Depression, anxiety, and antidepressant treatment in women: association with in vitro fertilization outcome.

OBJECTIVE: To investigate associations between depression, anxiety, and antidepressants before in vitro fertilization (IVF) and IVF cycle outcomes, including pregnancy, live birth, and miscarriage. DESIGN: Nationwide register-based cohort study. SETTING: Not applicable. PATIENT(S): Nulliparous women undergoing their first IVF cycle recorded in the Swedish Quality Register of Assisted Reproduction, January 2007 to December 2012 (n = 23,557). INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Associations between diagnoses of depression/anxiety, antidepressants, and IVF cycle outcome evaluated using logistic regression to produce adjusted odds ratios (AOR) and 95% confidence intervals (CI). RESULT(S): In total, 4.4% of women had been diagnosed with depression/anxiety and/or dispensed antidepressants before their IVF first cycle. The odds for pregnancy and live birth were decreased (n = 1,044; AOR = 0.86; 95% CI, 0.75-0.98; and AOR = 0.83; 95% CI, 0.72-0.96, respectively). For women with a prescription for a selective serotonin reuptake inhibitor (SSRI) only (n = 829), no statistically significant associations were found. Women with non-SSRI antidepressants (n = 52) were at reduced odds of pregnancy (AOR = 0.41; 95% CI, 0.21-0.80) and live birth (AOR = 0.27; 95% CI, 0.11-0.68). Women with a depression/anxiety diagnosis with no antidepressant (n = 164) also had reduced odds of pregnancy (AOR = 0.58; 95% CI, 0.41-0.82) and live birth (AOR = 0.60; 95% CI, 0.41-0.89). Among the women who became pregnant (39.7%), there were no statistically significant associations between exposure and miscarriage except for the women taking non-SSRI antidepressants (AOR = 3.56; 95% CI, 1.06-11.9). CONCLUSION(S): A diagnosis of depression/anxiety and/or treatment with antidepressants before IVF was associated with slightly reduced odds of pregnancy and live birth. Women with the presence of depression/anxiety without antidepressants had a more pronounced reduction in odds, implying that the underlying disorder is important for the observed association.

International Committee for Monitoring Assisted Reproductive Technologies world report: Assisted Reproductive Technology 2006.

STUDY QUESTION: What are the access, effectiveness and safety of assisted reproductive technology (ART) worldwide in 2006? SUMMARY ANSWER: ART access, effectiveness and safety vary markedly among countries. Overall, there was an increase in the use of ICSI, single embryo transfer (SET) and frozen embryo transfer (FET). There was a decline in the multiple delivery rate (DR) and preterm birth rate. WHAT IS KNOWN ALREADY: ART is widely practiced worldwide and there is a need for its continuous monitoring to improve the comprehensiveness and quality of ART data and services. STUDY DESIGN, SIZE, DURATION: This is a retrospective, cross-sectional survey of ART cycles undertaken worldwide in 2006. PARTICIPANTS, SETTING, METHODS: A total of 2352 clinics in 56 countries provided data. Data were analyzed at a country and regional level. The forms for data collection were developed by the International Committee Monitoring Assisted Reproductive Technologies (ICMART) and sent to each country or regional ART register. MAIN RESULTS AND THE ROLE OF CHANCE: A total of >1,050,300 initiated cycles resulted in an estimated >256,668 babies. The overall pregnancy rates (PRs) and DRs per aspiration for IVF were 30.7 and 22.8%, respectively, and for ICSI 29.7 and 20.0%, respectively. The PRs and DRs for FETs were 26.4 and 17.8%, respectively. Multiple DR per PR were 22.2% for twins and 1.5% for triplets following fresh IVF/ICSI and 16.4% for twins and 0.8% for triplets for FETs. Ovarian hyperstimulation syndrome complicated >4585 cycles (0.6%). Access to ART varied from 11 to 3988 cycles per million population. ICSI comprised 66.0% of all initiated cycles, FET 27.4% and SET 20.7%. Perinatal mortality rate was 25.2 per 1000 births for fresh IVF/ICSI and 17.5 per 1000 for FETs. LIMITATIONS, REASONS FOR CAUTION: 44.6% of the countries provided incomplete data. Quality of data varies among individual countries and is dependant on the policy of the local regulatory authority for monitoring ART clinics. Continuous efforts are needed to improve comprehensiveness and quality of data collected. WIDER IMPLICATIONS OF THE FINDINGS: Adopting the policy of SET, FET and the cessation of transferring more than two embryos should be widely applied. ICMART will continue helping countries and regions to establish their own ART registries. STUDY FUNDING/COMPETING INTEREST(S): ICMART receives financial support from medical societies: European Society for Human Reproduction and Embryology (ESHRE), American Society for Reproduction Medicine (ASRM), Fertility Society of Australia (FSA), Japan Society for Reproductive Medicine (JSRM), Latin American Network for Reproductive Medicine (REDLARA) and Middle East Fertility Society (MEFS) and Society for Assisted Reproductive Technology (SART). All authors have no conflict of interest in relation to this work. We declare no support or financial relationship with any organizations or any activities that could appear to have influenced the submitted work.

