Number Of Previous Miscarriages Research Articles

Why do patients decline amniocentesis? Analysis of factors influencing the decision to refuse invasive prenatal testing

BackgroundIn recent years, determination of personalized risk for fetal chromosomal anomalies emerged as an important component of prenatal genetic counseling. Women in whom fetal risk for chromosomal aberrations is elevated are offered further testing. The aim of this study was to identify factors that may influence the decision to refuse invasive prenatal testing aimed at determination of fetal karyotype in a group of patients at increased risk of trisomy 21.MethodsThe analysis included 177 patients with singleton pregnancy, whose personalized risk score for trisomy 21 calculated on the basis of the combined test exceeded 1:300. Diagnostic amniocentesis was performed in 125 patients from this subset, since the remaining 52 women declined invasive prenatal testing. The following factors were analyzed as potential determinants of the decision to refuse amniocentesis: maternal age (≥35 years), gravidity, number of miscarriages in previous pregnancies, educational status, marital status, indications to prenatal testing, gestational age at the time of prenatal testing, personalized risk score for fetal chromosomal aberrations and nuchal translucency (NT) value.ResultsA statistically significant relationship was found between the decision to refuse amniocentesis and the number of previous miscarriages, maternal educational level, NT values and personalized risk score for fetal chromosomal aberrations. Multivariate logistic regression analysis identified primary maternal education and history of more than two miscarriages as independent significant predictors of declining amniocentesis. Women with personalized risk scores for trisomy 21 greater than 1:100 opted out of invasive prenatal diagnosis significantly less often than the remaining participants.ConclusionIn conclusion, the key role of high quality and accuracy of non-invasive diagnostic tests conducted in the first trimester should be emphasized as personalized risk score for fetal chromosomal aberrations determined based on their results is pivotal for further management of pregnancy. Equally important is to provide the patients with an accurate and comprehensible information about potential benefits and risks of invasive testing.

Lymphocyte immunotherapy for recurrent miscarriages: Predictors of therapeutic success.

To evaluate the predictors of successful pregnancies in women with a history of recurrent miscarriages (RMs) having undergone lymphocyte immunotherapy (LIT). Retrospective, multicenter, observational study which involved 702 pregnant women with history of RM treated with LIT. Comparative analysis of women with a history of RM having undergone LIT and experienced treatment success vs those having experienced treatment failure along with the analysis of the association between the number of prior miscarriages and the efficacy of LIT. A total of 421 women were able to carry the pregnancy to term, with treatment success rate of 60%. The multivariate analysis showed that age, the association between autoantibodies and thrombophilia, and the number of previous miscarriages were factors associated with LIT failure. Secondary RMs alone were not found to be a factor predictive of LIT success or failure; however, secondary RMs among women with a history of 5 or more RM were found to be a predictor of LIT success (OR: 10.24; 95% CI: 1.9-55.8; P=.007). Age, the number of previous miscarriages, and the association between autoantibodies and thrombophilia are associated with LIT failure. A higher number of previous miscarriages in cases of secondary RM resulted in better LIT outcomes.

Association between previous spontaneous abortion and pre-eclampsia during a subsequent pregnancy.

To determine the impact of a history of spontaneous abortion on pre-eclampsia during a subsequent pregnancy. A cross-sectional study enrolled pregnant women admitted to obstetrics and gynecology wards at 103 hospitals in Tehran, Iran for delivery between July 6 and July 21, 2015. Consenting participants were interviewed by midwives; data were collected using a five-part questionnaire and patients' medical records were retrieved. Patient data were analyzed by multiple logistic regression to identify variables associated with increased odds of pre-eclampsia. In total, 5170 patients were interviewed and 252 had experienced pre-eclampsia. The number of previous spontaneous abortions was found to be associated with pre-eclampsia, and a higher number of previous spontaneous abortions was associated with increased odds of patients having experienced pre-eclampsia (adjusted odds ratio 1.28, 95% confidence interval 1.03-1.59; P=0.025). A history of spontaneous abortion was associated with increased odds of pre-eclampsia during a subsequent pregnancy.

Low-Molecular-Weight Heparin for the Treatment of Unexplained Recurrent Miscarriage With Negative Antiphospholipid Antibodies: A Randomized Controlled Trial.

