Severe ovarian hyperstimulation syndrome and tubal pregnancy after in vitro fertilization

We report a case of a 38 year old woman with tubal pregnancy and severe ovarian hyperstimulation syndrome (OHSS) following in-vitro fertilization and intrauterine embryo transfer. The diagnostic and therapeutic problems in the coexistence of ectopic pregnancy and OHSS are discussed both in terms of the case-history and the literature.     

Genotypic analysis of the 5''-untranslated region of a pestivirus strain isolated from human leucocytes

Ovarian hyperstimulation syndrome (OHSS) is a relatively common and potentially life-threatening complication of ovarian stimulation, the pathogenesis of which remains unclear. To clarify the predictive values of serum estradiol levels and oocyte number in severe OHSS, and to investigate the impact of high serum estradiol levels on pregnancy outcome, we retrospectively analyzed clinical data from 431 cycles of ovarian stimulation for assisted reproduction performed from 1993 through 1995. Receiver operating characteristic plots were used to estimate the predictive power of the measured variables. The overall frequency of severe OHSS was 5.5%. Using a serum estradiol level of 3,600 pg/mL as the minimum cut-off value, the sensitivity was 58%, with a specificity of 92%, a positive predictive value of 29%, and a negative predictive value of 97%. The predictive power was similar when a cut-off point of 20 oocytes retrieved was used. The two criteria together gave a sensitivity of 33%, a specificity of 92%, a positive predictive value of 40%, and a negative predictive value of 98%. One of seven oocyte donors developed severe OHSS. The pregnancy rate was higher in patients with severe OHSS than in patients who did not develop this syndrome (73.9% vs 32.5%) but the pregnancy outcomes were not significantly different. We conclude that elevated estradiol concentrations and oocyte number appear to be helpful in predicting severe OHSS, but neither parameter by itself is predictive. This syndrome is rare in the absence of luteal hCG support, either exogenous or pregnancy-derived; when it occurs, there are usually extremely high preovulatory estradiol concentrations and numerous oocytes retrieved. High serum estradiol levels are unlikely to have adverse effects on pregnancy outcome in patients with severe OHSS.     

Cryopreservation of all prezygotes in patients at risk of severe hyperstimulation does not eliminate the syndrome, but the chances of pregnancy are excellent with subsequent frozen-thaw transfers

In-vitro fertilization patients (n = 15) at risk of ovarian hyperstimulation syndrome (OHSS) (oestradiol > or =4500 pg/ml on the day of human chorionic gonadotrophin administration and 25 or more follicles of intermediate or large size) underwent aspiration of all follicles and cryopreservation of all fertilized oocytes at the pronuclear stage. Patients were monitored for up to 2 weeks post-retrieval. Subsequent transfer of cryopreserved-thawed embryos was performed in programmed cycles using exogenous oestrogen and progesterone for endometrial preparation. Two patients (13%) developed OHSS necessitating hospitalization and vaginal aspiration of ascitic fluid. Two other patients (13%) developed moderate OHSS requiring ascitic fluid vaginal aspiration in the office setting, with dramatic improvement of the condition. Subsequent transfer of cryopreserved-thawed embryos yielded a clinical pregnancy rate of 58% per transfer and ongoing or delivery rates of 42 and 67% per transfer and per patient respectively. By eliminating pregnancy potential with cryopreservation of all prezygotes and examining the pregnancy potential with subsequent cryopreserved-thawed transfers, it is concluded that OHSS is reduced, but not eliminated for patients at risk. Subsequent transfer of cryopreserved-thawed prezygotes in a programmed cycle with exogenous steroids yields an excellent pregnancy rate.     

A severe case of ovarian hyperstimulation syndrome: 65 liters of ascites aspirated in an on-going IVF-ET twin pregnancy

Ovarian hyperstimulation syndrome (OHSS) is the most serious life-threatening iatrogenic complication of ovulation induction. Presented here is an unusual case where 62 l of intraperitoneal and 3.2 l of intrapleural fluid were aspirated in order to stabilize a severe life-threatening case of OHSS resulting from an on-going IVF-ET twin pregnancy.     

Does ovarian hyperstimulation syndrome affect the quality of oocytes?

