Endometrial preparation protocols prior to frozen embryo transfer - convenience or safety?

The number of frozen embryo transfer (FET) cycles is increasing rapidly worldwide. Different endometrial preparations for FET result in comparable live birth rates. However, several recent publications have reported higher maternal risks for hypertensive disorders of pregnancy (HDP), pre-eclampsia and postpartum haemorrhage (PPH) in programmed cycles (PC-FET) compared with natural cycles and modified natural cycles with an intact corpus luteum. Nevertheless, PC-FET is frequently used in ovulatory women despite the increased risks for HDP, pre-eclampsia and PPH. Although randomized controlled studies have been suggested, PC-FET raises several methodological problems. Large study populations would be required to investigate the outcomes in question, and the inclusion of ovulatory women, where the intervention may increase the risk of a negative outcome, is ethically troublesome. In the authors' opinion, the existing evidence from large observational studies and systematic reviews is sufficiently strong to recommend an endometrial preparation strategy that aims to maintain or stimulate the corpus luteum to minimize the risk of HDP and pre-eclampsia after FET cycles.

Vaginal progesterone as luteal phase support in natural cycle frozen-thawed embryo transfer (ProFET): protocol for a multicentre, open-label, randomised controlled trial.

INTRODUCTION: Vaginal progesterone supplementation is frequently given to patients receiving frozen embryo transfer (FET) in the natural cycle aiming to increase the chance of pregnancy and live birth. To date, only a few studies have investigated if progesterone supplementation is beneficial in these cycles and the level of evidence for progesterone supplementation is very low. METHODS AND ANALYSIS: The ProFET trial is a multicentre, open-label, randomised controlled trial powered for this investigation, including 1800 women with regular menstrual cycles (24-35 days), aged 18-43 years planned for natural cycle-FET receiving a single blastocyst for transfer. Participants are randomised (1:1:1) to either luteal phase progesterone for 3 weeks, luteal phase progesterone for 7 weeks or no luteal phase progesterone. The participating study centres consist of 12 in vitro fertilisation-clinics in Sweden and 1 in Iceland. The primary outcome is to investigate if luteal phase support (LPS) by vaginal progesterone increases the chance of a live birth per randomised patient in a natural FET cycle compared with no LPS. ETHICS AND DISSEMINATION: The trial was approved by the Swedish Ethical Review Authority (ID 2020-06774, 2021-02822 and 2022-01502-02) and the Swedish Medical Products Agency (ID nr 5.1-2020-102613). All participants are required to provide written informed consent. The outcome of this study will be disseminated to the public through broadcasts, newspapers and presentations at scientific congresses as well as publications in international scientific journals. TRIAL REGISTRATION NUMBER: NCT04725864.

The Association Between High Birth Weight and Long-Term Outcomes-Implications for Assisted Reproductive Technologies: A Systematic Review and Meta-Analysis.

Background: Studies have shown that the prevalence of children born with high birth weight or large for gestational age (LGA) is increasing. This is true for spontaneous pregnancies; however, children born after frozen embryo transfer (FET) as part of assisted reproductive technology (ART) also have an elevated risk. In recent years, the practice of FET has increased rapidly and while the perinatal and obstetric risks are well-studied, less is known about the long-term health consequences. Objective: The aim of this systematic review was to describe the association between high birth weight and LGA on long-term child outcomes. Data Sources: PubMed, Scopus, and Web of Science were searched up to January 2021. Exposure included high birth weight and LGA. Long-term outcome variables included malignancies, psychiatric disorders, cardiovascular disease, and diabetes. Study Selection: Original studies published in English or Scandinavian languages were included. Studies with a control group were included while studies published as abstracts and case reports were excluded. Data Extraction: The methodological quality, in terms of risk of bias, was assessed by pairs of reviewers. Robins-I (www.methods.cochrane.org) was used for risk of bias assessment in original articles. For systematic reviews, AMSTAR (www.amstar.ca) was used. For certainty of evidence, we used the GRADE system. The systematic review followed PRISMA guidelines. When possible, meta-analyses were performed. Results: The search included 11,767 articles out of which 173 met the inclusion criteria and were included in the qualitative analysis, while 63 were included in quantitative synthesis (meta-analyses). High birth weight and/or LGA was associated with low to moderately elevated risks for certain malignancies in childhood, breast cancer, several psychiatric disorders, hypertension in childhood, and type 1 and 2 diabetes. Conclusions: Although the increased risks for adverse outcome in offspring associated with high birth weight and LGA represent serious health effects in childhood and in adulthood, the size of these effects seems moderate. The identified risk association should, however, be taken into account in decisions concerning fresh and frozen ART cycles and is of general importance in view of the increasing prevalence in high birthweight babies.