Recurrent miscarriage (RM) is one of the most common clinical problems in reproduction with no definite cause in about 50% of the cases. The study aims to evaluate the effect of low-molecular-weight heparin (LMWH) in the treatment of women with RM negatively tested for antiphospholipid antibodies (APAs). An open-labeled registered randomized controlled study (NCT 01608347) included women who attended the outpatient clinic in Assiut Women Health Hospital and Nag-Hamady Central Hospital, Egypt, with 3 or more unexplained RM. Eligible participants were randomly assigned into 2 groups. The study group included 150 patients receiving LMWH (Tinzaparin sodium 4500 IU) subcutaneous daily injection with 500 µg folic acid once daily orally started once positive pregnancy test till the 20th week of gestation. The control group included 150 patients receiving the same dose of folic acid alone. The primary outcome of the study was the rate of continuation of a viable pregnancy after 20 weeks of gestation. There was no significant difference between both groups as regards age, parity, or number of previous miscarriages. There was a significant increase in women who continued their pregnancy beyond 20 weeks in the study group compared to the control group (73.3% vs 48%, respectively; P = .002). The take-home baby rate was also significantly higher in the LMWH group compared to the control group ( P = .001). Early start of LMWH decreases the incidence of miscarriage in the first 20 weeks of pregnancy in women with unexplained RM negative for APAs.

Recurrent miscarriage in translocation carriers: no differences in clinical characteristics between couples who accept and couples who decline PGD.

Do clinical characteristics of recurrent miscarriage couples with a chromosomal abnormality and who opt for PGD differ from couples that decline PGD after extensive genetic counselling? No differences in clinical characteristics are identified between recurrent miscarriage couples carrying a structural chromosomal abnormality who opt for PGD compared with those that decline PGD after extensive genetic counselling. Couples who have experienced two or more miscarriages (recurrent miscarriage) are at increased recurrence risk if one of the partners carries a structural chromosomal abnormality. PGD can be offered to avoid (another) miscarriage or pregnancy termination when (invasive) prenatal diagnosis shows an abnormal result. To date, no reports are available that describe reproductive decision-making after genetic counselling on PGD in these specific couples. Retrospective cohort study of 294 couples carrying a structural chromosomal abnormality seeking genetic counselling on PGD between 1996 and 2012. Participants were recurrent miscarriage couples carrying a structural chromosomal abnormality. They had been referred for genetic counselling to the only national licensed PGD centre. Clinical characteristics analysed included couple associated characteristics, characteristics concerning reproductive history and external characteristics such as type of physician that referred the couple for genetic counselling and the clinical geneticist performing the counselling on PGD. Of 294 couples referred for counselling on PGD, 26 were not accepted because they did not meet the criteria for IVF-PGD. The remaining cohort of 268 couples consisted of two-thirds female and one-third male carriers. Main PGD indications were reciprocal translocations (83.9%) and Robertsonian translocations (16.7%). Following genetic counselling, 76.9% of included couples chose PGD as their reproductive option, the others declined PGD. Reproductive choice is not influenced by sex of the translocation carrier (P = 0.499), type of chromosomal abnormality (P = 0.346), number of previous miscarriages (P = 0.882), history of termination of pregnancy (TOP) because of an unbalanced fetal karyotype (P = 0.800), referring physician (P = 0.208) or geneticist who performed the counselling (P = 0.410). This study only included recurrent miscarriage couples carrying a structural chromosomal abnormality, who were actually referred to a PGD clinic for genetic counselling. We lack information on couples who were not referred for PGD. Some of these patients may not have been informed on PGD at all, while others were not referred for counselling because they did not opt for PGD to start with. This study shows that reproductive choices in couples with recurrent miscarriage on the basis of a structural chromosomal abnormality are not influenced by characteristics of the couple itself, nor by their obstetric history or external characteristics. These findings suggest that a couples' intrinsic attitude towards PGD treatment is a major factor influencing their reproductive choice. Future research will focus on these personal motives that seem to push reproductive decision-making following genetic counselling in a given direction.

Neonatal outcome in pregnant patients with antiphospholipid syndrome.

