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Cumulative probability of clinical pregnancy and live birth after a multiple cycle IVF package: a more realistic assessment of overall and age-specific success rates?

OBJECTIVE: To provide an assessment of pregnancy and live birth probabilities for women presenting for in vitro fertilisation treatment for the first time, when committed in advance to have up to three cycles of treatment in one year. DESIGN: Up to three cycles of in vitro fertilisation within one year, committed in advance. SETTING: A tertiary referral centre for assisted reproduction. PARTICIPANTS: Two hundred and thirty-two women, undergoing a total of 536 cycles of in vitro fertilisation or intracytoplasmic sperm injection between August 1993 and December 1995. METHODS: Analysis of cumulative clinical pregnancy and live birth rates for women having IVF treatment for the first time and undertaking a three-cycle package, using the life-table approach. MAIN OUTCOME MEASURES: Cumulative clinical pregnancy and live birth rates. RESULTS: The cumulative probabilities of clinical pregnancy and live birth after two cycles of treatment were 38.2% and 33.2%, respectively, compared with 54.2% and 48.2%, respectively, after three cycles of treatment. Cumulative clinical pregnancy and live birth rates after three cycles of treatment for women up to the age of 40 years were 57.8% and 51.3%, respectively. Cumulative clinical pregnancy and live birth rates declined with increasing age (P = 0.02 and P= 0.01, respectively). CONCLUSION: The three-cycle package encourages couples to have multiple treatment cycles, thereby improving their ultimate chances of a live birth. The cumulative clinical pregnancy and live birth rates after such a package provide a more realistic assessment of overall and age-specific success rates after multiple treatment cycles.

Adult↗

Outcome of very low birth weight infants: multiple gestation versus singletons.

OBJECTIVE: Multiple gestation infants are overrepresented in intensive care nurseries, and have been reported to have greater morbidity than singletons. A cohort of very low birth weight infants was examined to determine outcome of premature infants based on gestation type (multiple or single) and hypothesized that at this low birth weight, the outcome of the groups would be similar. METHOD: The sample was composed of all infants with birth weights < or = 1250 g born in a 10-year period (September 1977 through September 1987). Ninety-two percent (n = 364) of the infants discharged were seen at 1 year of age, and 73% (n = 249) were observed to school age. Morbidity was assessed by neurodevelopmental examinations and standard developmental tests. RESULTS: At 1 year of age and at school age, there were no differences in neurologic or neurosensory outcome between multiple gestation and single gestation infants. Logistic regression analyses were performed on the school age data, using cognitive outcome as the dependent variable and gestation type, birth weight, gestational age, intracranial hemorrhage, chronic lung disease, and a social risk factor as predictor variables. Gestation type was not associated with cognitive outcome at school age. Social risk factors and chronic lung disease showed an association with cognitive outcome at school age. CONCLUSIONS: Multiple gestation was not related to increased morbidity in this very low birth weight group. The developmental outcome of all infants with birth weights < or = 1250 g in this study was related to medical and social risk factors. These findings were consistent for a large group of infants over a 10-year period.

Developmental Disabilities↗

Cumulative first live birth after elective cryopreservation of all embryos due to ovarian hyperresponsiveness.

OBJECTIVE: To estimate cumulative chance for first live birth after elective pronuclear stage cryopreservation of all embryos due to ovarian hyperresponsiveness. DESIGN: Retrospective analysis with longitudinal follow-up. SETTING: Academic hospital. PATIENT(S): Thirty subjects with elective cryopreservation of all embryos due to ovarian hyperresponsiveness. INTERVENTION(S): Elective cryopreservation of all embryos at the pronuclear stage (n = 30) and subsequent cryopreserved-thawed ET (n = 51). MAIN OUTCOME MEASURE(S): Cumulative chance for first live birth. RESULT(S): Cumulative chance for first live birth was 77% when analyzed by intention to treat and 82% by treatment with ET. Nearly 40% of live births were multiple. CONCLUSION(S): Cumulative first live birth increased with repetitive ET after elective pronuclear stage cryopreservation of all embryos due to ovarian hyperresponsiveness. Multiple births, however, were frequent. In the context of initial ET attempts in young women, transfer of no more than two cryopreserved-thawed embryos is advised.

Adult↗

Birth cohort effects in multiple sclerosis.

