Outcomes of in-vitro fertilization after bariatric surgery: a national register-based case-control study.

STUDY QUESTION: Does previous bariatric surgery (BS) in women affect cumulative live birth rate in IVF? SUMMARY ANSWER: Women having had BS seem to have the same cumulative live birth rate as non-operated women of the same BMI at IVF treatment. WHAT IS KNOWN ALREADY: Because of the perinatal risks of obesity to mother and infant as well as impaired outcomes of IVF, obese women are advised to reduce their weight, but it is not clear whether previous BS could affect IVF results. STUDY DESIGN, SIZE, DURATION: This national register-based case-control study included all cases of BS (n = 30 436) undergoing IVF (n = 153) from 2007 until 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Swedish women between 18 and 45 years operated with BS, with at least one first started cycle of IVF after surgery, were included. For each woman having IVF after BS (n = 153), up to five non-operated control women (n = 744) starting their first IVF cycle during the study period were matched for age, parity and BMI at treatment. The primary outcome in this study was the cumulative live birth rate (CLBR) after the first IVF cycle, defined as all live births after the first cycle including fresh and frozen embryo transfers. MAIN RESULTS AND THE ROLE OF CHANCE: There was no significant difference in CLBR between the BS group and the matched controls (29.4% compared to 33.1%), even though the number of retrieved oocytes (7.6 vs 8.9, P = 0.005) and frozen embryos (1.0 vs 1.5, P = 0.041) were significantly fewer in the BS group. There was no association between cumulative live birth and BS, adjusted odds ratio 1.04, 95% CI (0.73, 1.51). However, the birth weight was significantly lower in the children born to mothers with previous BS, mean (SD) 3190 (690) vs 3478 (729) g, P = 0.037. LIMITATIONS, REASONS FOR CAUTION: Confounders such as age, BMI and previous childbirth were accounted for by the matching design of the study, but there were no data on indication for IVF, anti-Müllerian hormone, smoking or previous comorbidities. The study was exploratory and did not reach sufficient power to detect potential smaller differences in live birth rates. WIDER IMPLICATIONS OF THE FINDINGS: The findings concur with those in previously published smaller studies and provide somewhat reassuring results considering IVF outcomes after BS with a CLBR comparable to that of controls, despite a lower mean birth weight. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by grants from the Southern Health Care Region of Sweden. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Cumulative live birth rates after weight reduction in obese women scheduled for IVF: follow-up of a randomized controlled trial.

STUDY QUESTION: Did weight reduction in obese women scheduled for IVF increase cumulative live birth rate (CLBR) after 2 years? SUMMARY ANSWER: Weight loss prior to IVF did not increase CLBR. WHAT IS KNOWN ALREADY: Few studies have investigated the effect of weight reduction in obese infertile women scheduled for IVF. In a recent randomized controlled trial (RCT), including one IVF cycle, we found no increase in live birth rate after weight reduction. Weight regain after obesity reduction treatment often occurs, and children born to obese women have a higher risk of childhood obesity. STUDY DESIGN SIZE DURATION: A 2-year follow-up of a multicenter, RCT running between 2012 and 2018 was performed. Out of 317 women randomized to weight reduction followed by IVF treatment or IVF treatment-only, 305 remained in the full analysis set. Of these women, 90.5% (276/305) participated in this study. PARTICIPANTS/MATERIALS SETTING METHODS: Nine infertility clinics in Sweden, Denmark and Iceland participated in the RCT. Obese women under 38 years of age having a BMI ≥30 and < 35 kg/m2 were randomized to weight reduction and IVF or IVF-only. In all, 160 patients were randomized to a low calorie diet for 12 weeks and 3-5 weeks of weight stabilization, before IVF and 157 patients to IVF-only. Two years after randomization, the patients filled in a questionnaire regarding current weight, live births and ongoing pregnancies. MAIN RESULTS AND THE ROLE OF CHANCE: 42 additional live births were achieved during the follow-up in the weight reduction and IVF group, and 40 additional live births in the IVF-only group, giving a CLBR, the main outcome of this study, of 57.2% (87/152) and 53.6% (82/153), respectively (P = 0.56; odds ratio (OR) 1.16, 95% CI: 0.74-1.52). Most of the women in the weight reduction and IVF group had regained their pre-study weight after 2 years. The mean weight gain over the 2 years was 8.6 kg, while women in the IVF-only group had a mean weight loss of 1.2 kg. At the 2-year follow-up, the weight standard deviation scores of the children born in the original RCT (index cycle) were 0.218 (1.329) (mean, SD) in the weight reduction and IVF group and - 0.055 (1.271) (mean, SD) in the IVF-only group (P = 0.25; mean difference between groups, 0.327; 95% CI: -0.272 to 0.932). LIMITATIONS REASON FOR CAUTION: All data presented in this follow-up study were self-reported by the participants, which could affect the results. A further limitation is in power for the main outcome. The study is a secondary analysis of a large RCT, where the original power calculation was based on live-birth rate after one cycle and not on CLBR. WIDER IMPLICATIONS OF THE FINDINGS: The follow-up indicates that for women with a BMI ≥30 and < 35 kg/m2 and scheduled for IVF, the weight reduction did not increase their chance of a live birth either in the index cycle or after 2 years. It also shows that even in this highly motivated group, a regain of pre-study weight occurred. STUDY FUNDING/COMPETING INTERESTS: The 2-year follow-up 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 ALFGBG-77690), Merck AB, Solna, Sweden (an affiliate of Merck KGaA, Darmstadt, Germany), Hjalmar Svensson Foundation. Ms Kluge has nothing to disclose. Dr Bergh has been reimbursed for lectures and other informational activities (Ferring, MSD, Merck, Gedeon Richter). Dr Einarsson has been reimbursed for lectures for Merck and Ferring. Dr Thurin-Kjellberg reports grants from Merck, and reimbursement for lectures from Merck outside the submitted work. Dr Pinborg has been reimbursed for lectures and other informational activities (Ferring, MSD, Merck, Gedeon Richter). Dr Englund has nothing to disclose. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT01566929.

