Ovarian hyperstimulation syndrome

Overview

Ovarian Hyperstimulation Syndrome (OHSS) is a potentially serious iatrogenic (treatment-induced) complication that occurs in some women undergoing fertility treatments, particularly those involving ovulation induction with injectable gonadotropins. OHSS is characterized by excessive stimulation of the ovaries, leading to enlarged ovaries and fluid shifts from the intravascular space to the third spaces (e.g., abdominal cavity, pleural cavity), which can result in ascites, pleural effusion, and even thromboembolic events in severe cases.

OHSS can be mild, moderate, or severe, with most cases being self-limiting. However, in rare instances, it can lead to significant morbidity and may even be life-threatening. Careful monitoring and individualized treatment protocols during assisted reproductive techniques (ART), such as in vitro fertilization (IVF), are key to minimizing the risk of OHSS.

Causes

OHSS is caused by an exaggerated ovarian response to ovulation induction medications, particularly exogenous gonadotropins such as human chorionic gonadotropin (hCG) or recombinant follicle-stimulating hormone (FSH). These hormones stimulate the growth of multiple ovarian follicles, leading to the release of vasoactive substances like vascular endothelial growth factor (VEGF), which increase capillary permeability and cause fluid leakage into third spaces.

Risk Factors

• High doses of gonadotropins

• Young age (typically under 30)

• Low body weight

• Polycystic ovary syndrome (PCOS)

• High estradiol levels during stimulation

• Large number of developing follicles (>20)

• Pregnancy after ovulation induction (especially with hCG trigger)

• Previous history of OHSS

Symptoms

The symptoms of OHSS typically appear within 4–10 days after ovulation induction or egg retrieval. They can vary in severity and are categorized as mild, moderate, or severe.

Mild OHSS

• Abdominal bloating

• Mild to moderate pelvic discomfort

• Ovarian enlargement (usually less than 8 cm)

Moderate OHSS

• More pronounced abdominal distension

• Nausea and vomiting

• Ultrasound showing significant ovarian enlargement (8–12 cm)

• Ascites may be detected on imaging

Severe OHSS

• Severe abdominal pain

• Rapid weight gain due to fluid accumulation

• Ascites and pleural effusion

• Oliguria (low urine output)

• Hemoconcentration and electrolyte imbalances

• Shortness of breath (due to pleural effusion)

• Thromboembolic events (e.g., deep vein thrombosis or pulmonary embolism)

Diagnosis

Diagnosis of OHSS is based on clinical presentation, recent fertility treatment history, physical examination, and imaging studies. Laboratory tests are used to evaluate the severity and rule out complications.

Clinical History

• Recent ovulation induction or IVF cycle

• Symptom onset within days after hCG administration

Physical Examination

• Abdominal distension and tenderness

• Signs of fluid accumulation (e.g., shifting dullness)

• Signs of dehydration or low blood pressure in severe cases

Imaging

• Transvaginal ultrasound: To assess ovarian size and the presence of multiple enlarged follicles

• Abdominal ultrasound: To detect ascites or pleural effusion

Laboratory Tests

• Hemoglobin and hematocrit (to assess hemoconcentration)

• Electrolytes and kidney function (to detect dehydration and renal impairment)

• Beta-hCG test (to confirm pregnancy, which may worsen OHSS)

• D-dimer and coagulation profile (in severe cases with suspected thrombosis)

Treatment

Treatment depends on the severity of the syndrome and whether the patient is pregnant. Mild to moderate OHSS can usually be managed on an outpatient basis, while severe OHSS often requires hospitalization and intensive care.

Outpatient Management (Mild to Moderate OHSS)

• Encourage oral hydration

• Monitor weight, abdominal girth, and urinary output

• Avoid strenuous activity and intercourse (to prevent ovarian rupture or torsion)

• Analgesics for pain relief (avoid NSAIDs if pregnant)

• Anti-emetics if nausea is significant

Inpatient Management (Severe OHSS)

• Intravenous fluids: To maintain hemodynamic stability

• Paracentesis: For symptomatic ascites or respiratory distress

• Thromboprophylaxis: Low molecular weight heparin for preventing blood clots

• Electrolyte correction: If imbalances are present

• Oxygen therapy: If pleural effusion leads to hypoxia

• Intensive monitoring: For urine output, renal function, and vital signs

Prevention

• Use of lower doses of gonadotropins in high-risk patients

• Monitoring estradiol levels and follicle number during stimulation

• Coasting: Withholding gonadotropins when estradiol levels are too high

• Using a GnRH agonist trigger instead of hCG in certain protocols

• Cycle cancellation: In very high responders at risk of severe OHSS

Prognosis

Most cases of OHSS are self-limiting and resolve within 1 to 2 weeks, especially if pregnancy does not occur. In cases where pregnancy is achieved, symptoms may persist longer and require more careful monitoring due to the continued production of endogenous hCG.

With timely diagnosis and appropriate management, the majority of patients recover fully without long-term complications. However, severe OHSS carries a risk of serious complications such as renal failure, thromboembolism, and, rarely, death. Preventive strategies and individualized stimulation protocols are essential to reduce the incidence of OHSS in assisted reproductive technology.