Women's preferences concerning IVF treatment: a discrete choice experiment with particular focus on embryo transfer policy.

STUDY QUESTION: What outcomes are important for women to decide on the day of embryo transfer (ET) in IVF? SUMMARY ANSWER: The highest cumulative live birth rate (cLBR) per treatment was the most important treatment outcome for women undergoing an IVF treatment, regardless of the number of transfers needed until pregnancy and impact on quality of life. WHAT IS KNOWN ALREADY: Cleavage stage (Day 3) and blastocyst stage (Day 5) ETs are common transfer policies in IVF. The choice for one or the other day of ET differs between clinics. From the literature, it remains unclear whether the day of transfer impacts the cLBR. Patient preferences for the day of ET have not been examined yet. STUDY DESIGN SIZE AND DURATION: A discrete choice experiment (DCE) was performed to investigate female patients' preferences and their values concerning various aspects of an IVF treatment, with a particular focus on ET policy. A multicenter DCE was conducted between May 2020 and June 2020 in which participants were asked to choose between different treatments. Each treatment was presented using hypothetical scenarios containing the following attributes: the probability of a healthy live birth per IVF treatment cycle, the number of embryos available for transfer (for fresh and frozen-thawed ET), the number of ETs until pregnancy and the impact of the treatment on the quality of life. PARTICIPANTS/MATERIALS SETTING METHODS: Women (n = 445) were asked to participate in the DCE at the start of an IVF treatment cycle in 10 Dutch fertility clinics. Participating women received an online questionnaire. The attributes' relative importance was analyzed using logistic regression analyses. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 164 women participated. The most important attribute chosen was the cLBR. The total number of embryos suitable for transfer also influenced women's treatment preferences. Neither the number of transfers needed until pregnancy, nor the impact on quality of life influenced the treatment preferences in the aggregated data. For women in the older age group (age ≥36 years) and the multipara subgroup, the impact on quality of life was more relevant. Naive patients (patients with no prior experience with IVF treatment) assigned less value to the number of ETs needed until pregnancy and assigned more value to the cLBR than the patients who had experienced IVF. LIMITATIONS REASONS FOR CAUTION: An important limitation of a DCE study is that not all attributes can be included, which might be relevant for making choices. Patients might make other choices in real life as the DCE scenarios presented here are hypothetical and might not exactly represent their personal situation. We tried to avoid potential bias by selecting the attributes that mattered most to the patients obtained through patient focus groups. The final selection of attributes and the assigned levels were established using the input of an expert panel of professionals and by performing a pilot study to test the validity of our questionnaire. Furthermore, because we only included women in our study, we cannot draw any conclusions on preferences for partners. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study may help fertility patients, clinicians, researchers and policymakers to prioritize the most important attributes in the choice for the day of ET. The present study shows that cLBR per IVF treatment is the most important outcome for women. However, currently, there is insufficient information in the literature to conclude which day of transfer is more effective regarding the cLBR. Randomized controlled trials on the subject of Day 3 versus Day 5 ETs and cLBR are needed to allow evidence-based counseling. STUDY FUNDING/COMPETING INTERESTS: This work received no specific funding and there are no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Volumetric evaluation of CT images of adrenal glands in primary aldosteronism.

