Ovulation Disorders and Infertility Flashcards
what is oligomenorrhea
reduction in frequency of periods to less than 9/year
what is primary amenorrhea
failure of menarche (first menstrual cycle, or first menstrual bleeding) by the age of 16 years
what is secondary amenorrhea
cessation of periods for >6 months in an individual who has previously menstruated
causes of primary amenorrhea
congenital
- Turner’s syndrome, Kallman’s syndrome
causes of secondary amenorrhea
Ovarian problem: PCOS, Premature Ovarian Failure
Uterine problem: uterine adhesions
Hypothalamic Dysfunction: weight loss, over exercise, stress, infiltrative
Pituitary: high PRL, hypopituitarism
physiological causes of amenorrhea
pregnancy
post-menopause
Hx of amenorrhea
Sx of oestrogen deficiency
- flushing, libido, dyspareunia (difficult, painful intercourse)
Hypothalamic problem
- exercise, weight loss, stress
Features of PCOS/androgen excess: hirsutism/acne
Anosmia - in Kallman’s, loose ability to smell
Symptoms of hypopituitarism/pituitary tumour including galactorrhea
Ix of amenorrhea
First line:
LH, FSH, Oestradiol
Thyroid function, Prolactin
Second line:
Ovarian ultrasound +/- endometrial thickness
Testosterone if hirsutism
Pituitary function tests + MRI pituitary if hypothalamic pituitary probems suspected
what should be considered in amenorrhea
hypogonadism
how does hypogonadism present in females
low levels of oestrogen
what is cause of primary hypogonadism
Problem with the ovaries
High LH/FSH – hypergonadotrophic hypogonadism
e.g. premature ovarian failure
what is cause of secondary hypogonadism
Problem with hypothalamus or pituitary
Low LH/FSH – hypogonadotrophic hypogonadism
e.g. high PRL, hypopituitarism
what is classified as premature ovarian failure (POF)
Amenorrhea
Oestrogen deficiency
Elevated gonadotrophins occuring
what is diagnostic of POF
FSH 430 on 2 separate occasions > 1 month apart
causes of POF
Chromosomal abnormalities
e.g. Turner’s, Fragile X
Gene mutations e.g. FSH/LF receptor
Autoimmune disease e.g. association with Addison’s
Iatrogenic
- radio/chemotherapy
what is secondary hypogonadism and how is it characterised
Hypogonadism as a result of hypothalamic or pituitary disease
Characterised by low oestradiol with low/normal LH/FSH
causes of secondary hypogonadism
Hypothalamic problem:
- functional hypothalamic disorder
- Kallman’s syndrome
- Idiopathic hypogonadotrophic hypogonadism (IHH)
Pituitary problem
what can cause functional hypothalamic disorder
weight change stress exercise anabolic steroids systemic illness iatrogenic Kallman's syndrome recreational drugs head trauma infiltrative disorder e.g. sarcoidosis
what is pathway of hypothalamic dysfunction
Low GnRH Loss of pulsatile secretion >> Low or low normal LH/FSH >> Low oestradiol
what is Kallman’s syndrome
genetic disorder characterised by a loss of GnRH secretion +/- anosmia
M > F
how can pituitary dysfunction cause amenorrhea
Loss of LH/FSH stimulation due to: - Non-functioning pituitary macroadenoma (pressure effects lead to hypopituitarism) - Empty Sella - Pituitary infarction
Hyperprolactinemia
due to:
- Micro- or macro-prolactinoma
- Drugs (e.g. dopamine antagonists)
what is empty sella
pituitary gland shrinks or becomes flattened, filling the sella turcica, or “Turkish Saddle”
what are ovarian causes of Amenorrhea
PCOS Ovarian failure (high gonadotrophin) Congenital problem with ovarian development
what is hirsutism
excess hair growth in a male distribution in females
what causes hirsutism
caused by androgen excess at the hair follicle
- due to excess circulating androgen
what causes the excess production of androgen
ACTH
what is the best way to investigate adrenal and ovarian tumour
MRI
Tx of amenorrhea
Depends on cause
PCOS
- Oral contraceptive pill
- Anti-androgens
- local anti-androgens
Late onset CAH
- Low dose glucocorticoid to suppress ACTH drive
what is Turner Syndrome
when there is only 1 X chromosome
clinical features of Turner’s
short stature webbed neck shield chest with wide spaced nipples cubitus valgus (deformity of the elbow resulting in an increased carrying angle) lymphoedema
