Is severe OHSS associated with adverse pregnancy outcomes? Evidence from a case–control study

Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially life-threatening complication of fertility treatment. This study evaluated pregnancy outcomes of women hospitalized for severe OHSS. A case–control study was performed of 125 women who were hospitalized due to severe OHSS compared with a control group, consisting of 156 women matched by age and aetiology of infertility, who conceived via IVF and did not develop OHSS. Among women with singleton pregnancies, patients with severe OHSS delivered significantly earlier (37.96 versus 39.11 weeks) and had smaller babies (2854 g versus 3142 g) compared with the matched controls. Similarly, rates of preterm delivery (<34 weeks of gestation: 8.9% versus 0%, P < 0.01; <37 weeks of gestation: 20.5% versus 5.1%, P < 0.01) were significantly increased among patients in the study group. There were no between-group differences in the rates of gestational diabetes, gestational hypertension and intrauterine growth restriction. In contrast, twin pregnancies following OHSS were not significantly different from matched control twins, with regard to the rates of delivery <34 weeks and <37 weeks of gestation, gestational diabetes, gestational hypertension and intrauterine growth restriction. In conclusion, severe OHSS at early gestation is associated with adverse pregnancy outcome only in singleton gestations.     

Increased prevalence of thrombophilia among women with severe ovarian hyperstimulation syndrome

OBJECTIVE: To determine the prevalence of markers of thrombophilia in women hospitalized for severe OHSS. DESIGN: Prospective study. SETTING: Academic research center. PATIENT(S): Women undergoing induction of ovulation complicated by severe OHSS (n = 20) and women undergoing induction of ovulation without development of severe OHSS (n = 41). INTERVENTION(S): Blood samples to test for markers of thrombophilia were obtained during the luteal phase of the treatment cycle. MAIN OUTCOME MEASURE(S): Blood samples were analyzed for markers of thrombophilia, such as plasma levels of antithrombin, protein S and protein C, antiphospholipid antibodies, the factor V Leiden mutation, and 677T polymorphism in the 5,10 methyltetrahydrofolate reductase (MTHFR 677T) gene. RESULT(S): Seventeen of 20 patients with severe OHSS (85%) and 11 of 41 controls (26.8%) had one or more positive markers of thrombophilia. Of the women with severe OHSS, 6 had a decreased antithrombin level, 8 had decreased levels of protein S, 7 were homozygous for the MTHFR 677T mutation, 1 was heterozygous for the factor V Leiden mutation, and 5 had antiphospholipid antibodies. Eight women with OHSS and no controls had more than one positive marker of thrombophilia. CONCLUSION(S): The prevalence of thrombophilia is increased in women with severe OHSS. These findings suggest that prophylactic screening for this disorder and possible use of heparin prophylaxis for thromboembolic phenomena should be considered in these patients.     

Outcomes in an obstetrical population with hereditary thrombophilia and high tobacco use

Objective: The purpose of this study was to examine birth outcomes in women treated or untreated for thrombophilia during pregnancies affected or not by tobacco exposure.

Methods: This was a retrospective cohort study of consecutive women from a single maternal fetal medicine clinic who delivered between January 2009 and December 2013. We compared birth outcomes by four groups of thrombophilia and smoking combinations and then by treated or untreated groups.

Results: Of the 8889 pregnant women in this study, 113 had thrombophilia and 97 received treatment. Thromboprophylaxis included: low molecular weight heparin, aspirin, unfractionated heparin, folic acid, and combinations of these. Smokers with thrombophilia had significantly higher rates of preeclampsia, intrauterine growth restriction, preterm birth (<37?weeks gestation) and low birth weight (all p?≤?.001). Conversely, this group had significantly lower rates of hemolysis, elevated liver enzymes, low platelet count (HELLP syndrome) and placental abruption. Women with thrombophilia who received thromboprophylaxis had lower rates of adverse birth outcomes, reaching significance for preterm birth?<32?weeks gestation (4.3% versus 21.1%, p?=?.026).

Conclusion: Pregnant women who smoke and have thrombophilia may be more likely to experience adverse birth outcomes and receive more benefit from thromboprophylaxis than their nonsmoking counterparts.     