Cumulative live birth rate after IVF: trend over time and the impact of blastocyst culture and vitrification.

STUDY QUESTION: Has cumulative live birth rate (CLBR) improved over time and which factors are associated with such an improvement? SUMMARY ANSWER: During an 11-year period, 2007-2017, CLBR per oocyte aspiration increased significantly, from 27.0% to 36.3%, in parallel with an increase in blastocyst transfer and cryopreservation by vitrification. WHAT IS KNOWN ALREADY: While it has been shown that live birth rate (LBR) per embryo transfer (ET) is higher for fresh blastocyst than for fresh cleavage stage embryo transfer, CLBR per oocyte aspiration, including one fresh ET and all subsequent frozen embryo transfers (FET), does not seem to differ between the two culture strategies. STUDY DESIGN SIZE DURATION: A national register study including all oocyte aspirations performed in Sweden from 2007 to 2017 (n = 124 700 complete IVF treatment cycles) was carried out. Oocyte donation cycles were excluded. PARTICIPANTS/MATERIALS SETTING METHODS: Data were retrieved from the Swedish National Registry of Assisted Reproduction (Q-IVF) on all oocyte aspirations during the study period where autologous oocytes were used. CLBR was defined as the proportion of deliveries with at least one live birth per oocyte aspiration, including all fresh and/or frozen embryo transfers within 1 year, until one delivery with a live birth or until all embryos were used, whichever occurred first. The delivery of a singleton, twin, or other multiples was registered as one delivery. Cryopreservation of cleavage stage embryos was performed by slow freezing and of blastocyst by vitrification. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 124 700 oocyte aspirations were performed (in 61 313 women), with 65 304 aspirations in women <35 years and 59 396 in women ≥ 35 years, resulting in 38 403 deliveries with live born children. Overall, the CLBR per oocyte aspiration increased significantly during the study period, from 27.0% to 36.3% (odds ratio (OR) 1.039, 95% CI 1.035-1.043) and from 30.0% to 43.3% if at least one ET was performed (adjusted OR 1.055, 95% CI 1.050-1.059). The increase in CLBR was independent of maternal age, number of oocytes retrieved and number of previous IVF live births. The CLBR for women <35 and ≥35 years both increased significantly, following the same pattern. During the study period, a substantially increasing number of blastocyst transfers was performed, both in fresh and in FET cycles. Other important predicting factors for live birth, such as number of embryos transferred, could not explain the improvement. An increased single embryo transfer rate was observed with time. LIMITATIONS REASONS FOR CAUTION: The retrospective design implicates that other confounders of importance for CLBR cannot be ruled out. In addition, some FET cycles might be performed later than 1 year post oocyte aspiration for the last year (2017) and are, thus, not included in this study. In addition, no data on 'dropouts', i.e. patients that do not continue their treatment despite having cryopreserved embryos, are available, or if this drop-out rate has changed over time. WIDER IMPLICATIONS OF THE FINDINGS: The results suggest that blastocyst transfer, particularly when used in FET cycles and in combination with vitrification, is an important contributor to the improved live birth rates over time. This gives a possibility for a lower number of oocyte aspirations needed to achieve a live birth and a shortened time to live birth. STUDY FUNDING/COMPETING INTERESTS: The study was financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-70940) and by Hjalmar Svensson's research foundation. None of the authors declares any conflict of interest.

Alcohol and illicit and non-medical prescription drug use before and during pregnancy in Stockholm, Sweden: A cross-sectional study.

OBJECTIVES: To provide current estimates of alcohol and drug use among pregnant women attending antenatal care lectures in preparation for childbirth in Stockholm, Sweden. STUDY DESIGN: A cross-sectional study. Data was collected anonymously among women attending lectures in preparation for childbirth. MAIN OUTCOME MEASURES: The prevalence of alcohol and illicit and non-medical prescription drug use among pregnant women attending antenatal care lectures in preparation for childbirth. RESULTS: Nine hundred and thirty-six pregnant women attending lectures in preparation for childbirth participated. Among those answering all questions about alcohol use during pregnancy, 4.2 percent reported use (95% confidence interval (CI), 3.0-5.7%) and among those answering all questions about illicit or non-medical prescription drug use during pregnancy, 0.5 percent reported such use (95% CI, 0.1-1.3%). The prevalences of binge drinking during pregnancy and alcohol and drug use before pregnancy are presented. Comparisons of anonymously and non-anonymously collected data are included. CONCLUSIONS: Approximately one in 25 women reported using alcohol and approximately one in 200 reported using illicit or non-medical prescription drugs while pregnant. Alcohol use during pregnancy may have decreased in Stockholm, Sweden.

