Maternal and infant outcomes in women with sickle cell disease: a matched cohort study.

OBJECTIVE: Women with sickle cell disease (SCD) have adverse maternal and infant outcomes. Our aim was to determine whether the outcomes of SCD mothers and their infants differed from African or Caribbean women not affected by SCD and whether there were differences between SCD individuals with the haemoglobin SS (HbSS) or haemoglobin SC (HbSC) genotypes. Furthermore, we wished to determine if any differences related to deprivation. DESIGN: A matched cohort study. SETTING: Tertiary perinatal centre in London PATIENTS: 4964 African or Caribbean women without SCD and 148 with SCD. MAIN OUTCOME MEASURES: Mode of delivery, maternal exchange transfusion, birthweight, neonatal unit admission, neonatal death and deprivation indices RESULTS: SCD women were more likely to be delivered by caesarean section (p<0.001) and had babies of lower birthweight (p<0.001). Their infants were no more likely to be admitted to neonatal intensive care unit or suffer a neonatal death. There were no significant differences between the SCD women and those without SCD in their deprivation index or deprivation decile. The women with the HbSS genotype compared to those with the HbSC genotype were more anaemic (p<0.02), required more exchange transfusions (p<0.001) and were more likely to be delivered by caesarean section (p=0.008). The infant outcomes did not differ significantly between the genotypes. CONCLUSIONS: Although, the SCD women, particularly those with the HbSS genotype, had greater morbidity, infant morbidity, and mortality was similar in mothers with the HbSS or HbSC genotypes and those without SCD.

The "lived" experience of menstruating women commencing anticoagulants.

Background: Although there is increased recognition that many menstruating women commenced on anticoagulants experience heavy menstrual bleeding, little research has been published describing what women go through and actually experience. Objectives: The aim of this study was to understand the "lived" experience of menstruating women commencing anticoagulants. Methods: We undertook a qualitative study using semistructured interviews. Women who had taken part in the parent PERIOD study and expressed an interest in an in-depth interview were recruited. Interviews were conducted online, and transcripts were generated through MS Teams. Data were analyzed using thematic analysis. Ethics committee approval: REC reference: 19/SW/0211. Results: A total of 15 participants were interviewed. The median age of the participants was 36 years (range, 20-49 years). The following 7 primary themes emerged from the interviews: (1) information received when commencing anticoagulation, (2) mood, (3) strategies used to manage heavy bleeding, (4) social/family life, (5) work life, (6) finances, and (7) multiple health issues-with saturation of themes achieved following 9 interviews. Women affected by heavy menstrual bleeding experienced a negative change in their work/social life and mood. Conclusion: Heavy menstrual bleeding experienced by women commencing anticoagulants has a significant impact on their lives. Recognized measures should be employed to support and minimize the problem for menstruating people.

How do anticoagulants impact menstrual bleeding and quality of life? - The PERIOD study.

Background: There is increasing recognition that menstruating women prescribed anticoagulants experience heavy menstrual bleeding. Objectives: The aim of this study is to report the extent of bleeding in menstruating women after commencing anticoagulants and the impact it has on their quality of life. Methods: Women aged 18 to 50, initiated on anticoagulant therapy, were approached to take part in the study. In parallel, a control group of women was also recruited. Women were asked to complete the menstrual bleeding questionnaire and a pictorial blood assessment chart (PBAC) during their next 2 menstrual cycles. Differences between the control and anticoagulated group were compared. Significance was considered at < .05. Ethics committee approval: REC reference: 19/SW/0211. Results: Fifty-seven women in the anticoagulation and 109 women in the control group returned their questionnaires. Women in the anticoagulated group reported an increase in the median length of their menstrual cycle from 5 to 6 days after commencing anticoagulation, compared to 5 days for women in the control group (P < .05). Anticoagulated women reported significantly higher PBAC scores as compared to the control group (P < .05), with two-thirds of women in the anticoagulation group reporting heavy menstrual bleeding. Women in the anticoagulation group reported worsening quality of life scores following the initiation of anticoagulation, compared with women in the control group (P < .05). Conclusion: Heavy menstrual bleeding occurred in two-thirds of women commencing anticoagulants, who completed a PBAC, which had negative impact on their quality of life. Clinicians commencing anticoagulation therapy should be mindful of this, and recognized measures should be taken to help minimize this problem for menstruating individuals.