Maternal Mental Health in Assisted and Natural Conception: A Prospective Cohort Study

ObjectiveThis study sought to compare the pregnancy and postpartum self-reported mood and mental health status of women who conceived with assisted reproductive technology (ART) with those of women who conceived spontaneously.MethodsIn this prospective cohort study, 1176 pregnant women from prenatal clinics in the Ontario Birth Study were enrolled. In the pregnancy and the postpartum period, women who conceived with ART, including in vitro fertilization and intrauterine insemination, were compared with women who conceived spontaneously regarding depression and anxiety at 12–16 weeks and 24–28 weeks gestation and 6–10 weeks postpartum. The following main outcome measures were used: Edinburgh Postnatal Depression Scale, two-item Patient Health Questionnaire, State Trait Anxiety Inventory six-item scale, and two-item Generalized Anxiety Disorder scale (Canadian Task Force Classification II-2).ResultsWomen who conceived with ART demonstrated a decreased likelihood of depression compared with women who spontaneously conceived (SC) at 24–28 weeks gestation (Edinburgh Postnatal Depression Scale: ART 3.6% vs. SC 15%; P < 0.01; two-item Patient Health Questionnaire: ART 0.0% vs. SC 4.0%; P = 0.027), as well as decreased perceived stress (mean score: ART 3.25 vs. SC 4.02; P < 0.01). Women in the ART group also had a lower percentage of positive two-item Generalized Anxiety Disorder scores (ART 2.7% vs. SC 7.5%; P = 0.049). There was no difference in self-reported depression, anxiety, or perceived stress between groups at 12–16 weeks gestation or at 6–10 weeks postpartum.ConclusionWomen who conceived using ART reported decreased rates of depressive symptoms, perceived stress, and generalized anxiety during the second trimester of pregnancy compared with women who had SC pregnancies, and both groups experienced similar mental health status earlier in gestation and in the postpartum period.     

Successful administration of recombinant human antithrombin in a pregnant Japanese woman with hereditary antithrombin deficiency

ObjectiveHereditary antithrombin (AT) deficiency increases the risk of venous thromboembolism (VTE) in pregnant woman. We report the first case of administration of recombinant human antithrombin (rhAT) to a pregnant Japanese woman with AT deficiency.Case reportA 30-year-old woman, gravida 2 para 0, was referred to our hospital because of AT deficiency. Unfractionated heparin was administered from 13 weeks of gestation and rhAT was administered from labor onset. A cesarean section was performed and the patient and her baby were healthy, with no sequelae.ConclusionWe concluded that rhAT was effective for preventing VTE during delivery, with no potential infection risks.     

Female age is associated with the optimal number of oocytes to maximize fresh live birth rates: an analysis of 256,643 fresh ART cycles

Research questionWhat is the optimal number of oocytes retrieved at which maximum live birth rate is observed after fresh autologous assisted reproductive technology (ART) cycles for women of different ages?DesignRetrospective cohort study of all fresh autologous ART aspiration cycles (n = 256,643) undertaken in Australia and New Zealand between 2009 and 2015. Primary outcome measure was live birth rate (LBR) (delivery of at least one liveborn baby at 20 weeks’ gestation or over per fresh aspiration cycle). Cycles were grouped according to female age (<30, 30–34, 35–49, 40–44 and ≥45 years) and ovarian response (one to three, four to nine, 10–14, 15–19, 20–25 and ≥25 oocytes). Secondary outcome was incidence of ovarian hyperstimulation syndrome (OHSS) requiring hospitalization.ResultsAt different oocyte yields, LBR per fresh aspiration cycle peaked and then declined at, depending on female age: <30 years: six to 11 oocytes (LBR 31–34%); 30–34 years: 11–16 oocytes (LBR 29–30%); 35–39 years: nine to 17 oocytes (LBR 21–24%); and 40–44 years: 15–17 oocytes (LBR 11–12%). The incidence of OHSS increased significantly with the number of oocytes retrieved, from 1.2% with 15 oocytes retrieved to 9.3% with 30 or more oocytes retrieved (P < 0.001).ConclusionThe optimal number of oocytes at which maximum LBR was observed in a fresh aspiration cycle was highly dependent on age. Because of the observational nature of the results, a cause–effect relationship between the number of oocytes retrieved and LBR should not be assumed; evidence from well-designed randomized control trials is required before clinical advice can be suggested.     