PURPOSE: To identify potential birth cohort effects in multiple sclerosis in Sweden and particularly in Stockholm county. METHODS: Data on multiple causes of death from multiple sclerosis during 1962 to 1995 in Sweden and 1968 to 1995 in Stockholm county were analyzed using age-period-cohort models and curvature. RESULTS: Mortality from multiple sclerosis was higher in Sweden than in Stockholm county, with stable time trends, slight period effects and marked age effects. Cohorts born before or after a central period, from 1910 through 1930, registered lower mortality. A periodic wave-form mortality pattern was identified, following a 5-to-6-year cycle for cohorts born before 1925 both in and outside Stockholm county, and changing to longer or irregular cycles for cohorts born after 1930. CONCLUSIONS: Although methodological constraints inducing the saw-tooth pattern cannot be excluded, these results are consistent with etiologic hypotheses claiming a role for environmental factors in multiple sclerosis.

Adult↗

Multiple sclerosis and birth order: a longitudinal cohort study.

BACKGROUND: Genetic epidemiological studies suggest both genetic and environmental factors have a role in multiple sclerosis (MS). Environmental effects are strongly suggested from geographical gradients, migration data, and discordance rates in twins. In epidemiological studies, risk of MS in offspring of small families and in those with an early birth-order position has been reported and interpreted in the context of the hygiene hypothesis, which is that infections at an early age, introduced by older siblings, are protective. We aimed to study the effect of birth order on MS risk. METHODS: A longitudinal, population-based sample of individuals with MS and their healthy siblings were identified from the Canadian Collaborative Project on Genetic Susceptibility to MS. Data were grouped according to single (simplex) or multiple (multiplex) siblings with MS in a sibship. Separate analyses were done for each sibship size. FINDINGS: We studied 10 995 individuals with MS and 26 336 healthy siblings, and found no relation between MS risk and birth-order position. In simplex sibships of at least seven siblings, slightly more siblings who were born late in the birth order had MS; the same was found for the first-born sibling with MS in a multiplex sibship. Siblings with MS were slightly younger (p<0.0001) than those without MS, contrary to the expected age at onset bias. INTERPRETATION: These findings do not support the hygiene hypothesis and could be due to a cohort effect resulting from increasing MS incidence. Birth order has no effect on MS risk in most families, and there is no support for the hypothesis that having older siblings protects against MS.

Birth Order↗

Children conceived by in vitro fertilisation after fresh embryo transfer.

AIMS: To compare the outcome in in vitro fertilisation (IVF) children (after fresh embryo transfer) from multiple and singleton births with one another, and with normally conceived control children. METHODS: A cohort of 278 children (150 singletons, 100 twins, 24 triplets and four quadruplets), conceived by IVF after three fresh embryos had been transferred, born between October 1984 and December 1991, and 278 normally conceived control children (all singletons), were followed up for four years after birth. They were assessed for neonatal conditions, minor congenital anomalies, major congenital malformations, cerebral palsy and other disabilities. Control children, all born at term, were matched for age, sex and social class. RESULTS: The ratio of male:female births was 1.03. Forty six per cent of IVF children were from multiple births; 34.9% were from preterm deliveries; and 43.2% weighed less than 2500 g at birth. The IVF singletons were on average born one week earlier than the controls, weighed 400 g less, and had a threefold greater chance of being born by caesarean section. The higher percentage of preterm deliveries was largely due to multiple births and they contributed to neonatal conditions in 45.0% of all IVF children. The types of congenital abnormalities varied: 3.6% of IVF children and 2.5% of controls had minor congenital anomalies, and 2.5% of IVF children and none of the controls had major congenital malformations. The numbers of each specific type of congenital abnormality were small and were not significantly related to multiple births. IVF children (2.1%) and 0.4% of the controls had mild/moderate disabilities. They were all from multiple births, including two children with cerebral palsy who were triplets. CONCLUSIONS: The outcome of IVF treatment leading to multiple births is less satisfactory than that in singletons because of neonatal conditions associated with preterm delivery and disabilities in later childhood. A reduction of multiple pregnancies by limiting the transfer of embryos to two instead of three remains a high priority.

Cerebral Palsy↗

Breastfeeding triplets: the at-home experience.

