Internal jugular vein thrombosis after ovarian stimulation

Thromboembolic events are serious, but fortunately rare, complications following ovarian stimulation for IVF. Here, we report a case of internal jugular vein thrombosis after ovarian stimulation with gonadotrophins. Most of the cases of thrombosis are late complications of ovarian hyperstimulation syndrome (OHSS) or hereditary hypercoagulability. Screening for these risk factors in our patient was negative. The patient was successfully treated with low molecular weight heparin and a twin pregnancy is ongoing.     

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.     

The impact of obesity and insulin resistance on the outcome of IVF or ICSI in women with polycystic ovarian syndrome

The impact of insulin resistance on the outcome of IVF or intracytoplasmic sperm injection (ICSI) in women with polycystic ovarian syndrome (PCOS) was examined. Insulin sensitivity was measured by the continuous infusion of glucose with model assessment (CIGMA) test. Insulin-resistant (n = 26) and non-insulin-resistant women (n = 30) with PCOS underwent a total of 100 cycles of long-term down-regulation with buserelin acetate, stimulation with human recombinant FSH, and IVF or ICSI. Blood samples were taken throughout ovarian stimulation for hormone assays. Insulin-resistant and non-insulin-resistant women had similar concentrations of FSH, LH, testosterone and androstenedione throughout stimulation, but insulin-resistant women had hyperinsulinaemia and lower sex hormone binding globulin concentrations. Insulin-resistant women also had lower oestradiol concentrations during stimulation and required higher FSH doses, but these differences disappeared after controlling for the higher body weight in the group of insulin-resistant women. Groups had similar number of oocytes collected, similar implantation and pregnancy rates, and the incidence of ovarian hyperstimulation syndrome was also similar. Obesity, independent of hyperinsulinaemia, was related to a lower oocyte count and increased FSH requirement. It is concluded that in PCOS women receiving long-term down-regulation and stimulation with recombinant FSH, insulin resistance is neither related to hormone levels nor to IVF outcome. Obesity, independent of insulin resistance, is associated with relative gonadotrophin resistance.     

Does subfertility explain the risk of poor perinatal outcome after IVF and ovarian hyperstimulation?

BACKGROUND: The primary objective of this study was to investigate whether subfertility explains poor perinatal outcome after assisted conception. A secondary objective was to test the hypothesis that ovarian hyperstimulation rather than the IVF procedure may influence the perinatal outcome. METHODS: Using data from a Dutch population-based historical cohort of women treated for subfertility, we compared perinatal outcome of singletons conceived after controlled ovarian hyperstimulation (COHS) and IVF (IVF + COHS; n = 2239) with perinatal outcome in subfertile women who conceived spontaneously (subfertile controls; n = 6343) and in women who only received COHS (COHS only; n = 84). Furthermore, we compared perinatal outcome of singletons conceived after the transfer of thawed embryos with (Stim + Cryo; n = 66) and without COHS (Stim - Cryo; n = 73). RESULTS: The odds ratios (ORs) for very low birthweight (<1500 g) and low birthweight (1500-2500 g) were 2.8 [95% confidence interval (95% CI) 1.9-3.9] and 1.6 (95% CI 1.2-1.8) in the IVF + COHS group compared with the subfertile control group. The ORs for very preterm birth (<32 weeks) and for preterm birth (32-37 weeks) were 2.0 (95% CI 1.4-2.9) and 1.5 (95% CI 1.3-1.8), respectively. Adjustment for confounders did not materially change these risk estimates. The difference in risk between the COHS-only group and the subfertile group was significant only for very low birthweight (OR 3.5; 95% CI 1.1-11.4), but the association became weaker after adjustment for maternal age and primiparity (OR 3.1; 95% CI 1.0-10.4). No significant difference in birthweight and preterm delivery was found between the group of children conceived after ovarian stimulation/ovulation induction and (Stim + Cryo) and the group of children conceived after embryo transfer of thawed embryos in a spontaneous cycle without ovarian stimulation/ovulation induction (Stim - Cryo). CONCLUSIONS: The poor perinatal outcome in this database could not be explained by subfertility and suggests that other factors may be important in the known association between assisted conception and poor perinatal outcome.     