OBJECTIVES: To investigate whether adrenal volumetry provides better agreement with adrenal vein sampling (AVS) than conventional CT for subtyping PA. Furthermore, we evaluated whether the size of this contralateral adrenal was a prognostic factor for clinical outcome after unilateral adrenalectomy. METHODS: We retrospectively analyzed volumes of both adrenal glands of the 180 CT-scans (88/180 with unilateral and 92/180 with bilateral disease) of the patients with PA included in the SPARTACUS trial of which 85 also had undergone an AVS. In addition, we examined CT-scans of 20 healthy individuals to compare adrenal volumes with published normal values. RESULTS: Adrenal volume was higher for the left than the right adrenal (mean and SD: 6.49 ± 2.77 ml versus 5.25 ± 1.87 ml for the right adrenal; p < 0.001). Concordance between volumetry and AVS in subtyping was 58.8%, versus 51.8% between conventional CT results and AVS (p = NS). The volumes of the contralateral adrenals in the patients with unilateral disease (right 4.78 ± 1.37 ml; left 6.00 ± 2.73 ml) were higher than those of healthy controls reported in the literature (right 3.62 ± 1.23 ml p < 0.001; left 4.84 ± 1.67 ml p = 0.02). In a multivariable analysis the contralateral volume was not associated with biochemical or clinical success, nor with the defined daily doses of antihypertensive agents at 1 year follow-up. CONCLUSIONS: Volumetry of the adrenal glands is not superior to current assessment of adrenal size by CT for subtyping patients with PA. Furthermore, in patients with unilateral disease the size of the contralateral adrenal is enlarged but its size is not associated with outcome.

Cost-effectiveness of sacral neuromodulation for chronic refractory constipation in children and adolescents: a Markov model analysis.

AIM: This study aimed to assess the cost-effectiveness of sacral neuromodulation (SNM) compared with conservative treatment in children and adolescents with constipation refractory to conservative management. METHOD: A Markov probabilistic model was used, comparing costs and effectiveness of SNM and conservative treatment in children and adolescents aged 10-18 years with constipation refractory to conservative management. Input for the model regarding transition probabilities, utilities and healthcare costs was based on data from a cohort of patients treated in our centre. This cohort consisted of 30 female patients (mean age 16 years) with functional constipation refractory to conservative management. The mean duration of laxative use in this group was 5.9 years. All patients had a test SNM, followed by a permanent SNM in 27/30. Median follow-up was 22.1 months (range 12.2-36.8). The model was run to simulate a follow-up period of 3 years. RESULTS: The mean cumulative costs for the SNM group and the conservative treatment group were €17 789 (SD €2492) and €7574 (SD €4332) per patient, respectively. The mean quality adjusted life years (QALYs) in the SNM group was 1.74 (SD 0.19), compared with 0.86 (SD 0.14) in the conservatively managed group. The mean incremental cost-effectiveness ratio was €12 328 per QALY (SD €4788). Sensitivity analysis showed that the outcomes were robust to a wide range of model assumptions. CONCLUSION: Chronic constipation seriously affects the quality of life of children and adolescents. Preliminary evidence suggests that SNM can improve symptoms and quality of life at a reasonable cost.

The yield of diagnostic work-up of patients presenting with myalgia, exercise intolerance, or fatigue: A prospective observational study.

Myalgia, fatigue, and exercise intolerance are cause for referral to a neurologist. However, the diagnostic value of history, neurological examination, and ancillary investigations in patients with these symptoms is unknown. This study provides a sound footing for deciding which ancillary investigations should be conducted. A prospective observational study of the diagnostic approach in 187 patients with myalgia, exercise intolerance, or fatigue as their predominant symptom was performed. The primary outcomes were independent contribution of referral letter, history, examination, and ancillary investigations to a myopathy diagnosis. The secondary outcome was diagnostic value of combined ancillary investigations. 27% of patients had a myopathy. Positive family history (OR 3.2), progressive symptoms (OR 2.2), atrophy (OR 9.7), weakness (OR 10.9), and hyporeflexia (OR 4.4) were associated with a myopathy. Positive predictive values for myopathy were calculated for CK (0.32), EMG (0.66), ultrasound (0.47), and muscle biopsy (0.78). All contributed significantly in predicting myopathy. Multivariate analysis yielded a diagnostic algorithm facilitating a more efficient work-up in future patients. CK levels, EMG, ultrasound, and muscle biopsy independently contribute to predicting a myopathy. The diagnostic algorithm shows which combination of ancillary investigations should be employed in different subgroups and when to omit invasive techniques. This algorithm may drastically improve diagnostic efficiency.

Timing of surgery for primary exotropia in children.