Two wives of a Muslim with severe male factor infertility had simultaneous intracytoplasmic sperm injection (ICSI) treatments. One wife developed ovarian hyperstimulation syndrome (OHSS), and 19 of 27 oocytes retrieved were subjected to ICSI but only one fertilized; the other wife had a normal response to ovarian stimulation, normal fertilization following ICSI, successful treatment and has recently delivered a live-born infant. The wife who suffered from OHSS has since had another ICSI cycle with a normal response to ovarian stimulation, a normal fertilization rate but no pregnancy. The only variable that determined the different rate of fertilization in the simultaneous ICSI cycles appears to be oocyte quality. While the results of frozen embryo replacement cycles following the decision to freeze all embryos following OHSS is generally satisfactory, it is important to counsel couples about the possible detrimental effects of OHSS on oocyte quality.     

A clinical retrospective evaluation of FA/HA coated (Biocomp) dental implants. Results after 1 year

The development of ovulation-inducing drugs has enabled clinicians to more effectively treat the hypothalamic, pituitary, and ovarian abnormalities resulting in infertility. Pregnancy rates have been improved with the use of agents such as clomiphene citrate (CC), human menopausal gonadotropin [hMG or follicle-stimulating hormone (FSH) preparations], with gonadotropin-releasing hormone (GnRH) and its analogs, stimulating the development of multiple ovarian follicles and increasing the number of fertilizable oocytes. The use of these drugs is not without certain detrimental or "toxic" consequences. The negative effects from superovulation can occur during follicle development, decreasing the number of healthy oocytes and embryos capable of leading to viable pregnancy. Ovulation induction can lead not only to higher incidences of spontaneous abortions, and multiple and ectopic pregnancies, but also to poor pregnancy rates, due, in part, to asynchrony between embryonic development and the uterine environment. Diseases such as ovarian hyperstimulation syndrome (OHSS), resulting in the secretion of supraphysiologic levels of estradiol, can lend to severe health complications, possibly requiring hospitalization. Most drugs used for ovulation induction can lead to OHSS. Although incidences of OHSS following CC use are less frequent, CC has been associated with hot flushes, multiple gestations, visual disturbances, cervical mucus abnormalities, and luteal phase deficiency. Finally, there are reports that link any or all of the ovulation-inducing drugs with a higher incidence of ovarian and breast cancer, however, a cause-effect relationship has yet to be proven.     

Treatment of non-extractable common bile duct stones with combination ursodeoxycholic acid plus endoprostheses

To assess the effect of timing of human chorionic gonadotrophin (HCG) administration in ovarian stimulation cycles, the serum oestradiol concentration and follicle profile were compared with the clinical pregnancy rate in 582 ovarian stimulation-intra-uterine insemination (OS-IUI) cycles and 3917 in-vitro fertilization-embryo transfer (IVF-ET) cycles. The pregnancy rates increased exponentially with increasing oestradiol in both OS-IUI and IVF-ET cycles (R2 = 0.720, P < 0.001) but then decreased in OS-IUI cycles when the oestradiol concentration exceeded 5000 pmol/l (R2 = 0.936, P < 0.004) at HCG administration. In OS-IUI cycles the percentages of cycles with three or more mature follicles (> or = 18 mm diameter) increased up to an oestradiol concentration of 5000 pmol/l then declined, mirroring the pregnancy rate (R2 = 0.900, P = 0.01). The exponential increase in pregnancy rate with increasing oestradiol concentration in IVF-ET cycles suggests that high oestradiol concentration does not have a deleterious effect on endometrial receptivity. The decrease in pregnancy rate in OS-IUI cycles when oestradiol concentration exceeded 5000 pmol/l reflected fewer mature follicles, resulting from premature administration of HCG to avoid severe ovarian hyperstimulation syndrome (OHSS). We recommend that HCG administration be delayed until multiple follicles have reached maturity, and reducing the risk of severe OHSS by converting high risk OS-IUI cycles to IVF-ET, or if funds or facilities are unavailable, transvaginally draining all but four or five mature follicles.     

