Transcript Anovulation: Etiology and Management

Anovulation: Aetiology and
Management
Dr. Darron Halliday
Outline
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Introduction
Causes suitable for ovulation induction
Causes unsuitable for ovulation induction
Drug induced
Diagnosis of anovulatory subfertility
Management of anovulation
Anovulation :Aetiology and
Management
Introduction
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Disorders of ovulation account for about 20% -30% of
infertility and often present with oligomenorrhoea or
amenorrhoea
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The majority fall into the WHO group II category
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Many of the treatments are simple and effective
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Anovulation can sometimes be treated with medical or
surgical induction
Anovulation :Aetiology and
Management
ACOG 2002, Fairley and Taylor BMJ 2003
Anovulation :Aetiology and
Management
Anovulation :Aetiology and
Management
Causes of anovulation suitable for
ovulation induction treatment
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Hypothalamic
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Low concentration of gonadotrophin
realeasing hormone (hypogonadotrophic
hypogonadism)
Weight or exercise related amenorrhoea
Kallman's syndrome
Stress
Idiopathic
Anovulation :Aetiology and
Management
Causes of anovulation suitable for
ovulation induction treatment
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Pituitary
• Hyperprolactinaemia
• Pituitary failure (hypogonadotrophic
hypogonadism)
• Sheehan's syndrome
• Craniopharyngioma or hypophysectomy
• Cerebral radiotherapy
Anovulation :Aetiology and
Management
Causes of anovulation suitable for
ovulation induction treatment
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Ovarian
• Polycystic ovaries
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Other endocrine
• Hypothyroidism
• Congenital adrenal hyperplasia
Anovulation :Aetiology and
Management
Causes suitable for ovulation
induction
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Hypogonadotrophic hypogonadism is
characterised by a selective failure of the
pituitary gland to produce luteinising
hormone and follicle stimulating hormone
BMI < 20 Kg/m2
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gymnasts, marathon runners, ballerinas—may
develop amenorrhoea because of a physiological
reduction in the hypothalamic production of
gonadotrophin releasing hormone
Anovulation :Aetiology and
Management
Weight-related amenorrhoea
Anorexia Nervosa
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Abnormal body image, intense fear of
weight gain, often strenuous exercise
Mean age onset 13-14 yrs (range 10-21 yrs)
Low estradiol  risk of osteoporosis
Bulemics less commonly have amenorrhea
due to fluctuations in body wt, but any
disordered eating pattern (crash diets) can
cause menstrual irregularity.
Treatment :  body wt. (Psychiatrist referral)
Anovulation :Aetiology and
Management
Causes suitable for ovulation induction
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Sheehan's syndrome - caused by infarction
of the anterior pituitary venous complex
(usually after massive postpartum
haemorrhage or trauma)
Kallman's syndrome- (amenorrhoea with
anosmia caused by congenital lack of
hypothalamic production of gonadotrophin
releasing hormone).
Anovulation :Aetiology and
Management
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cerebral irradiation
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RX for craniopharyngioma or some forms of
leukaemia
may affect the hypothalamus or the pituitary
may resulting in hypogonadotrophic
hypogonadism
Anovulation :Aetiology and
Management
Hyperprolactinaemia
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caused by a pituitary microadenoma.
causes reduction in the production of pituitary luteinising
hormone and follicle stimulating hormone.
Causes secondary amenorrhoea, galactorrhoea,
headaches or disturbed vision
treatment with drugs result in subsequent resumption of
menses and fertility
Anovulation :Aetiology and
Management
Polycystic ovary syndrome
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The most common cause of chronic anovulation (70%)
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Hyperandrogenism ;  LH/FSH ratio
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Insulin resitance is a major biochemical feature ( blood insulin
level hyperandrogenism )
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Long term risks: Obesity, hirsutism, infertility, type 2 diabetes,
dyslipidemia, cardiovasular risks, endometrial hyperplassia and
cancer
Treatment depends on the needs of the patient and preventing
long term health problems
Anovulation :Aetiology and
Management
Transvaginal scan of
a polycystic ovary.
Typically 10 or more
follicles of <10 mm in
diameter ("string of
pearls") are in a
single transverse or
longitudinal section
through the ovary.