Impact of diet and bariatric surgery on anti-Müllerian hormone levels.

STUDY QUESTION: Do serum levels of anti-Müllerian hormone (AMH) change in women of reproductive age following dietary and surgery-induced weight loss? SUMMARY ANSWER: AMH levels increased after very low-calorie diet (VLCD) before surgery and decreased at 6 and 12 months after Roux-en-Y gastric bypass (RYGB), beyond expected normal age-related decline. WHAT IS KNOWN ALREADY: Obesity has negative effects on fertility and IVF outcomes, and possibly also on AMH levels. AMH correlates to the number of growing follicles and is used to predict the response to IVF treatment. However, AMH might decrease after bariatric surgery. STUDY DESIGN, SIZE, DURATION: A prospective cohort study of 48 women followed first for 8 weeks preoperatively, then operated with RYGB and followed postoperatively for 1 additional year. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 18-35 years with a mean (SD) BMI 40.9 (3.6) kg/m2 were included at baseline (BL). After the VLCD, a RYGB was performed. Body weight and height were measured at BL and 1 year postoperatively. Hormones were analysed at BL, after VLCD on the day before surgery, and at 6 and 12 months postoperatively. MAIN RESULTS AND THE ROLE OF CHANCE: Median AMH levels were 30.0 pmol/L at BL and rose significantly after VLCD (median: 35.0 pmol/L; P = 0.014). Median AMH at 6 and 12 months postoperatively were significantly lower (19.5 and 18.0 pmol/L, respectively; P = 0.001). Free androgen index (FAI) was significantly lower after 12 months, compared to BL (1.2 vs 3.5, P < 0.0005). LIMITATIONS REASONS FOR CAUTION: Ultrasound for PCOS diagnosis was not performed. The change in laboratory methods for AMH analysis during the study might be a limitation. WIDER IMPLICATIONS OF THE FINDINGS: Obese young women might choose bariatric surgery also for fertility reasons, and the observed decrease in FAI is in line with improved fertility. More research is needed to evaluate the clinical effects of the decrease of AMH, and the effect of bariatric surgery prior to IVF treatment. STUDY FUNDING/COMPETING INTEREST(S): Study-specific laboratory analyses were funded by the Swedish Regional Research Fund (ALF). Authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

The addition of anti-Müllerian hormone in an algorithm for individualized hormone dosage did not improve the prediction of ovarian response-a randomized, controlled trial.

