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.
Potential complications
Thromboembolism. Thromboembolic disease complicates approximately 1 of every 128 cases of severe OHSS.22 Hemoconcentration, bed rest, and venous stasis from vena caval compression by the enlarged ovaries and ascites predispose to lower-extremity deep venous thrombosis (DVT). Interestingly, although 75% of thromboses described in the literature are venous, only 40% of those involve the lower extremities, while DVT of the head, neck, and upper extremities occur in 60% of cases. The remaining 25% of thromboses are arterial—mainly intracerebral.23 (In the general population, the incidence of upper-limb DVT is only about 4%, and arterial thrombosis is very rare in young women.) The mean time from hCG administration to the presentation of DVT was 38 days compared with 14 days for arterial thrombosis, suggesting a different pathogenic mechanism.
In the future, recombinant LH may render exogenous gonadotropins obsolete.
Although the etiology of upper-limb DVT and arterial thrombosis is uncertain, hypercoagulability is thought to play a role.24 However, most OHSSpatients have normal coagulation profiles, even in the presence of hemoconcentration.22 Changes that occur in the coagulation profile of OHSS patients include increases in factor V, fibrinogen, profibrinolysin, D-dimers, fibrinolytic inhibitors, clot lysis times, and platelets. In addition, decreases have been observed in antithrombin III, α2 plasmin inhibitor, prekallikrein, and activated partial thromboplastin time (aPTT). These changes cause an imbalance between coagulation and thrombolysis that may predispose patients to thromboembolic disorders.
While full anticoagulation with heparin is the treatment for thromboembolism in OHSS, it is controversial when, or if, prophylactic heparin should be used in the absence of abnormal coagulation. Prophylactic heparin is recommended for patients on bed rest who have compromised venous return and/or hemoconcentration.12 The duration of prophylaxis also is unclear, as thromboses have occurred following the complete resolution of OHSS—even when the patient has received heparin during hospitalization.
Ovarian torsion. Approximately 15% of OHSS patients experience ovarian torsion, 75% of whom are pregnant. The diagnosis of ovarian torsion may be difficult to make in OHSS, as the presentation of abdominal pain and tenderness, nausea, vomiting, and leukocytosis is common to both conditions. Prompt unwinding of the adnexa is essential to its preservation. Detorsion may be performed via laparotomy or laparoscopy, with care taken to avoid rupture of the ovarian cysts with the Veress needle and trocar insertion. (At the same time, however, it is recommended that the cysts be punctured or aspirated to facilitate unwinding the ovary.)
Laparoscopy in pregnancy poses a risk to the patient and her fetus due to decreased venous return from vena cava compression of the pneumoperitoneum and to hypercarbia from peritoneal absorption of the carbon dioxide used for insufflation. The risk is compounded by the fact that pregnant OHSS patients already are hypovolemic. To increase the margin of safety, an open technique for trocar insertion may be advisable to reduce the risk of injuring the enlarged ovaries and pregnant uterus. Gasless laparoscopy may eliminate the insults on venous return and acid-base balance.25
Pulmonary complications. Twenty percent of patients with severe OHSS experience pleural effusions.22 These effusions generally are right-sided and are commonly seen with tense ascites from seepage through diaphragmatic lymph vessels. The effusion usually improves with paracentesis.4
Adult respiratory distress syndrome (ARDS) is a rare complication. When it occurs, the patient experiences respiratory failure with refractory hypoxemia that fails to respond to 100% oxygen. The chest x-ray reveals diffuse bilateral alveolar infiltrates, and the pulmonary-arterial-wedge pressure is low. The patient should be intubated and ventilated with 100% oxygen with positive end-expiratory pressure (PEEP). If not treated promptly, 90% of these patients will go into cardiopulmonary arrest.4
When the patient experiences a life threatening complication such as ARDS, renal failure, hypovolemic shock, and thromboembolic disease, therapeutic pregnancy termination may be considered when all other treatments have failed.
Conclusion
OHSS remains a feared complication of exogenous gonadotropin administration despite more than 3 decades of widespread clinical use of these agents. However, we are gaining a better understanding of the syndrome’s pathogenesis, and new treatment options are being evaluated. It is hoped that the clinical availability of recombinant LH (to induce the ovulatory surge) and improvements in the in vitro maturation of immature oocytes will render exogenous gonadotropins obsolete. When that happens, OHSS will become an entity of historical interest only.
The author reports no financial relationship with any companies whose products are mentioned in this article.