The study aim was to evaluate pregnancy outcomes in patients with antiphospholipid syndrome (APS) and to determine which clinical parameters present risk factors for adverse pregnancy outcomes in these patients. The study included 55 patients with APS treated at the Clinic for Ob/Gyn, Clinical Center of Serbia, from 2006 to 2012. The control group consisted of 55 healthy pregnant women. Data regarding previous pregnancies and conception method were registered. Immunological and laboratory tests were performed. Pregnancy outcomes, including miscarriage, intrauterine fetal death, hypertensive disorders, diabetes mellitus, phlebothrombosis, fetal growth restriction, premature delivery, delivery method, perinatal asphyxia, respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis were followed. The premature delivery rate in APS patients was 31.8%, and pregnancy loss was 18.2%. Significantly more patients with APS had thrombocytopenia, pregnancy losses, intrauterine growth restriction, and perinatal asphyxia compared with the control group. More miscarriages, preterm delivery, lower birth weight, preeclampsia, and IgM anticardiolipin antibody levels significantly correlated with adverse pregnancy outcomes. Although rare, respiratory distress syndrome can also worsen neonatal health status. According to ROC analysis, previous miscarriages correctly explained 66.3% of adverse pregnancy outcome cases. We generated four equations of adverse pregnancy outcome risk factors. The most important prognostic factor for pregnancy outcome in APS patients is the number of previous miscarriages. Using appropriate current therapeutic protocol can enable live birth of a healthy newborn in most cases.

Is recurrent miscarriage a useful clinical concept?

Many treatments have been used to increase the chances of an ongoing pregnancy after recurrent miscarriage (RM). Yet no clear evidence for an effective intervention has been found. Therefore, the clinical concept RM should be reconsidered. Both the statistical and clinical bases for RM are poor. If the individual risk is taken into account, then simple calculations explain the observed frequency of RM. Most miscarriages, either sporadic or recurrent, are abnormal in construction or development. Although some risk factors for miscarriage have been identified, such as age and number of previous miscarriages, the importance of other factors remains uncertain. RM has a favorable prognosis: the cumulative live birth rate is usually over 90% after two or three more attempts. So maternal systemic pathology does not seem to play a major role in the cause of RM. Little benefit can be expected from any intervention aimed at increasing the chance of a live birth. RM does not appear to be a real pathological entity that requires a special explanation. Moral support should replace medical interventions in most cases.

Time to conception and time to live birth in women with unexplained recurrent miscarriage

What is the time to conception in a cohort of women with unexplained recurrent miscarriage (RM). Median time to conception in women diagnosed with unexplained RM was 21 weeks (interquartile range (IQR) 8-55 weeks), with a cumulative incidence of conception of 74% after 12 months of trying to conceive. There is no effective treatment in couples with unexplained RM. Adequate counselling about their prognosis, for example time to conception and time to a live birth, is therefore very important. So far, there are no studies that give insight on these issues. A nested prospective cohort study was performed from February 2004 through July 2009 within a multicentre randomized placebo-controlled trial (ALIFE trial) on anticoagulant treatment in 364 women with unexplained RM. A total of 251 women who were not pregnant at the time of diagnosis of unexplained RM were included in this study. Of these, 13% became pregnant with ART, and all other women conceived naturally. The primary outcome was time to conception in weeks, calculated from the moment of diagnosis until conception measured by a urinary HCG. Secondary outcome was time to a live birth in the subsequent pregnancy. The relative prognostic significance of female age, the number of preceding miscarriages, interventions within the trial and the presence or absence of a preceding late miscarriage, a previous live birth and factor V Leiden mutation, was evaluated by Cox regression for time to conception and by competing risk modelling for time to live birth, respectively. The cumulative incidence of conception was 56% after 6 months, 74% after 12 months and 86% after 24 months of which 65% resulted in a live birth. The median time to conception was 21 weeks (IQR 8-55 weeks). Of potential prognostic factors, the presence of the factor V Leiden mutation resulted in a significantly shorter median time to conception of 11 weeks for carriers versus 23 weeks for non-carriers (hazard ratio (HR) 1.94, 95% confidence interval (CI) 1.03-3.65). The cumulative incidence of a live birth of the subsequent pregnancy was 0% after 6 months, 23% after 12 months and 50% after 24 months. The median time to a live birth of the subsequent pregnancy was 102 weeks (IQR 82-115 weeks). The number of previous miscarriages was the only prognostic factor (HR 0.83, 95% CI 0.74-0.94) significantly associated with time to a live birth of the subsequent pregnancy. In our study only the subsequent pregnancy after diagnosing unexplained RM was included. A future collection of cumulative follow-up data of all the women included in this cohort may provide outcomes of all pregnancies following the diagnosis of unexplained RM. Time to conception in women diagnosed with unexplained RM appears to be comparable with time to conception in healthy fertile women, as reported in the literature. The interesting finding that women with Factor V Leiden mutation have a significant shorter time to conception may suggest a favourable embryo implantation process. Future research is needed to confirm these findings and unravel the biology of early implantation. The RCT used for this nested cohort study was funded by a grant (945-27-003) from the Netherlands Organization for Health Research and Development and a grant from GlaxoSmithKline. Study drugs (aspirin and placebo) were packaged and donated by Meda Pharma. This analysis was supported by a VIDI innovative research grant from the Netherlands Organisation for Scientific Research (NWO) 016.126.364. There are no potential conflicts of interest to declare. This cohort study was nested in the randomized controlled trial; ALIFE study (Current Controlled Trials number, ISRCTN 58496168).