Bilateral internal jugular venous thrombosis following successful assisted conception in the absence of ovarian hyperstimulation syndrome

The majority of the venous thromboembolic events seen in patient following gonadotropin administration were associated with the development of ovarian hyperstimulation syndrome (OHSS). However, in this case report, a 29-year-old woman that conceived by controlled ovarian hyperstimulation, intracytoplasmic sperm injection and subsequent embryo transfer without conjunction of OHSS was described. Bilateral jugular venous thrombi were detected by duplex Doppler in the 8th week of pregnancy when she was admitted to the emergency room for difficulty in swallowing and bilateral neck pain. She had unremarkable history and negative results for thrombophilia screening. Full anticoagulation with intravenous heparin was initiated and continued subcutaneously throughout pregnancy. She delivered two healthy babies at 36 weeks of pregnancy. Venous thromboembolism should be taken in account in patients undergoing gonadotropin administration for assisted conception with the complaint of extremity pain regardless of having risk factors for thromboembolism.     

Prevalence of thrombophilia in women with severe ovarian hyperstimulation syndrome and cost-effectiveness of screening

OBJECTIVE: To determine the prevalence of markers of thrombophilia in patients with severe ovarian hyperstimulation syndrome (OHSS) and to evaluate the cost-effectiveness of screening for factor V Leiden and prothrombin G20210A mutations in women entering an IVF program. DESIGN: Case-control study and cost-effectiveness analysis. SETTING: University teaching hospital. PATIENT(S): Women undergoing controlled ovarian hyperstimulation for IVF complicated by severe OHSS (group 1, n = 20), women undergoing controlled ovarian hyperstimulation for IVF without development of severe OHSS (group 2, n = 40), and healthy control subjects (group 3, n = 100). INTERVENTION(S): Investigation of markers of thrombophilia. Estimate of number of IVF patients needed to detect a case of severe OHSS and thrombosis associated with thrombophilia genetic mutation was calculated from the available data. MAIN OUTCOME MEASURE(S): Blood samples were analyzed for inherited (resistance to activated protein C due to the factor V Leiden mutation; prothrombin G20210A mutation; deficiencies in antithrombin, protein C, and protein S) and acquired (presence of circulating lupus anticoagulants and/or anticardiolipin antibodies; deficiencies of antithrombin and protein S; acquired protein C resistance) markers of thrombophilia. The cost of preventing one thrombotic event in a patient developing severe OHSS after IVF and having factor V Leiden or prothrombin G20210A mutations was calculated. RESULT(S): None of the OHSS patients or controls had antithrombin, protein C, or free protein S deficiencies. All of them tested negative for antiphospholipid antibodies. No patient in group 1 had the factor V Leiden or prothrombin G20210A mutations. The prothrombin G20210A mutation was detected in 1 out of 40 patients (2.5%) in group 2. Both factor V Leiden and prothrombin G20210A mutations were detected in two of the control subjects (2%) (group 3). The estimated cost of preventing one thrombotic event arising as a consequence of screening for factor V Leiden and prothrombin G20210A mutation is a minimum of 418,970 dollars and 2,430,000 dollars, respectively. CONCLUSION(S): The prevalence of thrombophilia is not increased in women with severe OHSS. Screening for V Leiden and prothrombin G20210A mutation in an IVF general population is not cost-effective.     

Severe ovarian hyperstimulation syndrome: is it really preventable by prophylactic intravenous albumin?

ObjectiveTo evaluate the effectiveness of IV albumin in preventing severe ovarian hyperstimulation syndrome (OHSS) in patients at risk.Design: Retrospective review and data analysis.Setting: University-based tertiary referral center for assisted reproductive technologies (ART).Patient(s): Sixty women at high risk of developing severe OHSS after superovulation for ART.Intervention(s): One liter of albumin (4.5%) administered IV during oocyte retrieval and immediately afterward.Result(s): Of the 60 women who had prophylactic IV albumin, 5 (8%) developed severe OHSS, which led to hospitalization. Eight (13%) developed moderate OHSS. Forty-seven (78%) did not develop any symptoms. Four of the 5 women who developed severe OHSS had ET and 3 of them (75%) were pregnant (1 twin and 2 singletons).Conclusion(s): Intravenous albumin administered at oocyte retrieval does not prevent the occurrence of severe OHSS, especially in cases associated with pregnancy. It is important that clinicians are not lured into a false sense of security by the early report, full of promise, on the use of IV albumin to prevent severe OHSS.     