Maternal and fetal factors which affect fetometry: use of in vitro fertilization and birth register data.

BACKGROUND: Fetometry dating of gestational age is the gold standard in most developed countries but may have some inborn errors. Dating pregnancies after in vitro fertilization can be used for the evaluation of fetometric studies and for studies of variables which may affect them. METHODS: We compared the actual gestational age of 9543 singleton and 869 twin pregnancies with estimates based on second-trimester fetometry. Mean gestational age, percentage of births classified as preterm, and skewness of the distribution of differences between actual and estimated gestational age were studied. Subanalyses were made of data on singletons for males and females, for infants born to overweight or obese women or to smoking women, for infants judged to be small or large for gestational age, and on twins. RESULTS: In the majority of cases, good agreement was found between actual and estimated gestational age but in singletons there was an excess of positive differences resulting in a moderate over-estimate of the rate of preterm births (8%), more marked for females (11%) than for males (6%) and increased for infants born to overweight (7%) or obese (16%) mothers. Singleton infants born small for gestational age also showed an excess of positive differences (3%). These differences were less marked for twins. CONCLUSIONS: In most IVF pregnancies, routine fetometry correctly predicts gestational age but deviations exist which indicate that ultrasound underestimates the age of fetuses that will be born small for gestational age and when the woman is obese. The differences between actual age and estimates based on fetometry seem to be smaller than those between estimates based on last menstrual period and fetometry.

Autism and mental retardation among offspring born after in vitro fertilization.

IMPORTANCE: Between 1978 and 2010, approximately 5 million infants were born after in vitro fertilization (IVF) treatments. Yet limited information on neurodevelopment after IVF exists, especially after the first year of life. OBJECTIVE: To examine the association between use of any IVF and different IVF procedures and the risk of autistic disorder and mental retardation in the offspring. DESIGN, SETTING, AND PARTICIPANTS: A population-based, prospective cohort study using Swedish national health registers. Offspring born between 1982 and 2007 were followed up for a clinical diagnosis of autistic disorder or mental retardation until December 31, 2009. The exposure of interest was IVF, categorized according to whether intracytoplasmic sperm injection (ICSI) for male infertility was used and whether embryos were fresh or frozen. For ICSI, whether sperm were ejaculated or surgically extracted was also considered. MAIN OUTCOMES AND MEASURES: Relative risks (RRs) for autistic disorder and mental retardation and rates per 100,000 person-years, comparing spontaneously conceived offspring with those born after an IVF procedure and comparing 5 IVF procedures used in Sweden vs IVF without ICSI with fresh embryo transfer, the most common treatment. We also analyzed the subgroup restricted to singletons. RESULTS: Of the more than 2.5 million infants born, 30,959 (1.2%) were conceived by IVF and were followed up for a mean 10 (SD, 6) years. Overall, 103 of 6959 children (1.5%) with autistic disorder and 180 of 15,830 (1.1%) with mental retardation were conceived by IVF. The RR for autistic disorder after any procedure compared with spontaneous conception was 1.14 (95% CI, 0.94-1.39; 19.0 vs 15.6 per 100,000 person-years). The RR for mental retardation was 1.18 (95% CI, 1.01-1.36; 46.3 vs 39.8 per 100,000 person-years). For both outcomes, there was no statistically significant association when restricting analysis to singletons. Compared with IVF without ICSI with fresh embryo transfer, there were statistically significantly increased risks of autistic disorder following ICSI using surgically extracted sperm and fresh embryos (RR, 4.60 [95% CI, 2.14-9.88]; 135.7 vs 29.3 per 100,000 person-years); for mental retardation following ICSI using surgically extracted sperm and fresh embryos (RR, 2.35 [95% CI, 1.01-5.45]; 144.1 vs 60.8 per 100,000 person-years); and following ICSI using ejaculated sperm and fresh embryos (RR, 1.47 [95% CI, 1.03-2.09]; 90.6 vs 60.8 per 100,000 person-years). When restricting the analysis to singletons, the risks of autistic disorder associated with ICSI using surgically extracted sperm were not statistically significant, but the risks associated with ICSI using frozen embryos were significant for mental retardation (with frozen embryos, RR, 2.36 [95% CI, 1.04-5.36], 118.4 vs 50.6 per 100,000 person-years]; with fresh embryos, RR, 1.60 [95% CI, 1.00-2.57], 80.0 vs 50.6 per 100,000 person-years). CONCLUSIONS AND RELEVANCE: Compared with spontaneous conception, IVF treatment overall was not associated with autistic disorder but was associated with a small but statistically significantly increased risk of mental retardation. For specific procedures, IVF with ICSI for paternal infertility was associated with a small increase in the RR for autistic disorder and mental retardation compared with IVF without ICSI. The prevalence of these disorders was low, and the increase in absolute risk associated with IVF was small.