Stromal density and
ovarian volume
increase
Anovulation :Aetiology and
Management
Psychogenic Hypothalamic Amenorrhea
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Amenorrhea and anovulation a definite history of
psychological and socioenvironmental trauma
Characterized by low to normal basal levels of
serum gonadotropins with normal responses to
GnRH, prolonged suppression of gonadotropins
in response to estradiol, and failure of a positive
feedback response to estradiol, increased basal
levels of cortisol and decreased levels of DHEAS
Anovulation :Aetiology and
Management
Psychogenic Hypothalamic Amenorrhea
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The mechanism by which emotional states or stressful experiences
cause psychogenic amenorrhea is not yet established.
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Higher centers have copious connections with the hypothalamus
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Evidence suggests that a cascade of neuroendocrine events that
may begin with limbic system responses to psychic stimuli impairs
hypothalamic-pituitary activity
It has been suggested that increased hypothalamic b-endorphin is
important in inhibiting gonadotropin secretion
Anovulation :Aetiology and
Management
Psychogenic Hypothalamic Amenorrhea
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Associated factors
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a history of previous pregnancy losses
stressful life events within the 6-month period
preceding the amenorrhea
poor social support or separation
psychosexual problems and socioenvironmental
stresses during the teenage years
have negative attitudes toward sexually related body
parts, more partner-related sexual problems, and
greater fear of or aversion to menstruation than do
eumenorrheic women
Anovulation :Aetiology and
Management
Psychogenic Hypothalamic Amenorrhea
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Treatment.
The treatment of patients with stress
induced hypothalamic chronic anovulation
is controversial.
Psychological therapy and support or a
change in lifestyle may cause cyclic
ovulation and menses to resume
Ovulation induction - as will be discussed
Anovulation :Aetiology and
Management
Causes unsuitable for ovulation
induction
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Ovarian failure
• Idiopathic
• Radiotherapy or
chemotherapy
• Surgical removal
• Genetic
• Autoimmune
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Chromosomal
• Turner's syndrome
(45,X)
• Androgen insensitivity
syndrome (46,XY)
Anovulation :Aetiology and
Management
Premature Ovarian Failure
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Ovarian failure before the age of 40 yrs is POF, absence
of menses for 3 cycles/6mths
Unfortunately this is an irreversible condition. The only
treatment option that can result in conception is the use
of donated eggs with in vitro fertilisation
Estrogen most effective rx for hot flashes, vag dryness,
urinary s/s, emotional lability (6m-5yrs), long term: CHD,
osteoporosis
Anovulation :Aetiology and
Management
Premature ovarian failure
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Serum estradiol < 50 pg/ml and FSH > 40
IU/ml on repeated occasions
10% of secondary amenorrhea
Few cases reported, where high dose
estrogen or HMG therapy resulted in
ovulation
Sometimes immuno therapy may reverse
autoimmue ovarian failure
Rarely  spont. ovulation (resistant ovaries)
Treatment: HRT (osteoporosis, atherogenesis)
Anovulation :Aetiology and
Management
Gonadal dysgeneis
Chromosomally incompetent
- Classic turner’s syndrome (45XO)
- Turner variants (45XO/46XX),(46X-abnormal X)
- Mixed gonadal dygenesis (45XO/46XY)
 Chromosomally competent
- 46XX (Pure gonadal dysgeneis)
- 46XY (Swyer’s syndrome)
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Anovulation :Aetiology and
Management
Gonadal dysgenesis
Classic
Turner’s
Turner
Variant
True
gonadal
Dysgenesis
Mixed
Dysgenesis
phenotype
Female
Female
Female
Ambiguous
Gonad
Streak
Streak
Streak
- Streak
- Testes
Hight
Short
- Short
- Normal
Tall
Short
Somatic
stigmata
karyotype
Classical
XO
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Nil
XX/XO or 46-XX(Pure)
abnormal
46-XY
X
(Swyer)
Anovulation :Aetiology and
Management
±
XO/XY
Turner’s syndrome
• Sexual infantilism and short stature.
• Associated abnormalities, webbed neck,coarctation of
the aorta,high-arched pallate, cubitus valgus, broad
shield-like chest with wildely spaced nipples, low
hairline on the neck, short metacarpal bones and
renal anomalies.
• High FSH and LH levels.
• Bilateral streaked gonads.
