3. Introduction
• Ovarian hyperstimulation syndrome (OHSS)
was first described in 1943 by Rydberg et al.
as a loss of control over the intended
therapeutic stimulation of the ovaries
• In 1951, the first fatal case of OHSS was
reported
4. Introduction
• Ovarian hyperstimulation syndrome (OHSS)
is an important and potentially fatal
complication of ovulation induction
• Generally self-limiting and varies from mild
to severe life-threatening symptoms that
may require hospital admission in up to
1.9% of all OHSS cases
5. Introduction
• Mainly associated with multifollicular
response seen with gonadotrophin
stimulation but may also occur following
use of clomiphene citrate, gonadotrophin-
releasing hormone and rarely, spontaneous
conception cycles
11. Clinical presentation
• OHSS is generally a self-limiting disorder and
symptoms typically resolve spontaneously
within 7 to 10 days
• Can be described as early or late depending
on time of onset of symptoms
12. Clinical presentation
• Early OHSS occurs within 10 days of hCG
trigger and reflects ovarian response to
exogenous hormone
• Late OHSS occurs more than 10 days after
hCG trigger (≈7 days after ET), response to
endogenous hCG from pregnancy –
prolonged course, risk of severity
19. Treatment
• Management is generally supportive until
spontaneous resolution occurs
• May require hospitalization for severe to
critical OHSS and moderate OHSS with
poor symptom control
20. Treatment
• Patient education – vital component
• Discontinue hCG for luteal support,
progesterone may be used
• Avoid strenuous exercise and sexual
intercourse – risk of torsion
21. Treatment – outpatient care
• Adequate hydration – drink to thirst
• Antiemetics – metoclopramide, cyclizine
• Analgesics – paracetamol, codeine. Avoid
NSAIDs – risk of renal compromise
• Monitoring of care – review every 2-3 days
usually adequate
22. Treatment – outpatient care
• Symptom monitoring – appearance of new
symptoms or worsening of existing ones
• Daily weight measurement –
>2pounds/day (≈1kg/day)
• Monitoring of urinary output
• Urgent clinical review may be required
23. Treatment - hospitalisation
• Usually required for severe cases, poor
symptom control, social considerations
• Multidisciplinary care, intensive care
• Mainly analgesics and antiemetics, fluid
management, thromboprophylaxis and
treatment of complications
24. Treatment - hospitalisation
•Fluid management:
• Oral fluid intake preferable to intravenous
• 2-3L/day of fluid with strict fluid balance
• Urine output >20-30ml/hr
• Avoid worsening third-space fluid shift
• Correction of hypovolaemia, hypotension
and haemoconcentration
25. Treatment - hospitalisation
• Fluid management:
• Crystalloids – use of physiological saline or
dextrose in normal saline preferred over
ringer’s lactate – hyponatraemia
• Colloids like albumin, mannitol, dextran,
hydroxyethyl starch (HES) may be required
for plasma expansion
26. Treatment - hospitalisation
•Fluid management:
• Diuretics avoided due to depletion of
intravascular volume. May have a role in
cases of persistent oliguria despite
adequate intravascular volume expansion
and normal intraabdominal pressure
(after paracentesis)
33. OHSS and pregnancy
• Severe OHSS commonly associated with
pregnancy
• Pregnancy may continue normally despite
OHSS
• No evidence of increased risk of congenital
abnormalities
34. Prevention
• Begins with identification of patients at-
risk
• Prior history of OHSS
• Young age
• Low BMI
• Polycystic ovarian syndrome (PCOS)
• Use of GnRH-agonists
35. Prevention
• Increased antral follicle count; ≥ 24
• High anti-Mullerian hormone; ≥ 3.36ng/ml
• Multiple follicles (>14 follicles with diameter of
11mm)
• Rapidly rising serum oestradiol level
• Prevention can be primary or secondary
36. Prevention – primary
• Reduced dose of gonadotrophins - chronic
low-dose step-up protocol, limited ovarian
stimulation, avoiding FSH on day of hCG
trigger; response monitored with serial
ultrasound scans and serum oestradiol
levels (2,500pg/ml threshold for risk)
37. Prevention – primary
• Reduced duration of exposure to
gonadotrophins – mild stimulation
protocol (clomiphene, GnRH-antagonists)
• Use of GnRH-antagonist protocols (cf
agonist) for controlled ovarian stimulation
38. Prevention – primary
• No use of hCG for luteal support
• In-vitro maturation of oocytes
• Use of insulin-sensitizing agents like
metformin in patients with PCOS
39. Prevention – secondary
• Coasting – withhold further gonadotropin
stimulation and delay hCG administration
until oestradiol levels plateau or decrease
significantly. No reduction in incidence of
moderate and severe OHSS in RCTs. Delay
usually less than 3 days.
40. Prevention – secondary
• Cycle cancellation – waste of resources,
risk of spontaneous ovulation
• Reduced hCG doses as ovulation trigger –
5,000 IU cf 10,000IU used successfully in
some centres
41. Prevention – secondary
•Alternative ovulation triggers –
• GnRH-agonists in antagonist-stimulated
cycles – likelihood of clinical pregnancy
lower
• recombinant LH – lower pregnancy rate,
poor cost/benefit ratio
42. Prevention – secondary
• Cryopreservation of oocytes – prevents
late OHSS and exacerbation of early OHSS
by pregnancy
• Dopamine agonists like cabergoline
reverse VEGF-mediated vascular
permeability. Started on day of hCG trigger
as 0.5mg for 8 days.
47. Conclusion
• Ovarian hyperstimulation syndrome is a
mostly iatrogenic and self-limiting disorder
• Good clinical acumen required to diagnose
• Multiple options of prevention available to
reduce incidence and limit severity
48. References
• Khalid S, Gray T, Hashim SS. Ovarian hyperstimulation
syndrome. InnovAiT: Education and inspiration for general
practice. 2015 Sep 1;8(9):531-8.
• Mahajan N. Ovarian hyperstimulation syndrome. Int J Infertil
Fetal Med. 2013 Sep;4:71-8.
• Onofriescu AL, Luca A, Bors A, HOLICOV M, ONOFRIESCU M,
VULPOI C. Principles of diagnosis and management in the
ovarian hyperstimulation syndrome. Curr Health Sci J. 2013 Jul
1;39:187-92.
• Kaur H. Prevention of Ovarian Hyperstimulation Syndrome.
Journal of Infertility and Reproductive Biology. 2013;1(4):63-8.
• Smith V, Osianlis T, Vollenhoven B. Prevention of Ovarian
Hyperstimulation Syndrome: A Review. Obstetrics and
gynaecology international. 2015 May 14;2015.