Perinatal outcomes of children born after frozen-thawed embryo transfer: a Nordic cohort study from the CoNARTaS group.

STUDY QUESTIONS: What are the risks of adverse outcomes in singletons born after frozen-thawed embryo transfer (FET)? SUMMARY ANSWER: Singletons born after FET have a better perinatal outcome compared with singletons born after fresh IVF and ICSI as regards low birthweight (LBW) and preterm birth (PTB), but a worse perinatal outcome compared with singletons born after spontaneous conception. WHAT IS KNOWN ALREADY: Previous studies have shown a worse perinatal outcome in children born after IVF in general compared with children born after spontaneous conception. In singletons born after FET, a lower rate of PTB and LBW and a higher rate of large for gestational age (LGA) compared with singletons born after fresh IVF have been shown. STUDY DESIGN: A retrospective Nordic population-based cohort study of all singletons conceived after FET in Denmark, Norway and Sweden until December 2007 was performed. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Singletons born after FET (n = 6647) were compared with a control group of singletons born after fresh IVF and ICSI (n = 42 242) and singletons born after spontaneous conception (n = 288 542). Data on perinatal outcomes were obtained by linkage to the national Medical Birth Registries. Odds ratios were calculated for several perinatal outcomes and adjustments were made for maternal age, parity, year of birth, offspring sex and country of origin. MAIN RESULTS AND THE ROLE OF CHANCE: Singletons born after FET had a lower risk of LBW (adjusted odds ratio (aOR) 0.81, 95% confidence interval (CI) 0.71-0.91), PTB (aOR 0.84, 95% CI 0.76-0.92), very PTB (VPTB; aOR 0.79, 95% CI 0.66-0.95) and small for gestational age (SGA; aOR 0.72, 95% CI 0.62-0.83), but a higher risk of post-term birth (aOR 1.40, 95% CI 1.27-1.55), LGA (aOR 1.45, 95% CI 1.27-1.64), macrosomia (aOR 1.58, 95% CI 1.39-1.80) and perinatal mortality (aOR 1.49, 95% CI 1.07-2.07) compared with singletons born after fresh IVF and ICSI. Compared with children conceived after spontaneous conception, singletons born after FET had a higher risk of LBW (aOR 1.27, 95% CI 1.13-1.43), very LBW (aOR 1.69, 95% CI 1.33-2.15), PTB (aOR 1.49, 95% CI 1.35-1.63), VPTB (aOR 2.68, 95% CI 2.24-3.22), SGA (aOR 1.18, 95% CI 1.03-1.35), LGA (aOR 1.29, 95% CI 1.15-1.45), macrosomia (aOR 1.29, 95% CI 1.15-1.45) and perinatal (aOR 1.39, 95% CI 1.03-1.87) neonatal (aOR 1.87, 95% CI 1.23-2.84) and infant mortality (aOR 1.92, 95% CI 1.36-2.72). When analyzing trends over time, the risk of being born LGA increased over time for singletons born after FET compared with singletons born after fresh IVF and ICSI (P = 0.04). LIMITATIONS, REASONS FOR CAUTION: As in all observational studies, the possible role of residual confounding factors and bias should be considered. In this study, we were not able to control for confounding factors, such as BMI, smoking and reason for, or length of, infertility. WIDER IMPLICATIONS OF THE FINDINGS: Perinatal outcomes in this large population-based cohort of children born after FET from three Nordic countries compared with fresh IVF and ICSI and spontaneous conception were in agreement with the literature.

