Fostering Fertility: despite ovarian hyperstimulation
Ob/Gyns are increasingly likely to find themselves managing ovarian hyperstimulation syndrome, a troubling and potentially life-threatening complication of ovulation induction. Here, an expert discusses predicting, preventing, and treating this challenging condition.
Although follicle aspiration with IVF probably reduces the risk of early OHSS, late disease is still a threat if conception occurs. For this reason, cryopreservation of all embryos (for later transfer during a spontaneous ovulatory cycle) should eliminate that risk as well. The low rates of severe OHSS seen with oocyte donors testify to the effectiveness of this practice.18 In the near future, immature oocytes from unstimulated ovaries may be matured and fertilized in vitro with high efficiency, eliminating the need for exogenous gonadotropins and the risk of OHSS.
Albumin. Asch et al administered 50 g of albumin intravenously to 36 patients at risk for severe OHSS at oocyte retrieval for IVF, and none developed clinically significant OHSS.19 They hypothesized that albumin helps prevent OHSS by increasing oncotic pressure. Albumin also may act as a carrier protein to sequester a vasoactive substance secreted by the corpus luteum. However, the results of several subsequent studies were conflicting.
Further, although albumin appears to be safe, it is expensive and tends to cause flulike symptoms such as low-grade fever, chills, myalgia, and urticaria.16,19 Since we are unable to reliably predict which patients will develop severe OHSS, the use of albumin for patients undergoing gonadotropin superovulation is not advised at this time.
Treatment of OHSS
Because OHSS may develop despite our best efforts to predict and prevent it, all patients should be thoroughly counseled about its risks and implications prior to treatment with gonadotropins. Once OHSS occurs, the most important determination to be made is which patients should be hospitalized.
Patients with mild OHSS should be placed on pelvic rest. That is, they should avoid any activity that could cause the enlarged cystic ovaries to rupture or undergo torsion. Fortunately, OHSS usually resolves spontaneously within 2 weeks of hCG administration, although it may take longer for the cysts to involute completely.1,3
The management of moderate OHSS is outlined in Table 2. Patients should be placed on pelvic rest and advised to maintain adequate fluid intake and monitor their weight and abdominal girth daily. Any significant changes should be relayed to their physician immediately, as should decreased urine output, shortness of breath, nausea or vomiting, or worsening abdominal pain. A pregnancy test should be obtained if any of these effects occur, as the condition may deteriorate suddenly if conception occurs. In addition, patients should be monitored as needed with ultrasonography. Recommended laboratory studies include electrolytes, blood urea nitrogen (BUN), creatinine, and a complete blood count (CBC). Oral analgesics and antiemetics should be prescribed as needed.
As I mentioned at the beginning of this article, patients with severe OHSS should be hospitalized (Table 3). They should be restricted to bed rest with bathroom privileges and given a regular diet. Initial evaluation should include a CBC with platelets, coagulation profile, electrolytes, BUN, creatinine, liver function tests, early hCG, and pelvic ultrasonography.12,20 Serum total protein, albumin, and osmolarity may be helpful, as well as urinary electrolytes and osmolarity. The hematocrit appears to correlate best with the severity of the syndrome, with higher values indicative of more severe disease.21
If the patient is dyspneic and/or tachypneic, a chest x-ray should be obtained in addition to arterial blood gases or, at least, pulse oximetry. Daily monitoring of hospitalized patients includes weight, abdominal girth, CBC, electrolytes, creatinine, and BUN, with strict fluid intake and output. If the patient becomes oliguric, i.e., urine output of less than 30 mL per hour, a Foley catheter should be inserted. Central-venous-pressure (CVP) monitoring may be considered to better guide fluid replacement in the presence of renal or respiratory compromise or if the patient is hypotensive and/or tachycardic.
The underlying pathogenic mechanism of OHSS is increased vascular permeability with hypoproteinemia and a loss of fluid into the third space. In severe OHSS, this results in hypovolemia with decreased renal perfusion, which stimulates the proximal renal tubules to resorb sodium and water. Oliguria and increased urea absorption follow, causing azotemia and a rise in BUN. With less sodium reaching the distal tubules, the exchange for hydrogen and potassium decreases, resulting in hyperkalemia and metabolic acidosis.
Hypovolemia leads to hemoconcentration with increased plasma osmolarity. The increased intra-abdominal pressure from ascites compresses the vena cava and diminishes venous return and cardiac preload, further reducing arterial blood pressure, CVP, and renal perfusion. Cardiac output is maintained by compensatory tachycardia. Tense ascites can compromise respiratory function by increasing intrathoracic pressure and limiting diaphragmatic excursions.4
Other abnormalities include a generalized stress reaction and neutrophilia due to hemoconcentration. Mild hepatocellular and cholestatic damage may result from increased vascular permeability and elevated E2 levels.15 Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels have been reported in 25.8% of OHSS patients.22 However, the cholestatic jaundice with increased bilirubin, alkaline phosphatase, AST, and ALT generally resolve completely, requiring no intervention.
