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ABSTRACT: The aim of this study was to determine the incidence of congenital malformations in a complete cohort of children born after intracytoplasmic sperm injection (ICSI). The medical records were retrieved for 1139 infants, 736 singletons, 200 sets of twins and one set of triplets. The total number of infants with an identified anomaly was 87 (7.6%), 40 of which were minor. The incidence of malformations in children born after ICSI was also compared with all births in Sweden using data from the Swedish Medical Birth Registry and the Registry of Congenital Malformations. For ICSI children, the odds ratio (OR) for having any major or minor malformation was 1.75 [95% confidence interval (CI) 1.19-2.58] after stratification for delivery hospital, year of birth and maternal age. If stratification for singletons/twins was also done, the OR was reduced to 1.19 (95% CI 0.79-1.81). The increased rate of congenital malformations is thus mainly a result of a high rate of multiple births. The only specific malformation which was found to occur in excess in children born after ICSI was hypospadias (relative risk 3.0, exact 95% CI 1. 09-6.50) which may be related to paternal subfertility.
Human Reproduction 05/2000; 15(4):944-8. · 4.47 Impact Factor
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ABSTRACT: Premature birth is associated with increased perinatal morbidity and mortality. Spontaneous premature birth can be understood as a syndrome with a number of underlying causes including infection, maternal stress, uterine distention, placental hypoxia, bleeding and lack of prostaglandin dehydrogenase. Infection is probably the most important factor at low gestational age, with uterine distention and maternal stress increasing in significance further on. In the future we may become better able than we are at determining the specific reason in each individual case, which may lead to the development of more effective treatment. On the other hand, results have been very poor with respect to prevention, and in some countries we even note a slight increase in incidence. Although premature birth is often impossible to prevent, early detection and tocolytic therapy can delay labor long enough to permit effective corticosteroid therapy and transport when required to the appropriate obstetric clinic for optimal neonatal care.
Lakartidningen 02/2000; 97(4):301-6, 308-10.
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ABSTRACT: In-vitro fertilisation is an effective treatment for infertility, but there is concern about the health of children. We investigated, in a retrospective registry study, malformations, cancers, and deaths in the complete Swedish in-vitro-fertilisation birth cohort compared with the general population.
We collected data from all in-vitro-fertilisation clinics in Sweden and compared the obstetric outcomes of babies (n=5856) born between 1982 and 1995 with all babies born in the general population (n=1,505,724) during the same period, according to data from the Swedish Medical Birth Registry and the Registry of Congenital Malformations. We investigated the incidence of childhood cancer through the Swedish Cancer Registry. Data were stratified for maternal age, parity, previous subfertility, year of birth, and multiple of pregnancies.
Multiple births occurred in 27% of pregnancies compared with 1% in the control group. In the in-vitro-fertilisation group, more babies were born preterm (<37 weeks) than controls (30.3 vs 6.3%) and more had low birthweights (<2500 g, 27.4 vs 4.6%). The perinatal mortality was 1.9% in the in-vitro fertilisation group and 1.1% in the controls. For in-vitro-fertilisation singletons, the risk ratios, adjusted for year of birth, for very preterm birth (<32 weeks) and very low birthweight (<1500 g) were 3.54 (95% CI 2.90-4.32) and 4.39 (3.62-5.32), respectively. Malformations occurred in 5.4% of all babies in the in-vitro-fertilisation group (1.39 [1.25-1.54]), and the rates of neural-tube defects and oesophageal atresia were higher than those in the controls. There was no increase in childhood cancer in the in-vitro-fertilisation group.
A high frequency of multiple births and maternal characteristics were the main factors that led to adverse outcomes, and not the in-vitro-fertilisation technique itself. The clinical practice of in-vitro-fertilisation needs to be changed to lower the rate of multiple pregnancy.
The Lancet 11/1999; 354(9190):1579-85. · 38.28 Impact Factor
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ABSTRACT: To compare gestational age (GA) calculated from oocyte retrieval and from ultrasound measurements in pregnancies after in vitro fertilization (IVF).
In a retrospective study of 253 women with singleton and 84 women with twin pregnancies conceived from IVF, GA calculated from the day of oocyte retrieval was compared with GA calculated in the second trimester of pregnancy from ultrasound measurements of biparietal diameter (BPD) and femur length (FL).
For singletons, the mean GA calculated from ultrasound measurements was significantly shorter than the mean GA estimated from the day of oocyte retrieval. The mean difference was 1.9 days (SD 3.3; 95% CI 1.5-2.4) if only BPD was used and 2.1 days (SD 2.1; 95% CI 1.6-2.5) if BPD and FL were combined. For twins, the mean GA calculated from ultrasound measurements was also significantly shorter than the mean GA calculated from the day of oocyte retrieval. The mean difference was 1.4 days (SD 2.7; 95% CI 1.0-1.8) if BPD was used and 1.6 days (SD 2.5; 95% CI 1.2-2.0) if BPD and FL were combined.
