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Predictors of ongoing implantation in IVF in a good prognosis group of patients.

BACKGROUND: The aim of this study was to investigate whether, in a large randomized trial, it is possible to identify specific maternal and/or embryo variables that could independently correlate with ongoing implantation in IVF/ICSI. METHODS: In a Scandinavian study, 661 women were randomized to elective single embryo transfer or double embryo transfer. Women aged <36 years undergoing their first or second IVF cycle and with at least two good quality embryos were eligible. Only one cycle per subject was included. In the present study, cycles with 0 or 100% ongoing implantation (n = 520) were analysed regarding maternal and embryo variables. RESULTS: In this selected study group, the ongoing implantation rate was 195/734 (26.6%). In the univariate analysis, first IVF cycle, conventional IVF as fertilization method and 4-cell embryos showed a statistically higher ongoing implantation rate than did second IVF cycle, ICSI and non-4-cell embryos. In the multivariate analysis the same variables correlated independently to ongoing implantation. In addition, ovarian sensitivity correlated independently to ongoing implantation. CONCLUSION: This information should be used when selecting the number of embryos for transfer with the overall aim to reduce the rate of multiple births while maintaining a satisfactory birth rate.

Adult↗

Chromosome mosaicism in 6,000 amniocenteses.

Multiple cell-multiple flask mosaicism was found in 0.20% of 6,000 amniocenteses, and multiple cell-single flask mosaicism was found in 0.92%. Multiple cell-multiple flask mosaicism usually was found in fetal or infant tissues at delivery or elective abortion. Most multiple cell-multiple flask mosaicism involved sex chromosomes and was either 45, X/46, XY or 45, X/46, XX. Except for one fetus with 45, X/46, XX and an aortic coarctation, phenotypic abnormalities associated with sex chromosome mosaicism were not found in these patients. One normal boy has continued to show 45,X mosaicism during the first 4 years of life. Autosome abnormalities found in multiple cell-multiple flask mosaicism included del(18q) associated with fetal anomalies. Apparently normal phenotypes were associated with prenatal trisomy 17, two de novo supernumerary marker chromosomes, and monosomy 21. Since an aberrant cell line present in only one primary amniotic fluid cell culture was occasionally identified from another amniocentesis or at birth, multiple cell-single flask mosaicism involving a sex chromosome or a viable autosome abnormality cannot be assumed to be an in vitro event. Maternal cell contamination, which was found in 0.49% of amniocenteses, could have resulted in an erroneous diagnosis of fetal sex in two cases if cells from independent culture vessels were not examined.

Amniocentesis↗

Maternal morbidity and obstetric complications in triplet pregnancies and quadruplet and higher-order multiple pregnancies.

OBJECTIVE: The purpose of this study was to assess the risk of maternal morbidity and obstetric complications in women with triplet pregnancies and quadruplet and higher-order multiple pregnancies. STUDY DESIGN: We compared the outcomes in women with triplet pregnancies (n=5491) and quadruplet and higher-order multiple pregnancies (n=423) with women with twin pregnancies (n=152,238), with the use of the 1995 to 1997 Multiple Birth File of the United States. RESULTS: After an adjustment was made for important confounding factors, the risks of pregnancy-associated hypertension and eclampsia, anemia, diabetes mellitus, abruptio placenta, premature rupture of membrane, and cesarean delivery were increased in women with triplet pregnancies and quadruplet and higher-order multiple gestations than in women with twin pregnancies. A dose-response relationship was observed for pregnancy-associated hypertension, diabetes mellitus, and placental abruption, with higher odds ratios in women with quadruplet and higher-order multiple gestations than in women with triplet pregnancies. CONCLUSION: The risks of maternal morbidity and obstetric complications are increased in triplet pregnancies and quadruplet and higher-order multiple pregnancies than in twin pregnancies; for certain outcomes, there is a dose-response relationship.

Abruptio Placentae↗

Risk factors for neonatal encephalopathy in Kathmandu, Nepal, a developing country: unmatched case-control study.

