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U B Wennerholm

Publications and source records attributed to U B Wennerholm.

18 recordsLinked to original sources

What is the most relevant standard of success in assisted reproduction? Singleton live births should also include preterm births.

An intensive debate is ongoing in this journal concerning the most appropriate endpoint after assisted reproduction techniques. The endpoint suggested by the first authors was Birth Emphasizing a Successful Singleton at Term (BESST). We have evaluated the most appropriate endpoint from different perspectives: patients, public, health authorities, obstetric and IVF clinics. We find singleton live birth highly relevant as an outcome parameter as multiple pregnancies are the main factor responsible for the overall poorer obstetric and neonatal outcome in IVF pregnancies, and multiple pregnancies are mostly an avoidable iatrogenic complication. However, our proposal is that both preterm and term singletons should be included since the prematurity rate is an outcome that is largely uninfluenced by the IVF clinics. In conclusion, we propose singleton live birth per cycle initiated as the most appropriate main outcome after assisted reproduction. Prematurity should in addition be reported separately as a secondary outcome.

Congenital Abnormalities↗

Levels of dimethylarginines and cytokines in mild and severe preeclampsia.

BACKGROUND: The objectives were 1. to evaluate if the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine was altered in mild and severe forms of preeclampsia, and 2. to assess the relationship between dimethylarginines and the cytokine response in preeclampsia. METHODS: Asymmetric and symmetric dimethylarginine were measured with high performance liquid chromatography in women with mild (n=13) and severe (n=32) preeclampsia and in normotensive pregnant controls (n=20). Interleukin-4, -6, -8, -10 and tumor necrosis factor-alpha were analyzed by immunoassays in women with mild (n=8) and severe (n=17) preeclampsia and in normotensive pregnant controls (n=14). The Mann Whitney U-test and Spearman Rank test were used for statistical analysis. RESULTS: The plasma levels of dimethylarginine were increased in preeclamptic subjects. The elevation of symmetric dimethylarginine was more pronounced than that of asymmetric dimethylarginine. The control levels of interleukin-6, -8 and -10 were significantly higher at term than at gestational week 32-36. Interleukin-6 and -8 were significantly elevated in subjects with severe, but not mild, preeclampsia, whereas TNF-alpha and IL-10 were not significantly altered. Symmetric dimethylarginine levels correlated significantly with arterial blood pressure and serum levels of creatinine and uric acid. Dimethylarginine levels in plasma were, however, not related to the cytokine response. CONCLUSIONS: Plasma concentrations of both asymmetric and symmetric dimethylarginine were significantly elevated both in mild and severe preeclampsia. Symmetric, but not asymmetric, dimethylarginine correlated to the severity of the condition. Plasma levels of interleukin-6 and -8 were also elevated in severe preeclampsia but no direct correlations were found between these cytokines and dimethylarginines.

Arginine↗

[Spontaneous premature birth: physiopathology, predictors and management. The frequency is constant--early detection can improve therapeutic possibilities].

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.

Biomarkers↗

Incidence of congenital malformations in children born after ICSI.

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.

Chromosome Aberrations↗

Obstetric outcome of pregnancies following ICSI, classified according to sperm origin and quality.

The aim of this study was to report the outcome of all clinical pregnancies obtained after intracytoplasmic sperm injection (ICSI) performed during a 5 year period at two fertility clinics, with special reference to delivery outcome associated with different sperm origin and quality and the transfer of fresh or frozen-thawed pre-embryos. A total of 1293 clinical pregnancies was analysed. Deliveries occurred in 75.9% (n = 982) and early spontaneous abortion, late spontaneous abortion and ectopic pregnancy in 21.4, 1.0 and 1.2% respectively. Multiple birth occurred in 21.3% (208 sets of twins and one set of triplets) of the deliveries, with the highest incidence in the epididymal sperm group (30.2%) and lowest in the cryopreserved group (13.7%). A total of 1192 infants was born. Preterm birth occurred in 15.7% of all deliveries. Preterm birth was not related to sperm origin or quality but was related to multiple birth. The prematurity rate was 8.4%, 42.3% and 100% for singletons, twins and triplets respectively. Singleton infants born after cryopreservation as embryos had a significantly higher birthweight than the ejaculated sperm group with fresh embryo transfer. The perinatal mortality rate was 11.7 per 1000 born infants. Eighty-seven of the 1192 infants (7.3%) had a malformation, 40 of which were minor. The perinatal mortality rate and the malformation rate were similar in the different subgroups. Prenatal karyotyping was performed on 149 fetuses (12.5%) and abnormal results were found in four cases (2.7%). In conclusion, obstetric outcome of ICSI pregnancies was similar to that of conventional IVF and was not influenced by sperm origin or quality. The high incidence of multiple births is still the major concern.

Abnormalities, Multiple↗

Avoiding multiple pregnancies in ART: consideration of new strategies.

To maximize pregnancy rates, physicians who perform IVF, often transfer multiple embryos, which increases the multiple birth risk. Multiple birth infants are at significant risk for a number of adverse outcomes including preterm delivery, low birth weight, congenital malformations, fetal and infant deaths and long term morbidity and disability among survivors. Since the ultimate goal for an IVF treatment is the birth of a healthy infant, an important issue for all kinds of assisted reproductive technologies (ART) must be the reduction or elimination of multiple pregnancies. In this article, different strategies to avoid multiple births in ART are discussed.

