Severe ovarian hyperstimulation syndrome after combined GnRH-agonist and low-dose human chorionic gonadotropin trigger in a patient with a single kidney

Ovarian hyperstimulation syndrome (OHSS) following gonadotropin-releasing hormone agonist (GnRH-a) trigger is rare. Here, we report a case of severe OHSS after combined GnRH-a and low-dose human chorionic gonadotropin (hCG) trigger in a patient with a single kidney. The patient is a 32-year-old women with a two-year history of infertility. The patient’s history was significant for a single kidney, that is, she had donated a kidney to a family member three years ago. The patient underwent controlled ovarian stimulation (COS) for in vitro fertilization (IVF) and received a combined 2?mg GnRH-a and 1500?IU hCG ovulatory trigger. Estradiol (E₂) levels on the day of and after the trigger were 3800?pg/mL and 4001?pg/mL, respectively. Four days after the trigger, the patient began experiencing nausea, abdominal distention and dyspnea, and her blood testing revealed hemoconcentration (hemoglobin: 16.9?g/dL; hematocrit: 51.0%) and an elevated creatinine level (1.16?mg/dL). Fresh embryo transfer was deferred. The patient was admitted to the hospital for fluid monitoring and prophylactic anticoagulation. Following inpatient management, her hemoglobin, hematocrit and creatinine levels normalized. The current report highlights that the systemic effects of OHSS can be accentuated in patients with preexisting renal disease or a single kidney.     

Modern management of ovarian hyperstimulation syndrome.

The number of women receiving ovulation induction has markedly increased with the advent of medically assisted reproduction. Consequently, ovarian hyperstimulation syndrome (OHSS) has become a frequent clinical problem. It is a potentially life-threatening situation. In its severe forms it is complicated by haemoconcentration, hypovolaemia, hypotension, acute renal insufficiency and thromboembolism. The pathophysiology of OHSS is poorly understood. The occurrence of OHSS correlates well with the level of oestradiol, the number of follicles, and administration of human chorionic gonadotrophin (HCG). The risk is increased in polycystic ovarian disease. The aim of this paper is to review critically the published literature on prediction, prevention and modern management of OHSS. Complete prevention of OHSS is not possible although several methods are used to predict and reduce its occurrence. Endocrine profile and ultrasonic follicular monitoring are the mainstays of prediction. The presence of a large number of small and intermediate size follicles at sonography is a risk factor. Withholding HCG, continuation of gonadotrophin-releasing hormone analogues and cryopreservation of embryos are optional courses of action for prevention. Mild OHSS is usually self-limiting and requires no active therapy. Moderate and severe cases are treated by correction of fluid and electrolyte imbalance, and by prevention of thromboembolism. The use of surgery is limited to cases of torsion or rupture of ovarian cysts, or the presence of concomitant ectopic pregnancy. Aspiration of the ascitic fluid, preferably by the transvaginal route, is recommended in cases with severe ascites.     

Comparison between resveratrol and cabergoline in preventing ovarian hyperstimulation syndrome in a rat model

Objective: The aim of this study is to investigate the effects of resveratrol in a rat model of ovarian hyperstimulation syndrome (OHSS) and compare with cabergoline.

Design: Randomized controlled, animal study.

Animal(s): Female Wistar rats.

Material and methods: A rat OHSS model was used to investigate the effects of resveratrol compare with cabergoline administration for preventing OHSS. Body weight, ovary weight, diameter, vascular permeability (VP), vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) expression (immunohistochemistry), and serum estradiol (E2) levels were then compared.

Results: The ovarian VEGF concentration was significantly increased in the OHSS Groups (Groups 3–5) compared with the control groups (1 and 2). But vascular permeability, VEGF, and COX-2 expressions were reduced in animals treated with the resveratrol group compared with the cabergoline group (group 5) and the severe OHSS (group 3) group. Blood E2 levels were decreased in group treated with the resveratrol group compared with the cabergoline group (group 5) and severe the OHSS (group 3) group.

Conclusion(s): Our results in a rat model suggest that resveratrol has a beneficial effect on OHSS by reducing the increases in ovarian daimeter, VP, and VEGF expression associated with OHSS. These effects may be mediated by the COX-2 inhibitory capacity of resveratrol.     

