Laparoscopic therapy of an intact primary ovarian pregnancy with ovarian hyperstimulation syndrome: case report

A case of an intact primary ovarian pregnancy with ultrasonographic demonstration of heart motion following ovarian stimulation is presented. After preoperative ultrasonographic confirmation of an extrauterine pregnancy, proof of the ovarian localization was achieved by intra-operative ultrasonographic visualization during a diagnostic laparoscopy on post-menstrual day 48. A moderate ovarian hyperstimulation syndrome with a concomitant increase in size, vulnerability and vascularity of the ovaries presented an additional challenge for the surgical approach. However, thanks to the early diagnosis of the ectopic pregnancy localization, a laparoscopic organ-preserving removal of the intact ovarian pregnancy was successfully performed. In this way, the fertility of the patient, who had previously undergone contralateral ovariectomy, was preserved. To our knowledge, this represents the first such treatment to be reported in the medical literature. Improvements in diagnosis and therapy of ovarian pregnancy are reviewed.     

Spontaneous ovarian hyperstimulation mimicking an ovarian tumour

Ovarian hyperstimulation syndrome in a spontaneous singletonpregnancy is exceedingly rare. We report a case of ovarian hyperstimulationpresenting as bilateral ovarian masses in association with spontaneouspregnancy, occurring in a woman with disturbed liver function.A possible mechanism is discussed.     

Endocrinology: Ovarian hyperstimulation syndrome associated with spontaneous pregnancy

A case of ovarian hyperstimulation syndrome (OHSS) associatedwith a spontaneous pregnancy is reported with the hope of facilitatingearlier recognition of this condition. Although OHSS is usuallyan iatrogenic complication, it can also occur spontaneouslywithout any evidence of endocrinological disorder. Surgery wasperformed and induced a very rapid resolution of ovarian hyperstimulation.     

Recurrent cholestasis following ovarian hyperstimulation syndrome: case report.

This is a case report illustrating a patient who developed recurrent cholestasis during a twin pregnancy following in-vitro fertilization (IVF) treatment. On the first occasion cholestasis developed unusually in the first trimester, and on the second occasion, it presented in the way that obstetric cholestasis (OC) is commonly seen in the third trimester.     

Subclavian vein thrombosis following IVF and ovarian hyperstimulation: a case report

Thromboembolic phenomena are a serious consequence of assisted reproductive technology. We present a case of upper extremity deep vein thrombosis (DVT) at 7 weeks gestation following ovarian hyperstimulation syndrome (OHSS) and IVF. Three weeks after recovering from OHSS, the patient presented with left neck pain and swelling. Ultrasound revealed a thrombus in the left jugular vein and left subclavian vein. Low molecular weight heparin (LMWH) was initiated with symptom resolution within 1 week. The patient remained on LWMH throughout her pregnancy and delivered at term. A literature review showed 97 published cases of thromboembolism following ovulation induction. A majority of these cases was associated with OHSS and pregnancy and the site of involvement was predominantly in the upper extremity and neck. Infertility physicians and obstetricians should be aware of this complication and keep in mind that it may occur weeks after resolution of OHSS symptoms.     

Subclavian vein thrombosis: a late complication of ovarian hyperstimulation syndrome.

Two cases of subclavian vein thrombosis following ovarian stimulation for in-vitro fertilization and subsequent ovarian hyperstimulation syndrome (OHSS) are described. Both occurred several weeks after complete resolution of the OHSS. The site of the lesions and their timing suggest that there is a generalized disturbance of coagulation associated with OHSS, which persists beyond the duration of the clinical syndrome.     

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.     

CASE REPORT: Severe ovarian hyperstimulation syndrome, selective embryo reduction and heterotopic pregnancy

Ovarian hyperstimulation syndrome is common (21.4%) in patientswith polycystic ovarian disease, treated by gonadotrophins.It is much frequent (50%) in conceptual cycles. We report acase associated with a quadruplet pregnancy that underwent selectiveembryo reduction at 8 weeks' gestation to a twin pregnancy andwas subsequently found to have an unruptured ectopic pregnancyat 11 weeks' gestation. After laparotomy and partial salpingectomya successful twin pregnancy ensued.     

Severe ovarian hyperstimulation syndrome and combined intrauterine and tubal pregnancy after in-vitro fertilization and embryo transfer

Ovarian hyperstimulation syndrome (OHSS) and hetero-topic pregnancyare two well recognized entities occurring after in-vitro fertilization(TVF). This is the first reported case of a severe OHSS andcoexistent heterotopic pregnancy after FVF and embryo transfer.Diagnosis of tubal pregnancy was obscured both by stimulatedovaries which prevented accurate ultrasound definition and thecoexistence of an intrauterine pregnancy which accounted forhuman chorionic gonadotropbin (HCG) concentrations and alsofor aggravation of the OHSS. The roles of transvaginal ultrasound,diagnostic laparoscopy and early paracentesis in the managementof this rare complication of assisted reproductive technologiesare discussed.     