Withholding gonadotropin administration is an effective alternative for the prevention of ovarian hyperstimulation syndrome

OBJECTIVE: To evaluate the outcomes of IVF and the incidence of ovarian hyperstimulation syndrome (OHSS) after discontinuing gonadotropin therapy in patients at risk of developing OHSS by delaying hCG administration until a drop in serum E2 levels was observed. DESIGN: Retrospective study. SETTING: IVF program at a university center. INTERVENTIONS: Gonadotropin administration was withheld in 22 patients (group 1) when their serum E2 level was > or = 3,000 pg/mL (conversion factor to SI unit, 3.671). Patients continued GnRH analogue injections daily, and hCG was administered when serum E2 levels dropped to < or = 3,000 pg/mL. Outcomes were compared with 26 patients (group 2) in whom embryo transfer was canceled and all embryos cryopreserved for transfer during a subsequent unstimulated cycle. MAIN OUTCOME MEASURES: Outcomes of IVF and incidence of OHSS were compared in both groups of patients. In group 1, follicular and hormonal parameters before and after the coasting interval were compared in pregnant versus nonpregnant patients. In addition, serum hormonal profiles were evaluated daily during the coasting period to determine the effects of gonadotropin withdrawal. RESULTS: Although the mean number of oocytes retrieved was significantly higher in group 2, fertilization rates, miscarriage rates, delivery rates/stimulation cycle, and the incidence of OHSS did not differ significantly between the two groups. CONCLUSION: Withholding gonadotropin administration is an effective alternative to prevent the development of severe OHSS in a high-risk population. Although the risk of cancellation cannot be completely eliminated, this strategy can provide a high pregnancy rate without the need to repeat multiple frozen-thawed cycles.     

Ovarian hyperstimulation syndrome: facts and fallacies

Severe or critical ovarian hyperstimulation syndrome (OHSS) is a serious complication of ovarian hyperstimulation for assisted reproduction techniques (ART). The syndrome is characterized by cystic enlargement of the ovaries and fluid shifts from the intravascular to the third space. The morbidity in OHSS is mainly determined by the hemodynamic changes caused by increased capillary permeability. The incidence of OHSS depends on definitions, risk factors, ovarian stimulation protocols, luteal support and conception. Currently, research on the pathogenesis of OHSS is focused on increased capillary permeability. Several theories are reviewed. Until the pathogenesis of OHSS becomes clear, treatment is restricted to supportive therapy. The various proposals for management of OHSS are discussed and, based on the available data, directions for the management of various grades of OHSS are summarized. However, prevention and early recognition are still the most important tools to handle OHSS. A flowchart with preventive measures for OHSS is presented derived from the available literature.     

The clinical usefulness of urinary pyridinoline and deoxypyridinoline as potential markers of bone metastasis in patients with prostate cancer

The aims of this study were to investigate the effects of paracentesis on uterine and intraovarian haemodynamics by colour Doppler ultrasound and the influences of repeated paracentesis on pregnancy outcome in severe ovarian hyperstimulation syndrome (OHSS). Forty-one abdominal paracenteses were performed on seven pregnant women with tense ascites and eight thoracocenteses were performed on three pregnant women with pleural effusion. Pulsatility index (PI) and maximum peak systolic velocity (MPSV) of uterine and intraovarian arteries were measured before and after each intervention. The mean PI of uterine arteries was decreased significantly after paracentesis, but not after thoracocentesis. Furthermore, uterine PI was decreased in 13 out of 14 (92.9%) paracenteses with <2500 ml ascites removed, compared with eight out of 13 (61.5%) with >2500 ml ascites removed. After paracentesis, there were no significant changes in the intraovarian PI and MPSV in either group. The 24-hour urine output increased significantly in the paracentesis group, but not in the thoracocentesis group. There were no significant changes in haematocrit and electrolytes as a result of paracentesis. However, gradual falls in serum total proteins and albumin concentrations were observed in all patients after repeated paracentesis, necessitating post-paracentesis albumin infusion. There was no significant difference in miscarriage rates between the two groups. We conclude that repeated abdominal paracentesis increases uterine perfusion and has no adverse effects on pregnancy outcome in severe OHSS. Extraction of 2500 ml of ascitic fluid did not impair uterine perfusion.     

does intravenous administration of human albumin prevent severe ovarian hyperstimulation syndrome?