Conversion of cycles involving ovarian hyperstimulation with intra-uterine insemination to in-vitro fertilization

Conversion to in-vitro fertilization (IVF) and embryo transferas an alternative to cancellation was offered in 27 consecutivecycles of controlled ovarian hyperstimulation and intra-uterineinsemination (IUI) cycles with excessive follicular developmentin patients with idiopathic infertility. IVF and embryo transferwas performed in 25 cycles, resulting in 13 pregnancies (52%),with 22% of couples having at least two embryos cryopreserved.The pregnancies have resulted in one singleton and two twinbirths, one spontaneous abortion, and nine ongoing pregnancies(including one triplet gestation). Four patients developed severeovarian hyperstimulation syndrome (OHSS) after IVF and embryotransfer, including two cases requiring paracentesis. Threeof four OHSS patients were pregnant, resulting in live birthsof healthy twins, one spontaneous abortion and one ongoing singletongestation. In two cycles a spontaneous luteinizing hormone (LH)surge occured, preventing oocyte retrieval. For these two women,drainage of all follicles except the five most likely to fertilize(18–22 mm diameter) was performed, followed by IUI, withno pregnancies or OHSS observed. Conversion of patients fromIUI cycles to IVF/embryo transfer cycles avoids cancellationof the very cycles with the best chance of achieving pregnancy.OHSS remains a problem, necessitating extensive pre-IVF counsellingand post-transfer vigilance.     

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Thromboembolic events are serious but rare complications followingovarian stimulation for in-vitro fertilization (IVF). We reporta case of severe ovarian hyperstimulation syndrome (OHSS), presentingin a second IVF cycle with a late complication of right internaljugular vein thrombosis despite mini-dose heparin prophylaxis.Thrombosis and thromboembolism as late complications of OHSShave been reported by others but not after prophylactic heparinization.The patient was successfully treated with heparin and the twinpregnancy is ongoing. In pregnant patients with severe OHSSconsideration should be given to treatment with low dose heparinthroughout the first trimester to prevent the serious complicationsof thrombosis and thromboembolism.     

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.     

Minimal stimulation IVF with late follicular phase administration of the GnRH antagonist cetrorelix and concomitant substitution with recombinant FSH: a pilot study

BACKGROUND: The use of the natural cycle for IVF offers the advantage of a patient-friendly and low-risk protocol. Its effectiveness is limited, but may be improved by using a GnRH antagonist to prevent untimely LH surges. METHODS: In this pilot study, minimal stimulation IVF with late follicular phase administration of the GnRH antagonist cetrorelix and simultaneous substitution with recombinant FSH was applied for a maximum of three cycles per patient. Main outcome measures were pregnancy rates per started cycle and cumulative pregnancy rates after three cycles. RESULTS: A total of 50 patients completed 119 cycles (2.4 per patient). Fifty-two embryo transfers resulted in 17 ongoing pregnancies [14.3% per started cycle; 32.7% per embryo transfer; 95% confidence interval (CI) 7.9-20.7% and 19.7-45.7%, respectively]. One dizygotic twin pregnancy occurred after transfer of two embryos, the other pregnancies were singletons. The cumulative ongoing pregnancy rate after three cycles was 34% (95% CI 20.6-47.4%). Live birth rate was 32% per patient (95% CI 18.8-45.2%). CONCLUSIONS: Pregnancy rates after IVF with minimal, late follicular phase stimulation are encouraging. Considering the low-risk and patient-friendly nature of this protocol, it may be a feasible alternative to IVF with ovarian hyperstimulation.     