Incidences and risk factors of moderate-to-severe ovarian hyperstimulation syndrome and severe hemoperitoneum in 1,435,108 oocyte retrievals

Research questionWhat are the risk factors affecting the incidences of moderate-to-severe ovarian hyperstimulation syndrome (OHSS) and severe hemoperitoneum in assisted reproductive technology (ART) treatment cycles?DesignA retrospective cohort study was conducted on 1,435,108 oocyte retrieval cycles among Japanese ART registry data between 2007 and 2015. The study included 11,378 cycles with moderate-to-severe OHSS, 1182 cycles with severe hemoperitoneum, including 27 cycles with both conditions, and 1,422,575 cycles without moderate-to-severe OHSS and severe hemoperitoneum.ResultsThe incidences of moderate-to-severe OHSS and severe hemoperitoneum were 0.79% and 0.08%, respectively, and decreased by 0.57-fold and 0.29-fold from 2007 to 2015, respectively. In cycles with OHSS and cycles with hemoperitoneum women were younger (odds ratios [OR] 0.91 and 0.95, respectively) and had more retrieved oocytes (OR 1.09 and 1.01, respectively) compared with cycles without both complications. The use of a gonadotrophin-releasing hormone (GnRH) agonist protocol for ovarian stimulation was the highest risk factor in cycles with OHSS and hemoperitoneum (OR 1.83 and 1.24, respectively), followed by GnRH antagonist protocol (reference), gonadotrophin with or without oral medicine (OR 0.45 and 0.56, respectively) and natural or oral medicine (OR 0.02 and 0.19, respectively). In fresh embryo transfer, clinical pregnancy was associated with an increased risk of OHSS and hemoperitoneum (OR 1.19 and 2.34, respectively).ConclusionsThe highest risk factors affecting OHSS and hemoperitoneum were the use of a GnRH agonist protocol and clinical pregnancy following fresh embryo transfer. The incidences of OHSS and hemoperitoneum have decreased yearly with a reduction of GnRH agonist use and fresh embryo transfer.     

Venous thromboembolism in pregnancy and the puerperium: incidence and additional risk factors from a London perinatal database

Objective To determine the incidence of venous thromboembolism in pregnancy and the puerperium and to identify risk factors for pregnancy-related venous thromboembolism.
Design Cohort study and case–control study.
Setting London, UK.
Population 395,335 women with live births or pregnancies of 24 or more weeks of gestation between 1988 and 1997.
Methods Data extraction from the St Mary's Maternity Information System database. Random sample of 5% for case–control study.
Main outcome measures Incidence of venous thromboembolism; odds ratios for variables associated with venous thromboembolism.
Results The incidence of venous thromboembolism was 85/100,000 maternities. There were approximately twice as many postpartum as antepartum events. Blood group A, multiple pregnancy, caesarean section, cardiac disease, delivery at gestational age of <36 weeks, a body mass index of ≥25, or more and maternal age of 35 or over were all found to increase incidence of venous thromboembolism.
Conclusions Although venous thromboembolism is the leading cause of maternal deaths in the UK, it is still a rare event. Most of these events are deep vein thromboses occurring in the postpartum period. Antenatally multiple birth is an important risk factor. Postnatally women who have had a caesarean section, premature delivery or history of cardiac disease should be assessed carefully for venous thromboembolism.     

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.     

Severe Preeclampsia Associated with Coinheritance of Factor V Leiden Mutation and Protein S Deficiency

Background: Inherited thrombophilic disorders are associated with an increased risk of venous thromboembolism during pregnancy. Preliminary research suggests that these disorders might also increase the risk for preeclampsia.Case: A 29-year-old primigravida developed severe, early onset preeclampsia and postpartum deep venous thrombosis. Subsequent testing revealed coinheritance of the factor V Leiden mutation and protein S deficiency. Heparin prophylaxis was administered during two subsequent pregnancies without recurrence of either preeclampsia or venous thromboembolism.Conclusion: Our patient’s inherited thrombophilia may have played a role in the development of preeclampsia, and anticoagulation during subsequent pregnancies may have prevented preeclampsia recurrence. An association between inherited thrombophilic disorders and preeclampsia is biologically plausible.     

Afibrinogenemia Diagnosed During Pregnancy Successfully Managed with Targeted Cryoprecipitate Transfusion: A Case Report

BackgroundWe report a case of afibrinogenemia in a lady, which was detected for the first time during her pregnancy.CaseA 24-year-old G4A3 was referred as a case of vaginal bleeding, after a cervical cerclage at 14 weeks of gestation. Elastometry targeted correction of coagulopathy was done initially, and targeted cryoprecipitate transfusion was done to maintain her gestation. She underwent induced vaginal delivery at 34 weeks of gestation. Fourteen days postpartum, the mother and child were discharged home well.ConclusionCoagulation factor deficiency should be considered as a rare cause for RPL. Serum fibrinogen level of 50–100 mg/dl during pregnancy seems to be a safe and adequate target to maintain in pregnant patients with afibrinogenemia.     