The role of ultrasound imaging in the management of partial placental retention after third trimester livebirth.

OBJECTIVES: To evaluate the impact of different ultrasound signs in the management and the role of ultrasound guidance in the surgical evacuation of partial placental tissue retention. METHODS: This is an observational cohort study and retrospective case assessment of 82 patients with clinical symptoms of partial placental retention following a third trimester singleton livebirth between January 2013 and May 2019. The ultrasound signs were recorded using a standardized protocol and the outcome of the management strategy and the use of ultrasound guidance during any surgical procedure was evaluated. RESULTS: Out of the 64 patients who had a vaginal birth, 25 (39.1%) had a manual removal of the placenta at delivery. Fifteen patients were confirmed as not having retained placental tissue and did not require further treatment. Four patients were referred after failed surgical management and four after failed conservative management. All surgical procedures were vacuum aspiration and forceps removal under continuous ultrasound guidance. A significantly lower gestational age at delivery (p < .05), shorter interval between delivery and ultrasound diagnosis (p < .05) and lower number of patients presenting with heavy bleeding was found in the conservative compared to the surgical management subgroups (p < .05). The incidence of feeding vessels was significantly (p < .05) higher in the surgical than in the conservative management subgroups and associated with increased myometrial vascularity. Six patients developed intra-uterine adhesions. In four of these cases, ultrasound examination showed a hyperechoic mass surrounded by normal myometrial vascularity and no feeding vessel. CONCLUSIONS: Ultrasound imaging accurately differentiated between patient with and without partial placental retention after third trimester livebirth. Ultrasound-guided vacuum aspiration is safe and efficient in these cases.

Diagnosis and outcome of hydatidiform moles in missed-miscarriage: a cohort-study, systematic review and meta-analysis.

OBJECTIVE: To evaluate the ultrasound diagnostic rates of complete hydatidiform moles (CHM) and partial hydatidiform moles (PHM) in women presenting with a missed miscarriage, the clinical complications at diagnosis and the risk of gestational trophoblastic neoplasia (GTN) after surgical evacuation and to compare our findings with those of the published literature by completing a systematic review and meta-analysis STUDY DESIGN: Retrospective review of the data of 295 women diagnosed with a histologically confirmed hydatidiform moles (HM) over a 15-year period, including 128 CHM and 167 PHM. All women were referred to a regional specialist centre for follow-up and further management. An electronic search of PubMed, Google Scholar and MEDLINE was performed for studies published between September 1973 and September 2017 reporting on the early ultrasound diagnosis of hydatidiform mole. Only cohort studies which provided ultrasound data confirmed by histopathology were included. RESULTS: In the cohort study, ultrasound imaging diagnosed a significantly (p < 0.001) higher number of CHM (95/128 (74.2%) than PHM (68/167 (40.7%). Ovarian theca lutea cysts were observed in three CHM and one PHM. There were no cases of pre-eclampsia or thyrotoxicosis at the time of diagnosis. Maternal serum ß-human chorionic gonadotrophin levels were abnormally low (< 0.5 MoM) in 5/51 (10%) CHM and 23/43 (53%) PHM and abnormally high (> 2.0 MoM) in 20/51 (39%) CHM and 2/43 (5%) PHM. Seventeen (12.3%) CHM and two (1.4%) PHM developed a GTN requiring treatment. In the literature the proportion of histologically diagnosed HM, suspected on ultrasound in early pregnancy, ranged between 34.2 and 90.2% for HM, 57.8 and 95% for CHM and 17.6 and 51.6% for PHM. The meta-analysis indicated substantial heterogeneity in the overall ultrasound diagnosis of HM and in the differential diagnosis between CHM and PHM. CONCLUSION(S): As around a third of CHM and two thirds of PHM are not diagnosed on ultrasound in cases of missed miscarriage, histopathological examination of all products of conception in case of early pregnancy failure is essential to detect molar changes. This is particularly important for the management of women with CHM who have a higher risk of developing a GTN.