Obstetric and neonatal outcome after oocyte donation in 106 women with Turner syndrome: a Nordic cohort study.

STUDY QUESTION: What are the obstetric and neonatal outcomes of deliveries after oocyte donation (OD) in women with Turner syndrome (TS)? SUMMARY ANSWER: Pregnancies among women with TS carry a substantial risk, particularly for hypertensive disorders. Potentially life-threatening complications occurred in 3.3% of pregnancies. The neonatal outcomes were generally reassuring, with similar rates of preterm birth and low birthweight (LBW) as after conventional IVF and better than previously reported in deliveries after OD in women with TS. WHAT IS KNOWN ALREADY: OD pregnancies in women with TS are known to be high-risk pregnancies. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study included 106 women with TS who delivered after OD (n = 122 deliveries, n = 131 newborns) in three Nordic countries (Finland, Denmark, Sweden) between 1992 and 2011. PARTICIPANTS, SETTING AND METHODS: Women with TS who delivered after OD in three Nordic countries were identified (n = 110). Four women declined to participate or were lost to follow-up, thus 106 women were included in the study. The medical data from fertility clinics, antenatal clinics and the hospitals where the women had been treated and/or delivered were scrutinized. MAIN RESULTS AND THE ROLE OF CHANCE: In this cohort, the karyotype was 45,X in 44% of the women with TS. Ten women (9.4%) had a known cardiac defect before pregnancy. Single embryo transfer was performed in 70.3% of the cases and the multiple birth rate was 7.4%. In total, 35.0% of the pregnancies were associated with a hypertensive disorder including pre-eclampsia in 20.5%. Potentially life-threatening complications occurred in four pregnancies (3.3%), including one woman with aortic dissection, one with mild regurgitation of the tricuspid and mitral valve, one with a mechanical heart valve who developed HELLP syndrome (haemolysis, elevated liver enzymes, low platelets) and one who underwent a post-partum hysterectomy due to severe haemorrhaging. Neonatal outcomes were reassuring, with a preterm birth rate of 8.0% and LBW rate of 8.8% in singletons. Major birth defects were found in 3.8% of the children. The perinatal mortality was 2.3% (3/131), including a set of extremely preterm twins. LIMITATIONS, REASONS FOR CAUTION: Although this study was performed over a period of almost 20 years in three different countries, with a low drop-out rate and little missing data, much larger series are needed to assess rare events. This study also lacks an appropriate control group. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that cardiovascular evaluation before and during pregnancy may contribute to favourable obstetric outcomes in many cases. Maternal outcomes were in agreement with the literature while neonatal outcomes were generally better than previously reported. The outcomes were consistent across the three countries, supporting generalizability to similar populations.

Maternal drug use during pregnancy and asthma risk among children.