Complications of IVF and ovulation induction

BACKGROUND: The frequency and importance of complications of IVF and other ovulation induction (OI) are poorly known. We examined the occurrence of serious complications and miscarriages leading to hospitalization or operation after IVF (including microinjections and frozen embryo transfers) and OI treatment (with or without insemination). METHODS: Women who received IVF (n = 9175) or OI treatment (n = 10 254) 1996-1998 in Finland were followed by a register linkage study until 2000. RESULTS: After the first IVF treatment cycle, 14 per 1000 women had a serious case of OHSS (ovarian hyperstimulation syndrome), with 23 per 1000 throughout the study period (mean of 3.3 treatments). The corresponding values after OI were very low. The rates of registered ectopic pregnancies and miscarriages after IVF were nine and 42 respectively per 1000 women, with corresponding rates after OI of eight and 42. Infections and bleeding were not common after IVF and even rarer after OI. Overall, 15% of IVF and 8% of OI women had at least one hospital episode during the study period. CONCLUSIONS: Though there was a low risk of complications after each IVF treatment cycle, repeated attempts resulted in serious complications for many women, and these occurred much more often than after ovulation induction alone.     

GnRH激动剂联合小剂量HCG双扳机对PCOS患者IVF-ET临床结局的影响

目的比较使用人绒毛膜促性腺激素(HCG)与促性腺激素释放激素激动剂(GnRH-a)联合小剂量人绒毛膜促性腺激素(HCG)诱发排卵对多囊卵巢综合征(PCOS)患者IVF-ET的临床结局的影响。方法回顾性分析120例促排卵后行IVF-ET的PCOS患者,分别使用GnRH-a联合2 000 U HCG(双扳机组,31例)、低剂量HCG(8 000 U,37例)以及10 000U HCG(对照组,52例)诱导卵泡成熟,比较3组患者获卵数、受精率、卵裂率、优胚率、可移植胚胎数及卵巢过度刺激综合征(OHSS)发生率等并发症。结果优胚率双扳机组与低剂量HCG组及对照组相比显著升高(P0.05);双扳机组及低剂量HCG组的可移植胚胎数比对照组显著升高(P0.05,P0.01);双扳机组与低剂量HCG组和对照组相比较,OHSS发生率和平均住院天数显著降低(P0.05)。结论使用GnRH-a联合小剂量HCG诱发排卵可提高优胚率及可移植胚胎数,降低OHSS的发生风险。     

Acquired haemophilia due to factor VIII inhibitors in ovarian hyperstimulation syndrome: case report

A 31-year-old nulligravida woman developed an acquired factor VIII inhibitor associated with severe ovarian hyperstimulation syndrome (OHSS). She developed haematouria, ecchymosis, and intramuscular bleeding following the severe OHSS. Laboratory examinations showed a markedly prolonged activated partial thromboplastin time and a low level of factor VIII activity. Treatment with prothrombin complex concentrate and factor VIII inhibitor bypassing agent was successful in reducing the inhibitor so that she delivered a healthy baby via spontaneous vaginal delivery. Acquired haemophilia is a life-threatening disorder. This is the first case report of acquired haemophilia in OHSS.     

Increased early pregnancy loss in IVF patients with severe ovarian hyperstimulation syndrome.

BACKGROUND: Since severe ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication of assisted reproduction, the focus of attention in such cases is placed firmly upon the health of the patient, with the endeavour to achieve a pregnancy being considered of secondary importance. The aim of this study was to focus on the pregnancy rate and pregnancy outcome in IVF patients hospitalized for severe or critical OHSS, in one centre, during a period of 6 years. METHODS: We compared the characteristics of patients with severe OHSS: those who conceived with the ones who did not conceive, and among pregnant IVF patients, those with ongoing pregnancies with those that miscarried. RESULTS: Pregnancy was achieved in 60 of 104 (58%) patients with severe OHSS. Pregnancy continued until delivery in 37 of these 60 patients (62%), whereas the remaining 23 (38%) aborted. The pregnancy and abortion rates in patients with severe OHSS were significantly higher than those of IVF patients without OHSS, during the same time period [23% (1138/4922) and 15% (169/1138) respectively, P < 0.001]. The mean duration of hospitalization for OHSS was significantly shorter in those who delivered compared with those who aborted (5.9 +/- 3.2 versus 10.5 +/- 9.6 days, P < 0.01) and in the non-pregnant patients compared with the pregnant patients (5.2 +/- 3.2 versus 7.6 +/- 6.6 days, P < 0.02). CONCLUSIONS: The clinical pregnancy rate of IVF patients with severe OHSS was significantly higher than that of patients without the syndrome. A longer stay in hospital-reflecting a more severe form of OHSS-was correlated with a higher frequency of abortions. OHSS, necessitating hospitalization, is a detrimental clinical situation not only for the mother but also for the developing pregnancy.     