OBJECTIVE: To report our experience with i.v. albumin as a means to prevent ovarian hyperstimulation syndrome (OHSS) in high-risk patients. DESIGN: Retrospective case-series. SETTING: University hospital-based IVF program. PATIENTS: Five women undergoing controlled ovarian stimulation for IVF-Based on previous history and/or E2 measurements and number of ovarian follicles, these patients were considered to be at high risk for developing OHSS. INTERVENTIONS: Intravenous albumin was given at the time of oocyte retrieval. Additional doses were given 12 and 24 hours later. MAIN OUTCOME MEASURE: Development of OHSS. RESULTS: Four patients developed OHSS; two of them had the severe form of the syndrome. CONCLUSIONS: Severe OHSS may develop in high-risk patients despite the prophylactic administration of i.v. albumin.     

Severe ovarian hyperstimulation syndrome (OHSS) and icterus

Severe ovarian hyperstimulation syndrome (OHSS) leads to changes in laboratory analyte concentrations. Whereas elevated aminotransferase activity is often observed, a cholestatic course with hyperbilirubinaemia and icterus seldom occurs. In this report, the case of a 33 year old patient with polycystic ovary syndrome (PCOS) is described who, after stimulation with human menopausal gonadotrophin (HMG), developed severe OHSS with haemoconcentration, ascites, hydrothorax, elevated aminotransferases, hyperbilirubinaemia and icterus. The patient did not become pregnant and the OHSS regressed, together with the normalization of laboratory and clinical parameters and disappearance of the icterus. During the course of an OHSS cholestasis with icterus may occur, which could be explained by a reactive cholestatic hepatosis as a reaction to the hormonal changes induced by the stimulation therapy.     

Ovarian hyperstimulation syndrome--prevention and treatment

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic, potentially life-threatening condition associated with ovulation induction. With increasing numbers of women receiving various ovarian stimulation protocols as part of different infertility treatments, the number of cases is likely to increase. The syndrome has a wide spectrum of clinical and laboratory findings, and is classified into mild, moderate and severe OHSS. The pathophysiology of this syndrome is unclear, and medical management has traditionally been conservative and supportive consisting of bedrest, volume expanders and replacement of fluid. When ascites is present, paracentesis under ultrasound guidance has been found to improve the condition of the patient by reducing the hydrostatic pressure. Prevention is very important, but at present it is doubtful if OHSS can be completely avoided due to the existence of a relatively small margin of safety between successful induction of ovulation and the development of OHSS.     

Haematocrit, leukocyte and platelet counts and the severity of the ovarian hyperstimulation syndrome

Previous studies have shown that severe ovarian hyperstimulation syndrome (OHSS) is secondary to circulatory dysfunction due to the simultaneous occurrence of increased vascular permeability and marked arteriolar vasodilation which lead to an intense homeostatic stimulation of the renin-aldosterone and sympathetic nervous systems and antidiuretic hormone (ADH). In the present report, we have investigated the correlation between changes in haematocrit concentration, and white blood cell (WBC) and platelet counts and the severity of OHSS, as assessed by these markers of effective intra-arterial blood volume, in a series of 50 patients. In comparison with recovery values (4-5 weeks after hospital discharge), OHSS patients showed arterial hypotension, tachycardia, oliguria, very high plasma concentrations of renin, aldosterone, norepinephrine and ADH, and increased mean haematocrit values and WBC and platelet counts. The haematocrit concentration values were directly related to the plasma concentrations of vasoactive substances (plasma renin activity, aldosterone, norepinephrine and ADH) during OHSS (P < 0.001). In contrast, no correlation was evident between WBC or platelet counts and neurohormonal measurements during the syndrome. It is concluded that haematocrit, but not WBC or platelet counts, can act as a biological marker of the severity of OHSS as indicated by plasma measurement of volume-dependent endogenous vasoactive substances.     

Moderate ovarian hyperstimulation syndrome complicated by deep cerebrovascular thrombosis

This report describes two cases that developed moderate ovarian hyperstimulation syndrome (OHSS) without evidence of haemoconcentration. Both patients developed serious cerebrovascular thrombosis resulting in hemiparesis, and recovered after treatment with anticoagulants. This report emphasizes that other factors may contribute to vascular thrombosis, and illustrates that cerebrovascular accidents may complicate even moderate OHSS.     