• Karyotype - 80 % 45, X0
- 20% mosaic forms (46XX/45X0)
• Treatment: HRT
Anovulation :Aetiology and
Management
Turner’s syndrome
(Classic 45-XO)
Mosaic (46-XX / 45-XO)
Anovulation :Aetiology and
Management
Ovarian dysgenesis
Anovulation :Aetiology and
Management
Androgen insensitivity
Testicular feminization syndrome
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X-linked trait
Absent cytosol receptors
Normal breasts but no sexual hair
Normal looking female external
genitalia
Absent uterus and upper vagina
Karyotype 46, XY
Male range testosterone level
Treatment : gonadectomy after
puberty + HRT
Anovulation :Aetiology and
Management
Physiological
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Menarchy
Peri-menopause/ menopause
Pregnancy
Breast feeding
Anovulation :Aetiology and
Management
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20% of women are irregular cycles
Greatest variability found in years
following menarche and those preceding
menopause
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First 5-7 years post menarche are time of
increasing regularity and cycle shortening to
normal reproductive pattern
Most consistent cycles between the ages of 20
and 30
Highest rate of anovulation is <20 and >40
Anovulation :Aetiology and
Management
Hormonal Changes with Established Menopause
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FSH and LH levels undergo an accelerated rise in the last 2 to 3
years before menopause, with estrogen levels declining only
within approximately 6 months before menopause.
After menopause, when ovarian follicles are depleted, FSH and
LH levels continue to rise.
Eventually, there is a 20-fold increase in FSH levels and an
approximately threefold increase in LH levels, both of which peak
in the first 1 to 3 years after menopause
In comparison, ovarian estrogen production does not continue
beyond menopause, when ovarian follicles and their estrogenproducing granulosa cells are depleted
Anovulation :Aetiology and
Management
Lactational amenorrhea
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Elevated prolactin levels and a reduction of
gonadotropin-releasing hormone from the
hypothalamus during lactation suppress
ovulation
This leads to a reduction in luteinizing hormone
(LH) release and inhibition of follicular
maturation
Ovulation usually returns after 6 months despite
continuous nursing
Anovulation :Aetiology and
Management
Drugs
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OCP
Antipsychotic
Anovulation :Aetiology and
Management
STEROIDAL CONTRACEPTION
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oestrogens and progestogens based
The oestrogen in most pills
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The 'traditional' progestogens
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ethinyl estradiol using the lowest possible
ethynodiol, levonorgestrel and norethisterone
The newer progestogens
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desogestrel (DSG), gestodene (GSD) and
norgestimate bind more specifically to progesterone
receptors
Anovulation :Aetiology and
Management
STEROIDAL CONTRACEPTION
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Modes of action
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Inhibition of ovulation due to negative
feedback on the hypothalamo-pituitaryovarian axis
Induction of changes in cervical mucus,
endometrium, myometrium and fallopian
tubes
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makes them hostile to sperm and unfavourable for
ovum transplant and implantation
Anovulation :Aetiology and
Management
Psychotropic Medications
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Antipsychotics may block dopamine receptors in the pituitary
prolactin-secreting cells and prevent dopamine-induced reduction of
prolactin release
Hyperprolactinemia can result in galactorrhea, amenorrhea,
irregular menses, and anovulation; in men, impotence and
azoospermia, with or without lactation and gynecomastia, can occur.
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The treatment of choice is reduction of the antipsychotic dosage or
discontinuation of therapy.
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If adjustments to the antipsychotic dosage fail to resolve symptoms,
the dopamine agonists bromocriptine and amantadine may be tried.
Anovulation :Aetiology and
Management
INVESTIGATION
Anovulation :Aetiology and
Management
Anovulation :Aetiology and
Management
Hypogonadotrophic
hypogonadism
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A careful history
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surgery, radiotherapy, massive haemorrhage, lack of
smell, exercise, and eating habits
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a body mass index measurement will reveal the
cause.
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concentrations of luteinising hormone, follicle
stimulating hormone, and estradiol will be low
Anovulation :Aetiology and
Management
Hyperprolactinaemia
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A serum prolactin concentration of > 1000 IU/l
is diagnostic and usually indicates a
microadenoma.
MRI or CT should be arranged to detect whether
a macroadenoma is present.
Patients with a macroadenoma must have their
visual fields checked
Anovulation :Aetiology and
Management
Hyperprolactinemia
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LH and FSH concentrations are usually at the lower end
of the normal range with a low estradiol concentration.
Test for hypothyroidism and pregnancy
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In hypothyroidism thyrotropin releasing hormone may
stimulate prolactin secretion in addition to thyrotropin
releasing hormone from the anterior pituitary
Anovulation :Aetiology and
Management
Polycystic ovary syndrome
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A transvaginal ultrasound scan of the pelvis will confirm
the diagnosis.
