To investigate the success rate of expectant management of ectopic pregnancy thereby avoiding administration of methotrexate as advised by NICE as first-line management in the UK. Retrospective audit of all patients diagnosed with an ectopic pregnancy in the Early Pregnancy Unit from 1/1/2015–30/6/2015 were identified. Scan diagnosis, biochemical results and management and treatment details were recorded. Patients with non-tubal ectopic pregnancies were excluded. 61 women were diagnosed with a tubal ectopic pregnancy. Of these, 29 (47.5%) women had expectant management, 3 (5%) methotrexate and 29 (47.5%) surgical management as first-line management. 2 (66%) out of the 3 treated first-line with methotrexate required surgery. 3 (10%) of 29 women managed expectantly required sub-acute surgical management. 26 (90%) of the women who had first-line expectant management avoided surgical treatment however 4 (4/26, 15%) required methotrexate as second-line management. Overall, successful treatment modalities of tubal ectopic pregnancies were 56% surgical, 36% expectant and 8% methotrexate. UK national published guidance from NICE advises methotrexate or surgical management for ectopic pregnancy. However, successful expectant management in 36% of ectopic pregnancies avoided the need for this chemotherapeutic agent. First-line expectant management is comparable to first line methotrexate management for avoiding surgical intervention for the treatment of ectopic pregnancy in suitable cases.

To determine whether the sonographic appearance of the endometrium with an intact midline echo (IMLE) is a useful predictor of ectopic pregnancy (EP) in women with pregnancy of unknown location (PUL). A retrospective review of all pregnant women scanned at a regional University Hospital early pregnancy unit, between 1 June 2007 and 31 May 2008 was performed. Serum quantitative β human chorionic gonadotrophin (HCG) at presentation and at 48hours, the sonographic appearance of the endometrium (thickness and the presence or absence of an IMLE) and the final clinical diagnosis were recorded. Statistical analysis was performed using Fisher exact test. Likelihood ratios (LR) and relative risk (RR) for a diagnosis of EP in women with an IMLE in combination with HCG levels were calculated. The prevalence of EP was 3.7% in this population of women who attended our early pregnancy unit. A total of 1627 women were scanned, of which 134 (8%) were classified as PUL. Of the PUL group, 27 women were subsequently diagnosed with EP or persistent PUL requiring treatment (20%), 89 women with failing PULs (66%) and 18 women with IUPs (14%). Of the 134 women with a diagnosis of PUL, 37 had an IMLE and 97 had a disrupted MLE on ultrasound. The incidence of EP in those with IMLE was significantly higher than those with a disrupted MLE {13(35%) v 14(14%) (p < 0.01), RR 2.05 (95% confidence interval 1.2–3.5)}. An IMLE alone to predict EP had a sensitivity of 49%, specificity of 78% and a positive LR of 2.13. Combining an IMLE and HCG 48hr/0hr ratio 0.67–1.66 (plateau) predicted EP with a sensitivity of 41%, specificity of 93% and a positive LR of 5.4. In combination with the HCG ratio, the sonographic appearance of an IMLE may be a useful predictor of EP in women with a PUL.

Proliferation of cytotrophoblast in early gestation provides a pool of trophoblast stem cells critical for ongoing placental development. Premature cytotrophoblast differentiation in favour of syncytial fusion results in deficiencies of cytotrophoblast and rarification of villous trophoblast. Abnormal trophoblast differentiation in early gestation may be due to a premature onset of maternal perfusion of the placenta and may be a likely antecedent for conditions associated with failure of placentation such as recurrent miscarriage.

BACKGROUND: Some cases of recurrent miscarriage have a thrombotic basis. Thromboelastography is a rapid, reproducible test of whole-blood haemostasis. METHODS: Thromboelastography was performed in 494 consecutive, non-pregnant women (median age 35 years; range 21-48) with a history of miscarriages at <12 weeks gestation (median 4; range 3-12) and 55 parous women (median age 33 years; range 20-41) with no history of pregnancy loss. The prospective outcome of untreated pregnancies amongst 108 women with recurrent miscarriage was studied. RESULTS: The maximum clot amplitude (MA) (median 66.0 mm; range 48.0-76.0) was significantly higher and the rate of clot lysis (LY30) (median 2.5%; range 0.5-7.8) significantly lower amongst women with recurrent miscarriage compared with controls (MA 61.5 mm; range 50.0-67.0; P = 0.01; LY30 4.9%; range 2.9-9.7; P = 0.01). The pre-pregnancy MA was significantly higher amongst women who subsequently miscarried (median 66.0 mm; range 54.0-73.0) compared with those whose had a live birth (median 61.7 mm; 48.0-71.5; P < 0.01). A pre-pregnancy MA greater than or equal to64 mm has a sensitivity of 68% and specificity of 82% to predict miscarriage. CONCLUSIONS: Thromboelastography identifies a subgroup of women with recurrent miscarriage to be in a prothrombotic state outside of pregnancy. Women in such a state are at increased risk of miscarriage in future untreated pregnancies.