Dopamine treatment for severe ovarian hyperstimulation syndrome.

Seven oliguric patients with severe ovarian hyperstimulation syndrome following gonadotrophin treatment for in-vitro fertilization or gamete intra-Fallopian transfer, were treated with low doses of dopamine by peripheral infusion. Five patients were pregnant. The rationale for this therapeutic approach was to increase renal blood flow and glomerular filtration. In addition to dopamine, fluid intake was restricted to 500 ml/day and a protein and salt-rich diet was provided in order to increase serum osmolarity. Within 24-48 h from the beginning of the dopamine treatment, the syndrome started to regress in all cases. No adverse maternal or fetal effects occurred. We conclude that dopamine therapy may constitute a major advance towards the management of severe ovarian hyperstimulation syndrome.     

In-vitro fertilization and the ovarian hyperstimulation syndrome.

Eight patients who developed severe ovarian hyperstimulation syndrome (OHSS) were identified among 1302 patients undergoing in-vitro fertilization (IVF) over a 1 year period (prevalence of 0.6%); 63% had ultrasonically diagnosed polycystic ovaries (PCO) and 75% were undergoing their first attempt at IVF. Pretreatment with a superactive luteinizing hormone-releasing hormone (LHRH) analogue significantly increased the prevalence of severe OHSS (1.1% versus 0.2%, P less than 0.05) compared with ovarian stimulation with clomiphene citrate and human menopausal gonadotrophin (HMG). The mean serum oestradiol concentration on the day of human chorionic gonadotrophin (HCG) administration was 8200 +/- 2300 pmol/l. A mean of 19.6 +/- 6.8 follicles had been aspirated and 13.1 +/- 7.7 oocytes recovered at transvaginal ultrasound-directed oocyte recovery. All patients had an embryo transfer and luteal support in the form of HCG. The clinical pregnancy rate was 88%, multiple pregnancy rate 71% and implantation rate 63.5 +/- 41.3%. In a group of seven patients who were hospitalized for moderate OHSS during the same period, peak oestradiol levels were significantly lower than in those with severe OHSS (P less than 0.05). Of the group with moderate OHSS, 57% had PCO, the clinical pregnancy rate was 100% and multiple pregnancy rate 43%. Patients with ultrasound-diagnosed PCO have an increased risk of developing OHSS and the dose of HMG administered to them should be minimized. In patients at risk of developing OHSS, progesterone instead of HCG should be used for luteal support. Transfer of a maximum of two embryos or freezing all embryos for transfer in a subsequent cycle may reduce the likelihood of multiple pregnancy.     

Quintuplet pregnancy and third degree ovarian hyperstimulation despite withholding human chorionic gonadotrophin.

A patient who suffered from polycystic ovarian disease and anovulation, was treated with pure follicle stimulating hormone for induction of ovulation. The treatment was stopped and human chorionic gonadotrophin was not administered because of high serum oestradiol levels and multiple follicular development. Ovulation occurred 11 days after pure follicle stimulating hormone was discontinued, the patient developed third-degree ovarian hyperstimulation syndrome and conceived with a quintuplet pregnancy.     

Ovarian hyperstimulation syndrome and benign intracranial hypertension in pregnancy after in-vitro fertilization and embryo transfer: case report.

Ovarian hyperstimulation syndrome (OHSS) is a dangerous and sometimes life-threatening complication of ovulation induction with exogenous gonadotrophins. While many complications of severe OHSS are recognized we have only identified one review detailing neurological problems. This report concerns a 32-year-old patient with bilateral tubal blockage who achieved her first pregnancy following in-vitro fertilization (IVF) and embryo transfer. Shortly after embryo transfer she developed clinical signs of moderate OHSS with symptoms which were later diagnosed as benign intracranial hypertension (BIH). The BIH was treated effectively using repeated lumbar puncture and diuretics. Spontaneous labour and delivery occurred at 40 weeks' gestation. There was no neurological sequel and no recurrence of the BIH 2 years after the pregnancy. The possible link between OHSS and BIH is discussed as well as the risks of further pregnancy.     