In 80% of women testosterone concentration are >
2.4 nmol/l
LH concentrations are raised (> 10 IU/l) in 45-70% of
women with the syndrome
Anovulation :Aetiology and
Management
Management of anovulation
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Treating specific
causes
Anovulation :Aetiology and
Management
Change of weight
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Women with polycystic ovary syndrome
who are overweight (body mass index >
30) should be advised to lose weight.
Exercise, weight loss- reduces insulin and
free testosterone levels, resulting in
improved menstrual regularity, ovulation,
and pregnancy rates.
Anovulation :Aetiology and
Management
Change of weight
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Women who are underweight (body mass index
< 20) should be encouraged to gain weight
No infertility treatment should be offered until
their body mass has returned to the lower limits
of normal.
Anovulation :Aetiology and
Management
Hyperprolactinaemia
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Bromocriptine is safe and commonly used.
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starting dose of 1.25 mg (taken with food) at
night for the first fortnight and then increased to
2.5 mg for another fortnight.
The prolactin level should be checked, and if the
level is below 1000 IU/l, the dose should be
maintained.
Anovulation :Aetiology and
Management
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Side effects
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postural hypotension, nausea, vertigo, headache
Cabergoline and quinagolide are newer long
acting dopamine agonists with fewer side
effects.
Once prolactin < 1000 IU/l associated with
ovulation in 70-80% of women
Anovulation :Aetiology and
Management
Hypothyroidism
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In hypothyroidism thyrotropin releasing hormone
may stimulate prolactin secretion in addition to
thyrotropin releasing hormone from the anterior
pituitary
Correction of the hypothyroidism with thyroxine
replacement allows thyroid stimulating hormone
and prolactin levels to return to normal,
releasing the suppression to gonadotrophin
secretion and ovulation
Anovulation :Aetiology and
Management
Antioestrogen treatment: Clomifene
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Clomifene acts by blocking oestrogen receptors in the
pituitary
leads to an increased production of follicle stimulating
hormone, which then stimulates development of one or
more dominant follicles
Anovulation :Aetiology and
Management
Clomiphene Citrate - dose regimen
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After spontaneous menses or the induction of
menses with a progestin withdrawal,
clomiphene is started on cycle day 3, 4, or 5 at
50 mg daily for 5 days.
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Get Progesterone checked on D21
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Not ovulating
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Maximum recommended no of ovulatory cycles
to 100mg-150mg per day
-6
Anovulation :Aetiology and
Management
Clomiphene Citrate
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Ultrasound monitoring, because risk of ovarian
hyperstimulation syndrome
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70% of women with PCO will ovulate
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conception rate of 40-60% at six months.
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The incidence of twins is around 10%, and
triplets 1%.
Anovulation :Aetiology and
Management
Downsides to Clomiphene
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Unpleasant side effects
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irritability, hotflashes, abdominal discomfort,
visual disturbances
Multiple pregnancies
Endometrial hypotrophy esp. when used
for > 6 months
Hostile sperm cervical mucous interactions
Anovulation :Aetiology and
Management
Anovulation :Aetiology and
Management
Tamoxifen and Oligo-ovulation
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Dose of 20-40mg twice daily from day 2-5
Similar side effects
SERM with some estrogenic effects on the
endometrium
May improve sperm/mucus interactions
Similar rates of ovulation and pregnancy
OHSS rare and usually resolves on its own
Incidence of twins slighty increased
Boostanfar et al 2001
Anovulation :Aetiology and
Management
Aromatase Inhibitors
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Letrozole: an oral, reversible,
steroidal aromatase inhibitor.
no-
Dose: 2.5 mg/d from day 3-7
Results in ovulation in 9/12 in Clomiphene
resistant PCO
Addition of letrozole may reduce dose and
increase response to FSH
Anovulation :Aetiology and
Management
Letrozole
Mechanism of action:
1. Release of the estrogen negative feedback, increase GnTR, stimulate
ovarian follicle development
2. Increase sensitivity of follicles to FSH.
Advantages of letrozole over CC:
Because of the short half life (45h) & absence of ER depletion
No effect on the endometrial thickness or cervical mucous
Letrozole is effective for increasing follicle recruitment in UI (Mitwally
& Casper,2000)
Letrozole can replace CC in patients with UI undergoing ovulation induction
& IUI (Sammour,2001) .
