Clomifene citrate therapy can occasionally lead to OHSS, but the vast majority of cases develop after use of gonadotropin therapy (with administration of FSH), such as Pergonal, and administration of hCG to induce final oocyte maturation and/or trigger oocyte release, often in conjunction with IVF. The frequency varies and depends on a womans risk factors, management, and methods of surveillance. About 5% of treated women may encounter moderate to severe OHSS. Risk factors include polycystic ovary syndrome, young age, low BMI, high antral follicle count, the development of many ovarian follicles under stimulation, extreme elevated serum estradiol concentrations, the use of hCG for final oocyte maturation and/or release, the continued use of hCG for luteal support, and the occurrence of a pregnancy (resulting in hCG production). Mortality is low, but several fatal cases have been reported. Medications
Ovarian hyperstimulation syndrome is particularly associated with injection of a hormone called human chorionic gonadotropin (hCG) which is used for inducing final oocyte maturation and/or triggering oocyte release. The risk is further increased by multiple doses of hCG after ovulation and if the procedure results in pregnancy.Using a GnRH agonist instead of hCG for inducing final oocyte maturation and/or release results in an elimination of the risk of ovarian hyperstimulation syndrome, but a slight decrease of the delivery rate of approximately 6%. Pathophysiology
OHSS has been characterized by the presence of multiple luteinized cysts within the ovaries leading to ovarian enlargement and secondary complications, but that definition includes almost all women undergoing ovarian stimulation.
In mild forms of OHSS the ovaries are enlarged (5–12 cm) and there may be additional accumulation of ascites with mild abdominal distension, abdominal pain, nausea, and diarrhea. In severe forms of OHSS there may be hemoconcentration, thrombosis, distension, oliguria (decreased urine production), pleural effusion, and respiratory distress. Early OHSS develops before pregnancy testing and late OHSS is seen in early pregnancy. Criteria for severe OHSS include enlarged ovary, ascites, hematocrit > 45%, WBC > 15,000, oliguria, creatinine 1.0-1.5 mg/dl, creatinine clearance > 50 ml/min, liver dysfunction, and anasarca. Critical OHSS includes enlarged ovary, tense ascites with hydrothorax and pericardial effusion, hematocrit > 55%, WBC > 25,000, oligoanuria, creatinine > 1.6 mg/dl, creatinine clearance < 50 ml/min, kidney failure, thromboembolic phenomena, and ARDS. Prevention
Physicians can reduce the risk of OHSS by monitoring of FSH therapy to use this medication judiciously, and by withholding hCG medication. Cabergoline confers a significant reduction in the risk of OHSS in high risk women according to a Cochrane review of randomized studies, but the included trials did not report the live birth rates or multiple pregnancy rates. Cabergoline, as well as other dopamine agonists, might reduce the severity of OHSS by interfering with the VEGF system. A systematic review and meta-analysis concluded that prophylactic treatment with cabergoline reduces the incidence, but not the severity of OHSS, without compromising pregnancy outcomes.The risk of OHSS is smaller when using GnRH antagonist protocol instead of GnRH agonist protocol for suppression of ovulation during ovarian hyperstimulation.