The unprecedented rise in higher-order multiple (HOM) births and the subsequent increase in parents who want to breastfeed their babies presents community health nurses (CHNs) with complex challenges. The extraordinary diversity of the triplet breastfeeding experience once all infants are settled at home is illustrated through findings from a survey of nine mothers of triplets. Parents revealed how they managed the feedings over the multiples' first year: type of feedings (breast, expressed breast milk [EBM], formula); scheduled and demand feedings; adequacy of milk supply; frequency and duration of feedings; consecutive and simultaneous feedings; nighttime with three; weaning; effects of breastfeeding on their bodies and well-being; challenges and stresses; and spousal, family, and health professional attitudes and support. A number of strategies that CHNs can utilize are suggested. These include working with individual families as well as forming partnerships with parents of multiples' support groups, multiple birth associations, interested health professionals, and the community sector. It is through these actions that the accessibility, coordination, and quality of health, multiple birth education, and social support services can be strengthened and healthy public policies implemented which address the unique and enormous demands experienced by HOMs' families.

Breast Feeding↗

[Mortality and rate of low birth weight in multiple pregnancies--some statistical problems].

By means of statistical methods there will be demanded the increased rate of prematures and mortality of multiple pregnancies. Mortality by birthweight and percentiles by birthweight to gestational age are used at this study. The special position of multiple pregnancies has been discussed and compared with singletons related to the different distribution of birthweight and the associated problems.

Birth Weight↗

Patterns and trends of multiple congenital anomalies in birth defects surveillance systems.

Infants with multiple congenital anomalies (MCA) can provide important clues in the detection of teratogenic agents. Definition, classification, and ascertainment of MCA vary, however. We present comparative epidemiologic data on MCA from two U.S. surveillance systems: the Metropolitan Atlanta Congenital Defects Program, which ascertains major birth defects during the first year of life, and the Birth Defects Monitoring Program, a nationwide system that relies on newborn hospital-discharge diagnoses. This system has two components: the Commission on Public Hospitals Activities (CPHA) and the McDonnell Douglas Health Information System (MDHIS). Our analyses were based on over 600,000 births occurring in Atlanta, and over 5 million births occurring nationwide. Infants were classified as having MCA if they had two or more major defects from different categories (central nervous system, eye, orofacial, gastrointestinal, cardiovascular, genitourinary, and musculoskeletal). Additional analyses were also done on infants with three or more defects. Compared with the nationwide system, Atlanta showed 1) a much higher rate of MCA (16.2 per 10,000 births vs. 4.9 and 3.8 per 10,000 births in CPHA and MDHIS, respectively) and 2) a higher rate of MCA with chromosomal syndromes (2.0 per 10,000 births vs. 0.6 and 0.3 per 10,000 births in CPHA and MDHIS, respectively). Moreover, in Atlanta, the proportion of MCA with recorded chromosomal syndromes increased substantially during 20 years. These data point to differences in the ascertainment of MCAs in birth defects surveillance systems. More effort is needed to improve the ascertainment and comparability of MCA in surveillance systems, an important step toward better detection of human teratogens.

Abnormalities, Drug-Induced↗

An epidemiologic study of neural tube defects in Los Angeles County I. Prevalence at birth based on multiple sources of case ascertainment.

Epidemiologic studies of the neural tube defects (NTDs), anencephalus and spina bifida, have for the most part been based on single sources of case ascertainment in past studies. The present investigation attempts total ascertainment of NTD cases in the newborn population of Los Angeles County residents for the period 1966-1972. Design of the study, sources of data, and estimates of prevalence rates based on single and multiple sources of case ascertainment are here discussed. Anencephalus cases totaled 448, spina bifida 442, and encephalocele 72, giving prevalence rates of 0.52, 0.51, and 0.08 per 1000 total births, respectively, for these neural tube defects--rates considered to be low. The Los Angeles County prevalence rates are compared with those of other recent North American studies and support is provided for earlier suggestions of low rates on the West Coast.

Anencephaly↗

The type of catheter has no impact on the pregnancy rate after intrauterine insemination: a randomized study.

BACKGROUND: This study was done to test the hypothesis that intrauterine insemination (IUI) using a soft-tip catheter results in a higher live birth rate than IUI using a hard-tip catheter. METHODS: Five hundred and forty patients were randomized into those inseminated with a soft-tip catheter (group 1, n = 267) and those inseminated with a hard-tip catheter (group 2, n = 269). Four patients were excluded. Main outcome measures included pregnancy rate and live birth rate per cycle. RESULTS: Both groups were similar with regard to female age, duration of infertility, ovarian stimulation and sperm quality. No significant differences were observed between group 1 and group 2 regarding clinical pregnancy rate per cycle (20 versus 19%), live birth rate per cycle (15 versus 14%), multiple live birth rate per cycle (4 versus 6%) and multiple live birth per total of live births (5 versus 8%, overall 6%), respectively. CONCLUSION: Our hypothesis that IUI using a soft tip catheter results in a higher live birth rate per cycle than IUI using a hard-tip catheter was not confirmed in this study. Multiple live birth rate after treatment with low-dose gonadotrophins and IUI can be kept low (6%).