Anovulation :Aetiology and
Management
Metformin
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doses of 1500 mg a day similar effect to
weight loss) NB increase dose slowly
Lowers insulin
Lowers testosterone
Increases SHBG
Improves HDL:LDL ratio
Anovulation :Aetiology and
Management
Metformin
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Systematic review of metformin for PCO:
12 RCT’s, 2 cohort studies and 16 case
series
Metformin alone improves menstrual
cyclicity
Metformin plus CC improves pregnancy
rates
Costello, Eden 2003
Anovulation :Aetiology and
Management
Surgical induction
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Laparoscopic ovarian diathermy or "drilling" has
replaced wedge resection of the ovaries in
women with polycystic ovary syndrome.
At laparoscopy, five to six diathermy or laser
punctures are made in the ovary.
If too much ovarian tissue is destroyed there is a
potential risk of premature ovarian failure in the
future, although this risk is still being evaluated.
Anovulation :Aetiology and
Management
Ovarian Cautery for PCO
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8 trials comparing ovarian
drilling to other
interventions ( CC, FSH,
GnRHa/FSH)
Similar miscarriage rate,
22%
Multiple pregnancy rates
post cautery FSH seems
reduced 0% vs 10%
Anovulation :Aetiology and
Management
Human Gonadotropins –
Endocrinology Overview
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Link between hypothalamic-pituitary axis
and the ovary
Required at threshold levels for follicular
development
Anovulation :Aetiology and
Management
Human Gonadotropins
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Control of gonadotropin release occurs
through pulsatile hypothalamic production
of gonadotropin releasing hormone
(GnRH)
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Pulses vary over the course of the menstrual cycle.
The timing and amplitude of pulses determine
gonadotropin release from the pituitary.
Anovulation :Aetiology and
Management
Types of Gonadotropins
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In females, the reproductive axis is
responsive to two main gonadotropin
types:
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Follicle Stimulating Hormone (FSH)
Luteinizing Hormone (LH)
Anovulation :Aetiology and
Management
Pulsatile gonadotrophin releasing
hormone
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May be suitable in hypothalamic
cause of amenorrhoea
Mechinical device delivers a pulse
of gonadotrophin releasing
hormone subcutaneously every 90
minutes, and this usually leads to
unifollicular ovulation.
Local reactions may occur at the
injection site.
Conception rates are similar to
those in the normal population at
around 20-30% per cycle and 8090% after 12 months' use
Anovulation :Aetiology and
Management
Exogenous Gonadotropin
Therapy
Exogenous Gonadotropin Therapy
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Patient Types
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Substitution - hypogonadal women
Stimulation – women with hypothalamic dysfunction
Regulation - oligo-anovulatory women
Hyperstimulation therapy – women undergoing
Assisted Reproductive Technology procedures
Anovulation :Aetiology and
Management
Exogenous Gonadotropin
Therapy
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Objective: simulate a normal
menstrual cycle
Action: override the hypothalamicpituitary axis and direct:
the onset and duration of follicular
development
 the timing and number of follicles that
reach maturity
 the production of gonadal steroids
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Anovulation :Aetiology and
Management
Follicle stimulating hormone injections
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used in women with hypothalamic-pituitary causes of
anovulation, and for women with polycystic ovary
syndrome who have failed to respond to or conceive
using clomifene.
monitored by reproductive specialists with access to
ultrasonography and tertiary care facilities
complicated by ovarian hyperstimulation syndrome and
high order multiple pregnancy
Anovulation :Aetiology and
Management
Approved urinary derived gonadotropins and
recombinant gonadotropins
Trade Name
Established Name
Pergonal
Menotropins (LH,
FSH)
Menotropins (LH,
FSH)
Menotropins (LH,
FSH)
Urofollitropin (FSH)
Humegon®
Repronex
Metrodin HP
(Fertinex)
Bravelle
Gonal-F
Follistim
Urofollitropin (FSH)
Follitropin alpha
(FSH)
Follitropin beta
(FSH)
Anovulation :Aetiology and
Management
Types of Gonadotropin
Therapy Marketed
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Recombinant human gonadotropins
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follitropin alfa (Gonal-f®)
follitropin beta, (Follistim®)
chorionic gonadotropin alfa (Ovidrel®).
Anovulation :Aetiology and
Management
A Typical U.S. Gonadotropin
Treatment Protocol
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Baseline serum estradiol (E2) level
Baseline ultrasound scan
Administer daily for 7 - 10 days
Repeat E2 level and ultrasound
approximately every 2 to 3 days until
follicular maturity is achieved
Administer human chorionic gonadotropin
(hCG) to induce ovulation
Anovulation :Aetiology and
Management
FSH administration regimens
Chronic Low Dose (CLD): S. Franks et al.