BACKGROUND: Maternal use of some drugs, notably paracetamol and drugs for gastroesophageal reflux, has been associated with an increased risk of childhood asthma in the child. We wanted to analyze these associations with consideration to the confounding of maternal asthma. METHODS: Childhood asthma was identified from the Swedish National Prescription Register and maternal drug use during the latter part of pregnancy from antenatal records, computerized in the Swedish Medical Birth Register. Risks were estimated as odds ratios (OR) with 95% confidence intervals, using Mantel-Haenszel technique with adjustment for year of birth, maternal age, parity, smoking habits, and BMI. RESULTS: A statistical association between maternal use of many different drugs, including paracetamol, and childhood asthma existed but was mainly due to concomitant drug use, related to maternal asthma. The only associations that appeared to be true were with drugs for gastroesophageal reflux (adjusted (OR) = 1.32, 95% CI, 1.18-1.54) and with opiates (adjusted OR = 1.56 (96% CI, 1.05-2.34). CONCLUSIONS: Maternal use of paracetamol did not seem to increase the risk of childhood asthma, but the previously described association with drugs for gastroesophageal reflux was supported. The analysis is complicated by the confounding from maternal asthma.

Asthma in Swedish children conceived by in vitro fertilisation.

OBJECTIVES: To investigate a proposed association between in vitro fertilisation (IVF) and child asthma. DESIGN: The risk for asthma after IVF was estimated as ORs using Mantel-Haenszel analysis. SETTING: The Swedish Medical Birth Register. PATIENTS: Of the 2 628 728 children born in 1982-2007 and surviving the perinatal period, 31 918 were conceived by IVF. Presence of asthma was defined as at least five prescriptions of antiasthmatic drugs during the period 1 July 2005-31 December 2009 according to the Swedish Prescribed Drug Register (115 767 children, 2323 of whom were born after IVF). RESULTS: A significantly increased risk for asthma, albeit small, was found in children conceived by IVF (aOR 1.28, 95% CI 1.23 to 1.34), increasing the absolute risk from 4.4% to 5.6%. The risk increase for asthma was the same in boys and girls, in singletons and twins, and after caesarean section and vaginal delivery. The risk was higher for preterm than term singletons. For children with a low Apgar score, respiratory diagnoses, mechanical ventilation, continuous positive airway pressure or neonatal sepsis, the effect of IVF on asthma risk was low and statistically non-significant. Adjustment for length of involuntary childlessness eliminated the effect, and removal of infants whose mothers had used antiasthmatics in early pregnancy reduced the risk. CONCLUSIONS: This study verifies an association between IVF and asthma in children. This can be partly explained by neonatal morbidity and by maternal asthma acting as mediators, but the main risk factor is parental subfertility. The mechanism for this is unclear.

Association between preterm birth and intrauterine growth retardation and child asthma.

An association between preterm birth and an increased risk of childhood asthma has been demonstrated, but the importance of intrauterine growth retardation on asthma risk is unclear. Using data from Swedish health registers, infant characteristics and childhood asthma were studied. Analyses were made using Mantel-Haenszel methodology with adjustment for year of birth, maternal age, parity, smoking in early pregnancy and maternal body mass index. Preterm birth, birth weight and birth weight for gestational week were analysed and childhood asthma was evaluated from prescriptions of anti-asthmatic drugs. Neonatal respiratory problems and treatment for them were studied as mediating factors. Both short gestational duration and intrauterine growth retardation appeared to be risk factors and seemed to act separately. The largest effect was seen from short gestational duration. Use of mechanical ventilation in the newborn period and bronchopulmonary dysplasia were strong risk factors. A moderately increased risk was also seen in infants born large for gestational age. We conclude that preterm birth is a stronger risk factor for childhood asthma than intrauterine growth disturbances; however, the latter also affects the risk, and is also seen in infants born at term.

Infant and maternal health monitoring using a combined Nordic database on ART and safety.

OBJECTIVE: To evaluate infant and maternal health after assisted reproductive technology (ART), using data on over 90 000 ART children and their mothers in Denmark, Finland, Norway and Sweden. Data have been combined and will be compared with a control group of spontaneously conceived children and their mothers. The overall aim of this project is to evaluate the safety of ART. The size of the cohort should enable estimation of the prevalence of rare conditions such as birth defects, cancers, neurological impairments and imprinting diseases in the ART population compared to control children. Outcome data on the mothers of ART children can be used to study risks during pregnancy and obstetric complications after ART. METHODS: A personal identification number given to all Nordic residents allows cross-linkage of the national health registers and enables long-term follow-up of ART children. The medical birth registers in the Nordic countries make it possible to cross-link data from mother and child. When a child is identified as conceived by ART, we can obtain a list of all International Classification of Diseases (ICD) codes ever registered on that specific child. CONCLUSION: Combining the Nordic ART and health registers is a complicated but feasible task. The main strengths of this ongoing study are the size of the cohort of ART children and their mothers and the possibility to follow the children through the health registers. The limitations are related to the national differences in reporting and recording of data together with the heterogeneity of data.