OBJECTIVE: To determine the risk factors for neonatal encephalopathy among term infants in a developing country. DESIGN: Unmatched case-control study. SETTING: Principal maternity hospital of Kathmandu, Nepal. SUBJECTS: All 131 infants with neonatal encephalopathy from a population of 21 609 infants born over an 18 month period, and 635 unmatched infants systematically recruited over 12 months. MAIN OUTCOME MEASURES: Adjusted odds ratio estimates for antepartum and intrapartum risk factors. RESULTS: The prevalence of neonatal encephalopathy was 6.1 per 1,000 live births of which 63% were infants with moderate or severe encephalopathy. The risk of death from neonatal encephalopathy was 31%. The risk of neonatal encephalopathy increased with increasing maternal age and decreasing maternal height. Antepartum risk factors included primiparity (odds ratio 2.0) and non-attendance for antenatal care (2.1). Multiple births were at greatly increased risk (22). Intrapartum risk factors included non-cephalic presentation (3.4), prolonged rupture of membranes (3.8), and various other complications. Particulate meconium was strongly associated with encephalopathy (18). Induction of labour with oxytocin was associated with encephalopathy in 12 of 41 deliveries (5.7). Overall, 78 affected infants (60%) compared with 36 controls (6%) either had evidence of intrapartum compromise or were born after an intrapartum difficulty likely to result in fetal compromise. A concentration of maternal haemoglobin of less than 8.0 g/dl in the puerperium was significantly associated with encephalopathy (2.5) as was a maternal thyroid stimulating hormone concentration greater than 5 mIU/l (2.1). CONCLUSIONS: Intrapartum risk factors remain important for neonatal encephalopathy in developing countries. There is some evidence of a protective effect from antenatal care. The use of oxytocin in low income countries where intrapartum monitoring is suboptimal presents a major risk to the fetus. More work is required to explore the association between maternal deficiency states and neonatal encephalopathy.

Body Height↗

Triplet births in the United States. An epidemic of high-risk pregnancies.

OBJECTIVE: To more precisely understand the changes in triplet births in recent years. STUDY DESIGN: Analysis of recent government and medical publications pertaining to triplets. RESULTS: Triplet births are at much greater risk than singletons of poor birth outcomes. More than 9 of 10 triplet births are born preterm (< 37 completed weeks of gestation) as compared with < 1 of 10 singleton infants. The average weight of a triplet newborn (1,698 g) is one-half that of a singleton newborn (3,358 g). The infant death rate for triplet and other higher-order multiple births is 12 times higher than that for singletons (93.7 as compared with 7.8 infant deaths per 1,000 live births). CONCLUSION: Based on their frequency of preterm birth, low birth weight and infant death rate, it is appropriate to characterize all triplet pregnancies as high risk.

Adult↗

Differences in the obstetric practices of obstetricians and family physicians in Washington State.

In response to the obstetric malpractice crisis, both obstetrician-gynecologists and family physicians have raised their fees and preferentially selected lower risk patients. In addition, large numbers of general and family physicians have left obstetric practice altogether. The impact of these responses was explored by examining the differences in the demographic and clinical profile of patients served by these two disciplines in the State of Washington. Eighty-five percent (45,540) of all complete records from 1983 births attended by physicians in the State of Washington were matched to physician specialty information. These births represent 67% of the total deliveries in Washington State in 1983. Although twice as many general and family physicians as obstetricians were practicing obstetrics, obstetricians delivered 2.5 times as many infants as did general and family physicians. Obstetricians served an older patient population with more low-birthweight infants, multiple births, and complications of pregnancy than family physicians. General and family physicians were more likely to care for minorities, teenagers, and unmarried and rural mothers. Obstetricians cared for patients with higher medical risks, whereas general and family physicians provided care to more socially vulnerable and geographically isolated populations. To the extent that general and family physicians are differentially abandoning obstetric practice because of the current malpractice crisis, access to care for rural and socially vulnerable groups may deteriorate rapidly.

Adolescent↗

Treatment of unexplained infertility. Fallopian tube sperm perfusion (FSP).