Comparison of endocrine tests with respect to their predictive value on the outcome of ovarian hyperstimulation in IVF treatment: results of a prospective randomized study

BACKGROUND: This study was designed to compare endocrine tests [clomiphene citrate challenge test (CCT), exogenous FSH ovarian reserve test (EFORT) and basal FSH, basal estradiol (E(2)) and basal inhibin B as an integral part of all CCT and EFORT], with respect to their ability to estimate the stimulable cohort of follicles in the ovaries (ovarian capacity) and to analyse which test or combination of tests would give the best prediction of ovarian capacity. METHODS: A total of 110 regularly menstruating patients, aged 18-39 years, participated in this prospective study, randomized by a computer-designed 4-block system study into two groups. Fifty-six patients underwent a CCT, and 54 patients underwent an EFORT. In all patients, the test was followed by an IVF treatment. The result of ovarian hyperstimulation during IVF treatment, expressed by the total number of follicles, was used as gold standard. RESULTS: Univariate linear regression analysis showed that the best correlation with the number of follicles after ovarian hyperstimulation (Y) is found by the inhibin B increment (InhB incr.) in the EFORT (Y = 3.957 + 0.081 x InhB incr. (95% CI 0.061-0.101); r = 0.751; P < 0.001). Multiple linear regression analysis showed a significant contributing value of the variables basal FSH, E(2) increment of the EFORT and inhibin B increment to the basic model with the variable age. The best prediction of ovarian capacity (Y) was seen when E(2) increment and inhibin B increment were used simultaneously in a stepforward multiple regression prediction model [Y = 2.659 + 0.052 x InhB incr. (0.026-0.078) + 0.027 x E(2) incr. (95% CI 0.012-0.054); r = 0.796; P < 0.001]. The CCT could not be used in a prediction model. CONCLUSIONS: The EFORT is the endocrine test which gives the best prediction of ovarian capacity.     

Endocrinology: Repeated aspiration of ovarian follicles and early corpus luteum cysts in an in-vitro fertilization programme reduces the risk of ovarian hyperstimulation syndrome in high responders

A retrospective analysis of ovarian hyperstimulation syndromein high responders undergoing in-vitro fertilization (IVF) ispresented. High responders were defined as having > 20 folliclesand serum oestradiol > 3000 pg/ml after treatment with humanmenopausal gonadotrophin. Of the initial 30 IVF cycles in highresponders, 23 developed a moderate-to-severe ovarian hyperstimulationsyndrome (76.7%). Subsequently, 15 other IVF cycles in highresponders were combined with a repeated aspiration of ovarianfollicles and corpus luteum cysts just prior to embryo transfer.Only three patients (20%) developed a moderate ovarian hyperstimulationsyndrome (P = 0.0004). We conclude that repeated follicularaspiration is safe and results in a significant reduction inthe incidence and severity of this condition in high respondersundergoing IVF.     

Recombinant follicle stimulating hormone in in-vitro fertilization treatment-clinical experience with follitropin alpha and follitropin beta

The objective of this prospective study was to compare the outcome of ovarian hyperstimulation for in-vitro fertilization (IVF) using two different preparations of recombinant follicle stimulating hormone (FSH). The study was based on 296 consecutive IVF cycles in 1997, 199 performed using follitropin alpha (Gonal-F) and 97 performed using follitropin beta (Puregon). Outcome was compared regarding pregnancy rate, oestradiol and progesterone response, endometrial thickness, follicle number, number of retrieved oocytes, fertilized oocytes, sperm count and sperm motility. There was no significant difference in outcome of stimulation. Clinical pregnancy rate was similar, 29.1% for Gonal-F and 28.1% for Puregon. There was no difference in endometrial response, oestradiol response, number of smaller (12-15 mm) or larger (>15 mm) follicles, number of oocytes retrieved, fertilized, divided and replaced, in sperm counts or in sperm progressive motility. There was a lower follicle number in the Puregon group, but not statistically significant. The serum progesterone concentrations on the day of oocyte retrieval, however, were significantly lower in the Puregon group. In conclusion, it was not possible to find significant differences in the IVF programme with regard to stimulation outcome between Gonal-F and Puregon. The results of this study indicate that Gonal-F and Puregon may be equally suitable for use in ovarian stimulation for IVF.     