presentation of Turner’s in children
Short Stature
Failure to progress through puberty
presentation of Turner’s in adults
Primary or secondary amenorrhea
Infertility
risk factors for infertility
older women >35 y/o previous chlamydia infections obesity smoking high caffeine intake excessive alcohol Woman's BMI 30 Regular use of recreational drugs
definition of 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
what is the difference between primary and secondary infertility
primary - couple has never conceived
secondary - couple previously conceived. Pregnancy may not have been successful e.g. miscarriage or ectopic pregnancy)
female causes of infertility
ovulation failure - 50%
tubal damage - 25%
endometriosis - 10%
miscellaneous - 15%
what is a Anovulatory cycle
a menstrual cycle where an egg is not release
physiological causes of Anovulatory cycle
before puberty, pregnancy, lactation, menopause
gynaecological causes of Anovulatory cycle
Hypothalmic: anorexia/bulimia, excessive exercise,
Pituitary: hyperprolactinaemia, tumours, Sheehan syndrome
Ovarian: PCOS, premature ovarian failure
other causes of Anovulatory cycle
Chronic renal failure
CAH
Hypo/Hyperthyroidism
what is clinical features of anorexia nervosa
low BMI (below 18.5),
loss of hair, increased lanugo,
low pulse and BP,
anaemia
endocrine features of anorexia nervosa
low FSH, LH and oestradiol
what is the triad of PCOS
chronic Oligo/Amenorrhoea
polycystic ovaries
hyperandrogenism (clinical or biochemical) e.g. acne, hirsutism, male pattern baldness
need 2 out of 3 for diagnosis
clinical features of PCOS
obesity
hirsutism or acne
cycle abnormalities and infertility
endocrine features of PCOS
high free androgens,
high LH,
impaired glucose tolerance
what is premature ovarian failure
when a woman’s ovaries stop working before she is 40
causes of POF
idiopathic
genetic - Turner’s, fragile X
Chemo/radiotherapy
features of POF
clinical
- hot flushes, night sweats
- atrophic vaginitis
endocrine
- high FSH
- high LH
- low oestradiol
infective tubal disease causes
Pelvic inflammatory disease
- chlamydia, gonorrhoea, TB, syphilis
non-infective tubal disease cause
endometriosis surgical - sterilisation fibroids polyps congenital
what is a Hydrosalpinx and what can cause it
fallopian tube dilated with fluid
pelvic inflammatory disease
features of a hydrosalpinx
abdominal/pelvic pain febrile vaginal discharge dyspareunia cervical excitation menorrhagia dysmenorrhoea infertility ectopic pregnancy
what is endometriosis
presence of endometrial glands outside uterine cavity
clinical features of endometriosis
dysmenorrhoea (classically before menstruation), dysparenuia, menorrhagia, painful defaecation, chronic pelvic pain infertility
what is a characteristic sign seen on a scan of the ovary in endometriosis
‘chocolate’ cysts
Laparoscopic view
Ix for endometriosis
transvaginal ultrasound (TVUS)
male causes of infertility
idiopathic - 25% varicocele - 37% chryptorchisism - 6% obstruction - 6% testicular failure - 9% semen disorders - 10% other - 7%
what can cause erectile dysfunction in males
diabetes
spinal cord injury
congenital disease that can cause absence of vas defers and therefore infertility
Cystic fibrosis
endocrine causes of male infertility
hypogonadotropic hypogonadism (e.g. Kallmann syndrome, anorexia)
testicular failure
hyperprolactinaemia (macro or microadenoma)
acromegaly
Cushing’s disease
hyper or hypothyroidism
obstructive clinical features of male infertility
normal testicular volume (over 8cm - less 5cm fertility decreases)
normal secondary sexual characteristics
vas deferens may be absent
normal LH, FSH and testosterone
clinical and endocrine features of non-obstructive male infertility
low testicular volume
reduced secondary sexual characteristics
vas deferens present
High LH, FSH and low testosterone
Ex of infertility - male
BMI
General examination
Genital examination, assessing size/position testes, penile abnormalities, presence vas deferens, presence varicoceles
what is varicoceles
a mass of varicose veins in the spermatic cord.