Age Factors↗

Impaired adrenocortical function in very low birth weight infants after multiple pregnancies.

OBJECTIVE: To evaluate the differences in adrenal function between very low birth weight (VLBW) infants from singleton and multiple pregnancies. DESIGN AND METHODS: Forty infants of birth weights less than 1500 g underwent an ACTH test. Thirty infants born from singleton pregnancies (singleton group) and ten born from multiple pregnancies (multiple group) were enrolled. A baseline blood sample was drawn for cortisol measurement and thereafter serum cortisol was measured 1 and 2 h after an i.v. injection of ACTH. RESULTS: In multiple pregnancies, the median basal cortisol level of the infants was significantly lower than that in the singletons. The median cortisol level at 1 and 2 h after administration of ACTH was significantly lower in infants from multiple gestations than in singletons. Of infants from the multiple gestation group six, and of the singleton infants 12, had baseline cortisol levels lower than the reference values (P=0.48). One hour after ACTH stimulation all multiple and 53% of the singleton group infants showed a subnormal (<500 nmol/l, P=0.007) cortisol response. Two hours after ACTH, nine multiple group patients and 43% of the singletons had subnormal (<500 nmol/l, P=0.01) stimulated cortisol levels. CONCLUSIONS: We have concluded that VLBW infants from multiple gestations seem to be at an increased risk of insufficient postnatal adrenocortical function. In the future, specific attention should be paid to evaluate further newborn infants from multiple pregnancies with regard to a possible benefit of hydrocortisone substitution in stressful clinical situations.

Adrenal Cortex↗

RHD maternal-fetal genotype incompatibility and schizophrenia: extending the MFG test to include multiple siblings and birth order.

Rh incompatibility disease (ie Rh hemolytic disease of the fetus and newborn) has been implicated as a risk factor for schizophrenia. Here, we extend the maternal-fetal genotype incompatibility (MFG) test used in an earlier case-parent trio study that found significant evidence for an increased risk of schizophrenia in RHD MFG-incompatible children. We modify the MFG test for case-parent trios to include any number of siblings. This modified test enables us to use more of the available data from the earlier study. The increased sample size not only gives us greater power to test for MFG incompatibility but it also enables us to model the impact of previous RHD MFG-incompatible pregnancies on the relative risk of RHD MFG incompatibility in later-born siblings. This modeling is important, because RHD MFG incompatibility is a proxy for Rh incompatibility disease, and the risk of Rh incompatibility disease increases with the number of previous RHD MFG-incompatible pregnancies. The best-fitting models are consistent with the hypothesized effect that previous incompatible pregnancies increase the risk of schizophrenia due to RHD MFG incompatibility. There was significant evidence that the relative risk of schizophrenia in the second- and later-born RHD MFG-incompatible children is 1.7, consistent with earlier estimates. Our extension of the MFG test has general application to family-based studies of maternal-genotype and MFG interaction effects.

Birth Order↗

Predicting late-onset growth abnormalities using growth velocity between trimesters.

OBJECTIVES: To determine whether growth velocity parameters derived from routine prenatal ultrasound measurements at first, second and third trimester can identify normal growth at term as well as late-onset growth abnormalities. MATERIAL AND METHODS: Longitudinal study of fetal growth in normal singleton pregnancies with three normal ultrasound examinations and delivered at term. Fetuses were classified into 3 groups (<10th percentile, 10-90th percentile, >90th percentile) based on birth weight. Multiple regression on birth weight classification was used to build up a prediction equation of fetal growth potential (FGP) based on fetal biometry and fetal growth velocity parameters between ultrasound examinations. Best cut-off value for FGP predicting growth restriction and macrosomia were defined. RESULTS: 356 pregnancies were included. Fetal biometry growth velocities between examinations were calculated for all measurements. Using best cut-off values, the estimated sensitivity, specificity and odds ratio were: 60% [44;74], 91% [89;92] and 14.55 [6.30;33.98] and 53% [36;69], 89% [88;91] and 10 [4.27;23.49] for the prediction of growth restriction and macrosomia, respectively. DISCUSSION: Fetal growth potential can be derived and calculated from standard ultrasound measurements. It can improve identification of these fetuses at risk for late-onset growth abnormalities and their related morbidity.

Adolescent↗