Progestogen for preventing miscarriage

Progesterone, a female sex hormone, is known to induce secretory changes in the lining of the uterus essential for successful implantation of a fertilized egg. It has been suggested that a causative factor in many cases of miscarriage may be inadequate secretion of progesterone. Therefore, progestogens have been used, beginning in the first trimester of pregnancy, in an attempt to prevent spontaneous miscarriage. To determine the efficacy and safety of progestogens as a preventative therapy against miscarriage. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 August 2013), reference lists from relevant articles, attempting to contact authors where necessary, and contacted experts in the field for unpublished works. Randomized or quasi-randomized controlled trials comparing progestogens with placebo or no treatment given in an effort to prevent miscarriage. Two review authors assessed trial quality and extracted data. Fourteen trials (2158 women) are included. The meta-analysis of all women, regardless of gravidity and number of previous miscarriages, showed no statistically significant difference in the risk of miscarriage between progestogen and placebo or no treatment groups (Peto odds ratio (Peto OR) 0.99; 95% confidence interval (CI) 0.78 to 1.24) and no statistically significant difference in the incidence of adverse effect in either mother or baby.A subgroup analysis of placebo controlled trials did not find a difference in the rate of miscarriage with the use of progestogen (10 trials, 1028 women; Peto OR 1.15; 95% CI 0.88 to 1.50).In a subgroup analysis of four trials involving women who had recurrent miscarriages (three or more consecutive miscarriages; four trials, 225 women), progestogen treatment showed a statistically significant decrease in miscarriage rate compared to placebo or no treatment (Peto OR 0.39; 95% CI 0.21 to 0.72). However, these four trials were of poorer methodological quality. No statistically significant differences were found between the route of administration of progestogen (oral, intramuscular, vaginal) versus placebo or no treatment. No significant differences in the rates of preterm birth, neonatal death, or fetal genital anomalies/virilization were found between progestogen therapy versus placebo/control. There is no evidence to support the routine use of progestogen to prevent miscarriage in early to mid-pregnancy. However, there seems to be evidence of benefit in women with a history of recurrent miscarriage. Treatment for these women may be warranted given the reduced rates of miscarriage in the treatment group and the finding of no statistically significant difference between treatment and control groups in rates of adverse effects suffered by either mother or baby in the available evidence. Larger trials are currently underway to inform treatment for this group of women.

Peripheral natural killer cell activity as a predictor of recurrent pregnancy loss: a large cohort study

To determine the predictive value of preconceptional peripheral blood natural killer (pNK) cell activity in patients with recurrent pregnancy loss (RPL). Cohort study. University department. A total of 552 patients with a history of two to six consecutive miscarriages. None. The predictive value of preconceptional pNK cell activity for subsequent miscarriage was analyzed using multivariable logistic regression analysis, with age, number of previous miscarriages, and presence/absence of previous live births and bed rest as covariates. Age and number of previous miscarriages, but not high pNK cell activity, were found to be independent risk factors for a subsequent miscarriage. No effect of bed rest and previous live birth on the likelihood of live birth was observed (odds ratios 1.28 [95% confidence interval 0.81-2.02] and 0.91 [0.52-1.59], respectively). Elevated pNK cell activity was found to not be an independent risk factor for subsequent miscarriage. Clinicians should not measure the plasma NK activity as a systematic recurrent pregnancy loss examination, because its clinical significance is yet to be established.

Peripheral natural killer cell activity as a predictor of recurrent miscarriage: large cohort study