Study question: Does the addition of anti-Müllerian hormone (AMH) to a conventional dosage regimen, including age, antral follicle count (AFC) and BMI, improve the rate of targeted ovarian response, defined as 5-12 oocytes after IVF? Summary answer: The addition of AMH did not alter the rate of targeted ovarian response, 5-12 oocytes, or decreased the rate of ovarian hyperstimulation syndrome (OHSS) or cancelled cycles due to poor ovarian response. What is known already: Controlled ovarian hyperstimulation (COH) in connection with IVF is sometimes associated with poor ovarian response resulting in low pregnancy and live birth rates or leading to cycle cancellations, but also associated with excessive ovarian response, causing an increased risk of OHSS. Even though it is well-established that both AMH and AFC are strong predictors of ovarian response in IVF, few randomized trials have investigated their impact on achieving an optimal number of oocytes. Study design, size and duration: Between January 2013 and May 2016, 308 patients starting their first IVF treatment were randomly assigned, using a computerized randomization program with concealed allocation of patients and in the proportions of 1:1, to one of two dosage algorithms for decisions on hormone starting dose, an algorithm, including AMH, AFC, age and BMI (intervention group), or an algorithm, including only AFC, age and BMI (control group). The study was blinded to patients and treating physicians. Participants/materials, setting, methods: Women aged >18 and <40 years, with a BMI above 18.0 and below 35.0 kg/m2 starting their first IVF cycle where standard IVF was planned, were eligible. All patients were treated with a GnRH agonist protocol and recombinant FSH was used for stimulation. The study was performed as a single-centre study at a large IVF unit at a university hospital. Main results and the role of chance: The rate of patients having the targeted number of oocytes retrieved was 81/152 (53.3%) in the intervention group versus 96/155 (61.9%) in the control group (P = 0.16, difference: -8.6, 95% CI: -20.3; 3.0). Cycles with poor response (<5 oocytes) were more frequent in the AMH group, 39/152 (25.7%) versus the non-AMH group, 17/155 (11.0%) (P < 0.01), while the number of cancelled cycles due to poor ovarian response did not differ 7/152 (4.6%) and 4/155 (2.6%) (P = 0.52). An excessive response (>12 oocytes) was seen in 32/152 (21.1%) and 42/155 (27.1%) patients, respectively (P = 0.27). Moderate or severe OHSS was observed among 5/152 (3.3%) and 6/155 (3.9%) patients, respectively (P = 1.0). Live birth rates were 48/152 (31.6%) and 42/155 (27.1%) per started cycle. Limitations, reasons for caution: The categorization of AMH values in predicted low, normal and high responders was originally established using the Diagnostic Systems Laboratories assay and was translated to more recently released assays, lacking international standards and well-established reference intervals. The interpretation of AMH values between different assays should therefore be made with some caution. Wider implications of the findings: An individualised dosage regimen including AMH compared with a non-AMH dosage regimen in an unselected patient population did not alter the number of women achieving the targeted number of oocytes, or the cancellation rate due to poor response or the occurrence of moderate/severe OHSS. However, this study cannot answer the question if using an algorithm for dose decision of FSH is superior to a standard dose and neither which ovarian reserve test is the most effective. Study funding/competing interest: Financial support was received through Sahlgrenska University Hospital (ALFGBG-70 940) and unrestricted grants from Ferring Pharmaceuticals and the Hjalmar Svensson Research Foundation. None of the authors declares any conflict of interest. Trial registration: The study was registered at www.clinicaltrials.gov NCT02013973. Trial registration date: 6 December 2013. DATE OF FIRST PATIENT RANDOMIZED: 14 January 2013.

The correlation between AMH assays differs depending on actual AMH levels.

STUDY QUESTION: What is the correlation of serum anti-Müllerian hormone (AMH) levels between two frequently used laboratory assays? SUMMARY ANSWER: A considerable difference was found in serum AMH levels measured with the two different assays, particularly for low AMH values. WHAT IS KNOWN ALREADY: AMH is regarded as being a robust, highly sensitive and specific biomarker for ovarian response and has become widely used as the basis for fertility treatment decisions. However, several available assays with different reference values, in addition to inter-laboratory variations and issues of sample stability, make interpretation of the AMH values and their clinical implications complicated. STUDY DESIGN SIZE DURATION: An observational study was performed including 269 serum samples from infertile women, originating from a RCT conducted in 2013-2016 (www.clinicaltrials.gov NCT02013973). PARTICIPANTS/MATERIALS SETTING METHOD: Serum AMH levels analysed with the Modified Beckman Coulter Gen II ELISA assay (Premix method) were compared to AMH levels analysed with the Beckman Coulter Gen II ELISA original assay (Gen II original). All samples were handled identically and analysed with the two assays in a parallel setting. MAIN RESULTS AND THE ROLE OF CHANCE: The slope of the regression line showed a mean of 18% higher values with the Premix method compared to the Gen II original assay, and more than 40% higher values for AMH levels in the lower range. LIMITATIONS REASONS FOR CAUTION: The Gen II original assay is no longer in clinical use as it has been replaced by the Premix method, which, in turn, recently has been further developed into an automated method. WIDER IMPLICATIONS OF THE FINDINGS: The finding of differences in AMH levels between assays is clinically important and may imply an incorrect classification in the assessment of ovarian reserve. The robustness of serum AMH as a marker for ovarian reserve and as a tool for fertility counselling has to be investigated further. There is an urgent need for international standards on interpretation of AMH values for different assays. STUDY FUNDING/COMPETING INTERESTS: Financial support was received through Sahlgrenska University Hospital (ALFGBG-70940) and the Hjalmar Svensson Research Foundation. None of the authors declares any conflict of interest.

