The burden of very early dropout in infertility care: a nationwide population-based cohort study.

STUDY QUESTION: What is the frequency and the associated factors of very early dropout following unsuccessful clomiphene citrate (CC)/gonadotropin treatment in the context of full coverage of treatment cost. SUMMARY ANSWER: Despite free treatment, almost one in four women had a very early dropout following unsuccessful CC/gonadotropin treatment, with patients below the poverty line being more likely to drop out early. WHAT IS KNOWN ALREADY: Success of infertility care is tarnished by very high dropout rates. Infertility care dropout has been considered as resulting principally from financial barriers because of the high cost of treatment. Nearly all previous work addressed dropout following IVF/ICSI. Factors associated with dropout following CC/gonadotropins may be different and also need to be investigated. STUDY DESIGN, SIZE, DURATION: Nationwide population-based cohort study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Using the French national health insurance and hospital databases, we included in the cohort 27 416 women aged 18-49 years unsuccessfully treated with CC/gonadotropins in 2017. The main outcome was very early dropout, defined as discontinuation of all infertility treatment after unsuccessful treatment for 1-3 months. Very early treatment dropout was analysed by multivariate logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: Among women unsuccessfully treated with CC/gonadotropins, 22% dropped out of infertility care within 3 months. In multivariate analysis, higher early dropout following unsuccessful CC/gonadotropin treatment was associated with older and younger ages (≥35 and <25 years), being below the poverty line, being treated with CC prescribed by a general practitioner and lack of infertility tests or monitoring. LIMITATIONS, REASONS FOR CAUTION: This study is based on health administrative data that do not include reasons for dropout and record only a limited amount of information. It is thus not possible to analyse the reason for early dropout. WIDER IMPLICATIONS OF THE FINDINGS: Despite full coverage of all infertility treatment, women under the poverty line have a higher risk of very early dropout following unsuccessful CC/gonadotropin treatment. Better understanding is needed of the non-financial barriers and difficulties faced by these patients. To address disparities in infertility treatment, practitioner training could be reinforced to adapt to patients from different social and cultural backgrounds. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the ANR StimHo project, grant ANR-17-CE36-0011-01 from the French Agence Nationale de la Recherche. The authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Chronic conditions, subjective wellbeing and risky sexual behaviour among adolescents and young adults.

The purpose of this study is to clarify the relationship between having a chronic condition (CC) and several types of risky sexual behaviour (RSB) among adolescents and young adults. We used data from a multicentre cross-sectional study carried out on 14,431 adolescents from 137 French schools. Logistic regression was used to assess the association between several types of RSB and CCs among the 2680 participants aged 17 years or over who reported sexual intercourse. Survival analysis was conducted to assess the association between CCs and age at first sexual intercourse across the whole sample. Analyses were conducted separately by gender with and without adjustment for the parents' education level, early menarche and subjective wellbeing (relationship with mother and father, depression, perceived health status and liking school). Among boys, having a CC was associated with a higher risk of RSB in both univariate (OR: 1.58 [95% CI: 1.10-2.27]) and multivariate analyses (aOR: 1.62 [95% CI: 1.11-2.38]). Among girls, the association between chronic condition and RSB in univariate analysis was non-significant (OR: 1.30 [95% CI: 0.97-1.76]) and disappeared after adjustment on subjective wellbeing (aOR: 1.08 [95% CI: 0.78-1.49]). There was no association between CC and age at first sexual intercourse.    Conclusion: There were major gender differences. Boys with a CC were more prone to engage in RSB independent of their subjective wellbeing, whereas in girls, subjective wellbeing seemed to mediate the relationship between CC and RSB. Clinicians should be aware of those gender differences in order to deliver preventive strategies regarding sexuality that target both genders. What is Known: • Young people with chronic conditions have a higher likelihood of engaging in risky sexual behaviour. • Engaging in such behaviours can be much more costly, as it can weaken their underlying state of health. What is New: • We found major gender differences. Boys were more prone to engage in risky behaviour independent of their subjective wellbeing, whereas in girls, it seemed to play an important role. • By understanding how risky sexual behaviour differs according to gender, clinicians can deliver prevention messages that target both genders.

Strong social disparities in access to IVF/ICSI despite free cost of treatment: a French population-based nationwide cohort study.