Endocrinology: Predictive value of serum oestradiol concentrations and oocyte number in severe ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is a serious complicationof gonadotrophin usage but it is difficult to accurately predictits occurrence. Previous investigators have identified the combinationof high oestradiol concentrations and oocyte number as beingpredictive in 80% of cases. In this study we sought to identifythe incidence of severe OHSS in patients with high oestradiolconcentrations and large numbers of oocytes and to evaluatethe importance of pregnancy in the development of OHSS. Between1990 and 1993, we studied 139 cycles using two assisted reproductivetechniques [oocyte donor, n =72; in-vitro fertilization (IVF),n = 67] in which either oestradiol (>4000 pg/ml), oocytenumber (>25), or both were elevated. OHSS was diagnosed bystandard criteria. There were no cases of severe OHSS in theoocyte donor group and six in the IVF group. Among 10 patientswith oestradiol concentration >6000 pg/ml and >30 oocytes,only one had OHSS (10%). The relative risk of OHSS with pregnancywas 12 (confidence interval 2.18–66.14). We conclude thatthe risk of OHSS even at high levels of stimulation is lowerthan previously believed. Secondly, donors have a very low riskof OHSS, probably because of the absence of pregnancy. As such,cryopreservation of all oocytes in IVF cycles is a reasonablealternative to cycle cancellation or use of adjunctive medication.     

Interleukin-2 and ovarian hyperstimulation syndrome: a pilot study

A prospective case-controlled study was conducted to evaluatethe association between the concentrations of interleukin-2(IL-2) in human follicular fluid obtained at the time of oocytecollection for in-vitro fertilization (IVF) and the developmentof ovarian hyperstimulation syndrome (OHSS). Follicular fluidwas obtained at the time of oocyte collection for IVF consecutivelyfrom 40 patients at risk of developing OHSS. Among the 40 patientsparticipating in the study, seven subsequently developed OHSS.Their follicular fluid samples, together with those of an additionalseven patients matched by age who did not develop OHSS, weretested for osmolality, total protein content and IL-2 concentrations,and mean serum oestradiol concentrations at the time of humanchorionic gonadotrophin (HCG) administration and the mean numberof aspirated oocytes were also measured. Follicular fluid IL-2concentrations were significantly higher (P < 0.002) in theOHSS group as compared to the control group. No significantdifferences were found between the two groups regarding themean serum oestradiol concentration on the day of HCG administration,or the mean number of aspirated oocytes, follicular fluid osmolality,or total protein concentrations. This study suggests an associationbetween follicular fluid IL-2 concentration and OHSS. IL-2 isknown to cause ‘vascular leak syndrome’, which resemblesOHSS. These observations, together with the established interactionbetween the immune and the reproductive systems, may suggesta pivotal role of IL-2 in the pathogenesis of OHSS.     

Androstenedione as a predictor of ovarian hyperstimulation syndrome.

Serum concentrations of testosterone, 4-androstene-3,17-dione (androstenedione), dehydroepiandrosterone (DHA) and its sulphate and sex hormone-binding globulin (SHBG) were measured in 30 ovulatory women before and after down-regulation with gonadotrophin releasing-hormone analogue, prior to ovarian stimulation in a programme of in-vitro fertilization and embryo transfer. Nine of the women developed ovarian hyperstimulation syndrome (OHSS) while the others did not. Pretreatment values of androstenedione and the androstenedione:DHA ratios were higher and the testosterone:androstenedione ratios lower in the OHSS women. The decrease in androstenedione levels during down-regulation was greater and the absolute levels following down-regulation were lower in the OHSS group. Higher levels of SHBG and lower testosterone:SHBG ratios, an index of biologically active testosterone, were observed in the OHSS group. The isolated elevation in pretreatment androstenedione levels and the high SHBG levels make the OHSS group different from patients with polycystic ovarian disease. Pretreatment values of testosterone:androstenedione or testosterone/SHBG:androstenedione ratios and/or the decrease in androstenedione during down-regulation may be used as markers, prior to stimulation, for identifying women at risk of developing OHSS.     

Endocrinology: Plasma inflammatory cytokines correlate to the ovarian hyperstimulation syndrome

The objective of this study was to follow the kinetics of fourinflammatory cytokines in the plasma and aseitic fluid of sevenpatients who developed severe ovarian hyperstimulation syndrome(OHSS) after induction of ovulation for in-vitro fertilization.Blood samples were obtained from these patients at three differenttimes: upon hospitalization; when significant clinical improvementwas evident; and after complete resolution. Samples were analysedfor interleukin-1 (IL-i), interleukin-6 (IL-6), interleukin-8(IL-8) and tumour necrosis factor (TNF-). Ascitic fluid wasobtained by therapeutic paracentesis from all study patientsduring the active phase and analysed for these cytokines. Twocontrol groups were available: the first Included 15 women undergoingcontrolled ovarian stimulation for in-vitro fertilization withoutdeveloping OHSS, while the second consisted of 25 healthy womennot undergoing ovulation induction or any other medical treatment.High concentrations of IL-1, IL-6, and TNF- were detected inall individuals upon admission for severe OHSS. Concentrationsdropped significantly along with clinical improvement, reachingnormal values after complete resolution. A statistically significantcorrelation was found between plasma cytokine concentrationsand certain biological char acteristics of the syndrome suchas leukocytosis, increased haematocrit, and elevated plasma17--oestradiol concentrations. Ascitic fluid obtained from thestudy patients contained high IL-6 and IL concentrations, whileother cytokines were unaltered. These results suggest closeassociation between inflammatory cytokines and the pathophysiologyof the ovarian hyperstimulation syndrome.     