No benefit of culturing embryos in a closed system compared with a conventional incubator in terms of number of good quality embryos: results from an RCT.

STUDY QUESTION: Does culture in a closed system result in an increased number of good quality embryos (GQE) on Day 2 compared with culture in a conventional system? SUMMARY ANSWER: Culture in a closed system up to 2 days after microinjection results in similar embryo development and morphological quality compared with culture in a conventional incubation system. WHAT IS KNOWN ALREADY: Time-lapse imaging (TLI) incubators are rapidly being introduced into IVF laboratories worldwide, despite the lack of large prospective randomized trials demonstrating improvement in embryo development or pregnancy rates. STUDY DESIGN, SIZE, DURATION: A randomized controlled trial including 364 patients (365 cycles) was conducted between May 2010 and February 2014. After oocyte collection, randomization was carried out and all of a patients' oocytes were allocated to culture in either a conventional incubator or a closed incubator system in proportion 1:2 until embryo transfer on Day 2. A total of 1979 oocytes were injected and cultured in the closed system, and 1000 in the standard incubator. The primary end-point was the number of GQE in the two groups. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: In total, 364 patients undergoing their first IVF cycle using ICSI, where at least one oocyte was retrieved, were randomized in a university hospital setting. Two hundred and forty patients were randomized for culture in a closed system and 124 patients for culture in the conventional incubator system (control group). Embryo assessments and final morphological scoring before transfer and cryopreservation were carried out at the same time points for embryos cultured in the conventional incubator and in the closed system. MAIN RESULTS AND THE ROLE OF CHANCE: There was no significant difference in the mean ± SD number of GQEs between groups: 2.41 ± 2.27 for the closed system group and 2.19 ± 1.82 for the control group (P = 0.34, difference 0.23, 95% confidence interval 0.69; -0.24). No significant differences were found in the number of 4-cell embryos, implantation-, pregnancy- or ongoing pregnancy rates. A significantly higher miscarriage rate was found in the TLI group compared with the control group (33.3 and 10.2%, P = 0.01). LIMITATIONS, REASONS FOR CAUTION: Culture media, temperature and gas levels were similar in the open and closed incubator systems, but different culture dishes were used. Culturing embryos for longer time period (to the blastocyst stage) may give different results. Only ICSI patients were included, which may limit the generalizability of the results. Finally, the number of GQEs on Day 2 was used as a surrogate outcome for live birth. WIDER IMPLICATIONS OF THE FINDINGS: The results are consistent with other, smaller randomized trials showing no difference in embryo quality when comparing culture in a conventional incubator with that of a closed TLI incubator system.

Who becomes a sperm donor: personality characteristics in a national sample of identifiable donors.

OBJECTIVE: To study the personality characteristics of identifiable sperm donors in a national sample in comparison with the same characteristics of a control group. DESIGN: Descriptive study. SETTING: All clinics (n=7) performing gamete donation in Sweden. POPULATION: All Swedish sperm donors recruited during 2005-08. An age-matched group of Swedish men served as controls. METHODS: Standardised questionnaires were used to measure personality. MAIN OUTCOME MEASURES: Demographics and the Temperament and Character Inventory (TCI). RESULTS: The mean age of the donors was 33.8±7.8 years (18-56 years). About one-third (36.5%) of the donors had biological children of their own. With regard to personality, significant differences were present on harm avoidance, with lower means for sperm donors (P=0.002, 95% CI -3.74 to -0.85), and on self-directedness and cooperativeness, with higher means for donors (P=0.002, 95% CI 0.97-4.19; P=0.001; 95% CI 0.75-2.95, respectively), compared with controls. This indicates that the donors in general feel less worried and suffer less from uncertainty, shyness and fatigability than controls. They also perceive themselves as being autonomous, with a capacity to take responsibility, to behave in a goal-directed manner, to be resourceful and self-acceptant, and to behave in a manner guided by meaningful values and goals. Furthermore, they describe themselves as being well integrated in humanity or society, and having a good capacity for identification with and acceptance of other people. CONCLUSIONS: The screening process at the clinics seems to generate a group of stable, mature and well-integrated donors, and this is a promising result for the future.