A systematic review and meta-analysis on the association between ICSI and chromosome abnormalities.

BACKGROUND: In the decade following the introduction of ICSI, a higher prevalence of de novo chromosome abnormalities, in particular sex chromosome and autosomal structural abnormalities, as well as inherited abnormalities was described in children conceived by ICSI compared to both naturally conceived (NC) children and children conceived by standard IVF. The explanation for the observed increase in prevalence is not clear and has been suggested to reflect parental factors (e.g. age or sperm quality) or to be a result of the ICSI procedure itself. Over the years, the procedure, as well as the patient group, and indications for ICSI treatment have changed. OBJECTIVE AND RATIONALE: The objective of this systematic review and meta-analysis was to assess the prevalence of chromosome abnormalities in ICSI pregnancies and children and to examine any potentially increased risk compared to standard IVF and NC. SEARCH METHODS: Pubmed, Embase, Cochrane Libraries and Web of Science up to October 2020 were searched. Primary outcome measures were overall chromosome abnormalities and de novo abnormalities (including sex chromosome abnormalities and autosomal abnormalities). The secondary outcome was inherited abnormalities. We followed the PRISMA guidelines and relevant meta-analyses were performed. OUTCOMES: The search included 4648 articles, out of which 27 met the inclusion criteria, and 19 were included in quantitative synthesis (meta-analyses). The prevalence of chromosome abnormalities varied considerably between studies, possibly explained by large differences in sample size and patient demographics. Only five studies were eligible for pooled analyses on adjusted data. All studies had a critical risk of bias. Results from pooled adjusted data showed no evidence of an increased risk of overall chromosome abnormalities when comparing ICSI to either standard IVF (aOR 0.75 (95% CI 0.41-1.38)) or NC (aOR 1.29 (95% CI 0.69-2.43)). In contrast, meta-analyses on unadjusted data showed an increased risk of overall chromosome abnormalities in ICSI compared to both standard IVF (OR 1.42 (95% CI 1.09-1.85)) and NC (OR 2.46 (95% CI 1.52-3.99)) and an increased risk of de novo abnormalities in ICSI compared to NC (OR 2.62 (95% CI 2.07-3.31)). Yet, based on a very low certainty of evidence, the conclusion remains, that no indication of an increased risk of chromosome abnormalities in ICSI offspring could be found. If an increased risk of chromosome abnormalities in selected ICSI offspring should exist, the absolute risk continues to be small. WIDER IMPLICATIONS: This review provides an extensive overview of the existing evidence on the relationship between ICSI and chromosome abnormalities in the offspring. We highlight the need for well-designed large, prospective, controlled studies with systematic cytogenetic testing. Existing data are limited and, in many cases, marred by critical levels of bias.

Potentially traumatic events, fear of childbirth and posttraumatic stress disorder during pregnancy in Stockholm, Sweden: A cross-sectional study.

OBJECTIVES: To estimate the prevalence of potentially traumatic events (PTEs), fear of childbirth (FOC), and support for it as well as posttraumatic stress disorder (PTSD) among pregnant women attending maternal care in Stockholm, Sweden. METHODS: A cross-sectional study was conducted. Pregnant women attending lectures in preparation for childbirth at the major hospitals in Stockholm were asked to complete questionnaires anonymously. Main outcome measures were the prevalence of PTEs, FOC, support for FOC and PTSD. RESULTS: One thousand one hundred fifty-seven women in late pregnancy attending lectures in preparation for childbirth at hospitals in Stockholm, Sweden, were asked to participate, 945 chose to participate, resulting in a response rate of 81.7 percent. Most pregnant women, 78.5 percent (95% confidence interval (CI) 75.6-81.3), reported having experienced at least one PTE. The prevalence of having experienced different types of violence is presented. FOC was found among 28.8 percent (95% CI 25.7-32.0) of pregnant women, while only 10.9 percent (95% CI 10.5-11.2) received support for FOC. The prevalence of current PTSD was 4.1 percent (95% CI 2.8-5.8). CONCLUSIONS: The majority of pregnant women had experienced PTEs, and experiences of violence were common, as was FOC. Approximately one in 25 women attending general maternal care in Stockholm, Sweden, was estimated to have current PTSD. This highlights the need to prevent violence, find pregnant women suffering from FOC or PTSD, to develop an evidence-based treatment for FOC and to provide such treatment for PTSD.