ObjectiveTo confirm the predictive value of pre-conceptional peripheral blood natural-killer (pNK) cell activity in patients with recurrent miscarriage (RM).DesignCohort study.Materials and MethodsPatients: 552 patients with a history of 2-6 consecutive miscarriages, who had their subsequent pregnancy, in the OG/GYN clinic of our university hospital. Main outcome measurement: The predictive value of pre-conceptional pNK cell activity for subsequent miscarriage was analyzed using multivariate logistic regression analysis, with the age, number of previous miscarriages, presence/absence of previous live births and bed rest as covariates. The effect of bed rest from 4 to 8 weeks of gestation was also examined.ResultsAge, but not high pNK cell activity and number of previous miscarriages, was confirmed to be independent risk factors for a subsequent miscarriage. The live birth rate of patients with normal NK cell activity tended to be higher than that of patients with low NK cell activity (OR: 0.559; 95% confidence interval [CI]: 0.311-1.003, p=0.051). No effect of bed rest and previous live birth on the likelihood of live birth was observed (OR: 1.280; 95% CI: 0.812-2.016, OR: 0.908; 95% CI: 0.519-1.587).ConclusionLow, but not elevated pNK cell activity was found to be a marginally independent risk factor for subsequent miscarriage. Clinicians should not measure the plasma NK activity as a systematic RM examination, because its clinical significance is yet to be established. ObjectiveTo confirm the predictive value of pre-conceptional peripheral blood natural-killer (pNK) cell activity in patients with recurrent miscarriage (RM). To confirm the predictive value of pre-conceptional peripheral blood natural-killer (pNK) cell activity in patients with recurrent miscarriage (RM). DesignCohort study. Cohort study. Materials and MethodsPatients: 552 patients with a history of 2-6 consecutive miscarriages, who had their subsequent pregnancy, in the OG/GYN clinic of our university hospital. Main outcome measurement: The predictive value of pre-conceptional pNK cell activity for subsequent miscarriage was analyzed using multivariate logistic regression analysis, with the age, number of previous miscarriages, presence/absence of previous live births and bed rest as covariates. The effect of bed rest from 4 to 8 weeks of gestation was also examined. Patients: 552 patients with a history of 2-6 consecutive miscarriages, who had their subsequent pregnancy, in the OG/GYN clinic of our university hospital. Main outcome measurement: The predictive value of pre-conceptional pNK cell activity for subsequent miscarriage was analyzed using multivariate logistic regression analysis, with the age, number of previous miscarriages, presence/absence of previous live births and bed rest as covariates. The effect of bed rest from 4 to 8 weeks of gestation was also examined. ResultsAge, but not high pNK cell activity and number of previous miscarriages, was confirmed to be independent risk factors for a subsequent miscarriage. The live birth rate of patients with normal NK cell activity tended to be higher than that of patients with low NK cell activity (OR: 0.559; 95% confidence interval [CI]: 0.311-1.003, p=0.051). No effect of bed rest and previous live birth on the likelihood of live birth was observed (OR: 1.280; 95% CI: 0.812-2.016, OR: 0.908; 95% CI: 0.519-1.587). Age, but not high pNK cell activity and number of previous miscarriages, was confirmed to be independent risk factors for a subsequent miscarriage. The live birth rate of patients with normal NK cell activity tended to be higher than that of patients with low NK cell activity (OR: 0.559; 95% confidence interval [CI]: 0.311-1.003, p=0.051). No effect of bed rest and previous live birth on the likelihood of live birth was observed (OR: 1.280; 95% CI: 0.812-2.016, OR: 0.908; 95% CI: 0.519-1.587). ConclusionLow, but not elevated pNK cell activity was found to be a marginally independent risk factor for subsequent miscarriage. Clinicians should not measure the plasma NK activity as a systematic RM examination, because its clinical significance is yet to be established. Low, but not elevated pNK cell activity was found to be a marginally independent risk factor for subsequent miscarriage. Clinicians should not measure the plasma NK activity as a systematic RM examination, because its clinical significance is yet to be established.

First trimester assessment of pentraxin-3 levels in women with primary unexplained recurrent pregnancy loss.

To evaluate the potential role of measuring first-trimester maternal Pentraxin-3 levels in patients with primary unexplained recurrent pregnancy loss. A case control study was conducted in Ain Shams University Maternity Hospital. Cases included 45 women with primary unexplained recurrent pregnancy loss and early pregnancy failure admitted for medical or surgical termination of pregnancy. Controls (45 women) included a matched group of apparently healthy pregnant women who had at least one previous uneventful pregnancy with no previous obstetric history of adverse pregnancy outcomes. Maternal venous blood samples were collected for assay of Pentraxin-3 using enzyme-linked immunosorbent assay. The main outcome measure was the pregnancy outcome in women with elevated Pentraxin-3 levels. 90 participants were statistically analyzed. In the patient group, the mean Pentraxin-3 level was 12.00 ± 4.07 ng/ml, while in the control group it was 1.69 ± 0.91 ng/ml. The difference was statistically significant (p<0.001). In the patient group, Pentraxin-3 showed a significant positive correlation with the number of previous miscarriages (p=0.038). Abnormally elevated Pentraxin-3 levels indicate the presence of an abnormally exaggerated intrauterine inflammatory or innate immune response that may cause pregnancy failure in women with primary unexplained recurrent pregnancy loss.