Use of metformin before and during assisted reproductive technology in non-obese young infertile women with polycystic ovary syndrome: a prospective, randomized, double-blind, multi-centre study.

BACKGROUND: To study the effect of metformin before and during assisted reproductive technology (ART) on the clinical pregnancy rate (CPR) in non-obese women with polycystic ovary syndrome (PCOS). METHODS: A multi-centre, prospective, randomized, double-blind study was conducted in eight IVF clinics in four Nordic countries. We enrolled 150 PCOS women with a body mass index <28 kg/m(2), and treated them with 2000 mg/day metformin or identical placebo tablets for ≥ 12 weeks prior to and during long protocol IVF or ICSI and until the day of pregnancy testing. The primary outcome measure was CPR. Secondary outcome measures included spontaneous pregnancy rates during the pretreatment period, and the live birth rate (LBR). RESULTS: Among IVF treated women (n = 112), biochemical pregnancy rates were identical in both groups (42.9%), and there were no significant differences in the metformin versus the placebo group in CPR [39.3 versus 30.4%; 95% confidence interval (CI): -8.6 to 26.5]. The LBR was 37.5 versus 28.6% (95% CI: -8.4 to 26.3). However, prior to IVF there were 15 (20.3%) spontaneous pregnancies in the metformin group and eight (10.7%) in the placebo group (95% CI: -1.9 to 21.1; P = 0.1047). According to intention to treat analyses (n = 149); significantly higher overall CPR were observed in the metformin versus placebo group (50.0 versus 33.3%; 95% CI: -1.1 to 32.3; P = 0.0391). LBR was also significantly higher with use of metformin versus placebo (48.6 versus 32.0; 95% CI: 1.1 to 32.2; P = 0.0383). No major unexpected safety issues or multiple births were reported. More gastrointestinal side effects occurred in the metformin group (41 versus 12%; 95% CI: 0.15 to 0.42; P < 0.001). CONCLUSIONS: Metformin treatment for 12 weeks before and during IVF or ICSI in non-obese women with PCOS significantly increases pregnancy and LBRs compared with placebo. However, there was no effect on the outcome of ART per se. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00159575.

Personality characteristics in a Swedish national sample of identifiable oocyte donors.

OBJECTIVE: To study the personality characteristics of identifiable oocyte donors in a national sample in comparison with normal values. DESIGN: Descriptive study. SETTING: All Swedish donation programmes. SAMPLE: In total, 181 women out of 221 donors recruited during 2005-2008. METHODS: Standardised questionnaires were used to measure personality characteristics. MAIN OUTCOME MEASURE: Demographics, temperament and character inventory (TCI). RESULTS: The majority (69%) of the donors had biological children of their own. The results from the TCI indicate that the oocyte donors were all within the normal range of character. With regard to personality, a significant difference was evident between the two groups: oocyte donors showed lower means for harm avoidance and higher scores for persistence than the controls. This indicates that the donors felt less worried, and displayed a lower level of fear of uncertainty, shyness and fatiguability, and a higher level of persistence, than the controls. In the present sample, 29 (16%) of the donors were so-called 'known donors', that is the recipient couples and the donors were known to each other. 'Known donors' displayed a mature and stable character. CONCLUSION: We found that the women who had been accepted for inclusion in this nationwide oocyte donor programme were all well adjusted and mature.

Two decades after legislation on identifiable donors in Sweden: are recipient couples ready to be open about using gamete donation?