The association between the number of oocytes retrieved for IVF, perinatal outcome and obstetric complications.

STUDY QUESTION: Is there an association between the number of oocytes retrieved for IVF, and perinatal and obstetric outcomes? SUMMARY ANSWER: No significant association was found between the number of oocytes retrieved and perinatal outcomes, while an association was found for placenta praevia and male gender. WHAT IS KNOWN ALREADY: Previous studies have shown that between 6 and 15 oocytes retrieved is optimal for the live birth rate in fresh cycles. In a recent study, we showed that the cumulative live birth rate, including fresh and all cryopreservation cycles following one OPU, increases by the number of oocytes retrieved, up to approximately 20 oocytes. However, there was also an increase in serious side effects such as severe ovarian hyperstimulation syndrome (OHSS). A few studies, with contradictory results, have investigated whether the number of oocytes retrieved might also be associated with negative obstetric and perinatal outcomes. STUDY DESIGN, SIZE, DURATION: A retrospective population-based registry study including all singleton babies born after fresh IVF cycles from 2002 to 2015 (n = 27 359) in Sweden. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on treatment characteristics from the Medical Birth/IVF Registry and the Swedish National Quality Registry of Assisted Reproduction, including all fresh IVF cycles performed in public or private infertility clinics during the study period and resulting in singleton deliveries, were cross-linked to the Medical Birth Registry and the National Patient Registry for maternal and neonatal outcome. Data on educational level, ethnicity and paternal age were obtained through cross-linking to Statistics Sweden. Oocyte donation cycles were excluded. Main perinatal outcome variables were preterm birth (PTB <37 gestational weeks), very PTB (<32 gestational weeks), small for gestational age (SGA: <2 SD), peri/neonatal death and major birth defects. Main obstetric outcome variables were hypertensive disorders of pregnancy and placenta praevia. Univariable and multivariable analyses were used to explore the association between the number of oocytes retrieved and outcome variables. Adjustments were performed for maternal age, parity, smoking, BMI, cause of infertility, maternal educational level, maternal country of birth, treatment period, embryo stage, fertilization method (IVF/ICSI), number of embryos transferred, OHSS and vanishing twin. MAIN RESULTS AND THE ROLE OF CHANCE: The number of oocytes retrieved was analyzed as a continuous variable as well as categorized as <10, 10-14, 15-19 and >20 oocytes. A number of between four and nine oocytes was used as a reference. Single embryo transfer was performed in 20 910 (76.4%) of the cycles. Blastocyst transfer was performed in 3478 (12.7%) and cleavage stage embryo transfer was performed in 23 881 (87.3%) of the cycles. No significant association was observed between the number of oocytes retrieved (continuous variable) and PTB (adjusted odds ratio [AOR] 1.002, 95% CI 0.994-1.011), very PTB (AOR 1.013, 95% CI 0.994-1.032), SGA (AOR 0.998, 95% CI 0.988-1.009), peri/neonatal death (AOR 1.008, 95% CI 0.975-1.043) or major birth defects (AOR 1.009, 95% CI 0.998-1.020). Concerning obstetric outcomes, a significant association was found for placenta praevia (AOR 1.021, 95% CI 1.005-1.037) while no association was found for hypertensive disorders of pregnancy (AOR 0.991, 95% CI 0.981-1.001). Furthermore, a significant association was detected between the number of oocytes retrieved and the secondary outcome variable gender distribution, with a higher rate of males after >20 oocytes (AOR 1.126, 95% CI 1.014-1.249). LIMITATIONS, REASONS FOR CAUTION: As in all observational studies, unknown confounders may affect outcomes. WIDER IMPLICATIONS OF THE FINDINGS: These results are reassuring, indicating that there is no association between adverse neonatal outcomes and the number of oocytes retrieved. The association between the number of oocytes and placenta praevia was significant, though weak. The finding of an association with gender should be interpreted with caution. STUDY FUNDING/COMPETING INTEREST(S): Financial support was received through Sahlgrenska University Hospital (ALFGBG-70 940) and the Hjalmar Svensson Research Foundation. None of the authors declares any conflict of interest.

The number of oocytes retrieved during IVF: a balance between efficacy and safety.