BACKGROUND:The true impact of congenital uterine anomalies on reproductive outcomes is unknown. The aim of this study was to examine differences in the morphology of uterine anomalies found in women with and without a history of recurrent miscarriage.METHODS:A total of 509 women with a history of unexplained recurrent miscarriage and 1976 low risk women were examined for the presence of congenital uterine anomalies by three-dimensional ultrasound. The anomalies were classified according to the American Fertility Society classification. In addition, the size of fundal distortion (F) and the length of the remaining uterine cavity (C) were measured to calculate a distortion ratio (F/F+C). The findings were compared with the measurements obtained in low risk women with an incidental finding of uterine anomaly.RESULTS:In all, 121 anomalies were detected in the recurrent miscarriage group and 105 in low risk women. There was no significant difference in relative frequency of various anomalies or depth of fundal distortion between the two groups. However, with both arcuate and subseptate uteri, the length of remaining uterine cavity was significantly shorter (P < 0.01) and the distortion ratio was significantly higher (P < 0.01) in the recurrent miscarriage group.CONCLUSION:The distortion of uterine anatomy is more severe in congenital anomalies, which are found in women with a history of recurrent first trimester miscarriage.

OBJECTIVE: To examine whether there are characteristic histological features in placentas from ongoing pregnancies of patients with a history of recurrent miscarriage, with and without primary antiphospholipid antibody syndrome, in relation to clinical pregnancy outcome.METHODS: Patients attending a recurrent miscarriage clinic were investigated and treated according to an established protocol. One hundred twenty-one consecutive patients achieving a potentially viable pregnancy (at least 24 completed weeks' gestation), including 60 primary antiphospholipid antibody syndrome-positive cases and 61 primary antiphospholipid antibody syndrome-negative cases were included. After delivery, placental pathologic examination was carried out by a pathologist unaware of the clinical details. Histological sections were examined by two pathologists independently. Pregnancy outcome and placental findings were reviewed in relation to the maternal antiphospholipid antibody status.RESULTS: Pregnancy outcome was similar in primary antiphospholipid antibody syndrome-positive and primary antiphospholipid antibody syndrome-negative groups regarding gestation at delivery and antepartum obstetric complications. Several histological placental abnormalities were identified in both groups, but most pregnancies were clinically uncomplicated, with no significant placental abnormalities. In cases with pregnancy complications, the placental pathology was primarily that of uteroplacental vasculopathy, such as placental infarction and preeclampsia, but there were no specific placental lesions or patterns of abnormalities characteristic of primary antiphospholipid antibody syndrome-positive patients. A small subgroup of primary antiphospholipid antibody syndrome-positive patients may be at increased risk of development of maternal floor infarction or massive perivillus fibrin deposition.CONCLUSION: There are no specific histopathologic placental abnormalities characteristic of treated patients with antiphospholipid antibody syndrome and poor reproductive history, but complications of uteroplacental disease are more common. (C) 2003 by The American College of Obstetricians and Gynecologists.

Objective To examine the reproducibility of the diagnosis of congenital uterine anomalies and the repeatability of measurements of uterine cavity dimensions using three-dimensional (3D) ultrasound.Methods The reproducibility of diagnosis of congenital uterine anomalies was examined by re-slicing stored 3D ultrasound volumes. Each data set was evaluated by two independent observers. Assessment of uterine morphology was performed in a standardized plane, with the interstitial portions of the Fallopian tubes used as reference points. Additionally, in 35 cases of congenital uterine anomalies the width of the uterine cavity (W), fundal distortion (F) and the length of unaffected uterine cavity (C) were measured. Intraobserver and interobserver variabilities were evaluated by each observer performing all three measurements twice.Results Eighty-three 3D ultrasound volumes were examined. Both operators classified 27 uteri as normal, 33 as arcuate, 19 as subseptate and three as unicornuate. A single case of uterine anomaly was described as arcuate uterus by one operator and subseptate by another (kappa 0.97). The intraobserver variability for each of the three measurements (W, F and Q was satisfactory with limits of agreement ranging from +/-1.43 to +/-2.51 mm. The examination of the interobserver variability showed no significant differences between the two observers (F = 0.484, P > 0.05).Conclusion 3D ultrasound is a reproducible method for the diagnosis of congenital uterine anomalies and for the measurement of uterine cavity dimensions. Copyright 2003 ISUOG. Published by John Wiley Sons, Ltd.