PATIENTS AND METHODS: Fifty-one couples with unexplained infertility were enrolled in the fallopian tube sperm perfusion (FSP) program. FSP is in short a combination of ovarian hyperstimulation, ovulation induction and intrauterine and intrafallopian tube insemination using a sperm suspension of 4 ml volume. RESULTS: One hundred cycles were started; 93 of these were completed, resulting in 27 pregnancies (29.0% per cycle). The pregnancy rate in the first treatment cycle (41.2%) was significantly higher than in the subsequent treatment cycles (14.3%, p < 0.01). Total pregnancy loss was 22.2% (2 ectopic pregnancies and 4 spontaneous abortions). The multiple birth rate was 14.2% (two sets of twins and one set of triplets). Twenty-two couples not conceiving following a maximum of three FSP treatment, were offered IVF treatment. Forty-three IVF cycles were started resulting in 27 embryo replacements in 15 patients. Seven pregnancies occurred in six couples. In 11 of the couples treated, IVF treatment revealed a possible explanation for the infertility; development of multiple small follicles following ovarian hyperstimulation, empty follicle syndrome and partial or total fertilization failure. Only in five of the couples who did not conceive, no cause for the infertility could be found. CONCLUSIONS: In the treatment of couples with unexplained infertility, the FSP procedure seems to give a birth rate of about 40% in less than two treatment cycles. FSP is less invasive and less expensive than alternative procedures such as GIFT, ZIFT and IVF and does not require the expertise and facilities for culturing of human oocytes and embryos.

Fallopian Tubes↗

[Influence of the mode of delivery on perinatal mortality in infants less than 32 weeks gestational age].

Survival rate of 96 low-birth-weight infants less than 32 weeks post-conceptional age at birth was studied in relation with the mode of delivery. Twenty-two infants were delivered by elective cesarean section because of abnormalities during pregnancy with 3 neonatal deaths. Seventy-four infants were born after untreatable premature onset of labor with 9 intrapartum and 7 neonatal deaths. Poor prognosis was associated with gestational age (less than 29 weeks), non cephalic vaginal delivery and multiple births. In these cases, cesarean section should be discussed.

Delivery, Obstetric↗

[Informing the patient about alternative surgical methods of delivery].

The article discusses a judgment passed by the Düsseldorf Supreme Court on 30 January 1986. An obstetrician had resorted to vacuum extraction during multiple birth (twins) because one twin was in imminent danger of hypoxia. It was found only later that during this procedure he had caused a fracture of the parietal bone with subsequent subdural hematoma. This damage inflicted on the infant had initially remained unnoticed and resulted in hemiplegia of the left side. The infant, legally represented by his parents, filed a suit for compensation against the Board of Governors of the hospital. The Düsseldorf Supreme Court ruled on 30 January 1986 that the respondent was liable to compensation. The Court was convinced that the consent obtained from the infant's mother to proceed with vacuum extraction had been invalid at that time because the physician had failed to draw her attention beforehand to the available alternative surgical method of delivery, namely, to Caesarean section. Hence, the Court argued, the procedure followed during birth was against the law so that the Board of Governors was directly liable independent of whether the responsible obstetrician had or had not been guilty of malpractice. In addition, the liability of the Board of Governors follows from the fact that the infant had not been examined by a paediatrician immediately after birth as would have been mandatory had delivery been conducted lege artis.(ABSTRACT TRUNCATED AT 250 WORDS)

Extraction, Obstetrical↗

Multiple gestation and infertility treatment: registration, reflection and reaction--the Belgian project.

