Description

• Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic physiologic complication of controlled ovarian hyperstimulation (COH) (most often related to treatment for infertility).
• Results in ovarian enlargement, increased vascular permeability with resulting third-space loss and intravascular fluid depletion, electrolyte imbalance, hemoconcentration, and ascites
• Classification of OHSS is based on clinical symptoms and ultrasound (US) findings:
  • Mild: abdominal distension and discomfort
  • Moderate: abdominal distension, enlarged ovaries (8 to 10 cm³), and ascites on US (largest pocket <3 cm)
  • Severe: clinical evidence of ascites and/or hydrothorax, hemoconcentration >45%
  • Critical: hemoconcentration >55%, creatinine clearance <50 mL/min, renal failure, thromboembolism, acute respiratory distress syndrome (ARDS)
• Symptoms of OHSS may occur early (within 10 days of human chorionic gonadotropin [hCG] administration) or late (>10 days after hCG administration). Late OHSS is usually associated with a pregnancy and may often be more severe.

Epidemiology

Incidence

• Predominant age: women of reproductive age
• With COH and in vitro fertilization (IVF)
  • Mild OHSS: 20–33% of cycles
  • Moderate OHSS: 3–6% of cycles
  • Severe OHSS: 0.1–2% of cycles

Etiology and Pathophysiology

• Ovarian hyperstimulation leads to increased capillary permeability and intravascular fluid shifts.
• Fluid shifts can lead to ascites and pleural effusions.
• Intravascular volume depletion can lead to hemoconcentration, decreased renal perfusion, and thrombosis.
• The ovarian renin–angiotensin system, cytokines, and other inflammatory mediators, such as vascular endothelial growth factor (VEGF), may play a role in the pathophysiology of OHSS.
• OHSS is an iatrogenic syndrome that occurs during COH for infertility treatment.
• Generally, OHSS is associated with the use of exogenous gonadotropins, such as recombinant or purified follicle-stimulating hormone (FSH).

Risk Factors

• Previous history of OHSS
• Young age
• Low body weight
• Polycystic ovary syndrome (PCOS) or polycystic ovaries on US
• Large number of resting follicles (>10 follicles between 2 and 8 mm) per ovary
• High doses of gonadotropins
• Large number of intermediate-sized follicles
• Number of oocytes retrieved
• Rapidly rising estradiol levels
• High estradiol levels >3,000/4,000 pg/mL
• Use of hCG for luteal support
• Achievement of a pregnancy
• Multiple pregnancy

General Prevention

• Patients who have had OHSS are more at risk for OHSS in the future, and this should be taken into consideration in subsequent treatment cycles. Patients need to inform their health care providers of a history of OHSS when considering further assisted reproductive technology treatment.
• A general principle in the prevention of OHSS is to recognize patients at high risk based on the above-list risk factors and to use a GnRH antagonist protocol, low doses of stimulation, and frequent monitoring.
• If a patient develops risk factors during stimulation, consideration should be given to the use of a GnRH agonist to trigger ovulation in GnRH antagonist cycles (1)[A].
• Other preventative measures can include cancelling the cycle by withholding the preovulatory injection of hCG, proceeding with a lower dose of hCG, “coasting” or withholding stimulatory drugs for several days to allow for estradiol levels to plateau or decrease, avoiding the use of hCG for luteal supporting, or freezing all viable embryos without proceeding with an embryo transfer (1)[C].
• Off-label use of dopamine agonists (cabergoline 0.5 mg) after hCG administration may decrease the incidence of OHSS (2)[A].
• GnRH antagonists may reduce the incidence of early OHSS (3)[B].
• Plasma expanders may reduce the incidence of moderate or severe OHSS in patients at high risk (4)[B].

Commonly Associated Conditions

• Infertility
• PCOS
• Assisted reproductive technologies