Vascular endothelial growth factor levels in serum and plasma from patients undergoing controlled ovarian hyperstimulation for IVF

BACKGROUND: Vascular endothelial growth factor (VEGF) has been investigated as a marker of ovarian response to controlled ovarian hyperstimulation and as a predictor of ovarian hyperstimulation syndrome (OHSS) in IVF cycles. In most studies, serum has been used for circulating VEGF concentration measurement, but it has been suggested that plasma is the preferred medium to measure VEGF levels because of the potential contribution of VEGF released from platelets during blood clotting. This study investigated VEGF concentrations in paired serum and plasma samples from patients undergoing controlled ovarian hyperstimulation for IVF. METHODS: Serum and plasma VEGF levels, as well as the number of platelets, were measured in 30 IVF patients who comprised three study groups delineated according to the estradiol (E(2)) serum concentration reached on the day of HCG administration: 10 patients having low E(2) serum levels (<1500 pg/ml, group L), 10 patients having intermediate E(2) serum levels (1500-3000 pg/ml, group I) and 10 patients having high E(2) serum levels (>3000 pg/ml, group H). RESULTS: There was a statistically significant correlation between plasma and serum VEGF levels (rho = 0.61; P < 0.005) for the entire population studied, although serum values were higher by a factor of approximately 6-fold. No significant correlation was found between peripheral blood VEGF concentrations and serum E(2) or follicle number on HCG day or the number of oocytes collected. Similarly, paired serum and plasma VEGF measurements did not correlate with platelet count. CONCLUSIONS: Serum and plasma VEGF concentrations are strongly correlated in paired samples from infertile patients undergoing controlled ovarian hyperstimulation. However, neither serum nor plasma VEGF levels were correlated with parameters associated with ovarian follicular activity. Peripheral blood VEGF levels were not correlated with platelet count.     

Effect of follicular aspiration on hormonal parameters in patients undergoing ovarian stimulation

The effect of follicular aspiration and oocyte retrieval on hormonal parameters was examined in women undergoing ovarian stimulation for in-vitro fertilization (IVF) compared to induced ovulation in women undergoing ovarian stimulation for intrauterine insemination (IUI). Blood samples were collected immediately before and 1 h after oocyte retrieval and 48 h later on the day of embryo transfer in 25 IVF patients and before the insemination and 48 h later in 20 IUI patients. A highly significant fall in serum levels of oestradiol (E2), progesterone (P) and human chorionic gonadotrophin (HCG), (P less than 0.001) was observed in the IVF group 1 h after follicular aspiration. The decline in serum E2 levels was maintained at 48 h. In contrast, there was no significant change in serum E2 levels in the IUI group during 48 h. The immediate decline in E2 levels after follicular aspiration might play a role in preventing ovarian hyperstimulation syndrome.     

Acute prerenal failure and liver dysfunction in a patient with severe ovarian hyperstimulation syndrome

We report a case of severe ovarian hyperstimulation syndrome which developed in a patient after ovarian stimulation for in-vitro fertilization (IVF). This was complicated by prerenal oliguria due to indomethacin therapy and liver dysfunction. The pathogenetic mechanisms involved are discussed.     

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.     

C-reactive protein levels in patients undergoing controlled ovarian hyperstimulation for IVF cycle