Objective: To investigate the relationship between Day 8 serum luteinizing hormone (LH) and testosterone (T) concentrations, and body mass index (BMI) with pregnancy outcome in women with recurrent miscarriage.Design: Prospective observational study.Setting: National recurrent miscarriage clinic.Patient(s): Three hundred forty-four women (median age 32 years; range 18-44) with a history of recurrent first trimester miscarriage (median 4; 3-14, <12 weeks gestation) who conceived spontaneously and who received no pharmacological treatment during pregnancy were studied. All women were antiphospholipid antibody negative and had a normal peripheral karyotype as did their partners.Intervention(s): Outcome of untreated pregnancies.Main Outcome Measure(s): Day 8 serum LH and T concentrations and BMI were correlated with pregnancy outcome.Result(s): One hundred and ninety-two (55.8%) women had a live birth and 152 (44.2%) women miscarried. Polycystic ovarian morphology was diagnosed in 174 women (50.6%). There was no significant relationship between follicular phase LH concentrations and pregnancy outcome, Pregnancy outcome was similar in women with normal and high serum T concentrations. BMI value was not significantly different between women who had a live birth and those who miscarried.Conclusion(s): The analysis of this large cohort of women with recurrent miscarriage demonstrates that prepregnancy Day 8 serum LH and T concentrations, and BMI do not have a statistically significant relationship with pregnancy outcome. (Fertil Steril(R) 2002;77:348-52. (C)2002 by American Society for Reproductive Medicine.).

BACKGROUND:Some cases of recurrent miscarriage and later pregnancy complications have a thrombotic basis. Factor V Leiden is a common thrombophilic mutation. METHODS:The prospective outcome of untreated pregnancies amongst 25 women heterozygous for the Factor V Leiden allele who had a history of either recurrent early miscarriages only (three or more miscarriages at <12 weeks gestation; n = 19) or of late miscarriage (>12 weeks gestation; n = 9) was studied. Control groups of women with a similar pregnancy history but who had a normal Factor V genotype were also studied. RESULTS:The live birth rate was significantly lower amongst women with a history of recurrent early miscarriage who carried the Factor V Leiden allele (6/16; 37.5%) compared with that amongst those with a normal Factor V genotype (106/153; 69.3%; odds ratio 3.75, 95% confidence intervals 1.3-10.9). The live birth rate was 11.1% (1/9) amongst those with a history of late miscarriage carrying the Factor V Leiden allele and 48.9% (22/45) amongst those with a normal Factor V genotype. CONCLUSIONS:Attention should be directed at screening women with recurrent miscarriage associated with placental thrombosis for Factor V Leiden and a policy of targeted thromboprophylaxis during future pregnancies should be assessed in the form of a randomized controlled trial.

We present three pregnancies in which massive perivillous fibrous deposition (MPVFD) and maternal floor infarction (MFI) occurred in patients with primary antiphospholipid antibody syndrome (PAPS) attending a recurrent miscarriage clinic, and who were treated with low dose aspirin and heparin. We hypothesise that PAPS may be a predisposing factor to the development of this condition. The increased prevalence of late pregnancy complications in PAPS patients with a history of early miscarriage suggests that aspirin and heparin therapy does not eradicate the underlying pathological process but merely reduces the severity. Therefore, untreated early pregnancy losses may be converted into treated pregnancies with late antenatal complications. Some patients with PAPS may therefore be prone to suffer either the previously reported complications of the uteroplacental vasculature, such as pre-eclampsia, and/or specific complications related to the environment of the intervillus space, such as MPVFD/MFI.

Background: Primary antiphospholipid antibody syndrome (PAPS) is an established cause of recurrent pregnancy loss, traditionally presumed to be due to 'intraplacental thromboses'. This study examines products of conception (POC) from early pregnancy failures to investigate the mechanism of pregnancy loss. Methods: POC from patients attending a recurrent miscarriage clinic and from terminations of pregnancy for non-medical reasons were examined histologically with particular regard to the presence or absence of vascular or intervillous thromboses and decidual endovascular trophoblast invasion. Results: There were 31 PAPS-positive, 50 PAPS-negative, 34 aneuploid and 20 control cases at 6-14 weeks gestation. Villous morphology and frequency of intervillous thrombosis were not different among groups. Normal intradecidual endovascular trophoblast invasion was identified significantly less frequently in PAPS+ cases (24%), compared with controls (75%), aneuploid (53%), or PAPS-cases (61%; Z = -3.0, P<0.01). In all cases there was apparently normal interstitial extravillous trophoblast invasion. Conclusions: Defective decidual endovascular trophoblast invasion, rather than excessive intervillous thrombosis, is the most frequent histological abnormality in PAPS+ associated early pregnancy loss. Furthermore, endovascular trophoblast invasion is not significantly reduced in the majority of fetal aneuploidy-associated pregnancy failures.