BACKGROUND Two decades after the introduction of Swedish legislation that allows children born as a result of gamete donation access to identifying information about the donor, a nationwide multicentre study on the psychosocial consequences of this legislation for recipients and donors of gametes was initiated in 2005. The aim of the present study was to investigate recipient couples' attitudes and behaviour regarding disclosure to offspring and others, attitudes towards genetic parenthood and perceptions of information regarding parenthood after donation. METHODS The present study is part of the prospective longitudinal 'Swedish study on gamete donation', including all fertility clinics performing donation treatment in Sweden. A consecutive cohort of 152 heterosexual recipient couples of donated oocytes (72% response) and 127 heterosexual recipient couples of donated sperm (81% response) accepted participation in the study. In connection with the donation treatment, male and female participants individually completed two questionnaires with study-specific instruments concerning disclosure, genetic parenthood and informational aspects. RESULTS About 90% of participants (in couples receiving anonymous donated gametes) supported disclosure and openness to the offspring concerning his/her genetic origin. Only 6% of all participants had not told other people about their donation treatment. Between 26 and 40% of participants wanted additional information/support about parenthood following donation treatment. CONCLUSIONS Two decades after the Swedish legislation of identifiable gamete donors, recipient couples of anonymously donated sperm and oocytes are relatively open about their treatment and support disclosure to offspring. Recipient couples may benefit from more information and support regarding parenthood after gamete donation. Further studies are required to follow-up on the future parents' actual disclosure behaviour directed to offspring.

Clinical effectiveness of elective single versus double embryo transfer: meta-analysis of individual patient data from randomised trials.

OBJECTIVE: To compare the effectiveness of elective single embryo transfer versus double embryo transfer on the outcomes of live birth, multiple live birth, miscarriage, preterm birth, term singleton birth, and low birth weight after fresh embryo transfer, and on the outcomes of cumulative live birth and multiple live birth after fresh and frozen embryo transfers. DESIGN: One stage meta-analysis of individual patient data. DATA SOURCES: A systematic review of English and non-English articles from Medline, Embase, and the Cochrane Central Register of Controlled Trials (up to 2008). Additional studies were identified by contact with clinical experts and searches of bibliographies of all relevant primary articles. Search terms included embryo transfer, randomised controlled trial, controlled clinical trial, single embryo transfer, and double embryo transfer. Review methods Comparisons of the clinical effectiveness of cleavage stage (day 2 or 3) elective single versus double embryo transfer after fresh or frozen in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatments were included. Trials were included if the intervention differed only in terms of the intended number of embryos to be transferred. Trials that involved only blastocyst (day five) transfers were excluded. RESULTS: Individual patient data were received for every patient recruited to all eight eligible trials (n=1367). A total of 683 and 684 women randomised to the single and double embryo transfer arms, respectively, were included in the analysis. Baseline characteristics in the two groups were comparable. The overall live birth rate in a fresh IVF cycle was lower after single (181/683, 27%) than double embryo transfer (285/683, 42%) (adjusted odds ratio 0.50, 95% confidence interval 0.39 to 0.63), as was the multiple birth rate (3/181 (2%) v 84/285 (29%)) (0.04, 0.01 to 0.12). An additional frozen single embryo transfer, however, resulted in a cumulative live birth rate not significantly lower than the rate after one fresh double embryo transfer (132/350 (38%) v 149/353 (42%) (0.85, 0.62 to 1.15), with a minimal cumulative risk of multiple birth (1/132 (1%) v 47/149 (32%)). The odds of a term singleton birth (that is, over 37 weeks) after elective single embryo transfer was almost five times higher than the odds after double embryo transfer (4.93, 2.98 to 8.18). CONCLUSIONS: Elective single embryo transfer results in a higher chance of delivering a term singleton live birth compared with double embryo transfer. Although this strategy yields a lower pregnancy rate than a double embryo transfer in a fresh IVF cycle, this difference is almost completely overcome by an additional frozen single embryo transfer cycle. The multiple pregnancy rate after elective single embryo transfer is comparable with that observed in spontaneous pregnancies.

Effects of reverberation time on the cognitive load in speech communication: theoretical considerations.

The paper presents a theoretical analysis of possible effects of reverberation time on the cognitive load in speech communication. Speech comprehension requires not only phonological processing of the spoken words. Simultaneously, this information must be further processed and stored. All this processing takes place in the working memory, which has a limited processing capacity. The more resources that are allocated to word identification, the fewer resources are therefore left for the further processing and storing of the information. Reverberation conditions that allow the identification of almost all words may therefore still interfere with speech comprehension and memory storing. These problems are likely to be especially serious in situations where speech has to be followed continuously for a long time. An unfavourable reverberation time (RT) then could contribute to the development of cognitive fatigue, which means that working memory resources are gradually reduced. RT may also affect the cognitive load in two other ways: RT may change the distracting effects of a sound and a person's mood. Both effects could influence the cognitive load of a listener. It is argued that we need studies of RT effects in realistic long-lasting listening situations to better understand the effect of RT on speech communication. Furthermore, the effect of RT on distraction and mood need to be better understood.