In IVF pregnancies, term prediction using ultrasound in the second trimester is reliable and may reduce the number of pregnancies subsequently classified as post-term, thus avoiding unnecessary obstetric interventions.
Ultrasound in Obstetrics and Gynecology 10/1998; 12(3):170-4. · 3.01 Impact Factor
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ABSTRACT: There is uncertainty about the health of children born from in-vitro fertilisation (IVF) with cryopreserved embryos. We investigated the postnatal growth and health (up to 18 months) of these children compared with those born after standard IVF with fresh embryos and those from spontaneous pregnancies.
255 children from cryopreserved embryos were matched by maternal age, parity, single or twin pregnancy, and date of delivery with 255 children born after IVF with fresh embryos, and 252 children from spontaneous pregnancies. The main endpoint was growth; secondary endpoints were the prevalence of chronic illness, major malformations, cumulative incidence of common diseases, and development during the first 18 months. Growth was assessed by comparison with standard Swedish growth charts and by standard deviation scores.
Growth features were similar for both singletons and twins in the three groups. There were 6 (2.4%) of 255, 9 (3.5%) of 255, and 8 (3.2%) of 252 major malformations in the cryopreserved group, standard IVF, and spontaneous groups, respectively (p=0.6 between the cryopreserved and standard IVF group). The prevalence of chronic diseases did not differ between the three groups, with 18.0%, 15.3%, and 16.7% of children with a chronic illness in the cryopreserved group, standard IVF, and spontaneous groups, respectively.
The cryopreservation process does not adversely affect the growth and health of children during infancy and early childhood. Minor handicaps, behavioural disturbances, learning difficulties, and dysfunction of attention and perception cannot be ruled out at this age.
The Lancet 05/1998; 351(9109):1085-90. · 38.28 Impact Factor
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ABSTRACT: The purpose was to determine the prognostic value of interleukin (IL) 1-alpha, IL-6 and IL-8 in cervico/vaginal secretion for preterm birth (<37 weeks of gestation) in twin pregnancies.
The study included screening of 121 women with twin pregnancies with sampling at 24, 26, 28, 30, 32 and 34 weeks of gestation. IL-1alpha, IL-6 and IL-8 was analyzed with ELISA immunoassays. The detection limit was 30 pg/mL for IL-1 and IL-8 and 40 pg/mL for IL-6. Vaginal fluid was smeared and dried for later evaluation of bacterial vaginosis (presence of clue cells).
Spontaneous preterm birth occurred in 36 women and 65 women were delivered at term. IL-8 was significantly higher (p=0.03) in samples from women delivered preterm (median 3.72 ng/g mucus, range <0.07-220.00) compared with samples from women delivered at term (median 3.03 ng/g mucus, range <0.08-378.60). At 28 weeks of gestation, IL-8 (cut off 1.75 ng/g mucus) was associated with preterm delivery (relative risk 2.2, CI 95% 1.1-4.5) with a sensitivity, specificity, positive and negative predictive value of 78.8, 45.8, 44.8 and 79.4%, respectively. The levels of IL-1alpha and IL-6 were not significantly associated with preterm birth. Bacterial vaginosis was found in 47/541 (8.7%) samples analyzed. The levels of IL-1alpha and IL-8 were significantly higher in samples positive for bacterial vaginosis than in negative samples (p<0.0001 and p<0.01, respectively). There was no significant association between the level of IL-6 and bacterial vaginosis.
IL-8, but not IL-1alpha and IL-6, was associated with preterm delivery but the relationship was too weak to be of predictive value for preterm birth in twin pregnancies. IL-1alpha and IL-8, but not IL-6, were associated with bacterial vaginosis.
Acta Obstetricia Et Gynecologica Scandinavica 05/1998; 77(5):508-14. · 1.77 Impact Factor
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ABSTRACT: To evaluate the predictive values of fetal fibronectin, bacterial vaginosis, endotoxin and cervical length for preterm birth (< 35 and < 37 weeks) and neonatal morbidity in twin pregnancies.
One-hundred and twenty-one women with twin pregnancies recruited into a prospective longitudinal study at three antenatal clinics in the southwest of Sweden.
Cervical or vaginal fluid was sampled and determined for fetal fibronectin (> or = 0.05 microgram/mL was used as cutoff), endotoxin (> or = 100 pg/mL) and bacterial vaginosis (presence of clue cells) at two week intervals from 24 to 34 weeks of gestation. The cervical length was measured with transvaginal sonography at the same time intervals.