Controlled ovarian hyperstimulation--a state of endothelial activation

PROBLEM: To aim of the study was to investigate whether controlled ovarian hyperstimulation (COH) causes endothelial activation and whether there is a correlation between endothelial activation and serum sex-steroid levels. METHOD OF STUDY: The study population consisted of 14 consecutive patients undergoing our routine IVF long gonadotropin-releasing hormone-analog protocol. Blood was drawn three times during the COH cycle: (1) day when adequate suppression was obtained (Day-S); (2) on the day of or the day prior to hCG administration (Day-hCG); and (3) on the day of ovum pick-up (Day-OPU). The levels of sex steroids and plasma soluble endothelial (E)-selectin were compared among the time points. Soluble E-selectin was measured with a commercial sandwich enzyme-linked immunosorbent assay. RESULTS: Soluble E-selectin levels were significantly higher on Day-OPU than Day-S and Day-hCG, whereas no difference was observed between Day-hCG and Day-S. No significant correlations were found between soluble E-selectin level and patient age, number of gonadotropin ampoules used, number of oocytes retrieved, or serum estradiol, progesterone and human chorionic gonadotropin levels. CONCLUSIONS: Human chorionic gonadotropin administration leads to endothelial activation regardless of the degree of ovarian response. Further studies are required to elucidate the relationship between COH and endothelial activation. These findings may lead to new strategies for predicting and preventing complications of COH, such as severe ovarian hyperstimulation syndrome.     

Early and late ovarian hyperstimulation syndrome: early pregnancy outcome and profile

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) in IVF/ICSI cycles may occur either as an early (early onset) or a late pattern (late onset). This observational study was designed to identify whether the onset pattern of OHSS is associated with the occurrence of pregnancy and the early pregnancy outcome. METHODS: Among 4376 consecutive IVF/ICSI cycles, 113 patients were hospitalized for OHSS after IVF/ICSI treatment and were included in the study. The setting was the Dutch-speaking Brussels Free University Hospital, between June 2000 and September 2002. RESULTS: Early OHSS occurred in 53 patients, and late OHSS complicated 60 patients. A total of 96.7% of the late OHSS cases occurred in a pregnancy cycle and were more likely to be severe than the early cases (P < 0.05). Although in the early group there initially was a 41.5% positive HCG rate per cycle, the clinical pregnancy rate fell to 28.3% as a result of a significantly (P < 0.05) increased preclinical pregnancy loss rate compared with the non-OHSS patients (31.8 versus 88.3%, respectively). The ongoing pregnancy rate per cycle was 14.4% in the early and 26.4% in the late group. Multiple pregnancy rates were high in both groups (40 and 45.5%, respectively), but only in the late group did the incidence reach significance compared with the non-OHSS population (45.5 versus 29.1%, P = 0.02). Estradiol levels and number of follicles on the day of HCG were significantly higher in the early OHSS group. However, there was no difference in estradiol values on the day of hospital admittance between the two groups. In addition, the number of follicles on the day of HCG administration appears to be a better prognostic indicator for the occurrence of severe OHSS than the estradiol values (87% of the severe cases had > or = 14 or follicles of a diameter > or = 11 mm, whereas only 50% of them had an estradiol value > or = 3000 ng/l). CONCLUSIONS: The early OHSS pattern is associated with exogenously administered HCG and a higher risk of preclinical miscarriage, whereas late OHSS may be closely associated with the conception cycles, especially multiple pregnancies, and is more likely to be severe. Further clarification of these two different clinical entities could have implications for research protocols as well as for preventive and management strategies for OHSS.