More or less independent.

PURPOSE: The aim of this study was to describe how persons with learning disabilities conceived their opportunities to participate in decisions in different environmental settings. Further, the study focused on factors that persons with learning disabilities conceived what facilitated or hindered their participation in decisions in everyday life. METHOD: Qualitative interviews were performed with 23 persons with mild to moderate learning disabilities. The youngest was 22 years and the oldest 63. Data were categorized in three levels of decision making, described as independent, interdependent and dependent. RESULTS: The participants were presented in five profiles depending on level of decision and in relation to the environmental arenas work and leisure. Most conceptions were categorized as dependent or interdependent regardless of arena. Few examples of independence were given. Factors that facilitated or hindered participation in decisions varied: national legislation, attitudes, and forms of daily routines and activities. CONCLUSIONS: This study showed a gap between official ideologies of every citizen's rights and the studied participants' conceptions of how they participate in decisions in everyday life. As a consequence of this, professionals have to develop methods promoting decision-making as conceived by the clients.

Residual 2H quadrupolar couplings in weakly aligned carbohydrates.

We report a novel two-dimensional NMR pulse scheme for the 1H-detected observation of 2H in isotopically 13C, 2H-enriched carbohydrates. This scheme is used for the indirect observation of residual quadrupolar couplings in 13C, 2H-enriched methyl-beta-D-glucopyranoside weakly aligned in a dilute lyotropic liquid-crystalline medium comprising 20% (w/v) dihexanoyl-phosphatidylcholine/dimyristoyl-phosphatidylcholine (1:3 mol/mol) in D2O. The observed residual quadrupolar couplings are substantially larger than residual dipolar one-bond 13C-1H couplings under the same experimental conditions. These quadrupolar couplings are thus a useful alternative to dipolar couplings for the structural analysis of small molecules that align very weakly in dilute liquid-crystalline media. Moreover, since the quadrupolar coupling constant is very uniform throughout endocyclic deuterons of the carbohydrate, these data suggest that adoption of a single average value of this parameter in 2H relaxation studies on the glycan moieties of glycoproteins and glycopeptides is a valid assumption.

A critical analysis of the Model of Human Occupation.

The aim of this paper is to begin a dialogue regarding the use of the Model of Human Occupation (MOHO) (Kielhofner, 1995). Three questions formed the basis for discussion: 1. Is the MOHO consistent with the values and beliefs of occupational therapy?; 2. Does the MOHO support the intervention process in occupational therapy? and; 3. Is the MOHO consistent and applicable to the current regulations and societal values in Sweden? The authors propose that the MOHO must be further developed in order to support assessment and intervention in occupational therapy. Specifically, they find the MOHO lacking with regard the influence of the environment on human behaviour, appreciation of the dialectic process between the human and the environment, and of the importance of the subsystem volition in the intervention process.

Perception of surface pressure applied to the hand.

The study aimed to determine the relationship between the physical magnitude and the subjective perception of applied pressure, and to determine discomfort and pain thresholds. Free modulus magnitude estimation of the subjective pressure level was made on three points: on the finger, the palm and the thenar area. The pressure was judged to be higher at the thenar point than at the finger and palm points. The slopes of the linear functions (log magnitude estimates as a function of log pressure) were 0.66, 0.78 and 0.76 for the finger, palm and thenar points respectively. The discomfort threshold was 38% of the pain pressure threshold at the finger point, 40% at the palm and 22% at the thenar point. The results are probably of importance in the performance of hand-intensive work, in particular in the design of hand tools.

Structural determination and biosynthetic studies of the O-antigenic polysaccharide from the enterohemorrhagic Escherichia coli O91 using 13C-enrichment and NMR spectroscopy.

The structure of the O-antigenic polysaccharide from the enterohemorrhagic Escherichia coli O91 has been determined using primarily NMR spectroscopy on the (13)C-enriched polysaccharide. The O-antigen is composed of pentasaccharide repeating units with the following structure: -->4)-beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->4)-beta-D-GlcpA-6-N- Gly -(1-->3)-beta-D-GlcpNAc-(1-->4)-alpha-D-Quip-3-N-[(R)-3-hydroxy butyra mido]-(1-->. The bacterium was grown with D-[UL-(13)C]glucose in the medium which resulted in an overall degree of labeling of approximately 65% in the sugar residues and approximately 50% in the N-acyl substituents, indicating some metabolic dilution in the latter. The (13)C-enrichment of the polysaccharide proved valuable since NMR assignments could be made on the basis of (13)C, (13)C-connectivity in uniformly labeled residues. The biosynthesis of the (R)-3-hydroxybutyramido substituent via C(2) fragments was identified by NMR spectroscopy. The (R)-configuration at C3 is in accord with fatty acid biosynthesis. Additional cultures with specifically labeled D-[1-(13)C]glucose or D-[6-(13)C]glucose corroborated the direct incorporation of glucose as the building block for the hexose skeletons in the polysaccharide and the biosynthesis of acyl substituents occurring via the triose pool followed by decarboxylation to give acetyl building blocks labeled with (13)C at the methyl group.