Ultrasound diagnosis of complete and partial hydatidiform moles in early pregnancy failure: An inter-observer study.

We evaluated the accuracy of the ultrasound signs suggestive of complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM) in a cohort of women with histologically confirmed hydatidiform mole (HM) who presented with early pregnancy failure, including 103 CHM and 95 PHM for which ultrasound images were available. The accuracy of the differential diagnosis was significantly (p < 0.001) greater during secondary examination of ultrasound images compared with the original primary ultrasound examination. The interobserver agreement analysis indicated only a fair to moderate agreement between the two examinations (kappa value 0.41; 95% CI 0.29-0.53). Most HM present as early pregnancy failure and identification of early ultrasound signs can improve the differential diagnosis between CHM and PHM.

Progesterone to prevent miscarriage in women with early pregnancy bleeding: the PRISM RCT.

BACKGROUND: Progesterone is essential for a healthy pregnancy. Several small trials have suggested that progesterone therapy may rescue a pregnancy in women with early pregnancy bleeding, which is a symptom that is strongly associated with miscarriage. OBJECTIVES: (1) To assess the effects of vaginal micronised progesterone in women with vaginal bleeding in the first 12 weeks of pregnancy. (2) To evaluate the cost-effectiveness of progesterone in women with early pregnancy bleeding. DESIGN: A multicentre, double-blind, placebo-controlled, randomised trial of progesterone in women with early pregnancy vaginal bleeding. SETTING: A total of 48 hospitals in the UK. PARTICIPANTS: Women aged 16-39 years with early pregnancy bleeding. INTERVENTIONS: Women aged 16-39 years were randomly assigned to receive twice-daily vaginal suppositories containing either 400 mg of progesterone or a matched placebo from presentation to 16 weeks of gestation. MAIN OUTCOME MEASURES: The primary outcome was live birth at ≥ 34 weeks. In addition, a within-trial cost-effectiveness analysis was conducted from an NHS and NHS/Personal Social Services perspective. RESULTS: A total of 4153 women from 48 hospitals in the UK received either progesterone (n = 2079) or placebo (n = 2074). The follow-up rate for the primary outcome was 97.2% (4038 out of 4153 participants). The live birth rate was 75% (1513 out of 2025 participants) in the progesterone group and 72% (1459 out of 2013 participants) in the placebo group (relative rate 1.03, 95% confidence interval 1.00 to 1.07; p = 0.08). A significant subgroup effect (interaction test p = 0.007) was identified for prespecified subgroups by the number of previous miscarriages: none (74% in the progesterone group vs. 75% in the placebo group; relative rate 0.99, 95% confidence interval 0.95 to 1.04; p = 0.72); one or two (76% in the progesterone group vs. 72% in the placebo group; relative rate 1.05, 95% confidence interval 1.00 to 1.12; p = 0.07); and three or more (72% in the progesterone group vs. 57% in the placebo group; relative rate 1.28, 95% confidence interval 1.08 to 1.51; p = 0.004). A significant post hoc subgroup effect (interaction test p = 0.01) was identified in the subgroup of participants with early pregnancy bleeding and any number of previous miscarriage(s) (75% in the progesterone group vs. 70% in the placebo group; relative rate 1.09, 95% confidence interval 1.03 to 1.15; p = 0.003). There were no significant differences in the rate of adverse events between the groups. The results of the health economics analysis show that progesterone was more costly than placebo (£7655 vs. £7572), with a mean cost difference of £83 (adjusted mean difference £76, 95% confidence interval -£559 to £711) between the two arms. Thus, the incremental cost-effectiveness ratio of progesterone compared with placebo was estimated as £3305 per additional live birth at ≥ 34 weeks of gestation. CONCLUSIONS: Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with threatened miscarriage overall, but an important subgroup effect was identified. A conclusion on the cost-effectiveness of the PRISM trial would depend on the amount that society is willing to pay to increase the chances of an additional live birth at ≥ 34 weeks. For future work, we plan to conduct an individual participant data meta-analysis using all existing data sets. TRIAL REGISTRATION: Current Controlled Trials ISRCTN14163439, EudraCT 2014-002348-42 and Integrated Research Application System (IRAS) 158326. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 33. See the NIHR Journals Library website for further project information.