75 IU
Days
7
14
hCG
150 IU
112.5 IU
75 IU
21
28
Step Down (SD): B. Fauser et al.
150 IU
112.5 IU
75 IU
hCG
Foll. ³ 10 mm
Sequential (SE): J.N. Hugues et al.
150 IU
112.5 IU
75 IU
6
½
75 IU
12
Foll. ³ 14 mm
hCG
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Anovulation :Aetiology and
Management
Cumulative pregnancy
rates for hypogonadotropic
anovulatory women
treated with
gonadotropins.
(From Lunenfeld B, Insler V. Human gonadotropins.
In: Wallach EE, Zacur HA, eds. Reproductive medicine
and surgery. St. Louis: Mosby-Year Book, 1995:617)
Pregnancy rate
Study
Fleming
1988
Homburg
1990
Hompes
1986
Total
GnRH-a +
Gonadotropin
14/40
Gonadotropin
5/38
5/57
6/65
0/5
4/6
19/102
12/106
Nugent et al Cochrane 2000
OHSS rate
Study
Bachus
1990
Homburg
1990
Hompes
1986
Total
GnRH-a +
Gonadotropin
1/33
Gonadotropin
2/26
8/57
5/65
0/3
0/3
9/93
7/94
Nugent et al Cochrane 2000
Ovarian hyperstimulation syndrome
(OHSS)
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The ovarian hyperstimulation syndrome is
an iatrogenic complication of ovulationinduction therapy
incidence of 0.5 to 5 percent among
patients undergoing ovulation-induction
therapy.
Anovulation :Aetiology and
Management
Ovarian hyperstimulation syndrome (OHSS)
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Causes:
1. increasing stimulated follicles and retrieved oocytes;
2. presence of PCOS;
3. high estrogen level;
4. HCG injection;
Pathophysiology:
1. local and systemic increase in capillary permeability;
2. Inflammatory responses;
Anovulation :Aetiology and
Management
Clinical finding: OHSS
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(1) Mild OHSS
(a) Grade 1, abdominal distention and discomfort
(b) Grade 2, plus nausea, vomiting, and/or diarrhea
associated with ovarian enlargement of 5-12 cm
(2) Moderate OHSS
(a) Grade 3, manifestations of the mild form plus
US evidence of ascites
(3) Severe OHSS
(a) Grade 4, features of moderate OHSS plus clinical evidence
of ascites and/or hydrothorax or breathing difficulties
(b) Grade 5, changes in blood volume, increased blood viscosity
due to hemoconcentration, coagulation abnormalities
and impaired renal function with oliguria Golan et al., Obstet Gynecol Surv 1989; 44:430-40
Anovulation :Aetiology and
Management
Ovarian hyperstimulation syndrome (OHSS)


Examinations:
1. Complete blood account, renal and liver function;
2. Prothrombin time, partial thromboplastin time;
3. Chest X-ray;
4. Trans-vaginal ultrasound;
5. Oxygen saturation;
6. Fluid balance;
7. Serum HCG measurement;
8. Pelvic exam is contraindicated;
Treatment:
1. Prevention of OHSS;
2. Follow-up: Vital signs, fluid intake and output measurement;
3. Admission to hospital;
Anovulation :Aetiology and
Management
Management of OHSS

Mild




Moderate




No need to admit
Increase oral fluid intake
Follow up at regular intervals and report if symptoms worsen
Admit to hospital and assess daily
Start thromboprophylaxis and maintain until patient is discharged
Monitor liver function, urea and electrolytes, full blood count, and
clotting
Severe



Strict fluid balance with input of 3 L or more
May need intravenous albumin
Drain ascites or pleural effusion if symptomatic
Anovulation :Aetiology and
Management
Anovulation :Aetiology and
Management
References

Peter Braude Paula Rowell, Assisted conception. III—Problems with assisted conception BMJ 2003;327:920-923 (18 October),
doi:10.1136/bmj.327.7420.920

Anovulation Diana Hamilton-Fairley, Alison Taylor BMJ 2003;327:546-549 (6 September), doi:10.1136/bmj.327.7414.546

Marken PA, Haykal RF, Fisher JN. Management of psychotropic-induced hyperprolactinemia.Clin Pharm. 1992 Oct;11(10):851-6

ACOG Practice Bulletin; Management of Infertility Caused by Ovulatory Dysfunction; ACOG NUMBER 34, FEBRUARY 2002
Anovulation :Aetiology and
Management