OBJECTIVE: To compare the postoperative alignment and sensory functions in patients with primary exotropia who had been operated at an early age (< 7 years) with those in patients who had been operated at an older age (> 7 years). METHODS: In a consecutive retrospective cohort study, 112 patients who had had a surgical intervention for primary exotropia between 1997 and 2003 were evaluated for postoperative results. After applying criteria for eligibility, the group of patients was divided into two groups: those who had had surgery before the age of seven years (n = 24) and those who had had surgery after the age of seven years (n = 36). Age at surgery, preoperative alignment and sensory functions were correlated with the postoperative status. The follow-up was at least one year (1.0 year to 7 years; median: 2.3 and 3.5 years, respectively). RESULTS: Patients who had had surgery before the age of seven had significantly better alignment and sensory functions. The univariate logistic regression model confirmed a statistically significant association between motor outcome (exodeviation less than 10 diopters) and age at the time of surgery (before or after the age of seven; p = 0.002). In the multivariate model, the association between age at time of surgery and motor outcome was even stronger. The number of re-operations in the group operated before the age of 7 years was significantly less than in the group operated after the age of seven (2 versus 12, p = 0.023). CONCLUSION: The postoperative alignment and sensory functions for patients with primary exotropia who had had a surgical intervention before the age of seven years were, in this study, better than those in patients who had had surgery after the age of seven years.

Month of birth related to fecundity and childlessness among contemporary women.

To determine the associations of fecundity and childlessness with month of conception and to find a causal mechanism for these associations, we reanalyzed some of our previous data according to the predictions of the seasonal optimal ripening oocyte (SOptRO) and seasonal preovulatory over-ripeness ovopathy (SPrOO) hypotheses. Prime and minor SOptRO months as well as high-risk, no-risk, and very high risk SPrOO months were defined on the basis of a priori knowledge of the existence of ovulatory and anovulatory seasons in mammals and of the general birth distribution in Europe. The month of birth was assessed among 899 mothers with three or more children and 388 childless women extracted from a 1% sample of the Austrian population. The women with three or more children were born in excess during the prime and less often during the minor SOptRO months (chi2 = 2.81; p = 0.045; relative risk = 1.16; 95% CI = 1.01-1.33). This is in line with the SOptRO predictions. The childless women were more frequently born during the high-risk SPrOO months compared to the no-risk months but less often during the very high risk months. The linear trend (chi2 = 8.43; p = 0.009) is in line with the SPrOO predictions. We suggest that fecundity and childlessness are dependent on the gradient of oocyte maturation reflected by mother's month of birth, which may modulate future constitution.

Timing of surgery for primary exotropia in children.

OBJECTIVE: To compare postoperative alignment and sensory functions in children with primary exotropia who were operated at an early age (< 7 years) with patients who were operated at an older age (> 7 years). METHODS: In a consecutive retrospective cohort study, 112 patients who had a surgical intervention for primary exotropia between 1997 and 2003 were evaluated for postoperative results. After applying criteria for eligibility, the group of patients was divided into two groups: those who had surgical intervention before the age of seven years (n = 24) and those who had surgery after the age of seven years (n = 36). Age at surgery, preoperative alignment and sensory functions were correlated with the postoperative status. The follow-up was at least one year (1.0 year to 7 years; median: 2.3 and 3.5 years, respectively). RESULTS: Children who had surgery before the age of seven had significantly better alignment and sensory functions. The univariate logistic regression model confirmed a statistically significant association between motor outcome (exodeviation less than 10 prism-diopters) and age at the time of surgery (before or after the age of seven; p = 0.002). In the multivariate model, the association between age at time of surgery and motor outcome was even stronger. The number of reoperations in the group operated before the age of 7 years was significantly less than in the group operated after the age of seven (2 versus 12, p = 0.023). CONCLUSION: The postoperative alignment and sensory functions in patients with primary exotropia who had surgical intervention before the age of seven years were, in this study, better than in patients who had surgery after the age of seven years.

The secular trends in male:female ratio at birth in postwar industrialized countries.