Miscarriage is a common complication of pregnancy that affects one in five pregnancies. Several small studies have suggested that progesterone, a hormone essential for maintaining a pregnancy, may reduce the risk of miscarriage in women presenting with early pregnancy bleeding. This research was undertaken to test whether or not progesterone given to pregnant women with early pregnancy bleeding would increase the number of live births when compared with placebo (dummy treatment). The women participating in the study had an equal chance of receiving progesterone or placebo, as determined by a computer; one group received progesterone (400 mg twice daily as vaginal pessaries) and the other group received placebo with an identical appearance. Treatment began when women presented with vaginal bleeding, were < 12 weeks of gestation and were found to have at least a pregnancy sac on an ultrasound scan. Treatment was stopped at 16 weeks of gestation, or earlier if the pregnancy ended before 16 weeks. Neither the participants nor their health-care professionals knew which treatment was being received. In total, 23,775 women were screened and 4153 women were randomised to receive either progesterone or placebo pessaries. Altogether, 2972 participants had a live birth after at least 34 weeks of gestation. Overall, the live birth rate in the progesterone group was 75% (1513 out of 2025 participants), compared with 72% (1459 out of 2013 participants) in the placebo group. Although the live birth rate was 3% higher in the progesterone group than in the placebo group, there was statistical uncertainty about this finding. However, it was observed that women with a history of one or more previous miscarriages and vaginal bleeding in their current pregnancy may benefit from progesterone. For women with no previous miscarriages, our analysis showed that the live birth rate was 74% (824 out of 1111 participants) in the progesterone group compared with 75% (840 out of 1127 participants) in the placebo group. For women with one or more previous miscarriages, the live birth rate was 75% (689 out of 914 participants) in the progesterone group compared with 70% (619 out of 886 participants) in the placebo group. The potential benefit appeared to be most strong for women with three or more previous miscarriages, who had a live birth rate of 72% (98 out of 137 participants) in the progesterone group compared with 57% (85 out of 148 participants) in the placebo group. Treatment with progesterone did not appear to have any negative effects.

Serial prophylactic exchange blood transfusion in pregnant women with sickle cell disease (TAPS-2): study protocol for a randomised controlled feasibility trial.

BACKGROUND: Pregnancies in women with sickle cell disease (SCD) are associated with a higher risk of sickle and pregnancy complications. Limited options exist for treating SCD during pregnancy. Serial prophylactic exchange blood transfusion (SPEBT) has been shown to be effective in treating SCD outside pregnancy, but evidence is lacking regarding its use during pregnancy. The aim of this study is to assess the feasibility and acceptability of conducting a future phase 3 randomised controlled trial (RCT) to establish the clinical and cost effectiveness of SPEBT in pregnant women with SCD. METHODS: The study is an individually randomised, two-arm, feasibility trial with embedded qualitative and health economic studies. Fifty women, 18 years of age and older, with SCD and a singleton pregnancy at ≤ 18 weeks' gestation will be recruited from six hospitals in England. Randomisation will be conducted using a secure online database and minimised by centre, SCD genotype and maternal age. Women allocated to the intervention arm will receive SPEBT commencing at ≤ 18 weeks' gestation, performed using automated erythrocytapheresis every 6-10 weeks until the end of pregnancy, aiming to maintain HbS% or combined HbS/HbC% below 30%. Women in the standard care arm will only receive transfusion when clinically indicated. The primary outcome will be the recruitment rate. Additional endpoints include reasons for refusal to participate, attrition rate, protocol adherence, and maternal and neonatal outcomes. Women will be monitored throughout pregnancy to assess maternal, sickle, and foetal complications. Detailed information about adverse events (including hospital admission) and birth outcomes will be extracted from medical records and via interview at 6 weeks postpartum. An embedded qualitative study will consist of interviews with (a) 15-25 trial participants to assess experiences and acceptability, (b) 5-15 women who decline to participate to identify barriers to recruitment and (c) 15-20 clinical staff to explore fidelity and acceptability. A health economic study will inform a future cost effectiveness and cost-utility analysis. DISCUSSION: This feasibility study aims to rigorously evaluate SPEBT as a treatment for SCD in pregnancy and its impact on maternal and infant outcomes. TRIAL REGISTRATION: NIH registry (www.clinicaltrials.gov), registration number NCT03975894 (registered 05/06/19); ISRCTN (www.isrctn.com), registration number ISRCTN52684446 (retrospectively registered 02/08/19).