Occurrence of preterm birth (< 35 and < 37 weeks of gestation) and neonatal morbidity.
All positive fetal fibronectin samples obtained at screening between 24 and 34 weeks predicted birth < 35 weeks (RR 18.0; 95% CI 2.2-145.9). A positive fetal fibronectin at 28 weeks of gestation predicted delivery < 35 weeks (RR 6.3; 95% CI 2.6-15.1) with a sensitivity, specificity, positive and negative predictive value of 50.0, 92.0, 62.5 and 87.3%, respectively. An independent association between fetal fibronectin at 28 weeks and preterm birth (< 35 weeks) was verified with logistic regression (P = 0.03). A positive fetal fibronectin at 28 weeks of gestation predicted neonatal morbidity (RR 5.1; 95% CI 2.4-11.0) and a longer period of care at the neonatal intensive care unit. The predictive power of cervical sonography was generally low but cervical length (cutoff < or = 33 mm) measured at 28 weeks of gestation was significantly associated with birth < 37 weeks (RR 2.2; 95% CI 1.1-4.2). The presence of endotoxin correlated to bacterial vaginosis, but these tests were not significantly related to preterm birth or neonatal morbidity.
Fetal fibronectin predicted preterm birth and neonatal morbidity in twin pregnancies. The predictive value of cervical length determinations was low. Endotoxin and bacterial vaginosis had no predictive power for preterm delivery in this study.
British Journal of Obstetrics and Gynaecology 12/1997; 104(12):1398-404.
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ABSTRACT: The main purpose of this study was to evaluate the obstetric and neonatal outcome of children conceived from cryopreserved embryos. The medical records of 270 infants (163 singletons, 98 twins and nine triplets) were reviewed and compared with two control populations of children born after in-vitro fertilization (IVF) with fresh embryos and children born after spontaneous pregnancies. The controls were matched according to maternal age, parity, plurality and date of delivery. In the cryopreserved group the gestational age at delivery for singletons was 279 +/- 13 days with birthweight 3476 +/- 616 g; for twins gestational age was 257 +/- 19 days with birthweight 2574 +/- 560 g; for triplets gestational age was 228 +/- 3 days with birthweight 1752 +/- 183 g. The incidence of preterm birth (< 37 weeks gestation) was 5.6% for singletons, 44.9% for twins and 100% for triplets. Seven children had major malformations (2.7%) and perinatal mortality occurred in two children (8/1000). Gestational age at delivery, birthweight, the incidence of malformations and the perinatal mortality were comparable with the two control groups both for singletons and twins. Significantly more singletons in the cryopreserved group were delivered by Caesarean section compared with the spontaneous group. The number of infants with low Apgar score (< 7 at 5 min) and the number of infants admitted to neonatal intensive care units were similar in the cryopreserved and spontaneous groups. In conclusion, the cryopreservation process did not seem to adversely influence fetal development and no increased perinatal risk was found.
Human Reproduction 08/1997; 12(8):1819-25. · 4.47 Impact Factor
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ABSTRACT: The aim of this study was to describe the obstetric and perinatal outcome for births following intracytoplasmic sperm injection (ICSI). Of 210 infants born, 140 were singletons and 70 were twins. There were no triplets or higher births. The multiple birth frequency was 20%. Overall, 17% of deliveries were preterm, although for singleton pregnancies the incidence was reduced to 9%. The median birth weight of all live born infants was 3168 g and singletons 3470 g. Of all infants, 17% had a low birth weight (<2500 g) and 2% had a very low birth weight (<1500 g). Two major malformations occurred in two singleton children and four minor malformations occurred in four children. This was within the range of expected values in Sweden. Karyotyping was performed in 58 pregnancies. All of them were normal. The perinatal mortality was 0.5%. In conclusion, in this observational study from Sweden of the first infants born after ICSI in our programme, the incidence of multiple births, preterm births, low birth weight babies and congenital malformations was low compared with other series of in-vitro fertilization pregnancies not associated with ICSI.