BACKGROUND: The aim of the present study was to determine serum and follicular fluid C-reactive protein (CRP) levels in patients undergoing controlled ovarian hyperstimulation (COH) for IVF-embryo transfer cycle, and their possible correlation to COH variables. PATIENTS AND METHODS: The subjects were 16 consecutive patients undergoing our routine IVF long GnRH agonist protocol. Blood was drawn three times during the COH cycle: (i) the day on which adequate suppression was obtained (Day-S); (ii) the day of, or prior to HCG administration (Day-HCG); and (iii) the day of (and before) oocyte pick-up (Day-OPU). Levels of sex steroids and serum and follicular fluid CRP were compared among the three time points. Serum and follicular fluid CRP were measured with a commercial immunoturbidimetric assay. RESULTS: Serum levels of CRP were significantly higher on Day-OPU and Day-HCG than on Day-S, and significantly higher on Day-OPU than on Day-HCG. No difference was observed between follicular and serum CRP levels on Day-OPU. No significant correlations were found between serum and follicular fluid CRP, or between serum CRP-to-BMI ratio and serum sex steroid levels or IVF treatment variables. CONCLUSIONS: The significant increase in serum CRP levels during COH, especially after HCG administration, suggests that COH potentiates a state of systemic inflammation.     

Embryonic development in vitro is compromised by the ICSI procedure

The implantation rates achieved with intracytoplasmic sperm injection (ICSI) are equivalent to those with conventional in-vitro fertilization (IVF) but information on embryonic development in vitro after ICSI is scant. In this paper we compare blastocyst formation after IVF and ICSI; we have also investigated the effect of the ICSI procedure with internal control of extrinsic (including paternal) factors. The first series comprised cases of IVF treatment (n = 101) for tubal infertility and ICSI (n = 96) for male infertility. The proportions of embryos developing to the blastocyst stage was significantly lower after ICSI (8.9%, P < 0.001) than after conventional IVF (23.5%). In order to investigate the effect of the ICSI procedure in isolation, blastocyst formation was analysed in a second series of eight cases, in which sibling oocytes were non-selectively subjected to ICSI (n = 78) or IVF (n = 67) with spermatozoa from the same semen sample. It was found that 20% of ICSI embryos and 50% of IVF embryos formed blastocysts (P < 0.01), demonstrating that the ICSI procedure contributes to a reduced capacity for blastocyst formation in vitro.     

Cortical vein thrombosis misinterpreted as intracranial haemorrhage in severe ovarian hyperstimulation syndrome: case report

A case of cortical vein thrombosis presenting as intracranial haemorrhage is described in a patient with ovarian hyperstimulation syndrome (OHSS) after IVF and embryo transfer. Veno-occlusive disease of the brain could appear as a haemorrhagic lesion on magnetic resonance imaging (MRI) and this made the initial diagnosis of cortical vein thrombosis difficult. The patient developed deep vein thrombosis 2 weeks after the intracranial event and the diagnosis of cortical vein thrombosis was made at that time on MRI study after the resolution of the haemorrhage. This patient actually developed generalized thrombosis as a complication to OHSS. Although the initial MRI picture may be misleading, the diagnosis of thrombosis should always be kept in mind, as it is the commonest cause of intracranial lesions after OHSS.     

Spontaneous ovarian hyperstimulation syndrome and deep vein thrombosis in pregnancy: case report.

This report describes a case of spontaneous ovarian hyperstimulation syndrome (OHSS) occurring in a pregnant woman carrying the factor V Leiden mutation. Even though prophylactic treatment for thrombo-embolism was adopted by administering low molecular weight heparin, the pregnancy was complicated by thromboses of the left subclavian, axillary, humeral and internal jugular veins during the second trimester of gestation. The pregnancy was managed conservatively and a healthy newborn was delivered at term. In order to avoid unnecessary laparotomy, we emphasize the importance of careful diagnosis in order to differentiate spontaneous OHSS from ovarian carcinoma, as well as the necessity to look for the presence of coagulation disorders in women affected by OHSS.     

Clinical complications during in-vitro fertilization treatment.

A questionnaire was sent to 12 large in-vitro fertilization (IVF) clinics in Nordic countries, asking about the number of clinical complications in connection with IVF treatment. The total number of cycles included was 10,125, with 7331 embryo transfers performed. Clinical complications were rare, although hyperstimulation syndrome was reported in 0.7% of the cycles started and follicle puncture complications in 0.5% of cycles. Post-operative infections were reported in 0.3% of embryo transfers.