The effect of body mass index on the outcome of pregnancy in women with recurrent miscarriage

Background:Maternal obesity is associated with menstrual disorders, infertility and sporadic miscarriages. Recurrent miscarriage (RM) affects at least 1% of couples trying to conceive. In over 50% of cases, the cause of the loss of pregnancy remains unexplained. The aim of this study was to determine the relationship between maternal Body Mass Index (BMI) and future outcomes of pregnancy in couples with “unexplained” RM.Methods and Results:All couples referred to the specialist recurrent miscarriage clinic at St. Mary's Hospital, London, were investigated for an underlying cause. Those with unexplained RM were eligible. Demographic and clinical data were retrieved from a computerised database and medical records. The World Health Organisation (WHO) classification of BMI was used. Univariate analysis demonstrated that BMI, maternal age, number of previous miscarriages and ethnicity were significantly associated with pregnancy outcome. Logistic regression demonstrated that maternal obesity (BMI ≥ 30 kg/m2) significantly increased the risk of miscarriage in couples with unexplained RM (OR 1.73; 95% CI 1.06 – 2.83). Asian women with a BMI similar to Caucasian women had a higher risk of a further miscarriage (OR 2.87, 95% CI, 1.52 – 5.39).Conclusions:Maternal obesity is an independent factor associated with an increased risk of miscarriage in couples with RM. All women with RM should have their BMI recorded at their first clinic visit. The potential effect of weight loss on the outcome of subsequent pregnancies should be assessed in future studies. The increased risk of miscarriage in Asian women needs to be explored further.

Progesterone supplementation in women with otherwise unexplained recurrent miscarriages

CONTEXT:Recurrent miscarriages, the loss of three or more consecutive intrauterine pregnancies before 20 weeks of gestation with the same partner, affect 1%–1.5% of the pregnant population. The inadequate secretion of progesterone in early pregnancy has been proposed as a cause of recurrent miscarriages.AIMS:The aim was to investigate the efficacy of progesterone supplementation in patients with unexplained recurrent miscarriages.SETTINGS AND DESIGN:This was a 9-year cohort study of women with otherwise unexplained recurrent miscarriages who attended a recurrent miscarriage clinic in a tertiary care university hospital.SUBJECTS AND METHODS:Women with at least three unexplained recurrent miscarriages were included in the study. They were divided into three groups according to their initial and 48-h repeat progesterone levels. For women with inadequate endogenous progesterone secretion, natural progesterone vaginal pessaries 400 mg 12-hourly were offered until 12 weeks gestation.STATISTICAL ANALYSIS:Proportions and 95% confidence intervals calculated for categorical variables and the chi-square test were used to show statistical significance. Medians and ranges were calculated for noncontinuous variables.RESULTS:Pregnancy cycles (n = 203) were analyzed to examine the miscarriage rate following progesterone supplementation. Overall live birth and miscarriage rates were 63% and 36%, respectively. When analyzed by the number of previous miscarriages there was a reduction in the miscarriage rate following progesterone supplementation in women with 4 previous miscarriages when compared with historical data.CONCLUSIONS:Progesterone supplementation may have beneficial effects in women with otherwise unexplained recurrent miscarriages.

Role of uterine artery Doppler velocimetry indices and plasma adrenomedullin level in women with unexplained recurrent pregnancy loss

To evaluate uterine artery Doppler flow resistance and plasma adrenomedullin levels in women with unexplained recurrent pregnancy loss (RPL) compared to controls. Eighty-three women, who attend the department of Obstetrics and Gynecology, Benha University, Egypt, participated in this study (RPL group: n=40, and control group: n=43). Uterine artery Doppler and plasma adrenomedullin (AM) (pg/mL) levels were measured for all women in the mid-luteal phase of a non-pregnant cycle. Both uterine artery pulsatility index (PI) and AM levels were significantly higher in RPL group compared to controls (2.71 ± 0.259 vs 2.06 ± 0.194 for PI and 287.5 ± 80.4 pg/mL vs 156.1 ± 39.8 pg/mL for AM, P<0.01). Uterine artery PI had a significant positive correlation with plasma AM levels both in the RPL group (r=0.645, P<0.001) and in the control group (r=0.384, P=0.011). Number of previous miscarriages in RPL group was significantly correlated with both uterine artery PI (r=0.838, P=0.015) and plasma AM levels (r=0.509, P=0.001). Uterine artery PI may be useful in identifying women with unexplained RPL who have impaired uterine circulation. Plasma AM may serve as a biochemical marker for RPL caused by impaired uterine perfusion.