Human Reproduction 05/1996; 11(5):1113-9. · 4.47 Impact Factor
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ABSTRACT: Intracytoplasmic sperm injection (ICSI) has been studied in this animal research programme since 1990. In 1993, the technique was first applied clinically and up to the present time (September 1994), a total of 456 couples have been studied in 538 cycles. The principal indication for the use of ICSI has been severe male sub-fertility as judged by a semen analysis. In addition, men with high titres of antisperm antibodies, blockage of the vas deferens and neurological disorders such as spinal cord lesions have been included in the programme. Men with genetic disorders such as cystic fibrosis and acrosome-deficient spermatozoa have also been treated successfully. The overall fertilization rate using ICSI was 59%, which is similar to the conventional in vitro fertilization (IVF) programme in Göteborg, however, the pregnancy rate per embryo transfer (29%) and the ongoing pregnancy rate per transfer (22%) were slightly lower. The total number of pregnancies was 144 with 111 of the pregnancies either ongoing or already delivered. To date, 36 healthy children have been born following 29 deliveries and no major malformations have been diagnosed. Being the first programme in Scandinavia to perform ICSI, this unit has experienced long waiting lists which indicates that severe male sub-fertility will be one of the major groups for treatment with assisted reproductive technologies in the future.
Reproduction Fertility and Development 02/1995; 7(2):263-7; discussion 268. · 2.11 Impact Factor
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ABSTRACT: During the past years a major change in the use of delivery position has occurred in Sweden. Recumbent delivery positions have been replaced by a variety of positions: squatting, standing, lateral, kneeling and quadruped. The consequences of this shift in obstetrical practice for development of perineal lacerations are largely unknown.
Retrospective comparison of uncomplicated deliveries in standing (n = 650) and sitting (n = 264) position with respect to third degree lacerations.
The standing and sitting delivery group were similar with respect to maternal, infant and delivery characteristics. The frequency of third degree tears was 2.50% in standing and 0.38% in sitting birth position (p < 0.05). In nulliparous women, third degree tears occurred in 4.2% in standing and 1.0% in sitting position.
The present data implies that the risk of third degree lacerations is considerably higher (7 x) in standing than in sitting birth positions.
Acta Obstetricia Et Gynecologica Scandinavica 09/1994; 73(8):630-3. · 1.77 Impact Factor
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ABSTRACT: Two hundred and six pregnancies occurring after in vitro fertilization (IVF) and embryo transfer (ET) during a 7-year period in Göteborg were analysed with respect to pregnancy outcome. The clinical abortion rate was 26%, the rate of ectopic pregnancy was 10%, the rate of ongoing pregnancies beyond 24 weeks was 15%, and the rate of deliveries was 49% (n = 100). The hospital records of 98 women with the 100 deliveries resulting in 131 infants were studied. Multiple pregnancy occurred in 27%, including one quadruplet and two triplet pregnancies. Preterm birth occurred in 30% of all pregnancies and in 20% of singleton pregnancies. Thirty-four percent of the infants had a birth weight of less than 2500 g. The perinatal mortality was 46/1000, as estimated from the 24th week of pregnancy. The incidence of major malformation, 2.3%, was similar to that reported from studies in the general population. The first 100 infants born were followed up for 18 months to 8 years. Long-term sequelae were associated with immaturity and low birth weight. No problems during follow-up were disclosed in children who had had an uneventful neonatal period. It is concluded that IVF pregnancies are an obstetric risk group requiring special attention.
Acta Obstetricia Et Gynecologica Scandinavica 02/1991; 70(7-8):565-73. · 1.77 Impact Factor
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I Ponjaert-Kristoffersen,
T Tjus,
J Nekkebroeck,
J Squires,
D Verté,
M Heimann,
M Bonduelle,
G. Palermo, U B Wennerholm,
Göteborg and New York,
on behalf of the Collaborative study of Brussels
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ABSTRACT: BACKGROUND: The developmental outcomes of children born after ICSI are still a matter of concern. The purpose of the present study was to investigate psychological outcomes for 5-year-old children born after ICSI and compare these with outcomes for children born after spontaneous conception (SC). METHODS: Three hundred singleton children born after ICSI in Belgium, Sweden and the USA were matched by maternal age, child age and gender. Outcome measures included the Wechsler Preschool and Primary scales of intelligence (WPPSI-R), Peabody Developmental Motor Scales, Parenting Stress Index and Child Behaviour Checklist. RESULTS: Regarding cognitive development, no significant differences were found on WPPSI-R verbal and performance scales between ICSI and SC children. However, some differences were noted on subtests of the Performance Scale. ICSI children more often obtained a score below 1 SD of the mean on the subtests: Object Assembly, Block Design and Mazes (all P <0.05). Significant differences by site (i.e. Belgium, Sweden and New York) were found on subtests related to parenting stress, child behaviour problems and motor development (all P <0.05). These findings can probably be explained by variables other than conception mode, such as cultural differences and selection bias. CONCLUSIONS: Although the finding that a higher proportion of ICSI children obtained scores below the cut-off on some of the visual–spatial subscales of the WPPSI-R warrants further investigation, ICSI does not appear to affect the psychological well-being or cognitive development at age 5.
