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Management of Ovarian Hyperstimulation Syndrome (GTG 5 - Feb 2016) -…
Management of Ovarian Hyperstimulation Syndrome
(GTG 5 - Feb 2016)
Epidemiology
True incidence unknown
as no mandatory reporting for mild and moderate cases
Lack of internally agreed classification system
Higher incidence
associated with treatments involving
greater degrees of ovarian stimulation
Incidence of mild OHSS
: 33% of IVF cycles
Incidence of moderate or severe OHSS
: 3.1%-8% of IVF cycles
Incidence of hospitalisation due to OHSS
: 0.3%
Commonest complication of IVF treatment
, rare following ovulation induction with clomifene or monofollicular ovulation induction with gondaodtrophins
Outcome of treatment influences incidence
: Higher incidence in cycles where conception occurs and those resulting in multiple pregnancy (role of endogenous HCG)
Reporting
Licensed centres should comply with HFEA and report cases of severe or critical OHSS
Units that treat women with OHSS should inform the licensed centre where fertility treatment was carried out
Any death related to OHSS must be reported to MBRRACE-UK
Pathophysiology
Complication of fertility treatment
which utilises pharmacological ovarian stimulation to increase the number of oocytes and therefore embryos available during assisted reproductive technology
Associated with significant physical and psychosocial morbidity, and even maternal death
Increased vascular permeability
leads to loss of fluid into the third space, manifesting as
ascites
or less commonly, pleural and pericardial effusions
Ovarian enlargement
with local and systemic effects of proinflammatory mediators, including increased vascular permeability and a prothrombotic effect, is responsible for clinical features
Hypovolaemia (severe OHSS
): Typical loss of 20% of calculated blood volume in the acute phase of OHSS.
Exposure of ovaries to HCG or LH following controlled ovarian stimulation by FSH underlies most cases. Exposure of hyperstimulated ovaries ot HCG leads to production of proinflammatory mediators. These include
vascular endothelial growth factor (VEGF)
but a variety of cytokines are also likely to be involved.
Reduced serum osmolality and sodium
: Paradoxical combination of hypovolaemia and hypo-osmolality has been ascribed to a "reset" of osmotic thresholds of vasopressin and thirst to lower osmolality and sodium levels as these women remain able to concentrate and dilute their urine around the new lower level of osmolality. Parallel reseeting of osmotic thresholds is thought to explain observed decreases in serum osmolality and sodium as opposed to electrolyte losses.
If conception occurs,
endogenous HCG
can lead to
worsening of OHSS
. In the absence of pregnancy, recovery is usually complete by the time of the withdrawal bleed.
Severe OHSS is a
prothrombotic state
due to haemoconcentration and vascular endothelial dysfunction. Incidence of thrombosis is between
0.7-10% of cases of OHSS
.
Management
Key principles
: Early recognition and prompt assessment and treatment of women with moderate or severe OHSS
Severe OHSS may require inpatient treatment to manage symptoms and reduce risk of further complications
Most cases self-limiting
, requiring supportive management and monitoring whilst awaiting resolution
Outpatient
Appropriate for
mild or moderate OHSS
and selected cases of severe OHSS
Fluid intake
: Advise to drink to thirst, at least 1 litre/day
Thromboprophylaxis with LMWH
: Women with severe OHSS are at increased risk of VTE
Output monitoring
: Maintain fluid input-output charts. Urine output <1000mls/24 hours or positive fluid balance >1000mls/24 hours should prompt medical review.
Analgesia
: Offer paracetamol and oral opiates including codeine.
Avoid NSAIDs
as they may compromise renal function.
Paracentesis of ascitic fluid
: May be carried out by the abdominal or transvaginal route under ultrasound guidance
Review urgently if worsening signs of symptoms, otherwise review every 2-3 days
Repeat baseline investigations if severity of OHSS worsening
Signs and symptoms of worsening OHSS
Increasing abdominal distension and pain
Shortness of breath
Tachycardia or hypotension
Reduced urine output <1000mls/24 hours or positive fluid balance >1000mls/24 hours
Weight gain and increased abdominal girth
Increasing haematocrit >0.45
Condition usually resolves over a
period of 7-10 days
Inpatient
Consider hospital admission for women who:
Are unable to achieve pain control
Are unable to maintain adequate fluid intake due to nausea
Show signs of worsening OHSS despite outpatient intervention
Are unable to attend for regular outpatient followup
Have critical OHSS
May require
intensive care/MDT
especially in severe or critical OHSS, if there is persistent haemoconcentration and dehydration
Analgesia and anti-emetics
: Offer paracetamol and oral opiates including codeine.
Avoid NSAIDs
as they may compromise renal function.
Correct intravascular dehydration
: Fluid replacement by the oral route, guided by thirst, is the most physiological approach. IV fluid therapy with crystalloids may worsen ascites in the presence of increased capillary permeability.