STUDY QUESTION: What is the relationship between the number of oocytes collected in fresh IVF treatments and the likelihood of cumulative delivery rate (fresh and frozen) per oocyte aspiration, severe ovarian hyperstimulation syndrome (OHSS) and thromboembolic events? SUMMARY ANSWER: Cumulative delivery rate per aspiration increases up to 20 oocytes retrieved and then evens out while the incidence of severe OHSS increases more rapidly from around 18 oocytes and thromboembolic events, although rare, occurs in particular if 15 or more oocytes are retrieved. WHAT IS KNOWN ALREADY?: Previous studies have shown that the number of oocytes retrieved for IVF is a positive predictor of live birth in fresh cycles. Few studies have investigated cumulative live birth rates and OHSS in relation to the number of aspirated oocytes. STUDY DESIGN, SIZE, DURATION: Retrospective population-based registry study including 39 387 women undergoing 77 956 fresh IVF cycles in the period 2007-2013 and 36 270 consecutive transfers of frozen/thawed embryos in the period 2007-2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from The Swedish National Quality Registry of Assisted Reproduction (Q-IVF) including all IVF cycles with oocyte retrieval performed in public or private infertility clinics during the study period, was cross-linked to the National Patient Register regarding diagnostic codes (ICD 10) for severe (OHSS) and thromboembolic events. Oocyte donation cycles were excluded. MAIN RESULTS AND THE ROLE OF CHANCE: Live birth delivery rate in fresh cycles increased up to 11 oocytes retrieved and then evened out, where the live birth rate was 30.3% for a 34-year-old woman. The cumulative delivery rate per aspiration, including fresh transfer and all subsequent transfers of frozen-thawed embryos (FET cycles) per oocyte retrieval, increased up to approximately 20 oocytes where it reached 45.8%. The adjusted odds ratio (AOR) for live birth by the number of oocytes was 1.064 (95% CI: 1.061; 1.067). The incidence of severe OHSS increased significantly by the number of oocytes, particularly if more than 18 oocytes were retrieved. The AOR for OHSS by the number of oocytes was 1.122 (95% CI: 1.08; 1.137). Thromboembolic events were rare, a total of 16 events in 14 patients were observed, and occurred in particular if 15 or more oocytes were retrieved. LIMITATIONS, REASONS FOR CAUTION: All FET cycles might not be included. Some embryos cryopreserved between 2010 and 2013 might still result in additional births until 2018. Furthermore the gonadotrophin dose was not included in the Q-IVF Registry in the study period, thus adjustment for dose was not possible. WIDER IMPLICATIONS OF THE FINDINGS: The results suggest a shift at approximately 18-20 oocytes where the cumulative delivery rate per aspiration levels off and, at the same time, the incidence of severe OHSS increases more rapidly. Thromboembolic events, although rare, should also be taken into consideration at stimulation regimes for IVF. Evaluating data taking both efficacy and the most serious safety aspects into account, is a new approach and of crucial importance both for patients undergoing IVF and their physicians. STUDY FUNDING/COMPETING INTEREST: Financial support was received through an agreement relating to research and the education of doctors (ALFGBG-70 940) and grant from the Hjalmar Svensson Research Foundation. None of the authors declares any conflict of interest.

Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE): A Pilot Study in Alcohol-dependent Women.

OBJECTIVES: Posttraumatic stress disorder (PTSD) and substance use disorders are highly comorbid. Effective treatments are largely lacking. This pilot study evaluated the safety and feasibility of a novel intervention, Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE), in preparation for a randomized controlled trial. METHODS: Twenty-two treatment-seeking women with current DSM-IV-TR PTSD and alcohol dependence (AD) were recruited. Participants received COPE. Safety and feasibility were evaluated, as were efficacy-related outcomes: PTSD and depression symptom severity, alcohol use, craving, and dependence severity. RESULTS: No adverse events occurred. COPE was implemented in routine clinical practice. Among the assessed women, 95.8% were eligible to participate. Treatment attendance and completion were higher than in previous studies. Post treatment, all efficacy-related outcomes, including PTSD and depression symptom severity, alcohol use, craving, and dependence severity, were significantly reduced. CONCLUSIONS: COPE was safe and feasible to use. Concerns that trauma-focused, exposure-based therapy might promote relapse in this population appear unwarranted. Our findings provide initial evidence suggestive of COPE efficacy for comorbid PTSD and AD in women. These results provide a strong rationale for investigating the efficacy of COPE for comorbid PTSD and AD in women in a randomized controlled trial.