Severe ovarian hyperstimulation syndrome in a 42-year-old woman with successful pregnancy after intracytoplasmic sperm injection embryo transfer

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of ovulation induction for infertile women. It has been shown that patients suffering from OHSS are generally young because OHSS depends on the patient's ovarian reserve. Therefore, women ≥40 years of age seldom suffer from the severe form of OHSS. In the present study, we report a case of severe OHSS that occurred in a 42-year-old woman with a successful pregnancy after intracytoplasmic sperm injection (ICSI)-embryo transfer. She had been diagnosed as having polycystic ovary syndrome (PCOS). After 5 cycles of unsuccessful treatment with gonadotropins plus intrauterine insemination for her husband's asthenozoospermia, the treatment with assisted reproductive technology (ART) was indicated. In the third ART attempt, the patient was treated by ICSI-embryo transfer (ET) and she developed severe OHSS at 4 weeks' gestation. On admission, marked hemoconcentration, oligouria and hypo-albuminemia were diagnosed. A continuous autotransfusion system of ascites, which was developed to expand circulating plasma volume without exogenous albumin, was carried out for 5 h at a rate of 100–200 mL/h once a day for a total of 5 days. The course of the pregnancy was uneventful. At 37 weeks' gestation, a healthy baby boy weighing 3336 g was born by cesarean section when the patient was 43 years of age. The postoperative course was also uneventful. To the best of our knowledge, the present report describes the oldest woman showing severe OHSS. (Reprod Med Biol 2005; 4 : 265–269)     

Histological Chorioamnionitis Associated with Preterm Prelabour Rupture of Membranes at Kingston General Hospital: A Practice Audit

ObjectiveTo determine the prevalence of histological chorioamnionitis associated with preterm prelabour rupture of membranes (PPROM) in women following spontaneous onset of labour, urgent delivery or planned delivery after 34 weeks’ gestation.MethodsCharts of all women admitted to Kingston General Hospital with PPROM prior to 34 weeks’ gestation over five years were collected. Obstetrical outcomes and histopathology reports were reviewed.ResultsTwo hundred forty-four women with PPROM were identified and reviewed. The majority of women (169; 69%) went into spontaneous labour and, of those, 24 (14%) had clinical chorioamnionitis and 79 (47%) had histological chorioamnionitis. Of the 45 women (18%) who required urgent delivery, 27 (60%) had clinical chorioamnionitis and 31 (69%) had histological chorioamnionitis. Only 26 of the original 244 women with PPROM (11%) were managed expectantly until 34 weeks’ gestation and then had a planned delivery. The prevalence of histological chorioamnionitis in this group whose placentas were sent for histopathologic review was 24%. Overall, the clinical suspicion of chorioamnionitis was found to be specific (91%) but not sensitive (37%) for identifying chorioamnionitis on the basis of histopathology.ConclusionHistological chorioamnionitis complicates almost one half of all cases of PPROM that occur prior to 34 weeks’ gestation. Most women will progress to spontaneous labour or require urgent delivery for clinical chorioamnionitis or other complications related to ruptured membranes before reaching 34 weeks’ gestation. Only a subset of women remain pregnant long enough to have labour induced, but among those the prevalence of histological chorioamnionitis is lower (24%).     

The development of ovarian hyperstimulation syndrome in the implementation of assisted reproductive technology in women with a background of endocrine pathology

Abstract

Known factors of the development of ovarian hyperstimulation syndrome (OHSS) are not informative enough, if considered independently. This is confirmed by the absence of initial predictors in cases of severe OHSS and, in contrast, not clinically apparent manifestations in patients seemingly having high risk of this pathology. These circumstances demand investigation of additional prognostic parameters of the OHSS.

Purpose: To find out additional OHSS risk factors alongside with the previously known ones in the course of implementation of assisted reproductive technologies (ART) in patients having initial metabolic and hormonal disorders.

Investigation data and methods: Retrospective analysis of clinical laboratory and functional parameters of hormonal and metabolic state of 133 women suffering OHSS was held. Classification by Schenker, 1995, was used to detect the diagnosis. Control group consisted of 347 women with the unverified OHSS. Basic and control study groups were similar in age and in number of mild and long protocols of ovarian stimulation held.