Febrile morbidity in severe and critical ovarian hyperstimulation syndrome: a multicentre study

The objective of this study was to define the incidence of febrile morbidity and its causes in severe and critical ovarian hyperstimulation syndrome (OHSS). For this purpose, we reviewed the medical records of all OHSS patients hospitalized in 16 out of 19 tertiary medical centres in Israel between January 1987 and December 1996. Febrile morbidity was defined as at least one episode of temperature rise above 38 degrees C lasting > or =24 h. A total of 2902 patients (3305 hospitalizations) with OHSS was identified, of whom 196 had severe, and 13 critical, OHSS. Among the 209 patients investigated the incidence of febrile morbidity was 82.3%, of which 20.5% was attributed to urinary tract infection, 3.8% to pneumonia, 3.3% to upper respiratory tract infection, 2.0% to intravenous line phlebitis, 1.0% to cellulitis at an abdominal puncture site, 1.0% to postoperative wound infections and 0.5 % to gluteal abscess at the site of progesterone injection. Non-typical organisms were frequently isolated, such as Pseudomonas, Proteus, Klebsiella and Enterobacter species. No infectious aetiology was found in 105 patients (50.2%). Hypoglobulinaemia was recorded in most patients, while ascitic and pleural fluids aspirated from these patients contained high globulin concentrations. We conclude that infection-related febrile morbidity in severe and critical OHSS is high, and may be attributed to some degree of immunodeficiency associated with loss of plasma globulins to the third space. However, non-infection-related febrile morbidity is even higher and may be attributed to endogenous pyrogenic mechanisms.     

Baby love. Interview by Charlotte Alderman

The authors present 3 cases of OHSS in 85 patients (3.5%), treated with long stimulation protocol. They propose an original grading of the severity of the syndrome as well as prophylactic and therapeutic measures.     

A novel approach to the treatment of ascites associated with ovarian hyperstimulation syndrome

Ascites is a clinical manifestation of severe ovarian hyperstimulation syndrome (OHSS) which may complicate the induction of ovulation using exogenous gonadotrophins. In severe OHSS severe ascites may occur and can lead to dyspnoea, abdominal discomfort and oliguria. To relieve ascites paracentesis is performed two to three times weekly as needed. We report three cases where an indwelling peritoneal catheter was used to decrease the need for repeated paracentesis. Under ultrasound guidance a closed system Dawson-Mueller catheter with 'simp-loc' locking design was inserted to allow continuous drainage of the ascitic fluid. A total of 23 l of the ascitic fluid were drained from the first, 20 l from the second and 28 l from the third patient with significant decrease in abdominal discomfort and improvement in the urine output. No complications or adverse reactions were noted. Continuous drainage of the ascitic fluid is efficient. It quickly decreases the abdominal discomfort, improves the urine output and prevents the need for multiple abdominal paracenteses which some patients may require.     

Role of vascular endothelial cell growth factor in Ovarian Hyperstimulation Syndrome

Controlled ovarian hyperstimulation with gonadotropins is followed by Ovarian Hyperstimulation Syndrome (OHSS) in some women. An unidentified capillary permeability factor from the ovary has been implicated, and vascular endothelial cell growth/permeability factor (VEGF) is a candidate protein. Follicular fluids (FF) from 80 women who received hormonal induction for infertility were studied. FFs were grouped according to oocyte production, from group I (0-7 oocytes) through group IV (23-31 oocytes). Group IV was comprised of four women with the most severe symptoms of OHSS. Endothelial cell (EC) permeability induced by the individual FF was highly correlated to oocytes produced (r2 = 0.73, P < 0.001). Group IV FF stimulated a 63+/-4% greater permeability than FF from group I patients (P < 0. 01), reversed 98% by anti-VEGF antibody. Group IV fluids contained the VEGF165 isoform and significantly greater concentrations of VEGF as compared with group I (1,105+/-87 pg/ml vs. 353+/-28 pg/ml, P < 0. 05). Significant cytoskeletal rearrangement of F-actin into stress fibers and a destruction of ZO-1 tight junction protein alignment was caused by group IV FF, mediated in part by nitric oxide. These mechanisms, which lead to increased EC permeability, were reversed by the VEGF antibody. Our results indicate that VEGF is the FF factor responsible for increased vascular permeability, thereby contributing to the pathogenesis of OHSS.