Can de novo stress incontinence after anterior wall repair be predicted?

OBJECTIVE: To locate preoperatively continent women with pelvic organ prolapse at risk of developing incontinence after surgery by means of reducing the prolapse preoperatively with a speculum and a pessary. DESIGN: Prospective observational cohort study. SETTING: Departments of Obstetrics and Gynecology at Northern Alvborgs County Hospital, Varbergs Hospital, and Sahlgrenska University Hospital, Sweden, between 2000 and 2004. POPULATION: Patients scheduled for anterior wall repair with no history of incontinence. METHODS: Data were collected using a questionnaire, a voiding diary, a gynecological examination including staging of prolapse with the Pelvic Organ Quantification System and clinical testing preoperatively and one year after vaginal repair. The first test included a cough test while the prolapse was reduced with a speculum. The second test was performed with the patient undergoing a standardized quantification test and a 48-hour pad test after reducing the prolapse with a pessary. Postoperatively, clinical testing was repeated one year after surgery without any device in place. MAIN OUTCOME MEASURES: Reported symptoms of leakage during movement or coughing. RESULTS: Seventy-four patients were included. Before surgery, six (8.1%) women tested positive during the speculum test and seven (9.5%) during the pessary test. Eight women (10.8%) were found to have subjective urinary stress incontinence after 1 year. This was only confirmed in four women during stress testing. The positive predictive values for subjective stress incontinence of the speculum and the pessary tests were 42.9% (95%CI 12.0-76.9) and 33.3% (95%CI -4.4 to +71.5), respectively. The negative predictive values of the tests were 92.5% (95%CI 90.3-1.00) and 91.1% (95%CI 88.5-99.7). CONCLUSIONS: The tested preoperative methods predicting de novo subjective stress incontinence after anterior wall repair did not show sufficient positive predictive values to be clinically useful.

Genetic moderators and psychiatric mediators of the link between sexual abuse and alcohol dependence.

BACKGROUND/OBJECTIVE: This study used a case-control female sample to test psychiatric mediators and genetic moderators of the effect of sexual abuse on later alcohol dependence. The study also tested differences between alcohol dependent women with or without a history of sexual abuse on variables that might affect treatment planning. METHODS: A case-control design compared 192 treatment-seeking alcohol dependent women with 177 healthy population controls. All participants were assessed for alcohol-related behaviors, sexual abuse history, psychiatric problems, and personality functioning. Markers were genotyped in the CRHR1, MAO-A and OPRM1 genes. RESULTS: The association of sexual abuse with alcohol dependence was limited to the most severe category of sexual abuse involving anal or vaginal penetration. Of the five psychiatric disorders tested, anxiety, anorexia nervosa, and bulimia met criteria as potential mediators of the abuse-alcohol dependence association. Severe sexual abuse continued to have an independent effect on alcohol dependence status even after accounting for these potential mediators. None of the candidate genetic markers moderated the association between sexual abuse and alcohol dependence. Of alcohol dependent participants, those with a history of severe abuse rated higher on alcoholism severity, and psychiatric comorbidities. CONCLUSION: Sexual abuse is associated with later alcohol problems directly as well as through its effect on psychiatric problems. Treatment-seeking alcohol dependent women with a history of abuse have distinct features as compared to other alcohol dependent women.

Early onset alcohol dependence with high density of family history is not "male limited".

OBJECTIVE: Based on classical adoption studies, early onset type II alcoholism was originally described as "male limited." We examined the possible expression of this subtype in present day alcohol-dependent women. Detailed systematic assessment was obtained from 200 treatment-seeking alcohol-dependent women and 189 healthy population controls. Women fulfilling type II alcoholism criteria had higher alcoholism severity as measured by The Alcohol Use Disorders Identification Test and markedly higher use of illicit drugs. Both alcoholism subtypes scored higher than normal on anxiety and impulsivity traits, but type II women scored markedly higher on aggression subscales than either of the other groups. Importantly, density of family history was markedly higher in type II women, suggesting a higher heritability. Despite its original description as male limited, early onset alcoholism with high density of family history is likely to be a valid construct in women. Its recognition has important implications for diagnosis, treatment, and research.

Characterization of 14C in Swedish light water reactors.

