Ovarian hyperstimulation syndrome: Causes and more

Ovarian hyperstimulation syndrome or OHSS is a clinical disorder that occurs following artificial reproductive technique most commonly following inject-able gonadotropins very rarely with clomiphene citrate.
Women with Ovarian hyperstimulation syndrome have a large number of growing follicles along with high estradiol levels. This leads to fluid leaking into the abdomen (belly), which can cause bloating, nausea, and swelling of the abdomen.
There is acute fluid shift into the extravascular space and there is ascites as well. When Ovarian hyperstimulation syndrome (OHSS) is severe, blood clots, shortness of breath, abdominal pain, dehydration, and vomiting are possible. Rare deaths are reported.


The cause of ovarian hyperstimulation syndrome isn’t fully understood. Having a high level of human chorionic gonadotropin (HCG) — a hormone usually produced during pregnancy — introduced into your system plays a role. Ovarian blood vessels react abnormally to HCG and begin to leak fluid. This fluid swells the ovaries, and sometimes large amounts move into the abdomen.

During fertility treatments, HCG may be given as a “trigger” so that a mature follicle will release its egg. OHSS usually happens within a week after you receive an HCG injection. If you become pregnant during a treatment cycle, OHSS may worsen as your body begins producing its own HCG in response to the pregnancy.

Injectable fertility medications are more likely to cause OHSS than is treatment with clomiphene, a medication given as a pill you take by mouth. Occasionally OHSS occurs spontaneously, not related to fertility treatments.


Symptoms of OHSS often begin within a week after using injectable medications to stimulate ovulation, though sometimes it can take two weeks or longer for symptoms to appear. Symptoms can range from mild to severe and may worsen or improve over time.

Mild to moderate OHSS

With mild to moderate OHSS, symptoms can include:

Ovarian hyperstimulation syndrome – classification

OHSS is of three forms

  • Mild Ovarian hyperstimulation syndrome
  • Moderate Ovarian hyperstimulation syndrome
  • Severe Ovarian hyperstimulation syndrome

Mild Ovarian hyperstimulation syndrome is classified as follows:

  • Grade 1: Abdominal distention and discomfort
  • Grade 2: Grade 1 disease plus nausea, vomiting, and/or diarrhea, as well as ovarian enlargement of 5-12 cm

Moderate Ovarian hyperstimulation syndrome (OHSS) is classified as follows:

  • Grade 3: Features of mild OHSS plus ultrasonographic evidence of ascites

Severe Ovarian hyperstimulation syndrome (OHSS) is classified as follows:

  • Grade 4: Features of moderate OHSS plus clinical evidence of ascites and/or hydrothorax and breathing difficulties
Grade 5: All of the above plus a change in the blood volume, increased blood viscosity due to hemoconcentration, coagulation abnormalities, and diminished renal perfusion and function

Ovarian hyperstimulation syndrome clinical features

  1. Abdominal pain, nausea and vomitting

This is because of accumulation of fluid in the abodminal cavity and enlargement of ovaires. Ovaries can enlarge to as much as 25 cm

2. Ascitis and abdominal distention

This  is bcause of accumulation of fluid in the abdominal cavity and causes discomfort due to increased abdominal presure due to distention. This is because of extravasation of fluid form the intravascular compartment into the abdominal cavity. Accumulation of fluid is also due to:

  • Rupture of follicles.
  • leakage of fluid from large follicle.
  • Increased capillary permeability

3. Localised or generalised peritonitis

This is caused by:

  •  The blood released by the ruptured follicles.
  • Protein rich fluid.
  • Inflammatory mediators

4. Acute abdominal pain

This is due to:

  • ovarian torsion
  • Rupture of follicles
  • Intraperitoneal hemorrage

5. Dyspnoea

This is due to:

  • enlarged ovary and ascitis that restrict diaphragmatic movement
  • Pleural effusion
  • Pulmonary edema
  • pericardial effusion
  • Atelectasis
  • Acute respiratory distress syndrome
  • Pulmonary embolism

6. Hypercoagulable state

This is  due to:
Hemoconcentration and hypovolemia due to extravasation and third space shift
Consequence of this state is:

  • Deep vein thrmbosis
  • Pulmonary embolism

7. Electrolyte imbalance

This is due to:

  • Extravasation of fluid
  • Renal dysfunction
  • Consequence of imbalance
  • increased absortion of sodium and water in proximal tubule so there is oliguria and reduced urinary sodium
  • Hydrogen and pottasium is exchanged for sodium in distal tubule so there is hyperkalemia and acidosis

8. Acute renal failure

This is due to:

  • hemoconcentration
  • hypercoagulable state
  • microthrombi in tubule leads to decreased renal perfusion

9. Hypotension and hypovolemia

Follicular fluid and perifollicular blood containing large amounts of vascular endothelial growth factor (VEGF), which is thought to increase vascular permeability, escape into the peritoneal cavity.

Blood vessels within and outside the ovary become functionally impaired, resulting in the leakage of fluid through those vessels and a massive fluid shift from the intravascular to the extravascular compartment.

This process results in intravascular hypovolemia with the concomitant development of edema, ascites, hydrothorax, and/or hydropericardium.

Risk factor for Ovarian hyperstimulation syndrome (OHSS)

  • age less than 35
  • low body mass index (BMI)
  • high estradiol concentration
  • large number of follicles
  • PCOD
  • administration of exogenous HCG

Epidemiology of  Ovarian hyperstimulation syndrome (OHSS)

Rate of occurence is as follows:

  • mild – 8-23%
  • moderate 1-7%
  • severe 0.25-5%

Risk is more in patients who take a combination of gonadotrophins and GnRH agonist. Its seen only in women of child bearing age group

Investigations for Ovarian hyperstimulation syndrome (OHSS)

Investigations and tests to be done are:

  • Weight and size of the belly is measured
  • Abdominal ultrasound and vaginal ultrasound
  • Chest Xray
  • Complete blood count
  • electrolyte panel
  • liver function test
  • urine output measurement

Prognosis of Ovarian hyperstimulation syndrome (OHSS)

In mild and moderate forms the prognosis is very good but to an extent morbidity is present. In severe form fatalities have been reported. The fatality is 1:400000. The fatality is due to pulmonary embolism, hypovolemia, electrolyte imbalance and haemorrhage

Complications of  Ovarian hyperstimulation syndrome (OHSS)

  • Blood clots
  • Kidney failure
  • Severe electrolyte imbalance
  • Severe fluid buildup in the abdomen or chest

Treatment of OHSS

  • Rest with legs raised this helps to release the extra fluid form the body. Mild activity is recommended.
  • 10-12 glasses of water to be taken
  • Alcohol, coffee and tea to be avoided
  • Exercise and sexual intercourse to be avoided as this would increase the chance of follicle rupture
  • pain relief is done with pain killers such as acetaminophen
  • everyday weight check




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