Results and their discussion: A significant correlation dependence was revealed between the fact of the OHSS development and some indicators of hormonal and metabolic state: HOMA index of insulin resistance; thyroid parameters: thyroid stimulating hormone (TSH), free thyroxine (fT4), thyroid peroxidase antibodies (AbTPO); and level of prolactin. The revealed correlation dependence of the OHSS development on the above parameters allows to use them for determination of the OHSS risk group and taking measures to prevent this complication of the ART.     

Ovarian Hyperstimulation Syndrome Complicating Spontaneous Molar Pregnancy: A Case Report and Review of the Literature

BackgroundOvarian hyperstimulation syndrome (OHSS) is traditionally associated with fertility treatments and results in elevated human chorionic gonadotropin (βhCG) levels and fluid shifts to extravascular compartments. Rarely, spontaneous pregnancies with significant βhCG elevations, such as molar pregnancies, can give rise to OHSS.CaseA 24-year-old woman was diagnosed as having a molar pregnancy at approximately 12 weeks gestation following spontaneous conception. Her initial βhCG was over 1 million IU/L. There was no evidence of metastatic disease. She underwent an uncomplicated dilation and curettage. Three days later, she presented with chest pain, shortness of breath, and abdominal discomfort. Massively enlarged ovaries were identified with bilateral pleural effusions requiring repeated thoracentesis.ConclusionThis case demonstrates rare sequelae of molar pregnancy. Treatment is mainly supportive, and close observation is required to manage complications. In patients with extremely elevated βhCG levels, clinicians must remain vigilant for signs suggesting OHSS, even following evacuation of the uterus.     

The effects of age,body mass index,smoking and general health on the risk of venous thromboembolism in users of combined oral contraceptives

Objectives To investigate the factors associated with idiopathic venous thromboembolism in combined oral contraceptive users and to estimate the crude and age-specific incidence rates of idiopathic venous thromboembolism among this population.

Methods The UK MediPlus Database and the General Practice Research Database were searched to identify women with evidence of venous thromboembolism while exposed to combined oral contraceptives. Cohort and nested case-control studies were carried out using the same methodology on both databases. We conducted a meta-analysis using the individual data for the cases and controls from the two case-control studies to identify factors associated with idiopathic venous thromboembolism in women using combined oral contraceptives.

Results The incidence rate of idiopathic venous thromboembolism among oral contraceptive users was 39.4 per 100 000 exposed woman-years. The age-specific incidence rates were found to rise sharply after the age of 39 years. Factors identified as being significantly associated with idiopathic venous thromboembolism in women using combined oral contraceptives were: body mass index of 25 kg/m² and over, the association rising dramatically in women with a body mass index of 35 kg/m² or more; smoking; general ill health; and asthma.

Conclusion We believe that, before prescribing combined oral contraceptives, the venous as well as the arterial factors need to be considered and, in addition, age, obesity and smoking are all relevant when assessing an individual patient's risk.     

Mid-trimester severe intrauterine growth restriction is associated with a high prevalence of thrombophilia

Objective To investigate the association between severe mid-trimester IUGR, whose causes are unknown in most cases, and maternal thrombophilias.
Design Case–control study.
Setting Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, The Sackler Faculty of Medicine, Tel Aviv University.
Population Twenty-six women with severe mid-trimester (22–26 weeks of gestation) IUGR (birthweight  <3rd centile  ) and 52 matched multiparous women with normal pregnancies (controls).
Methods After excluding pregnancies with vascular maternal disease, chromosomal and structural aberrations and cytomegalovirus infection, 26 women out of 35 with severe mid-trimester IUGR remained and composed the study group. Each was matched for age, ethnicity and smoking status with two healthy women who had normal pregnancies. All the women were tested for genetic and acquired thrombophilias at least eight weeks after delivery.
Main outcome measures Prevalence of maternal thrombophilias.
Results The frequency of thrombophilias was 69% in the study group compared with 14% in the control group [odds ratio (OR) 4.5; 95% confidence interval (CI) 2.3–9, P  < 0.001  ]. The frequencies of factor V Leiden mutation, prothrombin gene mutation and protein S deficiency were significantly increased in the study group compared with the control group. The frequency of multiple thrombophilias was 33% in the study group versus none among the controls. Of the 26 pregnancies with severe mid-trimester IUGR, 13 ended in intrauterine fetal death before 25 weeks of gestation: 10 of these women had thrombophilia.
Conclusion Women with mid-trimester severe IUGR have an increased prevalence of inherited and acquired thrombophilias.