This paper presents the results of a 4-y investigation of 14C in different waste streams of both boiling water reactors (BWRs) and pressurized water reactors (PWRs). Due to the potential impact of 14C on human health, minimizing waste and releases from the nuclear power industry is of considerable interest. The experimental data and conclusions may be implemented to select appropriate waste management strategies and practices at reactor units and disposal facilities. Organic and inorganic 14C in spent ion exchange resins, process water systems, ejector off-gas and replaced steam generator tubes were analyzed using a recently developed extraction method. Separate analysis of the chemical species is of importance in order to model and predict the fate of 14C within process systems as well as in dose calculations for disposal facilities. By combining the results of this investigation with newly calculated production rates, mass balance assessments were made of the 14C originating from production in the coolant. Of the 14C formed in the coolant of BWRs, 0.6-0.8% was found to be accumulated in the ion exchange resins (core-specific production rate in the coolant of a 2,500 MWth BWR calculated to be 580 GBq GW(e)(-1) y(-1)). The corresponding value for PWRs was 6-10% (production rate in a 2,775 MWth PWR calculated to be 350 GBq GW(e)(-1) y(-1)). The 14C released with liquid discharges was found to be insignificant, constituting less than 0.5% of the production in the coolant. The stack releases, routinely measured at the power plants, were found to correspond to 60-155% of the calculated coolant production, with large variations between the BWR units.

Hazardous alcohol users during pregnancy: psychiatric health and personality traits.

BACKGROUND: We examined alcohol use disorders, psychiatric symptoms and personality traits in women reporting alcohol use during pregnancy. METHODS: In a pilot cohort (n=139), subjects were screened for alcohol use disorders, and assessed for psychopathology, personality traits, and alcohol use during the first trimester. Those reporting consumption exceeding a conservative threshold for harmful use were offered a diagnostic psychiatric interview. The main findings of the pilot study were replicated using a large sample of women in the third trimester (n=715), who were screened for alcohol use disorders, had their consumption during pregnancy assessed, and were assessed for personality traits. RESULTS: In the pilot cohort, only a minority of women who consumed significant amounts of alcohol during pregnancy fulfilled alcohol dependence criteria, or had scores on the Alcohol Use Disorder Identification Test typically associated with such a diagnosis. Psychiatric morbidity was also unremarkable as assessed by self-reported symptom intensity. The distinguishing feature was high novelty seeking. The results were robustly confirmed in the replication study. CONCLUSIONS: Most women with significant alcohol consumption during pregnancy do not seem to be alcohol dependent. Instead, use during pregnancy may reflect impulsive personality traits, and be correlated with additional risk behaviors.

Assessment of the environmental contamination with long-lived radionuclides around an operating RBMK reactor station.

The presence of man-made gamma emitting radionuclides in the region within 32km radius of the Ignalina NPP/Lithuania has been investigated during the period 2001-2004, prior to the closure of the first of the two operating RBMK 1500-type reactors. Gamma spectrometric measurements of various terrestrial and aquatic plants as well as of soil samples showed moderate environmental contamination with the fission product (137)Cs and with the neutron activation products (60)Co and (54)Mn. Traces of the activation products (65)Zn and (110m)Ag were found in the nearest vicinity of the NPP. Activity concentrations were inhomogeneously distributed in the area of interest. Moss and algae samples showed the highest uptake of radionuclides. In addition to the gamma spectrometric measurements, the levels of (14)C were determined in the same bio-indicator samples using accelerator mass spectrometry.

Identifying hazardous alcohol consumption during pregnancy: implementing a research-based model in real life.

AIMS: It has been repeatedly demonstrated that hazardous alcohol use during pregnancy is rarely detected in regular antenatal care, and that detection can be markedly improved using systematic screening. A major challenge is to translate research-based strategies into regular antenatal care. Here, we examined whether a screening strategy using the Alcohol Use Disorder Test (AUDIT) and time-line follow-back (TLFB) could be implemented under naturalistic conditions and within available resources; and whether it would improve detection to the extent previously shown in a research context. METHODS: Regular midwives at a large antenatal care clinic were randomized to receive brief training and then implement AUDIT and TLFB ("intervention"); or to a waiting-list control group continuing to deliver regular care ("control"). In the intervention-condition, AUDIT was used to collect data about alcohol use during the year preceding pregnancy, and TLFB to assess actual consumption during the first trimester. Data were collected from new admissions over 6 months. RESULTS: Drop out was higher among patients of the intervention group than control midwives, 14% (23/162) versus 0% (0/153), and p<0.0001. A one-day training session combined with continuous expert support was sufficient to implement systematic screening with AUDIT and TLFB largely within resources of regular antenatal care. The use of these instruments identified patients with hazardous consumption during the year preceding pregnancy i.e. AUDIT score 6 or higher (17%, 23/139), and patients with ongoing consumption exceeding 70 g/week and/or binge consumption according to TLFB (17%, 24/139), to a significantly higher degree than regular antenatal screening (0/162). The AUDIT- and TLFB-positive populations overlapped partially, with 36/139 subjects screening positive with either of the instrument and 11/139 were positive for both. CONCLUSIONS: We confirm previous findings that alcohol use during pregnancy is more extensive in Sweden than has generally been realized. Systematic screening using AUDIT and TLFB detects hazardous use in a manner which regular antenatal care does not. This remains true under naturalistic conditions, following minimal training of regular antenatal care staff, and can be achieved with minimal resources. The proposed strategy appears attractive for broad implementation.