Reproductive outcome following midtrimester pregnancy loss

The aim was to analyse reproductive outcome in pregnancy subsequent to a previous midtrimester pregnancy loss.This was a retrospective case note review over a 4 year period. Patients who had...

Aspirin and Aspirin Combined with Low-Molecular-Weight Heparin in Women with Unexplained Recurrent Miscarriage: a Randomized Controlled Multicenter Trial (ALIFE Study).

Abstract 488▪▪This icon denotes an abstract that is clinically relevant. BackgroundUnexplained recurrent miscarriage (RM) is extremely stressful for women and effective treatment is eagerly awaited. Aspirin and (low-molecular-weight) heparin are being used increasingly, even though evidence to support its use is not availabel. The aim of the ALIFE study was to investigate whether aspirin alone or combined with low-molecular-weight heparin, compared to placebo, improved the live birth rate in women with unexplained RM. MethodsWe conducted a multicenter, randomized, controlled trial in 8 centers in The Netherlands. Women aged between 18 and 42 years were eligible if they were diagnosed with unexplained RM and attempted to conceive or were less than 6 weeks pregnant. RM was defined as at least 2 miscarriages with an upper gestational age of 20 weeks (calculated from the first day of the last menstrual period). Unexplained RM was diagnosed in case of normal parental karyotype, the absence of uterine pathology on pelvic ultrasound, absence of antiphospholipid syndrome (lupus anticoagulant and anticardiolipin IgG and IgM), and a normal fasting level of homocysteine (< 16 μmol/L). Exclusion criteria were previous venous or arterial thromboembolism, indication for anticoagulant treatment during pregnancy or endocrine disorders.After written informed consent was obtained, randomization was performed centrally with stratification for age (< or ≥36 years), number of previous miscarriages (2 or ≥3), and center.Oral medication was started at the day of inclusion. Aspirin was given as calcium carbasalate 100 mg (Ascal®, Vemedia BV, Diemen, The Netherlands), equivalent to 80 mg of acetylsalicylic acid. Aspirin and placebo study medication was packed in sachets of identical appearance. Patients, doctors, and trial nurses were blinded for these treatment allocations. Women allocated to receive open-label nadroparin 2850 IU s.c. received oral aspirin and started nadroparin injections when a viable intrauterine pregnancy was confirmed by ultrasound from 6 weeks of gestational age. Aspirin or placebo was given until 36 weeks of gestational age or stopped at time of miscarriage, ectopic pregnancy or premature delivery. LMWH was given throughout gestation and stopped 12 hours before delivery.The primary outcome measure was live birth rate. Secondary outcomes included miscarriage rate, uterine and umbilical blood flow profile and prevalence of obstetric complications. Differences in live birth rates will be expressed as relative risks and 95% confidence intervals with the placebo group as reference. Data were analyzed according to the intention-to-treat principle. Preliminary resultsBetween February 2004 and January 2008, 364 women were included in the trial. On July 1st 2009, 25 were not pregnant 2 years after inclusion, 16 were not pregnant, 8 were pregnant, 26 women had decided to withdraw from the study, and 3 had been included erroneously. The results presented in this abstract are based on a pre-scheduled interim analysis of 281 women who had reached an endpoint (live birth or miscarriage) on July 1st 2009.AspirinAspirin and nadroparinPlacebon=95n=91n=95Live birth, n (%)64 (67.4)65 (71.4)67 (70.5)Relative risk (95%CI)0.96 (0.79-1.16)1.01 (0.84-1.22)1 (reference)The live birth rate did not differ between women assigned to aspirin, aspirin combined with nadroparin, and placebo. The Data Safety Monitoring Board advised the Steering Committee of the ALIFE study that further continuation of the study was futile. At the time of submission of this abstract, the database is being finalized, with closure scheduled on October 1st 2009. We will present definite data, including those of the a priori defined subgroup of women with hereditary thrombophilia, at the ASH meeting in December 2009. ConclusionsAspirin, and aspirin combined with nadroparin did not improve the live birth rate in women with unexplained RM (Current Controlled Trial number, ISRCTN58496168).Funding: ZonMW, the Dutch Organization for Health Research and Development (945-27-003). Vemedia BV supplied study medication (calcium carbasalate and placebo). GlaxoSmithKline BV offered a grant. Funding sources were not involved in study protocol preparation, trial management or data analysis. Disclosures:Off Label Use: Calcium carbasalate (equivalent to acetyl salicylic acid) and nadroparin to prevent recurrent miscarriage.. Buller:GSK: Consultancy, Honoraria, Research Funding. Middeldorp:GSK: Consultancy, Honoraria, Research Funding.