A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy.

BACKGROUND: Bleeding in early pregnancy is strongly associated with pregnancy loss. Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone therapy may improve pregnancy outcomes in women who have bleeding in early pregnancy. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate progesterone, as compared with placebo, in women with vaginal bleeding in early pregnancy. Women were randomly assigned to receive vaginal suppositories containing either 400 mg of progesterone or matching placebo twice daily, from the time at which they presented with bleeding through 16 weeks of gestation. The primary outcome was the birth of a live-born baby after at least 34 weeks of gestation. The primary analysis was performed in all participants for whom data on the primary outcome were available. A sensitivity analysis of the primary outcome that included all the participants was performed with the use of multiple imputation to account for missing data. RESULTS: A total of 4153 women, recruited at 48 hospitals in the United Kingdom, were randomly assigned to receive progesterone (2079 women) or placebo (2074 women). The percentage of women with available data for the primary outcome was 97% (4038 of 4153 women). The incidence of live births after at least 34 weeks of gestation was 75% (1513 of 2025 women) in the progesterone group and 72% (1459 of 2013 women) in the placebo group (relative rate, 1.03; 95% confidence interval [CI], 1.00 to 1.07; P = 0.08). The sensitivity analysis, in which missing primary outcome data were imputed, resulted in a similar finding (relative rate, 1.03; 95% CI, 1.00 to 1.07; P = 0.08). The incidence of adverse events did not differ significantly between the groups. CONCLUSIONS: Among women with bleeding in early pregnancy, progesterone therapy administered during the first trimester did not result in a significantly higher incidence of live births than placebo. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment program; PRISM Current Controlled Trials number, ISRCTN14163439.).

Ultrasound diagnosis of molar pregnancy.

INTRODUCTION: The primary aims of this study were to establish what proportion of ultrasonically suspected molar pregnancies were proven on histological examination and what proportion of histologically diagnosed molar pregnancies were identified by ultrasound pre-operatively. The secondary aim was to review the features of these scans to help identify criteria that may improve ultrasound diagnosis. METHODS: This was a retrospective observational study conducted in the Early Pregnancy Unit at King's College Hospital London over an 11-year period. Cases of ultrasonically suspected molar pregnancy or other gestational trophoblastic disease were identified and compared with the final histopathological diagnosis. In addition, cases which were diagnosed on histopathology that were not suspected on ultrasound were also examined. In discrepant cases, the images were reviewed unblinded by two senior sonographers. Statistical analysis for likelihood ratio and post-test probabilities was performed. RESULTS: One hundred eighty-two women had gestational trophoblastic disease suspected on ultrasound examination (1:360, 0.3%); 106/182 (58.2%, 95% CI 51.0 to 65.2%) had histologically confirmed gestational trophoblastic disease. The likelihood ratio for gestational trophoblastic disease after a positive ultrasound was 607.27, with a post-test probability of 0.628.The sensitivity of ultrasound for gestational trophoblastic disease was 70.7% (95% CI 62.9% to 77.4%) with an estimated specificity of 99.88% (95% CI 99.85% to 99.91%); 102/143 (71.3%, 95% CI 63.4 to 78.1%) molar pregnancies were suspected on pre-op ultrasound; 60/68 (88.2%, 95% CI 78.2 to 94.2%) of complete moles were suspected on pre-op ultrasound, compared with 42/75 (56.0%, 95% CI 44.7 to 66.7%) of partial moles. On retrospective review of the pre-op ultrasound images, there were cases that could have been suspected prior to surgery. CONCLUSION: Detecting molar pregnancy by ultrasound remains a diagnostic challenge, particularly for partial moles. These data suggest that there has been an increase in both the predictive value and the sensitivity of ultrasound over time, with a high LR and post-test probability; however, the diagnostic criteria remain ill-defined and could be improved.