Maternal and child outcome after in vitro fertilization--a review of 25 years of population-based data from Sweden.

OBJECTIVE: To summarize data on deliveries after in vitro fertilization (IVF) performed in Sweden up to 2006. DESIGN: Cohort study of women and children, conceived after IVF, with comparisons of deliveries after IVF before and after 1 April 2001. SETTING: Study based on Swedish health registers. POPULATION: Births registered in the Swedish Medical Birth Register with information on IVF from all IVF clinics in Sweden. METHODS: Results from the second study period are summarized, and outcomes between the two periods are compared. Long-term follow-up is based on data from both periods. MAIN OUTCOME MEASURES: Maternal and perinatal outcomes, long-term sequels. RESULTS: Some maternal pregnancy complications decreased in rate, notably pre-eclampsia and premature rupture of membranes. The rate of multiple births and preterm births decreased dramatically, with a better neonatal outcome, including reduced neonatal mortality. No difference in outcome existed between IVF and intracytoplasmic sperm injection or between the use of fresh and cryopreserved embryos, but children born after blastocyst transfer had a slightly higher risk for preterm birth and congenital malformations than children born after cleavage stage transfer. An increased risk for cerebral palsy, possibly for attention deficit and hyperactivity disorder, for impaired visual acuity and for childhood cancer was noted, but these outcomes were rare also after IVF. An increased risk for asthma was demonstrated. No effect on maternal cancer risk was seen. CONCLUSION: A marked decrease in multiple births was the main reason for better pregnancy and neonatal outcome and may also have a beneficial effect on long-term results, notably cerebral palsy.

Is there an increased risk for drug treated attention deficit/hyperactivity disorder in children born after in vitro fertilization?

BACKGROUND: There is mounting evidence that children born after in vitro fertilization (IVF) run an increased risk of neurological complications and notably cerebral palsy. Whether developmental disturbances occur more often than expected is debated. AIM: To investigate the risk for ADHD in children conceived after IVF. METHODS: Children conceived after IVF and born between 1982 and 2005 were identified from all IVF clinics in Sweden. Children who developed attention deficit/hyperactivity disorder (ADHD) were identified with the use of a register over all prescribed drugs in Sweden, using prescriptions for methylphenidate or atomixetine as indicators of ADHD. Maternal and neonatal characteristics were obtained by linkage with the Medical Birth Register and relevant confounders were adjusted for using Mantel-Haenszel procedures. We studied 28 158 children born after IVF and compared them with 2 417 886 children in the population. RESULTS: After adjustment for year of birth, maternal age, parity, smoking, BMI, and maternal education and after exclusion of women who did not cohabit, a weak but statistically significant association was found with an odds ratio=1.18, 95% confidence interval 1.03-1.36. The effect was stronger in girls (OR=1.40) than boys (OR=1.11) but this difference could be random. After adjustment for length of involuntary childlessness, the OR decreased slightly and lost statistical significance. CONCLUSIONS: The study suggests a weak association between IVF and drug treated ADHD.

Cancer risk in children and young adults conceived by in vitro fertilization.

OBJECTIVES: Studies conducted so far have found no statistically significant increased risk for cancer among children who are born after in vitro fertilization (IVF). METHODS: We followed 26,692 children who were born after IVF during the years 1982-2005 by using the Swedish Cancer Register and compared the number of children who had cancer and were born after IVF with children who were not conceived by IVF. Adjustment was made for year of birth. RESULTS: Maternal age, parity, smoking, subfertility, previous miscarriages, BMI, and multiple births did not significantly affect cancer risk in offspring. High birth weight, premature delivery, and the presence of respiratory diagnoses and low Apgar score were risk factors for cancer. We identified 53 cases of cancer in children who were born after IVF against 38 expected cases: 18 of them with hematologic cancer (15 of them acute lymphoblastic leukemia), 17 with eye or central nervous system tumors, and 12 with other solid cancers. There were 6 cases of Langerhans histiocytosis against 1.0 expected. The total cancer risk estimate was 1.42 (95% confidence interval: 1.09-1.87). CONCLUSIONS: We found a moderately increased risk for cancer in children who were conceived by IVF. Putative intermediary factors could be preterm birth and neonatal asphyxia.

