Ovarian Hyperstimulation Syndrome (OHSS)

Ovarian Hyperstimulation Syndrome (OHSS)


Ovarian hyperstimulation syndrome (OHSS) is a rare complication of ovarian stimulation during infertility treatments.

During IVF treatment the ovaries are stimulated by daily hormone injections to retrieve enough number of eggs. However, the unpredictable response of the ovaries to ovulation induction makes the prediction and prevention of OHSS difficult. Hence, heightened clinical suspicion and early intervention of OHSS are paramount to the reduction of morbidity and mortality.

Ovarian stimulation for IVF is associated with up to a 5% risk of severe ovarian hyperstimulation syndrome. Human chorionic gonadotrophin (hCG) is given as a "trigger" so that a mature follicle will release its egg.

OHSS usually happens within a week after receiving an hCG injection. If pregnancy occurs during that treatment cycle, OHSS may worsen as the body also begins producing its own hCG in response to the pregnancy.

OHSS is characterized by ovarian enlargement due to multiple ovarian cysts and an acute fluid shift into the extravascular space. Complications of OHSS include ascites, hemoconcentration, hypovolemia, and electrolyte imbalances.

What are the risk factors for OHSS?

  • Polycystic ovary syndrome (PCOS)-anovulatory infertility,
  • Serum Anti-Müllerian Hormone (AMH) level >3.3ng/mL,
  • BMI less than 25 kg/m2,
  • OHSS history- Previous episodes of OHSS,
  • Age under 35,
  • Presence of >10 antral follicles in the ovary,
  • Presence of more than 15 follicles greater than 12 mm in diameter during ovulation stimulation,
  • High or rapidly rising serum estradiol concentration,
  • The risk increases as the number of oocytes collected in IVF increases,
  • Using hCG instead of progesterone for luteal phase support,
  • Establishment of a successful pregnancy.

Timing of OHSS

Early-onset OHSS: Early-onset OHSS developes in less than 10 days from egg collection, and related to ovarian stimulation protocols and hCG trigger shot.

Late-onset OHSS: Late-onset OHSS developes 10 days after egg collection, and related to endogenous hCG production from the pregnancy.

Stages of OHSS

The cause of ovarian hyperstimulation syndrome is not fully understood. Having a high level of human chorionic gonadotropin (hCG) — a hormone usually produced during pregnancy — introduced into the 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.

OHSS is generally self-limiting and conservative. It is a manageable disease. Pregnancy may cause symptoms to persist for a longer period of time. The key point in the management of OHSS is the correct management of patients. For this, it is important first of all to determine the stage of the disease.

  • Mild - 8-23%,
  • Moderate - 1-7%,
  • Severe - 0.25-5%.

Mild to moderate OHSS

With mild to moderate ovarian hyperstimulation syndrome, symptoms can include:

  • Mild to moderate abdominal pain,
  • Abdominal bloating or increased waist size,
  • Mild Nausea-Vomiting,
  • Diarrhea,
  • Tenderness in the area of ovaries,
  • In moderate form there is free fluid in the abdominal cavity (ascites).

Severe OHSS

  • Rapid weight gain — more than 1 kilogram in 24 hours,
  • Fluid collection in the abdomen and sometimes the chest,
  • Severe abdominal pain,
  • Tight or enlarged abdomen,
  • Severe, persistent nausea and vomiting,
  • Blood clots in large vessels, usually in the legs,
  • Electrolyte disturbances (sodium, potassium, others),
  • Twisting of an ovary (ovarian torsion),
  • Rupture of a cyst in an ovary, which can lead to serious bleeding,
  • Decreased urination,
  • Shortness of breath,
  • Low blood pressure and central venous pressure,
  • Syncope.

Critical OHSS

  • No urination/acute renal failure,
  • Arrhythmia,
  • Pericardial effusion,
  • Massive hydrothorax,
  • Thromboembolism,
  • Arterial thrombosis,
  • Acute respiratory distress syndrome (ARDS),
  • Sepsis,
  • Rarely death.

Prevention of OHSS

To decrease the risk of developing ovarian hyperstimulation syndrome, an individualized plan for fertility medications is needed.

Fortunately, with the prevention strategies, in particular with the increased utilization of GnRH-antagonist cycles, GnRH-agonist-only or dual hCG/GnRH-agonists triggers, and elective freeze-all cycles, and carefully monitoring the treatment cycle, including frequent ultrasounds to check the development of follicles severe OHSS has become increasingly rare in most IVF clinics.

Strategies to help prevent OHSS are

  • Adjusting medication: Using the lowest possible dose of gonadotropins to stimulate the ovaries and GnRH-antagonist for prevention of premature follicle rupture.
  • Adding medication: Giving women who have polycystic ovary syndrome the drug metformin during ovarian stimulation may help prevent hyperstimulation.
  • Coasting: If estrogen level is high or a large number of follicles developed, injectable medications are stopped for a few days before triggering ovulation. This is known as coasting.
  • Avoiding use of an HCG trigger shot: Because OHSS often develops after an hCG trigger shot is given, alternatives to hCG for triggering have been developed such as using GnRH-agonist-only or dual hCG/GnRH-agonists triggers.
  • Medications after egg collection: Some medications seem to reduce the risk of OHSS without affecting the chance of pregnancy. These are low-dose aspirin, dopamine agonists such as carbergoline and calcium infusions.
  • Freezing embryos: After egg collection, all mature eggs are fertilized and all embryos are frozen and the ovaries are allowed to rest. At a later date, a few months later when the body is ready, frozen-thawed embryos are transferred.

Management of OHSS

In PCOS women injectable fertility drugs generally causes a mild to moderate form of OHSS. This usually goes away after about a week. But, if pregnancy occurs, symptoms of OHSS may worsen and last several days to weeks.

Even if it is a mild case of OHSS observation for sudden weight gain or worsening symptoms is necessary. The developement of breathing problems or pain in the legs during the fertility treatment may indicate an urgent situation that needs prompt medical attention.

Indeed, mild OHSS patients can be treated as an outpatient, while severe and critical OHSS patients have an indication for hospitalization (sometimes even intensive care conditions).

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