New insights in the pathophysiology of complete hydatidiform mole.

OBJECTIVE: The majority of complete hydatidiform moles (CHM) are detected on ultrasound examination by the end of the first trimester when they present as multiple sonolucent cysts. To better understand the pathophysiology of this unique placental pathology and improve its prenatal diagnosis and management we have reviewed the ultrasound features of CHM before the appearance of cystic changes. STUDY DESIGN: We searched our database to identify all women diagnosed with a complete hydatidiform mole confirmed by histopathology who had an ultrasound examination before 9 weeks' gestation. We reviewed their ultrasound reports and all the corresponding images. RESULTS: The study group included 39 women with a positive pregnancy test and vaginal bleeding, 36 of whom had at least two ultrasound examinations before 9 weeks' gestation. At the first scan (mean gestation age 7 + 1 weeks; SD 1.1), 29 out 39 (74.4%) of CHM presented as a heterogeneous hyperechogenic mass with or without gestational sac and the remaining ten (25.6%) cases as a regular 4-week gestational sac. Cystic molar changes became apparent from the end of the second month of gestation. CONCLUSION: The development of a CHM follows a well-defined pattern starting with a macroscopically normal gestation sac at 4 weeks, which transforms into a polypoid mass between 5 and 7 weeks of gestation. The hydropic changes of the villous tissue is progressive and rarely visible in utero on ultrasound before 8 weeks of gestation. These findings should allow an earlier diagnosis and assist in the management counselling of women with CHM.

Are early pregnancy complications more common in women with hyperemesis gravidarum?

Ultrasound evaluation is usually requested for women presenting with hyperemesis gravidarum (HG) in early pregnancy. This is to check viability as well as to diagnose multiple pregnancies and exclude gestational trophoblastic disease (GTD). The aim of this retrospective case control study was to evaluate the early pregnancy outcomes in women with HG and to compare them with an asymptomatic control group. 790 women referred with HG between 2002 and 2014 were matched for gestational age and maternal age with an asymptomatic patient attending for a reassurance or dating scan. A higher proportion of women with HG had ongoing pregnancies compared with controls and conversely, embryonic demise was less frequent in the HG group. The risk of twin pregnancy was doubled in the HG group compared to controls. There was no evidence of an increase in the prevalence of GTD. There appears to be a limited role for ultrasound in women who present with HG alone.

The postpartum ultrasound scan.

Ultrasound assessment of the postpartum uterus has a significant role to play in the evaluation of a large proportion of symptomatic puerperal women. Often the imaging modality of choice for excluding retained placental tissue, correct application of postpartum ultrasound could enable more accurate identification of women requiring surgical intervention, with consequent reduction in patient morbidity and clinical workload. This article aims to review the current understanding and application of ultrasound in the puerperium and evaluate the current evidence investigating the physiological and pathological findings of the postpartum uterus and its contents.

Women with unexplained recurrent pregnancy loss do not have evidence of an underlying prothrombotic state: experience with calibrated automated thrombography and rotational thromboelastometry.

INTRODUCTION: Where unexplained recurrent pregnancy loss (RPL) is attributed to an underlying maternal prothrombotic state, empirical prophylactic anticoagulation may be recommended. MATERIALS AND METHODS: In the present study we used calibrated automated thrombography and rotational thromboelastometry to determine the procoagulant potential of these women as a rationale for anticoagulation. Fifty women with ≥three consecutive unexplained losses prior to 14 weeks' gestation or one loss after this time were compared with forty-one parous women with no miscarriages. Exclusion criteria included antiphospholipid syndrome, inherited thrombophilia and prior venous thromboembolism. Thrombin generation in platelet poor plasma and whole blood thromboelastometry was performed outside pregnancy to determine the presence or not of an underlying prothrombotic state. RESULTS: Peak thrombin and endogenous thrombin potential were not significantly increased in subjects relative to controls. The use of low tissue factor (1 pM) to better reflect physiological conditions and assay modification to better assess the protein C pathway (5 pM in the presence of thrombomodulin) provided no additional discrimination. Consistent results were shown with thromboelastometry; mean parameters were equivalent between subjects and controls. CONCLUSIONS: These data demonstrate that global coagulation assays provide no evidence of an underlying hypercoagulable state in women with unexplained RPL; this is in keeping with the results of recent randomised controlled trials and strengthens the evidence base against use of anticoagulants in this setting.