Female↗

Anal sphincter tears: prospective study of obstetric risk factors.

OBJECTIVE: To evaluate intrapartum risk factors for anal sphincter tear. DESIGN: A prospective observational study. SETTING: Delivery unit at the University Hospital in Göteborg, Sweden. PARTICIPANTS: 2883 consecutive women delivered vaginally during the period between 1995 and 1997. Information was obtained, from patient records and from especially designed protocols which were completed during and after childbirth. MAIN OUTCOME MEASURES: Anal sphincter (third and fourth degree) tear. RESULTS: Anal sphincter tear occurred in 95 of 2883 women (3.3%). Univariate analysis demonstrated that the risk of anal sphincter tear was increased by nulliparity, high infant weight, lack of manual perineal protection, deficient visualisation of perineum, severe perineal oedema, long duration of delivery and especially protracted second phase and bear down, use of oxytocin, episiotomy, vacuum extraction and epidural anaesthesia. After analysis with stepwise logistic regression, reported as odds ratio, 95% confidence interval, the following factors remained independently associated with anal sphincter tear: slight perineal oedema (0.40, 0.26-0.64); manual perineal protection (0.49, 0.28-0.86); short duration of bear down (0.47, 0.24-0.91); no visualisation of perineum (2.77, 1.36-5.63); parity (0.59, 0.40-0.89); and high infant weight (2.02, 1.30-3.16). Analysis of variance showed that manual perineal protection had a stronger influence on lowering the frequency, and lack of visualisation of perineum and infant weight had a stronger influence on raising the frequency, of anal sphincter tears in nulliparous compared with parous women. CONCLUSIONS: Perineal oedema, poor ocular surveillance of perineum, deficient perineal protection during delivery, protracted final phase of the second stage, parity and high infant weight all constitute independent risk factors for anal sphincter tear. Such information is essential in order to reduce perineal trauma during childbirth.

Adult↗

Deliveries and children born after in-vitro fertilisation in Sweden 1982-95: a retrospective cohort study.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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.

Cohort Studies↗

Postnatal growth and health in children born after cryopreservation as embryos.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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.

Body Height↗

Gestational age in pregnancies after in vitro fertilization: comparison between ultrasound measurement and actual age.

OBJECTIVE: To compare gestational age (GA) calculated from oocyte retrieval and from ultrasound measurements in pregnancies after in vitro fertilization (IVF). DESIGN: 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). RESULTS: 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. CONCLUSIONS: 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.

Adolescent↗

Interleukin-1alpha, interleukin-6 and interleukin-8 in cervico/vaginal secretion for screening of preterm birth in twin gestation.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Adult↗

Is paternal mitochondrial DNA transferred to the offspring following intracytoplasmic sperm injection?

During intracytoplasmic sperm injection (ICSI) the whole sperm, including head, midpiece and tail, is injected into the middle area of the oocyte. To find out what happens to the sperm mitochondria after ICSI, we checked the first six children born after ICSI treatment for occurrence of paternal mitochondrial DNA (mtDNA). The difference between maternal and paternal mtDNA in the investigated couples in our study was confined to single-base pair substitutions and we had to rely on restriction enzyme cleavage to differentiate between the mitochondrial genomes of the parents. With this kind of assay we were able to reach a sensitivity of about 0.2% for the paternal mtDNA. However, as uneven partition between tissues of heteroplasmic mtDNA is expected to occur, it would not be unlikely that an enrichment to 0.2% would occur in a given tissue if paternal mtDNA was transmitted by the ICSI procedure. We did not detect this level in the blood in any of the six children.

Adult↗

Obstetric and perinatal outcome of children conceived from cryopreserved embryos.

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.

Adult↗

Fetal fibronectin, endotoxin, bacterial vaginosis and cervical length as predictors of preterm birth and neonatal morbidity in twin pregnancies.

OBJECTIVE: 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. PARTICIPANTS: One-hundred and twenty-one women with twin pregnancies recruited into a prospective longitudinal study at three antenatal clinics in the southwest of Sweden. METHODS: 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. MAIN OUTCOME MEASURES: Occurrence of preterm birth (< 35 and < 37 weeks of gestation) and neonatal morbidity. RESULTS: 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. CONCLUSIONS: 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.

Adult↗

Obstetric and perinatal outcome of pregnancies following intracytoplasmic sperm injection.

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.

Birth Weight↗

Microfertilization techniques--the Swedish experience.

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.

Cryopreservation↗

Birth in standing position: a high frequency of third degree tears.

BACKGROUND: 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. METHOD: Retrospective comparison of uncomplicated deliveries in standing (n = 650) and sitting (n = 264) position with respect to third degree lacerations. RESULTS: 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. CONCLUSION: The present data implies that the risk of third degree lacerations is considerably higher (7 x) in standing than in sitting birth positions.

Delivery, Obstetric↗

Pregnancy complications and short-term follow-up of infants born after in vitro fertilization and embryo transfer (IVF/ET).

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.

Adult↗