Unexpectedly high prevalence of alcohol use among pregnant Swedish women: failed detection by antenatal care and simple tools that improve detection.

OBJECTIVE: We examined the use of alcohol during early pregnancy in urban Swedish women, the ability of Swedish antenatal care to identify alcohol-related risk pregnancies and the utility of some potential tools for improving its performance. METHOD: Women attending regular antenatal care were randomized to regular assessment only (control, n = 156) or intensified screening (intervention, n = 147). In the intervention group, alcohol use was determined using the Timeline Followback (TLFB) interview, alcohol use habits with the Alcohol Use Disorder Inventory Test (AUDIT), and biomarkers for alcohol use were analyzed. Data were typically obtained in pregnancy week 12. RESULTS: In the intervention group as a whole, average absolute alcohol consumption during the first 6 weeks of pregnancy was low but highly variable (mean [SD] = 24.9 [50.5] g/week; 4.8 [6.0] episodes for the entire 6 week period); 22 women (15%) drank at levels exceeding 70 g/week during any 2 or more weeks and/or in a heavy episodic drinking pattern, 60 g/episode, on 2 or more episodes. The AUDIT had a moderate sensitivity (54%) to identify these subjects. Biomarkers identified subjects with somatic illness rather than high alcohol consumption. In the control group, only 4 (3%) were identified as using alcohol, indicating a probable underestimation of alcohol use by regular antenatal screening procedures (p = .0001). CONCLUSIONS: An unexpected proportion of pregnant women in urban Sweden consume alcohol at levels likely to produce adverse effects. Regular antenatal care did not identify most of these risk pregnancies. The TLFB identified pregnant women with risk use of alcohol during pregnancy who were only partly identified by analyzing prepregnancy alcohol use patterns with the AUDIT. Elevated laboratory markers likely indicated somatic illness rather than harmful drinking.

Fetus at risk: prevalence of alcohol consumption during pregnancy estimated with a simple screening method in Swedish antenatal clinics.

AIMS: Maternal alcohol consumption is a major health hazard for the fetus. Sweden has an extensive system of public antenatal care clinics, whose mission is to detect and prevent this type of health hazards. However, very few cases of alcohol consumption during pregnancy are detected. The aim of this study was to examine the prevalence of hazardous or harmful alcohol consumption during pregnancy in a consecutive series of Swedish pregnant females. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: The Alcohol Use Disorders Identification Test (AUDIT) was used to collect anonymous data from consecutive pregnant subjects admitted during 1 year to an antenatal clinic in Stockholm, and signing up for parental education offered routinely (n = 1327). Data were obtained from 1101 subjects, typically in pregnancy week 30. A complete AUDIT form was filled out referring to alcohol use during the year prior to pregnancy. A separate form with the consumption items from AUDIT was filled out to report behaviour during pregnancy. FINDINGS: For the year preceding pregnancy, 17% of subjects reported AUDIT scores of 6 or higher, indicating hazardous or harmful alcohol use in women. Few individuals reported scores of 13 or higher (indicating abuse or dependence), but almost half the subjects (46%) reported binge drinking (six standard drinks on a single occasion) once/month or more often, and 6% reported binge drinking on every occasion of alcohol consumption. One-third of the subjects (30%) continued regular alcohol use during pregnancy, and 6% reported consumption two to four times/month. In a logistic regression model, AUDIT scores for the year prior to pregnancy and subject age, but not education level were significant predictors of continued alcohol use during pregnancy. CONCLUSIONS: Alcohol use during pregnancy is more extensive than has been presumed in Sweden. Simple, clinically useful screening methodology detects hazardous consumption during pregnancy in a manner which regular antenatal care does not. If this methodology can be shown to have similar sensitivity when administered under non-anonymous conditions, it should be made part of routine antenatal care.