Finnish investigators [Vartiainen et al. Environmental Chemicals and Changes in Sex Ratio: Analysis Over 250 Years in Finland. Environ Health Perspect 107:813-815 (1999)] presented the sex ratio of all newborn babies from 1751 to 1997 in order to evaluate whether Finnish long-term data are compatible with the hypothesis that the decrease in the ratio of male to female births after World War I and World War II in industrial countries is caused by environmental factors. They found an increase in the proportion of males from 1751 to 1920, which was interrupted by peaks in male births during World War I and World War II and followed by a decrease thereafter, similar to the trends in many other countries. The turning point of male proportion, however, preceded the period of industrialization and introduction of pesticides and hormonal drugs. Thus, a causal association between these environmental exposures and this decrease is unlikely. In addition, none of the various family parameters (e.g., paternal age, maternal age, age difference in parents, birth order) could explain the historical time trends. Vartiainen et al. concluded that at present it is unknown how these historical trends could be mediated. The postwar secular decline of the male:female ratio at birth is not an isolated phenomenon and parallels the decline of perinatal morbidity and mortality, congenital anomalies, and various constitutional diseases. This parallelism indicates a common etiology and may be caused by reduction of conceptopathology, as a correlate to increasing socioeconomic development. An inverted dose response or the dose-response fallacy due to vanishing male conceptuses explains the low sex ratios before World War I and World War II in newborns from black parents and from the lowest socioeconomic classes.

Impaired leukocyte phagocytosis in patients undergoing hemihepatectomy for liver metastases.

Patients undergoing partial hepatectomy have an increased susceptibility to infection. To investigate whether this increased risk is related to impaired leukocyte function, we studied polymorphonuclear leukocyte (PMN) phagocytosis in patients undergoing a hemihepatectomy because of liver metastasis (LM, n = 11) and in patients undergoing major abdominal surgery because of abdominal malignancy (AM, n = 8). Eight healthy volunteers (HVs) served as controls. Leukocyte suspensions were incubated with fluorescein isothiocyanate-labeled Staphylococcus aureus, and phagocytosis was measured by flow cytometry. Preoperative PMN phagocytosis, in the presence of autologous plasma, was significantly less in patients with LM compared with patients with AM or HVs. This impaired phagocytosis was potentially restored in the presence of normal plasma. The decreased phagocytic capacity of PMNs from patients with LM was not related to levels of known plasma opsonins or phenotypic changes of PMNs. Rather, it was related to a deficiency of unidentified plasma factors. After surgery, the phagocytic capacity of PMNs of patients with AM decreased by approximately 30%, which correlated with decreasing levels of immunoglobulin G and C3. In conclusion, patients with LM had a decreased PMN phagocytic capacity before surgery. This impairment in phagocytosis disappeared 1 week after surgery. We propose that the presence of LM leads to a deficiency of factor(s) in the blood that impairs PMN phagocytic capacity.

Collaborative study to improve the quality control of rare earth element determinations in environmental matrices.

In order to control the quality of rare earth determinations in environmental matrices, the Standards, Measurements and Testing Programme (formerly Community Bureau of Reference, BCR) of the European Commission has started a project, the final aim of which is to certify four types of matrices (tuna muscle, mussel tissue, aquatic plant and estuarine sediment) for their contents of a range of rare earth elements (Sc, Y and the lanthanides: La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu). The elements U and Th were added to the study. The first part of this project consisted of an interlaboratory study which aimed to test the feasibility of preparation of environmental reference materials and to detect and remove most of the pitfalls observed in rare earth determinations. This paper presents the preparation of the four matrices for the intercomparison study and for the candidate reference material. The main results are presented of the interlaboratory study that was carried out prior to the certification campaign. This collaborative trial is the first attempt ever carried out at this scale to evaluate the state-of-the-art of rare earth determinations in the environment. Its impact on the improvement of chemical measurements will have positive effects on the comparability of data necessary for environmental monitoring.