary - the pituitary then secretes a higher amount of LH / FSH
What is secondary hypogonadism?
Where the testes are capable of normal function and the hypothalamus / pituitary are affected
Both spermatogenesis and testosterone production are affected
What happens in secondary hypogonadism that leads to a decrease in LH / FDH levels?
Hypogonadotropic hypogonadism
The LH / LSH levels are lower than normal despite a low testosterone level
Give 2 congenital causes of primary hypogonadism?
Klinefelter’s syndrome
Y-chromosome deletion
Give at least 2 causes of acquired primary hypogonadism?
Testicular torsion / trauma
Chemo / radiotherapy
Varicocele
Orchitis (mumps infection)
Medications (glucocorticoids)
What is Klinefelter’s syndrome?
A NON INHERITED nondisjunction genetic cause of hypogonadism
How is Klinefelter’s syndrome diagnosed?
Karyotyping
Give clinical features of a patient with Klinefelter’s syndrome?
Infertile
Small, firm testes
Increased incidence of learning disability, cryptorchidism and psychosocial issues
Increased incidence of breast cancer and non-Hodgkin lymphoma
Give 2 congenital causes of secondary hypogonadism?
Kallmann’s syndrome
Prader-Willi syndrome
Give at least 2 acquired causes of secondary hypogonadism?
Pituitary damage (tumour, disease)
Hyperprolactinaemia
Obesity / diabetes
Medications (steroids, opioids)
Acute systemic illness
Eating disorders / excessive exercise
What is Kallmann’s syndrome?
A genetic disorder characterised by isolated GnRH deficiency and hyposmia (reduced sense of smell) or anosmia (no sense of smell)
What is isolated GnRH deficiency associated with?
Unilateral renal agenesis, red-green colour blindness, cleft lip / palate and bimanual synkinesis
Give signs and symptoms of pre-pubertal hypogonadism?
Small male sexual organs
Decreased body hair
High-pitched voice
Low libido
Gynaecomastia
‘Eunuchoidal’ habitus
Decreased bone and muscle mass
Give signs and symptoms of post-pubertal hypogonadism?
Normal skeletal proportions
Normal sexual organ size
Decreased libido
Decreased spontaneous erections
Decreased pubic / axillary hair
Decreased testicular volume
Decreased muscle and bone mass
Gynaecomastia
What is the first test for suspected low testosterone?
AM testosterone
If an AM testosterone is low two times?
Measure LH / FSH
If LH / FSH levels are elevated?
Hypergonadotropic hypogonadism
If LH / FSH levels are low / inappropriately normal?
Hypogonadotropic hypogonadism
When should testosterone be measured?
Between 8 and 11 am
How should hypogonadism be managed if fertility is important to the patient?
GnRH or gonadotrophin therapy
Sperm retrieval
Donor sperm
What does management aim to achieve in patients who are not concerned about fertility?
Establish / maintain secondary sexual characteristics
Maintain sexual function
Improve body composition
Improve quality of life
What is the choice of management of hypogonadism in patients not concerned about fertility?
Testosterone replacement therapy
Give 5 ways of administering testosterone replacement therapy?
Transdermal gel
Oral capsules
Transdermal patches
Intranasal
IM injections
Give the advantages and disadvantages of testosterone replacement therapy?
Advantages:
fast onset, convenient, mimics circadian rhythm
Disadvantages:
interpersonal transfer, skin irritation possible, non-compliance long term
Give known contraindications of testosterone replacement therapy?
Prostate / breast cancer
Haematocrit > 50%
Severe sleep apnoea / heart failure
What is the initial monitoring regime of testosterone replacement therapy?
What does the monitoring regime become after this?
Checks every 3-6 months in the beginning of treatment
Annually thereafter
What should be checked when monitoring testosterone replacement therapy?
General health
Testosterone concentration
DRE and PSA
Haematocrit
Symptoms of sleep apnoea
If anosmia is mentioned in an exam question - what hypogonadism condition is likely?
Kallmann’s syndrome
If a male patient presents with infertility what is the 2 tests that should be done?
Semen analysis
AM testosterone
Which hypogonadal condition ONLY affects males?