Cerebral palsy in children born after in vitro fertilization. Is the risk decreasing?

BACKGROUND: Infants born after in vitro fertilization (IVF) differ from spontaneously conceived infants in a number of aspects which could increase the risk for future cerebral palsy (CP), e.g., multiple births, preterm births, neonatal complications. AIMS: To follow up children conceived by IVF with respect to risk for CP. METHODS: Infants born after IVF were identified from all IVF clinics in Sweden 1982-2007. Perinatal characteristics were obtained by linkage with the Medical Birth Register. The presence of CP in children born after IVF and in other children was identified from the Patient Register which contains diagnoses given at hospitalizations or specialist outpatient clinics. The risk for CP after IVF was studied after adjustment for year of birth, maternal age, parity, and smoking, all factors which co-vary both with IVF and with CP. Stratification was made for singletons and multiple births and for various neonatal outcomes. RESULTS: The adjusted odds ratio for CP after IVF was 1.81 (95% confidence interval, 95% CI 1.52-2.13), lower and not statistically significant when singletons or when unlike-sexed twins were analyzed. Stratification for various neonatal characteristics also reduced odds ratios to non-significant levels. For the last few years of the study (2004-2007) when the twinning rate after IVF was <10%, the odds ratio for CP was 0.97 (95% CI 0.57-1.66). CONCLUSIONS: The moderately increased risk for CP was most likely a consequence of an increased risk of neonatal morbidity, notably associated with multiple births.

Ocular malformations or poor visual acuity in children born after in vitro fertilization in Sweden.

PURPOSE: To follow up children born after in vitro fertilization (IVF) with respect to eye malformations and poor visual acuity. DESIGN: Observational cohort study based on Swedish health registers. METHODS: Congenital eye malformations were studied in 32 091 children born from 1982 through 2007 and severe visual impairment was studied in 24 628 children born from 1985 through 2005 after IVF in Sweden. Comparisons were made with all children born in Sweden during corresponding periods with adjustment for various confounders. The main outcome measure was the presence of a congenital eye malformation and poor visual acuity. RESULTS: Thirty-six (1.1 per 1000) IVF infants with ocular malformations were identified, and the risk, compared with non-IVF children, was not increased when adjusted for maternal age, parity, smoking, and body mass index (odds ratio, 1.05; 95% confidence interval, 0.75 to 1.47). Severe visual impairment was identified in 25 cases (1.0 per 1000), and the risk increase was statistically significant (odds ratio, 1.65; 95% confidence interval, 1.12 to 2.45) and was only slightly reduced when adjustment as above was made (odds ratio, 1.55; 95% confidence interval, 1.04 to 2.32). When adjustment was made for known length of unwanted childlessness, the OR decreased to 1.15 (95% confidence interval, 0.61 to 2.16). Only 3 of the 25 children with visual impairment had ocular malformations. CONCLUSIONS: Although there is an increased risk for visual impairment among children born after IVF, the individual risk is small and may be secondary to parental characteristics. No increased risk for eye malformations was found.

Blastocyst versus cleavage stage transfer in in vitro fertilization: differences in neonatal outcome?

OBJECTIVE: To compare neonatal outcome of blastocyst and cleavage stage embryo transfers after IVF. DESIGN: Register study. SETTING: Births recorded in the Swedish Medical Birth Register after IVF performed, 2002-2006. PATIENT(S): Treatments reported from all Swedish IVF clinics. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Some neonatal characteristics were compared in 1,311 infants born after blastocyst-stage transfer and 12,562 infants born after cleavage-stage transfer. Comparisons were also made with all births, 2002-2007 (n = 598,687). RESULT(S): After adjusting for year of birth, maternal age, parity, smoking habits, and body mass index, the risk of preterm birth among singletons was significantly greater after blastocyst-stage transfer than after cleavage-stage transfer. The risk of congenital malformations was also significantly higher. When the analysis was restricted to clinics where blastocyst transfers were made, the risk estimates increased for preterm birth, low birth weight, low APGAR score, and respiratory diagnoses, but did not change for congenital malformations. CONCLUSION(S): The results indicate a small increase in risk associated with blastocyst transfer, perhaps owing to the longer period of in vitro culture. There is a possibility that this effect is due, at least in part, to a selection of women for blastocyst transfers. Further studies are needed either to verify or to refute the found associations.