Acute dehydration
: IV fluid therapy may be required to correct fluid balance, followed by oral fluids to maintain hydration. Crystalloids are useful for initial correction of dehydration in women unable to maintain oral intake.
Strict fluid balance
is needed.
Avoid diuretics
as they further deplete intravascular volume, but they may have a role if oliguria persists despite adequate fluid replacement and drainage of ascites
Paracentesis
Indications for paracentesis
Severe abdominal pain and distension secondary to ascites
Shortness of breath and respiratory compromise secondary to ascites and increased intra-abdominal pressure
Oliguria despite adequate volume replacement, secondary to increased abdominal pressure causing reduced renal perfusion
Should be carried out under
ultrasound guidance either abdominally or transvaginally
, to avoid trauma to enlarged vascular ovaries
Consider
IV colloid therapy
in women who have large volumes of fluid removed
Early drainage
may prevent disease progression and lower the risk of severe complications
Thromboprophylaxis with LMWH
Women with
severe or critical OHSS, have risk factors (reduced mobility, obesity, thrombophilia), or who have been admitted
, should have LMWH
Majority of delayed thromboses occur in the 1st trimester hence women with
severe OHSS
who conceive should be given
thromboprophylaxis until the end of the 1st trimester
Thrombosis in women with OHSS frequently affects
upper body sites and the arterial system
. Patients may present with unusual symptoms including dizziness, loss of vision, and neck pain, and may present
weeks after apparent resolution
of OHSS.
Surgery
: Only indicated if there is a coincident problem such as adnexal torsion, ovarian rupture, or ectopic pregnancy
Note that
risk of ovarian torsion or rupture is increased
in OHSS, particularly in the presence of pregnancy
Risk Factors
Previous history of OHSS or excessive ovarian response to stimulation
Polycystic ovarian syndrome
Increased antral follicle count (AFC)
High levels of anti-Mullerian hormone (AMH)
GnRH agonists > GnRH antagonists
Clinical Presentation
Classical
: Abdominal distension and discomfort following the trigger injection used to promote final follicular maturation prior to oocyte retrieval
History-taking
Time of onset of symptoms relative to trigger
Medication used for trigger (HCG or GnRH agonist)
Number of follicles on final monitoring scan
Number of eggs collected
Number of embryos replaced
Presence of polycystic ovarian syndrome
Time of presentation following trigger injection
1. Early
: Presents within 7 days of HCG injection, usually associated with an excessive ovarian response
2. Late (tends to be more prolonged and severe)
: Presents within 10 or more days after HCG injection, and is usually the result of endogenous HCG derived from an early pregnancy
Important differentials
: Pelvic infection, pelvic abscess, appendicitis, ovarian torsion, cyst rupture, bowel perforation, ectopic pregnancy
Symptoms
Abdominal distension and bloating
Abdominal pain and discomfort
Nausea and vomiting
Breathlessness, inability to lie flat or talk in full sentences
Reduced urine output
Oedema/swelling: Pedal, vulval, sacral
Associated comorbidities such as thrombosis
Examination
General: Oedema (pedal, vulval, sacral), dehydration, HR, RR, BP, body weight
Abdominal: Ascites, palpable masses, peritonism, measure girth
Respiratory: Pleural effusion, pneumonia, pulmonary oedema
Severity of OHSS
Mild
Abdominal bloating
Mild abdominal pain
Ovarian size usually <8cm
Moderate
Moderate abdominal pain
Nausea and vomiting
Ultrasound evidence of ascites
Ovarian size usually 8-12cm
Severe
Clinical ascites +/- hydrothorax
Oliguria <300ml/day or <30ml/hour
Haematocrit >0.45
Hyponatraemia <135
Hypo-osmolality <282
Hyperkalaemia >5
Hypoproteinaemia (albumin 35)
Ovarian size usually >12cm
Life-threatening complications
Renal failure
Acute respiratory distress syndrome (ARDS)
Haemorrhage from ovarian rupture
Thromboembolism
Critical
Tense ascites/large hydrothorax
Haematocrit >0.55
White cell count >25
Oliguria/anuria
Thromboembolism
Acute respiratory distress syndrome (ARDS)
Investigations
Ultrasound
: Ovarian size, pelvic and abdominal free fluid (ascites), ovarian Doppler
Diagnosis
: Combination of elevated haematocrit, hypo-osmolality, and hyponatraemia is indicative of OHSS
Full blood count
Haematocrit
: Haemoconcentration is a useful guide to the degree of intravascular volume depletion
C-reactive protein
: Monitors severity and recovery
Urea and electrolytes
: Hyponatraemia or hyperkalaemia
Serum osmolality
: Hypo-osmolality
Liver function tests
: Elevated enzymes and reduced albumin
Coagulation profile
: Elevated fibrinogen and reduced anti-thrombin
HCG
: To determine outcome of treatment cycle
Other tests
ABG
D-dimers
ECG/ECHO
Chest X-ray
VQ/CTPA
Risks associated with Pregnancy and OHSS
Pre-eclampsia
Pre-term delivery