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The management of ovarian hyperstimulation syndrome
 

As the number of Assisted Reproductive Techniques (ART) cycles in Malaysia increases, it is expected that the number of cases of Ovarian Hyperstimulation Syndrome (OHSS) will also increase in tandem. Most assisted conception treatment is conducted in very specialised settings and it is not surprising therefore that many gynaecologists are unfamiliar with the management of this condition, though they may come across it in their practice. This article attempts to provide the general gynaecologists a guide as to how to diagnose and treat this condition.

OHSS is a systemic disease resulting from the release of vasoactive products by hyperstimulated ovaries. It is typically associated with exogenous gonadotrophin administration. The pathophysiology revolves around an increase in capillary permeability resulting in a fluid shift from the intravascular space to third space compartments. Vascular endothelial growth factor (VEGF), a vascular permeability factor which plays an integral role in follicular growth, corpus luteum function and ovarian angiogenesis is implicated in this condition. The levels of VEGF correlate to severity of OHSS.

This is not an uncommon condition, with mild to moderate OHSS occurring in 33% of ART cycles while severe to critical OHSS, 3-8% of ART cycles. There are two typical timing to the onset of OHSS. The early onset OHSS occurs typically within 9 days after Human Chorionic Gonadotrophin (hCG) administration, and is likely to be due to precipitating effect of exogenous hCG. The late onset OHSS (after 9 days), is more likely to be due to endogenous hCG  from pregnancy.

It is important to recognise the risk factors for the development of OHSS. This includes young age (<30 yrs), low body weight, Polycystic Ovarian Syndrome (PCOS), the use of GnRH agonists, higher doses of exogenous gonadotrophins, high or rapidly rising serum oestradiol levels, exposure to Luteinizing Hormaone or hCG and previous episodes of OHSS.
 
 
Classification (modified Mathur 2005)
    
     
Mild

Abdominal bloating

Mild abdominal pain
Ovarian size<8cm
   
   
Severe
Clinical ascites (occasional hydrothorax)
Pulse rate≥100 bpm
Oliguria
Haemoconcentration (Hct>45%)
 

Moderate

Moderate abdominal pain
Nausea± vomiting
Pulse rate<100 bpm
US evidence of ascites
Ovarian size usually 8-12cm
   
Critical
Tense ascites or large hydrothorax
Pulse rate≥100 bpm
Haematocrit>55%
 
 
Outpatient Management with or without admission to Day Ward
 
Outpatient treatment is suitable for mild, moderate and some of severe OHSS. The mainstay of treatment is supportive with analgesics (opiods-DF118, PCM), antiemetics and antacids. The patient is advised to drink to thirst and concentrate on fluids like isotonic drinks. If possible she is advised to increase protein intake in her diet. The clinician should consider albumin 20% infusion about 50 to 100 mls. The patient’s weight and abdominal girth should be monitored and pelvic ultrasound is carried out to check the ovarian sizes and presence of ascites. Important laboratory  tests include haemoglobin, haematocrit, serum electrolytes, creatinine and liver function tests. The patient can be allowed home and is reviewed every two or three days. Her luteal support can be continued provided hCG is avoided.
   
Inpatient Management
 
Most patients with severe OHSS especially those with persistent haemoconcentration and dehydration, and all patients with critical OHSS should be admitted to hospital for further management. The management of this condition requires a multidisciplinary approach. The mainstay of treatment is also supportive care with intravenous fluids (2-3 L/day), albumin 20% infusion 100-150mls two or three times a day, analgesics and antiemetics. As the risk of thrombosis is 0.7-10%, thromboprophlaxis  should be considered. The patient’s fluid balance, abdominal girth and weight should be monitored. Consider performing chest ultrasound if hydrothorax is suspected as well as ECG or echocardiography as well if necessary. If the patient is very uncomfortable, consider paracentesis or pleural drainage.
   
 

Paracentesis:
Significant discomfort and respiratory embarassment
Persistent oliguria : relief of intraabdominal pressure may promote renal perfusion and improve urine output
Drainage of ascitic fluid may resolve hydrothorax
Rate of ascitic fluid drainage should be controlled (< 3 L/day)  to prevent cardiovascular collapse due to massive fluid shifts
Cover with intraveous colloids
 
   
Prevention
 

As the saying goes, prevention is better than cure. ART practitioners should consider using the lowest dose and duration of stimulatory drug as far as possible. The index of suspicion should be high in patients with risk factors. In women who are likely to be a hyper responder or has polycystic ovaries, consider the GnRH antagonist protocol or ovarian drilling prior to IVF, though this may not be agreeable to all practitioners.

If exaggerated ovarian response occurs, preventive measures can be employed which may help prevent one severe OHSS in every 18 treated. If there are 20-25 follicles above 12mm and the patient is asymptomatic, trigger with a reduced hCG dose of 5000-7500 iu (or Ovidrel 6500iu). Administer IV Albumin 20% 100 mls and 500 mls of Ringer’s lactate at the time of oocyte retrieval.

If there are more than 25 follicles above 12mm or more than 15 follicles above 12mm and the patient is symptomatic, the following should be considered:

  1. if leading follicle<16mm, reduce the FSH dose by 50-75 iu per day and scan every 2 days.
  2. if leading follicle>16mm, measure serum oestradiol. If the oestradiol level is between 10,000 to 15,000 pmol/l, reduce the FSH dose by 50-75 iu per day and when ready, trigger with hCG 5000iu and give Albumin and fluids during ooyte retrieval. If the oestradiol level is above 15,000 pmol/l, start coasting (i.e. omit FSH but maintain the GnRH Antagonist or GnRH agoinst). Check oestradiol level daily if the level is between 15,000-25,000 pmol/l or every two days if oestradiol level is above 25,000 pmol/l.
Consider triggering once the oestradiol level is below 15,000 pmol/l with hCG 5,000 iu and give albumin and fluids as above. Aspirate and flush all follicles to reduce the number of granulosa cells or increase suction pressure to 110 kP.

Coasting reduces the number of eggs collected but does not adversely affect the outcome of IVF unless prolonged (more than 3 days). We can also consider triggering  with GnRH agonist (eg leuprolide 0.5 to 1.0mg SC). However, this is useful only in cycles not involving long down regulation.

Luteal support using hCG should be avoided completely. The clinician should consider elective Single Embryo Transfer (SET) with blastocyst or in the worse case scenario, freeze all embryos if critical OHSS develops.
   
References
 

1. Ovarian Hyperstimulation Syndrome: ASRM Practice Committee. Fertility and Sterility Vol 86, Suppl 4, November 2006
2. The Management of Ovarian Hyperstimulation Syndrome: The RCOG Green-top Guideline No. 5, September 2006

Dr Wong Pak Seng, MOG, MRCOG
   
Disclaimer
 
For Patients:
The health information provided in this website is not intended as a substitute for medical advice, diagnosis, or treatment.  Always consult your own physician for your own specific medical condition.

For Health Professionals:
While efforts has been made to get the relevant experts in each topic to contribute, the views and opinions of authors expressed in this section do not necessarily reflect those of the OGSM.
   
     
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