Klinefelter’s syndrome
Which hypogonadal condition can affect both males and females, but much more commonly males?
Kallmann’s syndrome
How often should nebido injections be given?
Every 10-14 weeks
Give 3 infective causes of tubal disease?
- Pelvic inflammatory disease
- Transperitoneal spread
- Following procedure (IUCD insertion, hysteroscopy, HSG)
Give at least 3 non-infective causes of tubal disease?
- Endometriosis
- Surgical (sterilisation, ectopic)
- Fibroids
- Polyps
- Congenital
- Salpingitis isthmica nodosa
Give the classic clinical features of pelvic inflammatory disease?
Abdominal / pelvic pain
Vaginal discharge
Dyspareunia
Cervical excitation
Menorrhagia
Dysmenorrhoea
Infertility
Ectopic pregnancies
Give the definition of endometriosis?
The presence of endometrial glands outside of the uterine cavity
What is the most likely cause of endometriosis?
What are some other causes?
Retrograde menstruation
Others: altered immune function, abnormal cellular adhesion molecules, genetic causes
Give the classic clinical features of endometriosis?
Dysmenorrhoea
Dyspareunia
Menorrhagia
Painful defecation
Chronic pelvic pain
‘chocolate’ cysts on ovary USS
Infertility
Fixed and retroverted uterus (in some cases)
Give the definition of infertility?
Failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse (in a couple who have never had a child)
What is primary infertility?
When the couple have never conceived
What is secondary infertility?
The couple have previously conceived but the pregnancy was likely not successful - miscarriage or ectopic pregnancy
Name 6 main things that can affect fertility?
Age - under 30 increases chance
Timing of intercourse - ovulation
Weight - low / healthy BMI
Smoking - avoidance
Caffeine intake - less than 2 cups of coffee daily
Recreational drugs - avoidance
Give 5 common causes of secondary infertility?
- Age
- Weight
- Fibroids
- Tubal disease
- Endometriosis / adenomyosis
What leads to 30-50% of male infertility?
Name other reasons for male infertility?
Idiopathic causation
Hypogonadism, undescended testes, urogenital infection, sexual factors, systemic disease
Give pre-testicular reasons for male infertility?
Endocrine - hypogonadotropic hypogonadism, hypothyroidism
Coital disorders - erectile dysfunction, ejaculatory failure
Give testicular reasons for male infertility?
Genetic - Klinefelter’s syndrome, Y chromosome deletion
Congenital - infective, antispermatogenic agents (heat, irradiation, drugs, chemo)
Vascular - testicular torsion, varicocele
Immunological - infection
Give post-testicular reasons for male infertility?
Obstructive - congenital / infective epididymal reasons
Vasal - genetic (cystic fibrosis)
acquired - vasectomy, ejaculatory duct obstruction, idiopathic
Give clinical features of undescended testes?
Low testicular volume, reduced secondary sexual characteristics and a present vas deferens
Give endocrine features of undescended testes?
High LH
High FSH
Low testosterone
Give clinical features of a vasectomy?
Normal testicular volume and secondary sexual characteristics
Vas deferens may be absent
Give endocrine features of vasectomy?
Normal LH
Normal FSH
Normal Testosterone
How should female infertility be investigated?
Endocervical swab for chlamydia
Bloods for rubella immunity
Cervical smear (if due)
Midluteal progesterone level
Tubal patency test
When would a hysteroscopy be carried out in the case of female infertility?
In cases where there is high suspicion of or a known endometrial pathology
If hirsutism is present - what tests should be carried out?
Testosterone and SHGB levels
What should be done if there is amenorrhoea in infertile females?
An endocrine profile (anovulatory cycle)
Chromosome analysis
What investigations should be done in a suspected infertile male?
History taking
Genital examination
Semen analysis
How should a proper semen analysis be done?
Two samples should be taken for testing over 6 weeks apart
If semen analysis is abnormal what further tests should be done?
LH and FSH
Testosterone
Prolactin
Thyroid function
What should be done if there is abnormality on a male genital examination?
Scrotal ultrasound
If a semen analysis is severely abnormal what can be done?
An endocrine profile
Chromosome analysis
Cystic fibrosis screen
Testicular biopsy
