Severe ovarian hyperstimulation syndrome: role of peripheral vasodilation.

OBJECTIVE: To investigate the pathogenesis of the systemic hemodynamic disturbance and the renal production of vasodilator prostaglandins (PGs) in the ovarian hyperstimulation syndrome. DESIGN: Prospective longitudinal study. SETTING: Assisted Reproduction Unit of the Hospital Clínic i Provincial in Barcelona. PATIENTS: Five in vitro fertilization patients with ascites because of severe ovarian hyperstimulation syndrome. MAIN OUTCOME MEASURES: Measurement during the syndrome and 4 weeks after recovery of the following: cardiac output, arterial pressure, estimated peripheral vascular resistances, hematocrit, standard renal function tests, plasma renin activity, plasma aldosterone, norepinephrine and antidiuretic hormone concentrations, and urinary excretion of PGE2 and 6-keto-PGF1 alpha. RESULTS: During the syndrome, all patients showed arterial hypotension (74.2 +/- 3.8 versus 85.8 +/- 1.0 mm Hg), tachycardia, increased cardiac output (6.4 +/- 0.2 versus 4.4 +/- 0.1 L/min), low peripheral vascular resistance (929 +/- 52 versus 1,568 +/- 51 dyn/sec per cm-5), high plasma levels of renin (72 +/- 25 versus 0.5 +/- 0.1 ng/mL per h-1), norepinephrine (639 +/- 141 versus 203 +/- 21 pg/mL) and antidiuretic hormone (6.1 +/- 1.6 versus 1.5 +/- 0.1 pg/mL), and increased urinary excretion of PGE2 (551 +/- 152 versus 106 +/- 44 pg/min) and 6-keto-PGF1 alpha (470 +/- 76 versus 99 +/- 11 pg/min). No evidence of hemoconcentration, as assessed by hematocrit, was observed in any patient. CONCLUSIONS: (1) Severe ovarian hyperstimulation syndrome is related to marked arteriolar vasodilation that leads to underfilling of the arterial vascular compartment and stimulation of endogenous vasoconstrictor systems and (2) the increased urinary excretion of PGs probably represents a homeostatic response to antagonize the renal effects of these systems.     

Severe ovarian hyperstimulation syndrome: a reevaluated therapeutic approach

During the 10 years 1978 to 1987, 33 patients were hospitalized because of moderate and severe ovarian hyperstimulation syndrome (OHSS) in 39 treatment cycles. Twenty-five treatment cycles ended in moderate OHSS (group A), 7 had severe OHSS without a significant amount of ascites (group B1), and 7 had severe OHSS with ascites (group B2). Groups A and B1 received intravascular volume expander, electrolytes replacement, and indomethacin up to 300 mg/day. The patients in group B2 had significant clinical and biochemical improvement after abdominal paracentesis. Urinary output and creatinine clearance improved significantly, and a decrease in hematocrit, blood osmolarity, and weight reduction were achieved. A strategy for treatment of OHSS based on consecutive ultrasonographic examination, clinical and biochemical evaluation, and abdominal paracentesis in severe OHSS with clinically significant ascites is suggested.     

Case report: delirium associated with ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is one of the most important complications of assisted reproductive technologies. Mild OHSS is characterized by ovarian enlargement and abdominal discomfort. In severe cases anasarca, hepatic dysfunction, reduced blood volume, electrolyte imbalance, organ failure and thromboembolic phenomena may be observed. Delirium is a syndrome, not a disease, and has many causes, all of which result in a similar pattern of signs and symptoms relating to a patient's level of consciousness and cognitive impairment. Delirium remains an under-recognized and under-diagnosed clinical disorder. The case is presented of a 30-year-old woman with OHSS and delirium. She underwent intracytoplasmic sperm injection (ICSI) for severe male factor infertility. Five days after oocyte retrieval, ascite formation was observed in ultrasonographic evaluation, and embryo transfer was cancelled. Twelve days after retrieval she came to the emergency clinic with abdominal distension and pain. She was hospitalized and paracentesis was performed every other day three times. She had altered consciousness and psychomotor hypoactivity 1 h after the last paracentesis. Psychiatric consultation revealed that she was in a state of delirium, and haloperidol was administered for treatment. Her symptoms disappeared within a week. Her medication was stopped when symptoms resolved and she was still asymptomatic in psychiatric evaluation 1 week later.     

