Ovarian hyperstimulation syndrome (OHSS)
What is OHSS?
OHSS is a systemic clinical disorder and is the most serious complication of infertility treatment, particularly IVF. Any patient undergoing ovulation induction is at risk of developing OHSS, although some are at more risk than others. Severe OHSS is a life threatening complication following ovarian stimulation
Early onset within one to 5 days ogf HCG injection
Late onset between seven and fourteen days after embryo transfer
Incidence of OHSS
Despite careful monitoring, up to one-third of IVF treatment have been reported to be associated with mild forms of OHSS. Moderate and severe OHSS has been reported in 3-8% of IVF cycles (Delvigne and Rosenberg 2002).
How is OHSS diagnosed?
The symptoms usually begin within a week after the egg collection (early OHSS) or 10 days or more after egg collection (late OHSS). Late OHSS is ore likely to be severe and to last longer than early OHSS and is poorly predictable from the antecedent ovarian response to stimulation . Ovarian hyperstimulation syndrome may be classified as mild, moderate, severe or critical OHSS by symptoms, signs, biochemistry and blood tests and ultrasound scan findings. The majority of women have a mild or moderate form of the syndrome and invariably resolve within a few days unless pregnancy occurs, that may delay recovery. The worst cases tends to be associated with pregnancy. It is important to differentiate betwsen OHSS and other conditions that can present in a similar manner. These include ovarian torsion, haemorrhage and pelvic infection following egg collection, ectopic pregnancy and appendicitis.
- Mild OHSS- Patient may complain of abdominal discomfort, a bloated feeling and mild abdominal swelling and nausea. The ovaries are less than 8 cm
- Moderate OHSS- Symptoms of mild OHSS but the swelling and bloating is worse. Abdominal pain and vomiting. Ovarian are usually between 8-12 cm. Fluid may collect in the abdominal cavity (ascitis) causing discomfort.
- Severe OHSS- Symptoms of moderate OHSS but the swelling and bloating is worse. Abdominal pain and vomiting. The patient will feel ill and may suffer from shortness of breath and a reduction in the amount of urine produced. The varian size is usually more than 12 cm with large cysts. Blood tests will demonstrate low protein (hypoproteinaemia) and Haemoconcentration (Haematocrit nore than 45%). Hypoproteinaemia
- Critical OHSS-The abdomen will be severely distended with fluid, difficulty in breathing,The blood will be more concentrated ( (Haematocrit >55%), White cell count will be raised to more than 25 000 ml, and the patient may produce little or no urine (oligo/anuria). The patient may also develop complication such as blood clot and Adult respiratory distress syndrome (ARDS).
What are the complications of OHSS
Complications associated with severe OHHS include thrombosis (blood clot), which is a life threatening complication of OHSS with a reported incidence of 0.7–10% with a preponderance of upper body sites and frequent involvement of the arterial system. There are several case reports documenting ischaemic strokes, and carotid and vertebral artery. Venous thrombosis often presents several weeks after the apparent resolution of OHSS. Other OHSS complications include kidney damage, respiratory failure and twisted ovary (ovarian torsion). .
Causes of OHSS
Cause is unknown but it is likely due to the release of vasoactive products such as Vascular endothelial growth factor-A (VEGF-A) from the enlarged hyperstimulated ovaries caused by fertility drugs These vasoactive substances are released into circulation and causes blood vessels (capillaries) to leak fluid into the abdominal cavity (ascitis) , and in severe case into the space around the heart and the lungs (hydrothorax). Women at risk of developing OHSS include: (Tang et al. Human Reproduction 2006)
Around a third of cases of severe OHSS occur in cycles that would not be considered ‘high-risk’ on the basis of the above parameters, whilst the majority of cycles identified as being ‘high-risk’ do not result in OHSS.
Management options for women at risk of developing OHSS
- Stop HCG and all stimulation but continue with pituitary down regulation will abolish the risk of OHSS, albeit at the cost of wasting IVF treatment cycle.
- Proceed with the egg collection but adminster GnRH antagonist instead of HCG, inseminate the eggs but have any viable embryos frozen and not proceed to fresh embryo transfer in that cycle and undergo subsequent frozen embryo transfer treatment cycle. Concentrated human albumin may be given intravenously at the time of egg collection to reduce symptoms of OHSS.
- Coasting "withhold gonadotropin stimulation and continuing the agonist suppression until estrogen levels declines to acceptable levels before proceeding to egg collection". Coasting longer than 3 days may be associated with lower pregnancy rates.
- Administration of metformin for women with PCOS undergoing IVF shows a reduced incidence of OHSS
- Cabergoline 0.5 mg tablet daily starting on the day of HCG injection and continue for 8 days have been shown to reduce the risk of severe OHSS
What is the treatment of OHSS?
There is no specific treatment. Therapy is based on supportive care until the condition resolve spontaneously. Treatment is guided by the severity of OHSS. Women with mild OHSS and some women with moderate OHSS can be managed on an outpatient basis. The patient is advised to increase oral fluid intake, have regular follow up and to report if symptoms worsen.
Women with severe OHSS and some women with moderated OHSS require admission to the hospital.The aim of the treatment is to help relieving symptoms and prevent omplications. Resolution of symptoms usually occurs in 7 to 10 days if IVF treatment has not resulted in pregnancy. The course may be prolonged if pregnancy occurs in addition, there is a risk of increased severity due to endogenous hCG stimulation. The treatment include the following:
- Checking blood pressure, heart rate, respiratory rate and temperature (every 4-6 hours) depending on clinical status), weight (daily), and measuring abdominal girth (daily)
- Monitoring of fluid intake and output (daily or more often as needed)
- Pain relief with drugs such as paracetamol or codeine. Opiates can be taken if pain is severe. Non steroidal antiinflammatory drugs should not be used because they may compromise kidney function.
- Antisickness drugs to help reduce sickness and vomiting.
- An intravenous drip for hydration and correction of any electrolyte imbalance
- Support tocking and heparin injection to prevent blood clot in the arms, head, neck,lung,and legs etc.
- Paracentesis (a thin needle or a rubber catheter is inserted into the abdomen to drain ascitic fluid) may be required if the abdomen is tense and swollen or there is shortness of breath from severe ascitis.
- Patient need to continue progesterone luteal support.
- Patients with critical OHSS may require management in an intensive-care setting