Multiple pregnancies associated with infertility treatment are recognized as an adverse outcome and are responsible for morbidity and mortality related to prematurity and very low birthweight population. Due to the epidemic of iatrogenic multiple births, the incidence of maternal, perinatal and childhood morbidity and mortality has increased. This results in a hidden healthcare cost of infertility therapy and this may lead to social and political concern. Reducing the number of embryos transferred and the use of natural cycle IVF will surely decrease the number of multiple gestations. Consequently, optimized cryopreservation programmes will be essential. For non-IVF hormonal stimulation, responsible for more than one-third of all multiple pregnancies after infertility treatment, a strict ovarian stimulation protocol aiming at mono-ovulation is crucial. Multifetal pregnancy reduction is an effective method to reduce high order multiplets but carries its own risk of medical and emotional complications. Excellent data collection of all infertility treatments is needed in our discussion with policy makers. The Belgian project, in which reimbursement of assisted reproduction technology-related laboratory activities is linked to a transfer policy aiming at substantial multiple pregnancy reduction, is a good example of cost-efficient health care through responsible, well considered clinical practice.

Belgium↗

Prenatal and neonatal risk factors for childhood lymphatic leukemia.

BACKGROUND: Because the incidence of childhood acute lymphatic leukemia peaks between 2 and 4 years of age, the risk factors may exert their influence during the prenatal and/or the neonatal periods. Results of previous studies of perinatal risk factors have been contradictory, perhaps because most studies either have been hospital based or have been restricted to limited geographical areas. PURPOSE: A nationwide case-control study was carried out to identify maternal and perinatal risk factors for this disease. METHODS: The case-control study was nested in cohorts defined by all live births in Sweden recorded in the nationwide Medical Birth Register. Since 1973, this register has routinely collected information on all hospital births in regard to maternal demographic data, reproductive history, pregnancy, delivery, and the neonatal period. From the Swedish National Cancer Register, 613 case subjects were identified in successive birth cohorts from 1973 through 1989. Five control subjects per case subject were randomly selected from the pool of children matched by sex and month and year of birth. Conditional logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for potential risk factors and to estimate their effects after adjustment for possible confounders. RESULTS: Risk of childhood lymphatic leukemia at all ages increased with Down's syndrome (OR = 20.0; 95% CI = 4.2-94.2), maternal renal disease (OR = 4.4; 95% CI = 1.6-12.1), use of supplementary oxygen (OR = 2.3; 95% CI = 1.5-3.6), postpartum asphyxia (OR = 1.8; 95% CI = 1.2-2.6), birth weight of more than 4500 g (OR = 1.7; 95% CI = 1.1-2.7), and hypertensive disease during pregnancy (OR = 1.4; 95% CI = 1.0-1.9). Down's syndrome affected risk mostly in children younger than 5 years, whereas other factors affected those children 5 years old or older. Being one of a multiple birth also increased risk among older children (OR = 2.5; 95% CI = 1.0-6.0). Use of supplementary oxygen may act as a causal intermediate (surrogate) for postpartum asphyxia and its causes, as would high birth weight for its causes. CONCLUSIONS: Several maternal and perinatal risk factors were found to be associated with childhood lymphatic leukemia, but they showed age-specific differences. Overall, only a few risk factors were identified, and these accounted for a small proportion of cases. We concluded that most risk factors for childhood lymphatic leukemia remain unidentified in very young children.

Case-Control Studies↗

Prediction of fetal growth deviation by ultrasonic biometry. I. Methodology.

Early information of impaired or accelerated fetal growth is of importance for antenatal care. The present study has produced a mathematical formula which in the 33rd week of pregnancy permits prediction of fetal weight deviation at birth. The prediction was based on two ultrasonic examinations: in the 17th week of pregnancy the biparietal diameter (BPD) was measured to assess the fetal gestational age; in the 33rd week of pregnancy, BPD and the abdominal diameter (AD) of the fetus were measured. Fetal growth deviation was then described by comparing the assessed BPD and AD with the expected mean values for the gestational age on the day of this measurement. For 872 fetuses the growth deviation found in the 33rd week was related to the fetal weight deviation at birth; multiple regression analyses were performed and a mathematical formula developed. For practical purposes this formula is expressed in a nomogram.

Abdomen↗

The NICHD neonatal research network: changes in practice and outcomes during the first 15 years.