Severe ovarian hyperstimulation syndrome in assisted reproductive technology: definition of high risk groups.

In a retrospective analysis of 637 cycles of ovarian stimulation and transvaginal follicular aspiration for various assisted reproductive technologies, severe ovarian hyperstimulation syndrome (SOH) occurred in six (0.94%) cycles. The patients at a high risk of developing SOH in cycles of assisted reproduction were those who had excessive serum oestradiol levels on the day of human chorionic gonadotrophin (HCG) administration (oestradiol greater than 6000 pg/ml; 38% SOH) and a high number of oocytes obtained (greater than 30 oocytes; 23% SOH). In those patients with both oestradiol greater than 6000 pg/ml on the day of HCG administration and greater than 30 eggs retrieved, the chance of developing SOH was 80%. The higher the serum oestradiol levels and the more eggs retrieved, the higher the pregnancy rates observed. High oestradiol level did not appear to have a detrimental effect on pregnancy rates and outcome. Furthermore, our results are not consistent with suggestions that the addition of gonadotrophin-releasing hormone agonist to ovarian stimulation protocols, follicular aspiration and/or luteal support with progesterone may reduce the incidence of ovarian hyperstimulation syndrome.     

High pregnancy rates and successful prevention of severe ovarian hyperstimulation syndrome by 'prolonged coasting' of very hyperstimulated patients: a multicentre study

In a multicentre trial, 65 in-vitro fertilization (IVF)-embryo transfer cycles were severely hyperstimulated. Instead of cancelling the cycle, gonadotrophins were withheld for a 'coasting period' until serum oestradiol concentrations had dropped below 10,000 pmol/l (mean 4.3 days), and then human chorionic gonadotrophin was administered. Four cycles were cancelled and there were 61 oocyte aspirations. A total of 103 fresh embryos was transferred to 53 patients, resulting in a pregnancy rate of 42% per started cycle (51% per embryo transfer), with an implantation rate of 31%. Only one patient developed severe ovarian hyperstimulation syndrome (OHSS). Four patients developed moderate OHSS. In all, two patients were hospitalized for OHSS. In order to optimize the coasting procedure, it seems important that each IVF centre identifies its appropriate cut-off limits for serum oestradiol concentrations and follicle size for initiating and ending of the coasting period. Correctly handled, it seems to be a major advance in the search for improved stimulation policies for high-responders.     

Endocrinology: Prediction of ovarian hyperstimulation syndrome of baseline ovarian volume prior to stimulation

The aim of the study was to find out whether the estimationof the baseline ovarian volume prior to stimulation would bea suitable predictor for the risk of ovarian hyperstimulationsyndrome (OHSS). A total of 101 patients underwent in-vitrofertilization (IVF) and embryo transfer. They had a 3-D volumetricassessment of the ovaries and body weight estimations on thefirst day of hormonal stimulation. A second measurement wasperformed on the day of ovulation induction with human chorionicgonadotrophin (HCG) together with an oestradlol 17 estimationin serum. During the IVF programme 15 women developed OHSS and86 did not. There was a significant correlation between thebaseline ovarian volume and subsequent occurrence of OHSS (P=0.03).Other significant relationships were foimd between the occurrenceof OHSS and the number of follicles (P=0.002), the number ofoocytes retrieved (P=0.0001) and the length of the cycle (P=0.0001).The body weight before and after the stimulation was significantlylower in the group of women who did develop the syndrome (P=0.011resp.0.03). The oestradiol 17 concentration on the day of HCGadministration in the serum of the patients who had OHSS wassignificantly higher (P=0.0001). In conclusion, voluinetry ofthe ovaries could help to detect patients at risk and preventthe occurrence of OHSS by early adjustment of the hormonal dosage.Recent advances in ultrasound technology (3-D ultrasound) enablequick and highly accurate volumetric assessments. Furthermore,our study confirms previous observations that low body weightand long cycles seem to be additional risk factors for the developmentof OHSS.