Ex of infertility - female
BMI
General examination, assessing body hair distribution, galactorrhoea
Pelvic examination, assessing for uterine and ovarian abnormalities/tenderness/mobility
Ix of infertility - female
endocervical swab for chlamydia cervical smear if due blood for rubella immunity midluteal progesterone level (day 21 of 28 day cycle) test of tubal patency
what suggests ovulation
day 21 progesterone > 30 mol/l
how can tubal patency be tested
Hysterosalpingiogram
Laparoscopy
when would a hysteroscopy be preformed in suspected infertility
suspected or known endometrial pathology: i.e. uterine septum, adhesions, polyp
what test can be done if there is an abnormality on pelvic examination
pelvic ultrasound
Ix for male infertility
semen analysis - twice over 6 weeks apart
what are the two phases of the menstrual cycle
follicular
luteal
what is oligomenorrhea
light or infrequent menstrual periods
what is GnRH and where it is synthesised
Pulsatile release Stimulates FSH (low frequency pulses) and LH (high frequency pulses) synthesis / release
Synthesised in hypothalamus
what does FSH do and where is it produced
Stimulates follicular development
Thickens endometrium
secreted by anterior pituitary
what does LH do and where is it produced
Peak stimulates ovulation
Stimulates corpus luteum development
Thickens endometrium
secreted by anterior pituitary
what triggers ovulations
LH surge roughly 36 hours before ovulation begins
what peaks before ovulation
LH
Estradiol
when does progesterone peak and what makes it
following ovulation in luteal phase
produced by corpus luteum
what secretes oestrogen
primarily by the ovaries (follicles) and adrenal cortex
what also secretes oestrogen during pregnancy
placenta
what is function of oestrogen
thickening of the endometrium
responsible for fertile cervical mucus
what does high oestrogen concentration cause
inhibits secretion of FSH and prolactin (-ve feedback)
stimulates secretion of LH (+ve feedback)
why does the corpus luteum secrete progesterone and what takes over secreting it during pregnancy
maintain early pregnancy
the placenta takes over
other function of progesterone
Inhibits secretion of LH
Responsible for infertile (thick) cervical mucus
Maintain thickness of endometrium
Has thermogenic effect (increases basal body temperature)
Relaxes smooth muscles
how is ovulation confirmed
confirm by midluteal (D21) serum progesterone (>30 nmol/L) X 2 samples
what are the 3 WHO classifications for cause of infertile couples
Group I Hypothalamic pituitary failure
Group II Hypothalamic pituitary dysfunction
Group III Ovarian failure
what is seen in Hypogonadotrophic hypogonadism
Low levels FSH / LH Oestrogen deficiency - Negative progesterone challenge test Normal prolactin Amenorrhoea
Mx of hypothalamic anovulation
Stabilise weight (BMI >18.5) Pulsatile GnRH if hypog hypog Gonadotrophin (FSH+LH) daily injections
what is suggestive of hypothalamic pituitary dysfunction
Normal gonadotrophins / excess LH
Normal oestrogen levels
Oligo/amenorrhoea
what is commonly associated with PCOS and what does this cause
insulin resistance
Insulin acts as co-gonadotrophin to LH»_space; elevated LH
Insulin lowers sex hormone binding globulin»_space; increased free testosterone»_space; hyperandrogenism
Tx of PCOS
Weight loss
No smoking + alcohol
Folic Acid 5mg
Clomifene citrate
can add Metformin for insulin resistance
what treatments can be used for ovulation induction
Clomifene citrate
Gonadotrophin therapy: daily injections
Laparoscopic ovarian diathermy:
what are potential risks of ovulation induction
ovarian hyperstimulation
multiple pregnancy
risk ovarian cancer
what are the risks of multiple pregnancy
increased maternal pregnancy complications e.g. morning sickness, anaemia, postnatal depression
Twin-twin transfusion syndrome
increased risk of miscarriage
increased risk of low birth weight
increased risk prematurity and disability
increased risk of still birth
what are monochorionic and dichorionic twins
mono - identical twins/triplets
di - non-identical twins/triplets
what are the scan findings that can help identify mono or di-chornic twins
Lambda sign - dichorionic
T sign - monochorionic
what is twin-twin transfusion syndrome
unbalanced vascular communications/connection within placental bed
- Recipient develops polyhydramnios
- Donor develops oliguria, oligohydramnios and growth restriction
prematurity problems
early - respiratory distress syndrome
long term - Cerebral palsy, impaired sight, congenital heart disease
- lower IQ, ADHD
what is suggestive of ovarian failure
High levels gonadotrophins Raised FSH>30IU/L x 2 samples Low oestrogen levels Amenorrhea Menopausal symptoms; flushing, sweats
what is the difference between oogenesis and spermatogenesis
oogenesis - takes many years to complete, ceases at menopause (50/55 y/o), begins in utero, suspended for many years and then begins again a puberty
spermatogenesis- takes much less time; around 72 days, no sperm production before puberty, men keep producing sperm for the majority of their life
what are the female germ cells
Primordial germ cell
Oogonia
what are the earliest recognisable germinal cell and what are features of it
Primordial germ cell
Capable of mitosis
Migrate to genital ridge by week 6 of embryo development
what is a oogonia called when it completes its last pre-meiotic division
oocytes
what happens after oocytes enter meiosis
1st meiotic division - Primary oocytes -
2nd meiotic division - Secondary oocytes
what signifies sperm enter and completion of 2nd meiotic division
presence of two polar bodies
what is the follicular phase of the ovarian cycle
1st half of cycle
Maturation of egg, ready for ovulation at midcycle – ovulation signals end of follicular phase
what is the luteal phase of the ovarian cycle
2nd half of cycle
Development of corpus luteum.
Induces preparation of reproductive tract for pregnancy (if fertilisation occurs)
what signals start of new follicular phase
degeneration of corpus luteum
what hormone is most dominant in follicular phase
FSH
little LH
Tx of male infertility
Surgery to obstructed vas deferens (50% success following vasectomy)
Intrauterine insemination in mild disease
Intracytoplasmic sperm injection (ICSI)
ICSI combined with surgical sperm aspiration from epididymis or testicle
Donor insemination.
Mx of infertility - general factors
Sexual intercourse: 2-3 times per week Alcohol: females limit to 4 units per week Weight loss Stop Smoking Folic acid Rubella immunity Cervical smears Occupational factors Drugs: prescribed, over-the-counter and recreational