No beneficial effect of preimplantation genetic screening in women of advanced maternal age with a high risk for embryonic aneuploidy

Human preimplantation embryos generated through in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments show a variable rate of numerical chromosome abnormalities or aneuploidies. Preimplantation genetic screening (PGS) has been designed to screen for aneuploidies in high risk patients, with the aim of improving live birth rates in IVF/ICSI. We assessed whether the effect of PGS on live births rates differs in women of advanced maternal age with variable risks for embryonic aneuploidy, and weighed these effects against the results obtained after IVF/ICSI without PGS. The effect of PGS on live birth rates was compared between groups defined by maternal age, number of previous miscarriages, semen quality, total amount of recombinant FSH (rFSH) administered during ovarian stimulation and total number of top-quality embryos, using data from a randomized controlled trial among women of advanced maternal age (35-41 years). There was no significant differential effect of PGS in groups based on maternal age (P-value of interaction 0.16), the number of previous miscarriages (P-value of interaction 0.93), semen quality (P-value of interaction 0.26), rFSH dose (P-value of interaction 0.15) or the number of top-quality embryos (P-value of interaction 0.59). Live birth rates after IVF/ICSI with PGS were lower in all groups when compared with live birth rates after IVF/ICSI without PGS. The paradigm that the effect of PGS is determined by a woman's risk for embryonic aneuploidy seems incorrect. In fact, PGS has no clinical benefit over standard IVF/ICSI in women of advanced maternal age regardless of their risk for embryonic aneuploidy.

Effect of infertility, maternal age, and number of previous miscarriages on the outcome of preimplantation genetic diagnosis for idiopathic recurrent pregnancy loss

To determine whether preimplantation genetic diagnosis (PGD) would decrease spontaneous abortion rates in patients with idiopathic recurrent pregnancy loss (RPL). Controlled clinical study. IVF center and PGD reference laboratory. Patients with RPL with no known etiology. Preimplantation genetic diagnosis by fluorescence in situ hybridization analyzing nine chromosomes. The spontaneous abortion rate after PGD was compared to the patients' own expected risk of abortion. Patients were evaluated according to the number of previous losses, fertility, and maternal age. Preimplantation genetic diagnosis significantly reduced spontaneous abortions in patients with RPL, especially for patients with more than two previous losses (12.8% vs. 35.9% expected). The PGD significantly reduced the rate of spontaneous abortion in both fertile (15.2% vs. 33.8% expected) and infertile patients (13.0% vs. 29.5%), which also achieved similar delivery rates (37% and 34%, respectively). The beneficial effect of PGD was less pronounced in patients <35 years than in patients > or =35 years old (13.6% vs. 34.0% expected). Overall, the PGD reduced the miscarriage rate to a similar baseline of 14%-16% across all maternal ages. Preimplantation genetic diagnosis improves pregnancy outcome for women with idiopathic RPL, especially those with more than two previous losses, and >35 years of age, and that improvement is not affected by fertility status.

Maternal use of loperamide in early pregnancy and delivery outcome

To study delivery outcome including presence of infant congenital malformations after maternal use of loperamide in early pregnancy. Using the Swedish Medical Birth Register, women reporting the use of loperamide in early pregnancy were compared with other women for the period July 1, 1995-2004. Odds ratios (OR) or risk ratios (RR) were estimated after adjustment for some variables, which were associated with the use of loperamide (year of delivery, maternal age, parity, smoking, number of previous miscarriages). Characteristics of women using loperamide in early pregnancy were identified. An analysis of concomitant drug use indicated that only few of the women had inflammatory bowel disease. The risk of any congenital malformation was increased (OR = 1.43, 95% CI 1.04-1.96), based on 43 cases, but no major contributing type could be identified. The risk of hypospadias was significantly increased (RR = 3.2, 95% CI 1.3-6.6), based on seven cases. A statistically significant increase was seen also for placenta previa, large for gestational age and caesarean section. Maternal use of loperamide in early pregnancy may be associated with a moderate risk increase for a malformation in the infant. The finding should be evaluated from other large studies.