The National Institute of Child Health and Human Development (NICHD) Neonatal Research Network was founded in 1986 to perform trials that, because of their size and complexity, were beyond the scope of a single center and required the expertise and resources of many collaborating centers. This report briefly documents changes in mortality, selected morbidities, and therapies amongst Network centers. The Network registry incorporating perinatal and neonatal data on all infants with a birth weight 501-1500 g cared for at participating centers served as the database. Mortality and selected morbidities were compared for 3 time periods, 1987/1988, (7 centers 1,765 infants, presurfactant); 1993/1994 (12 centers, 4,593 infants, postsurfactant and moderate antenatal corticosteroid utilization); and 1999/2000 (15 centers, 5,848 infants, postsurfactant and widespread corticosteroid use). Detailed outcomes for infants with birth weights between 501 and 800 g, and gestational ages of 23 to 25 weeks are also presented because they dramatically document the changes over time. Mortality for the entire cohort decreased from 23% in 1987/1988 to 17% in 1993/1994 and 14% in 1999/2000. Between 1987/1988 and 1999/2000 mortality prior to discharge, decreased from 66% to 45% for infants weighing 501-750 g; from 34% to 12% for birth weight between 751 to 1000 g, and from 13% to 7% for infants between 1001 and 1500 g. Mortality was higher in boys. Survival free of major morbidity (chronic lung disease/bronchopulmonary dysplasia, necrotizing enterocolitis or grade III/IV intraventricular hemorrhage) did not change significantly over time. Since the inception of the Network, multiple births have increased from 18% to 26%; deliveries by Cesarean section from 47% to 57%, and antenatal corticosteroid use increased from 16% to 79%. Surfactant, which was not used prior to 1990, is now given to 57% of the infants, including 87% with birth weights between 501 and 750 g. There have been significant decreases in the incidence of grade III-IV intraventricular hemorrhage from 18% in 1987/1988 to about 11% since 1993/1994, and periventricular leukomalacia from 8% to 3%. However, other morbidities, including necrotizing enterocolitis, patent ductus arteriosus, and late onset sepsis, have not changed substantially. Advances in perinatal care within NICHD Network centers have resulted in marked improvements in survival. Further advances are required to increase survival free of neonatal morbidity or neurodevelopmental impairment.

Databases, Factual↗

Adverse neurodevelopmental outcomes among extremely low birth weight infants with a normal head ultrasound: prevalence and antecedents.

OBJECTIVE: Severe abnormalities of the head ultrasound (HUS) are important predictors of cerebral palsy (CP) and mental retardation, and a normal HUS usually ensures the absence of major impairments. With the increasing survival of extremely low birth weight (ELBW) infants (birth weight <1000 g), the prognostic significance of a normal HUS may differ. This study examined the prevalence of and risk factors for CP and impaired mental development among ELBW infants with a normal HUS. METHODS: Study infants were ELBW infants who were cared for in Neonatal Research Network centers in the years 1995-1999, had a normal early and late HUS, survived to discharge, and returned for follow-up assessments at 18 to 22 months' corrected age. The outcomes of interest were a score <70 on the Bayley Scales of Infant Development-II Mental Developmental Index (MDI) and CP. Risk factors included maternal demographics; infant characteristics; and interventions or morbidities related to the lung, infection, and nutrition. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A time-oriented approach was used to select variables for inclusion in logistic models. RESULTS: Of 1749 infants with a normal early and late HUS (performed at a mean age of 6 and 47 days, respectively), 1473 (84%) returned for follow-up assessment. Infants had a birth weight of 792 +/- 134 g (mean +/- SD) and gestational age of 26 +/- 2 weeks. Rates of CP and MDI <70 were 9.4% and 25.3%, respectively, and 29.2% of infants had either CP or MDI <70. In multivariate analyses, factors associated with CP were male gender (OR: 1.8; 95% CI: 1.2-2.6), multiple birth, (OR: 1.6; 95% CI: 1.1-2.5), decreasing birth weight (OR: 1.3 for each 100-g decrease; 95% CI: 1.1-1.5), pneumothorax (OR: 2.3; 95% CI: 1.2-4.4), and days of conventional ventilation (OR: 1.2 for each additional 10 days; 95% CI: 1.1-1.3). With the exception of pneumothorax, these same factors were associated with MDI <70, in addition to less maternal education (OR: 1.4; 95% CI: 1.0-1.9) and Medicaid or lack of coverage for maternal insurance (OR: 1.7; 95% CI: 1.2-2.4). CONCLUSIONS: Nearly 30% of ELBW infants with a normal HUS had either CP or a low MDI. Risk factors that are associated with this high rate of adverse outcomes include pneumothorax, prolonged exposure to mechanical ventilation, and educational and economic disadvantage. Improvements in pulmonary care to reduce duration of ventilation and avoid air leaks might improve neurodevelopmental outcome for ELBW infants.