The ovarian hyperstimulation syndrome

OBJECTIVE: To review the up-to-date literature concerning the pathogenesis of, risk factors for, prevention of, and therapy for the ovarian hyperstimulation syndrome, and to provide suggestions for management of this syndrome.Design: Literature review combined with on-site clinical experiences at the authors' institution of practice. PATIENT(s): Women who have risk factors for or manifest the ovarian hyperstimulation syndrome. INTERVENTION(s): Intravenous fluid management, thrombosis prevention techniques, paracentesis techniques, and critical care management protocols. MAIN OUTCOME MEASURE(s): Staging system of the ovarian hyperstimulation syndrome, criteria for outpatient versus hospitalization management, and indications for varying levels of interventional management. RESULT(s): The ovarian hyperstimulation syndrome, unique to the field of assisted reproductive technology, remains a largely elusive and unpredictable iatrogenic physiologic complication in the course of pharmacologic ovarian stimulation. Reliable information on risk factors, possible physiologic mechanisms, prevention techniques, and management is fortunately progressing, and overall advances are being made in this field. The present review is an attempt to summarize the modern literature regarding this syndrome and to use this current knowledge to provide a basis for acceptable management regimens. CONCLUSION(s): Ovarian hyperstimulation syndrome is a serious complication of assisted reproductive technology, with potential for critical morbidity and death. Physicians who prescribe medications known to be associated with this syndrome should be familiar with identifiable risk factors, means of prevention, and a system for staging and treating the disease and have a current knowledge base for putative models of pathogenesis.     

Clinical aspects of ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is characterized by massive transudation of protein-rich fluid (mainly albumin) from the vascular space into the peritoneal pleural and to a lesser extent to the pericardial cavities. The intensity of the syndrome is related to the degree of the follicular response in the ovaries to the ovulation inducing agents. OHSS is still a threat to every patient undergoing ovulation induction. The pathophysiology of OHSS is of extreme importance in the face of the increased use of ovulation induction agents as well as the development of sophisticated assisted reproductive techniques. The correlation found between plasma cytokine activities and the severity of OHSS suggests that plasma cytokines may be involved in the pathogenesis of OHSS and may serve as a means of monitoring the syndrome during the acute phase and throughout convalescence. The interactions between cytokine and non-cytokine mediators of the syndrome, such as the renin-angiotensin system and vascular endothelial growth factor were recently clarified. Awareness of possible mechanisms and factors in the pathophysiology of OHSS will hopefully provide opportunities to design specific treatment regimens effective for both prevention and treatment of this potentially fatal iatrogenic condition. Among IVF patients with severe and critical OHSS, pregnancy rates, multiple gestations, miscarriage, preterm premature rupture of the membranes, prematurity, and low birth weight rates are significantly higher than those reported previously for pregnancies after assisted conception. The incidence of other obstetrical complications, as well as congenital malformations and Cesarean section rates are not significantly different.     

Histamine levels in ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome was produced in rabbits by administration of human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). Histamine levels in the animals' plasma were determined by an enzymatic-isotopic assay. The results of this study show that there is no statistically significant difference between histamine levels in ovarian hyperstimulated animals as compared with control animals. Furthermore, no differences in the number of mast cells in the ovaries could be demonstrated between the 2 groups. It is concluded that histamine probably does not play a role in the pathogenesis of this syndrome. The relevance of this suggestion to other proposed mechanisms on the etiology of ovarian hyperstimulation syndrome is discussed.     

Severe ovarian hyperstimulation syndrome associated with long-acting GnRH agonist in oncofertility patients

PurposeTo report three cases of severe ovarian hyperstimulation syndrome (OHSS) among oncofertility patients receiving a long-acting GnRH agonist for ovarian suppression after controlled ovarian hyperstimulation (COH) with a GnRH antagonist protocolMethodsChart abstraction was completed for three patients at a single academic medical center. Patients included were undergoing fertility preservation prior to gonadotoxic chemotherapy. All patients underwent COH with GnRH antagonist protocol and embryo cryopreservation immediately followed by ovarian suppression with long-acting GnRH agonist. Main outcome measure was development of OHSS.ResultsDespite using GnRH agonist trigger and freezing all embryos, patients developed ascites, intermittent hyponatremia and hemoconcentration consistent with severe early-onset OHSS after receiving long-acting GnRH agonist immediately following oocyte retrieval for ovarian preservation.ConclusionsRisk of severe OHSS may be increased when a long-acting GnRH agonist is used for ovarian suppression immediately following oocyte retrieval. A delay in initiating long-acting GnRH agonist after oocyte retrieval in patients at high risk for developing OHSS should be considered.     

Severe unilateral hydrothorax as the only manifestation of the ovarian hyperstimulation syndrome

BACKGROUND: Unilateral hydrothorax is rarely the sole manifestation of the ovarian hyperstimulation syndrome (OHSS) and is suggestive of the severity of the disease. CASE: A 35-year-old woman presented with mild dyspnea 2 weeks after ovarian stimulation with hMG and hCG and IVF-ET. Chest X-ray revealed a large pleural effusion on the right side. Three consecutive thoracocenteses were needed to drain a total of 6,800 cm(3) of fluid. Following drainage, the respiratory symptoms disappeared. An uneventful pregnancy is in progress. CONCLUSIONS: Thoracocentesis is safe and efficient for the treatment of hydrothorax and may be repeated as often as necessary. Clinicians should be aware of the possibility of unilateral hydrothorax as the sole symptom of OHSS.     