Ovum transmigration after salpingectomy for ectopic pregnancy.

STUDY QUESTION: What proportion of pregnancies are a result of ovum transmigration after salpingectomy for ectopic pregnancy? SUMMARY ANSWER: Approximately one-third of spontaneously conceived pregnancies are a result of pick-up of the ovum from the ovary contralateral to the remaining tube in women with a history of salpingectomy. WHAT IS KNOWN ALREADY: The corpus luteum has been found contralateral to tubal ectopic pregnancies in 32% of reported cases. The rate of contralateral ovum pick-up in intrauterine pregnancies is not known. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study of clinical and ultrasound records collected over a 12-year period 1999-2010. Ten per cent of cases identified were excluded from the final analysis due to incomplete data or bilateral corpora lutea. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Included were 842 pregnancies in 707 women with a history of unilateral salpingectomy for ectopic pregnancy and subsequent spontaneous pregnancy. The study was set in the Early Pregnancy Unit of a large UK inner city teaching hospital. The outcome measure was the side of the corpus luteum in relation to the side of the remaining tube. MAIN RESULTS AND THE ROLE OF CHANCE: The corpus luteum was located in the ovary contralateral to the remaining tube in 266/842 pregnancies (31.6%; 95% CI 28.5-34.8%). There was no significant difference in this proportion between intrauterine and ectopic pregnancies [246/769 (32.0%) versus 21/73 (28.8%), P = 0.60]. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study and so did not address the conception rate according to the laterality of ovulation. WIDER IMPLICATIONS OF THE FINDINGS: Our findings were very similar to the frequency of ectopic pregnancies found contralateral to the corpus luteum described in previous studies. Ovum pick-up from the cul-de-sac probably occurs reasonably frequently and is unlikely to have a causative role in the pathogenesis of ectopic pregnancy. It is not known how often this phenomenon occurs in women with intact Fallopian tubes. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was obtained. The authors have no conflicts of interest to declare.

Clinical use of a model to predict the viability of early intrauterine pregnancies when no embryo is visible on ultrasound.

BACKGROUND: When a small gestational sac with no visible embryo is seen at an early pregnancy ultrasound scan, the clinician cannot distinguish a viable from a non-viable pregnancy. A test for the prediction of early pregnancy viability at the initial visit was developed in 2003. Maternal age, gestational sac diameter (GSD) and serum progesterone levels were used in a logistic regression model to create an algorithm for estimation of the probability of a viable pregnancy. The objective of this study was to assess how well the test performed in routine clinical practice. METHODS: This is a retrospective observational study of women who had the test performed in our Early Pregnancy Unit over a 6-year period. Inclusion criteria were a spontaneous conception, gestational sac of <20 mm mean diameter, no visible embryo on transvaginal ultrasound scan and outcome data regarding the viability of the pregnancy. RESULTS: Of 5163 potentially eligible women, 472 had the test performed (9.1%) and 400 met the inclusion criteria for the study. Women who were older or with vaginal bleeding, a more advanced gestational age or a history of previous first trimester miscarriages were more likely to have the test performed. At follow-up, 199/400 (49.8%) women had a viable intrauterine pregnancy, and 201/400 (50.2%) had a non-viable pregnancy. The logistic regression model performed better than serum progesterone, ß-hCG, mean GSD or maternal age alone as single parameters to differentiate between viable and non-viable pregnancies, but the area under the curve was lower than in the 2003 study [0.85 (standard error 0.021) versus 0.97 (standard error 0.011)]. CONCLUSIONS: Although less effective than in the original study, the logistic regression model was able to predict pregnancy viability with reasonable accuracy when applied in clinical practice. The test appears to be under utilized and further prospective studies are needed to establish if the test is of clinical benefit, for example, in reducing patient anxiety.