Cerebral Palsy↗

[Roaming through the methodology. XXVIII. More problems with longitudinal studies: dropouts, head-start effects and interval correlations].

The Amsterdam Growth and Health Longitudinal Study with about 300 teenage boys and girls illustrates a number of problems that can occur in a longitudinal study. By adopting a more complex study design (multiple birth cohorts and a separate control group without longitudinal measurements) confounding factors may be found. A problem with the longitudinal design are the dropouts: by comparing their study results in the period before the dropout with the results of the 'stayers' in the same period, selective dropout may be identified. In a multiple longitudinal design with overlapping cohorts, head-tail effects may occur: the most reliable results are found in the middle area where there is the most overlap. Interperiod correlations may assist in determining the stability and the accuracy of the measurements.

Adolescent↗

New technology and new challenges for assisted reproduction.

As assisted reproduction technology advances, more types of procedures are becoming available, bringing more success at solving many types of infertility. In vitro fertilization has become simpler and less invasive, with success rates as high as 30% per cycle. Intracytoplasmic sperm injection has solved many types of male infertility. This article explains in vitro fertilization technology and discusses such ethical issues as embryo ownership, multiple births, and embryo genetic testing.

Adult↗

Sri Lankan Twin Registry.

Sri Lanka is an island with genetic diversity between the five main population groups. Our twin registry is the first in the developing world. Initially, we established a volunteer cohort of 4600 twin pairs through a competition advertised in the media. In addition, we have volunteer cohorts, birth registration-based cohorts through hospitals, and community-based cohorts. There is also a nationwide population-based younger twin cohort (1992-1997) traced through the Department of Birth and Death Registration. Additionally, we have adapted a Zygosity determination questionnaire and validated it. Establishing ethical guidelines for twin research was a priority because the field of bio-ethics is at an early stage of development in Sri Lanka. These guidelines were from a developing world perspective. A sister organization, the Multiple Birth Foundation, was formed to cater to twins and their special needs and to represent their interests, and several branches have been formed. We intend to build capacity by establishing a genetic lab and through crosscultural collaboration. Our vision is to establish a multidisciplinary research foundation. Based on our research findings, we plan to build services to cater to needs of twins by working with professionals, statutory services and government policy makers.

Birth Certificates↗

Perinatal events in the Dunedin City population 1967-1973.

The incidence of an array of maternal, obstetric and neonatal events occurring in the Dunedin City population in the six years from 1 August 1967 is presented. This population was not truly representative of the total New Zealand population. The total births in Dunedin City were 10,091 and the perinatal mortality was 17.5 per 1000 total births. Some of the pertinent findings were: 8.8 percent of the mothers were either not married or were not living with their husbands; 36.5 percent were primigravida; 13.2 percent of mothers were less than 20 years of age; 9.6 percent of mothers had an adverse past obstetric history; 11.5 percent had a diastolic blood pressure in excess of 90mmHg during the pregnancy; 5.0 percent had an antepartum haemorrhage of which 45.4 percent occurred in the first trimester; 6.5 percent of newborns were non-European; 2.0 percent were multiple births; 0.8 percent had a single umbilical artery; in 27.4 percent the delivery was not spontaneous; 6.2 percent had a low birth weight; 4.0 percent were born preterm; 5.2 percent of newborns experience neonatal complications; 2.1 percent had a major, and 6.4 percent a minor congenital fault.

Birth Weight↗