A conformational study of the vicinally branched trisaccharide beta-D-glcp-(1 --> 2)[beta-D-glcp-(1 --> 3)]alpha-D-Manp-OMe by nuclear Overhauser effect spectroscopy (NOESY) and transverse rotating-frame Overhauser effect spectroscopy (TROESY) experiments: comparison to Monte Carlo and Langevin dynamics simulations.

The trisaccharide beta-D-Glcp-(1 --> 2)[beta-D-Glcp-(1 --> 3)]alpha-D-Manp-OMe, a model for branching regions in oligosaccharides, has been investigated by one-dimensional DPFGSE (1)H, (1)H nuclear Overhauser effect spectroscopy (NOESY) and transverse rotating-frame Overhauser effect spectroscopy (TROESY) experiments at 30 degrees C in water and in the solvent mixture water : dimethyl sulfoxide (7 : 3). Cross-relaxation rates were obtained from the nmr experiments and interpreted as proton-proton distances. From Metropolis Monte Carlo and Langevin dynamics simulations, distances were calculated and compared to those obtained from experiment. Using the previously determined dynamics from carbon-13 nmr relaxation measurements of the trisaccharide in the solvent mixture, intraresidue proton distances could be obtained that were in excellent to reasonable agreement with those calculated from simulations. In water, the isolated spin-pair approximation was used for comparison of interproton distances. The experimentally derived distances in both solvents showed that the trans-glycosidic distances were shorter between the anomeric proton of the glucosyl group and the proton at the linkage position, respectively, than to the proton on the adjacent carbon on the mannosyl residue. The interresidue distances calculated from the computer simulations, performed with three different force fields, namely HSEA, PARM22, and CHEAT95, resulted in the reverse order in all cases but one.

Structural analysis of the O-antigenic polysaccharide from Vibrio cholerae O10.

The structure of the O-antigenic polysaccharide part of the lipopolysaccharide isolated from Vibrio cholerae O10 has been determined. The main method used has been 1H- and 13C-NMR spectroscopy. Sugar and methylation analyses were also applied to the polysaccharide. The tetrasaccharide repeating unit of the polysaccharide was found to have the following structure: -->3)-alpha-D-ManpNAc-(1-->4)-beta-D-GlcpA-(1-->3)-beta-D-Ga lp-(1-->3)-beta-D-GlcpNAc-(1-->.

Structural basis for differential receptor binding of cholera and Escherichia coli heat-labile toxins: influence of heterologous amino acid substitutions in the cholera B-subunit.

The closely related B-subunits of cholera toxin (CTB) and Escherichia coli heat-labile enterotoxin (LTB) both bind strongly to GM1 ganglioside receptors but LTB can also bind to additional glycolipids and glycoproteins. A number of mutant CT B-subunits were generated by substituting CTB amino acids with those at the corresponding positions in LTB. These were used to investigate the influence of specific residues on receptor-binding specificity. A mutated CTB protein containing the first 25 residues of LTB in combination with LTB residues at positions 94 and 95, bound to the same extent as native LTB to both delipidized rabbit intestinal cell membranes, complex glycosphingolipids (polyglycosylceramides) and neolactotetraosylceramide, but not to non-GM1 intestinal glycosphingolipids. In contrast, when LTB amino acid substitutions in the 1-25 region were combined with those in the 75-83 region, a binding as strong as that of LTB to intestinal glycosphingolipids was observed. In addition, a mutant LTB with a single Gly-33-->Asp substitution that completely lacked affinity for both GM1 and non-GM1 glycosphingolipids could still bind to receptors in the intestinal cell membranes and to polyglycosylceramides. We conclude that the extra, non-GM1 receptors for LTB consist of both sialylated and non-sialylated glycoconjugates, and that the binding to either class of receptors is influenced by different amino acid residues within the protein.