Human placental metabolic adaptation to chronic hypoxia, high altitude: hypoxic preconditioning.

We have previously demonstrated placentas from laboring deliveries at high altitude have lower binding of hypoxia-inducible transcription factor (HIF) to DNA than those from low altitude. It has recently been reported that labor causes oxidative stress in placentas, likely due to ischemic hypoxic insult. We hypothesized that placentas of high-altitude residents acquired resistance, in the course of their development, to oxidative stress during labor. Full-thickness placental tissue biopsies were collected from laboring vaginal and nonlaboring cesarean-section term (37-41 wk) deliveries from healthy pregnancies at sea level and at 3,100 m. After freezing in liquid nitrogen within 5 min of delivery, we quantified hydrophilic and lipid metabolites using (31)P and (1)H NMR metabolomics. Metabolic markers of oxidative stress, increased glycolysis, and free amino acids were present in placentas following labor at sea level, but not at 3,100 m. In contrast, at 3,100 m, the placentas were characterized by the presence of concentrations of stored energy potential (phosphocreatine), antioxidants, and low free amino acid concentrations. Placentas from pregnancies at sea level subjected to labor display evidence of oxidative stress. However, laboring placentas at 3,100 m have little or no oxidative stress at the time of delivery, suggesting greater resistance to ischemia-reperfusion. We postulate that hypoxic preconditioning might occur in placentas that develop at high altitude.

Oxidative stress, gene expression, and protein changes induced in the human placenta during labor.

Malperfusion of the placenta has been implicated as a cause of oxidative stress in complications of human pregnancy, leading to release of proinflammatory cytokines and anti-angiogenic factors into the maternal circulation. Uterine contractions during labor are known to be associated with intermittent utero-placental perfusion. We therefore tested whether oxidative stress, proinflammatory cytokines, and angiogenic regulators were increased in placentas subjected to short (<5 hours) and long (>15 hours) labor compared with nonlabored controls delivered by cesarean section. In addition, broader changes in gene transcripts were assessed by microarray analysis. Oxidative stress, activation of the nuclear factor-kappaB pathway, tumor necrosis factor-alpha and interleukin 1beta all increased in placental tissues after labor. Stabilization of hypoxia-inducible factor-1alpha and increased vascular endothelial growth factor soluble receptor-1 were also observed. By contrast, tissue levels of placenta growth factor decreased. Apoptosis was also activated in labored placentas. The magnitude of these changes related to the duration of labor. After labor, 55 gene transcripts were up-regulated and 35 down-regulated, and many of these changes were reflected at the protein level. In conclusion, labor is a powerful inducer of placental oxidative stress, inflammatory cytokines, and angiogenic regulators. Our findings are consistent with intermittent perfusion being the initiating cause. Placentas subjected to labor do not reflect the normal in vivo state at the molecular level.

Transfer of folic acid inside the first-trimester gestational sac and the effect of maternal smoking.

OBJECTIVE: The objective of the study was to investigate the transfer pathways of folic acid inside the first-trimester gestational sac and to evaluate the impact of maternal smoking. STUDY DESIGN: Folate and cotinine levels were evaluated in maternal serum (n = 125) and coelomic fluid (n = 42), and immunostaining was used to identify folate receptors in placental villi, decidual tissue, and secondary yolk sacs from normal pregnancies at 6-12 weeks' gestation. RESULTS: Folate receptors-alpha were found on the apical surface of syncytiotrophoblast, uterine glandular epithelial cells, and mesothelial layer of the yolk sac. Significantly higher (P < .05) median folate levels were found in maternal serum than in coelomic fluid. The median folate maternal serum and coelomic levels were significantly (P < .0001 and P < .005) lower in smokers, compared with nonsmokers. CONCLUSION: Uterine glands and the secondary yolk sac play key roles in supplying folic acid to the developing fetus before the placental circulations are established, and maternal smoking does not seem to impair directly its transfer mechanism in early pregnancy.