Severe ovarian hyperstimulation syndrome in a twin pregnancy after intracytoplasmic sperm injection

A 35-year-old woman developed bilateral jugular thrombosis in the seventh gestational week in a twin pregnancy after severe ovarian hyperstimulation syndrome (OHSS) and intracytoplasmic sperm injection (ICSI). Due to progressive thrombosis and further complications despite anticoagulation therapy, the pregnancy was terminated in the ninth gestational week. Thromboembolic events are a serious complication associated with OHSS after assisted reproduction techniques. In these cases, a pregnancy can usually be protected by administering anticoagulation therapy, but our case shows that there may be exceptions to this. Screening for thrombophilia should be considered in patients who are at risk for OHSS and deep vein thrombosis.     

Recurrent spontaneous ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is an often complication of ovarian induction after ART methods, sometimes in cases of multiple pregnancies and trofoblastic disease. Spontaneous ovarian hyperstimulation syndrome is unusual in normal single pregnancies. The publications, where recurrent spontaneous OHSS is described, are extremely rare. The analysis of these publications was done and we report next rare case of spontaneous recurrent OHSS.     

Thrombosis following ovarian hyperstimulation syndrome

The aim of this review is to analyse the pathophysiology and complications of thrombosis in conjuction with ovarian hyperstimulation syndrome (OHSS) following ovulation induction and to suggest practical guidelines usefull for the prevention and treatment. Although the incidence of thrombosis varies from 0.2% among in vitro fertilization (IVF) cycles and up to 10% for severe cases of the syndrome, it represents the most dangerous complication of OHSS. Different changes in haemostatic markers have been found to create a state of hypercoagulability, but no single standard test is available to estimate the state of thrombosis. The role of markers for thrombophilia is controversial. Thromboses are mostly venous (67–75%) involving upper limbs and neck, then arterial (25–33%) which are mainly intracerebral. The predominant sites of venous thromboembolism in the upper part of the body may be explained by higher concentrations of estrogens drained through lymphatic ducts from ascites and by compression of rudimentary branchyal cysts. Once early diagnosis is established, it is crucial to use an anticoagulant treatment with heparin proceeded with thromboprophylaxis. However, identification of patients at risk and preventive measures of OHSS are the best means in reducing the risk of thrombosis after ovarian stimulation.     

Genetics of ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is typically iatrogenic following the administration of gonadotrophins. Sporadic and familial cases of spontaneous OHSS have generated an interest in genetic mechanisms for OHSS independent of exogenous gonadotrophins. The genetic studies have addressed the genes and receptors for FSH and luteinizing/human chorionic gonadotrophin hormones. Mutations in the FSH receptor (FSHR) could be activating, leading to a predisposition to OHSS, or inactivating, resulting in sterility. Polymorphisms of FSHR have been investigated and, to date, 744 single nucleotide polymorphisms have been identified in the FSHR gene, of which only eight are located in the coding region, exons, with the rest being intronic. Ovarian response is dependent on FSHR genotype. Clinical studies on the p.N680S polymorphism of the FSHR gene have demonstrated the homozygous Ser/Ser variant to be less sensitive to endogenous or exogenous FSH in terms of oestradiol production. Polymorphism of the FSHR, Ser680Asn, in the FSHR gene is a predictor of the severity of symptoms in patients who develop OHSS. OHSS is characterized by leakage of intravascular fluids resulting in ascites and haemoconcentration. These pathological changes are mediated for the most part by vascular endothelial growth factor (VEGF). Targeting the VEGF system at different levels has been the focus of intense research for the prevention of OHSS.     

卵巢过度刺激综合征的研究

卵巢过度刺激综合征 (ｏｖａｒｉａｎｈｙｐｅｒｓｔｉｍｕｌａｔｉｏｎｓｙｎｄｒｏｍｅ ,ＯＨＳＳ)主要是由于促超排卵行卵巢刺激后而发生的医源性并发症。近 2 0余年来 ,由于辅助生育技术 (ＡＲＴ)的广泛开展 ,应用促超排卵药物致使ＯＨＳＳ在临床屡见不鲜 ,因其具有一定的严重性 ,应予高度重视并正确防治。现结合临床治疗中的体会谈谈粗浅看法。一、临床表现ＯＨＳＳ多起始于应用人绒毛膜促性腺激素(ｈＣＧ)或内源性黄体生成激素 (ＬＨ)峰后。妊娠可加重症状 ,延长病程。ＯＨＳＳ的主要病理生理机制为血管通透性升高 ,体液渗漏至第三腔…