Modified natural cycle IVF and mild IVF: a 10 year Swedish experience.

Modified natural cycle IVF (mnc-IVF) or mild IVF (m-IVF) was offered to selected patients between 1996 and 2007; 43 patients during 129 cycles were treated with mnc-IVF and 145 couples during 250 cycles were treated with m-IVF. Comparison with outcome from conventional IVF cycles during the same time period and in the same clinic was performed. Although 53.5 and 39.6% of started cycles respectively never reached embryo transfer, the ongoing pregnancy rates per embryo transfer were 26.7% for mnc-IVF and 27.2% for m-IVF. During the same time period, cancellation rate for conventional IVF was 13.7% and the ongoing pregnancy rate per embryo transfer was 34.3%. For patients > or =38years of age, the ongoing pregnancy rate per embryo transfer was 17.5% in the m-IVF group. None of the patients aged > or =38years in the mnc-IVF group achieved an ongoing pregnancy. For patients treated with conventional IVF, the > or =38years of age pregnancy rate per embryo transfer was 27.0%. Costs of medication for m-IVF and mnc-IVF were 96.3 and 97.5% less than for the least expensive conventional IVF cycle respectively. Pregnancy rates per embryo transfer are acceptable for these treatment modalities, the cost for medication is low, risks for complications are dramatically reduced, and the treatments may be more psychologically acceptable to the patients.

Congenital malformations in infants born after in vitro fertilization in Sweden.

BACKGROUND: The risk for congenital malformations is increased in infants born after in vitro fertilization (IVF). Some specific malformations appear to be more affected than others. METHODS: The presence of congenital malformations in 15,570 infants born after IVF with an embryo transfer between April 1, 2001, and the end of 2006 were compared with all infants born in Sweden during 2001 to 2007 (n = 689,157). Risk estimates were made after adjusting for year of birth, maternal age, parity, smoking, and body mass index. The risks of specific malformations were compared with data from a previous study (1982 to March 31, 2001) of 16,280 infants born after IVF. Different IVF methods were compared to respect to malformation risk. RESULTS: Increased risks of a similar magnitude were found for most cardiovascular malformations and limb reduction defects for both study periods. For neural tube defects, cardiac septal defects, and esophageal atresia, there was still an increased risk, but it was lower during the second than during the first period. For small bowel atresia, anal atresia, and hypospadias, the risk increase observed during the first study period had disappeared during the second period. An increased risk was seen for some syndromes that have been associated with imprinting errors. No difference in malformation risk according to IVF method was apparent. CONCLUSIONS: A slightly increased risk for congenital malformations after IVF persists. A decreasing risk is seen for some specific malformations, either true or the result of multiple testing.

[Effect of different embryo transfer strategies on the outcome of assisted reproduction]. / Effekt unterschiedlicher Strategien beim Embryotransfer auf die Ergebnisse der assistierten Reproduktion.

Currently, there is a rising trend to consider a multiple delivery as a genuine complication of assisted reproduction, which can be prevented by the replacement of one single, selected embryo. Particularly previously infertile women due to their poor reproductive function are at risk of complications during gestation leading to premature delivery. Cerebral palsy is the most common consequence of multiple gestation and a significant cause of disabling among the offspring. Particularly Swedish specialists in reproductive medicine have been at the forefront of the development of single embryo transfer (denominated SET), which has become the main therapeutic strategy in IVF since 2004. In Sweden, approximately 70 % of all treatment cycles with assisted reproduction are now being performed with SET. Despite the transfer of fewer embryos per cycle, acceptable pregnancy rates are being achieved thereby reducing the multiple delivery rate to approximately 5 %. In Switzerland, however, legal restrictions ban the selection of embryos, so that all available embryos (not more than three) are still being transferred.