BACKGROUND: Access to IVF/ICSI is facilitated when the financial barrier is removed. In a national context where in vitro fertilisation (IVF)/intracytoplasmic sperm Injection (ICSI) treatment is cost-free, how many women do not access IVF/ICSI and what are the factors associated with non-access? METHODS: Using French national health insurance databases, the cohort included 20,240 women aged 18-43 years living in France who underwent unsuccessful treatment (no pregnancy) with clomiphene citrate (CC) and/or gonadotropins with treatment started between January and August 2016. The outcome measure was non-access to IVF/ICSI during the 24-month following start of infertility care. Factors associated with non-access to IVF/ICSI were explored using mixed effects logistic regression. RESULTS: In the cohort, 65.4% of women did not access IVF/ICSI. In multivariable analysis, non-access to IVF/ICSI was higher in younger women (18-25 years: (OR 2.17, 95% CI: 1.85-2.54) and in older women (40-43 years: (OR=3.60, 95% CI: 3.25-3.98)). Non-access was higher among women below the poverty line (OR=3.76, 95% CI: 3.34-4.23) and showed a significant upward trend with increasing deprivation of place of residence. Distance to the nearest fertility centre was not significantly associated with non-access to IVF/ICSI. CONCLUSIONS: In a national context of cost-free ART treatment, a large proportion of women did not access treatment, with a strong social gradient that raises important issues. We need to understand the underlying social mechanisms to develop an efficient and equitable health policy regarding infertility care.

Risk of hypoglycemia by anthropometric measurements in neonates of mothers with diabetes.

Macrosomia in neonates of diabetic women is a risk factor for neonatal hypoglycemia, with an over-risk for asymmetric macrosomia. This study aimed to study the association between anthropometric measurements and hypoglycemia in neonates of mothers treated for gestational diabetes. This is a secondary analysis of the INDAO trial study conducted between May 2012 and November 2016 in 13 French tertiary care university hospitals in 890 pregnant women with gestational diabetes treated with either insulin or glyburide. Neonatal anthropometric measurements were birthweight and weight-length ratio (WLR, defined as birth weight/length). Neonatal hypoglycemia was defined as capillary blood glucose below 36 mg/dL (2 mmol/L) or below 45 mg/dL (2.5 mmol/L) associated with clinical signs after 2 h of life. Their relationships were modeled with logistic regressions using fractional polynomials. Extreme categories of birthweight or WLR adjusted for gestational age at birth and sex were defined as Z-score < -1.28 or > 1.28. These categories were compared to Z-score between -1.28 and 1.28 by estimating odds ratios and confidence intervals for neonatal hypoglycemia. Neonatal hypoglycemia occurred in 9.1% of cases. The relationship between birthweight and WLR Z-scores and neonatal risk of hypoglycemia adjusted for maternal treatment was a U-shaped curve. Adjusted odds ratios for the risk of hypoglycemia were 9.6 (95% CI 3.5, 26.8) and 2.3 (95% CI 1.1, 4.9) for WLR Z-score below -1.28 and above 1.28, respectively, compared with WLR Z-score between -1.28 and 1.28.    Conclusion: Birthweight Z-score was associated with the risk of neonatal hypoglycemia in neonates from mothers treated for gestational diabetes. The risk of neonatal hypoglycemia was increased for both extreme birthweight Z-scores, regardless of maternal treatment. Small for gestational age neonates of diabetic mothers require special attention for the risk of neonatal hypoglycemia. What is Known: • Macrosomia in neonates of diabetic women is a risk factor for neonatal hypoglycemia, with an over-risk for asymmetric macrosomia. Few retrospective studies have assessed the risk for neonatal hypoglycemia among small for gestational age neonates born to diabetic mothers. What is New: • The risk of neonatal hypoglycemia among neonates of diabetic mothers increased for both low and high weight-length ratio, regardless of maternal medicinal treatment, gestational age at birth, and sex of the newborn.

Cesarean section rate changes after audit and feedback with the Ten Group Classification System in a French perinatal network: A retrospective pre-post study.

INTRODUCTION: The rise in the number of cesarean sections (CS) is a major health public problem which concerns nearly all countries. It is suggested that the Ten Group Classification System be adapted to a procedure of audit/feedback cycles, which could have an effect on CS practice. Therefore, we aimed to study changes in CS rates between maternity wards in a perinatal network after implementation of the Ten Group Classification System in an audit with feedback. MATERIAL AND METHODS: This was a retrospective pre-post study of all births from 1 January 2012 to 31 December 2018, in a French perinatal network of 10 maternity wards in the Yvelines district of France. All live births occurring at a gestational age ≥24 weeks in the network were included. During the pre-period (1 January 2012 to 31 December 2014), the audit and feedback provided only overall CS rates. During the post-period (1 January 2015 to 31 December 2018), CS rates for each Robson Ten Group Classification System group were provided. Regression models, adjusted for maternal characteristics and maternity ward, were used to compare CS rates globally and for each group of the system. Variability of CS rates between maternity wards was analyzed using the coefficients of variation. RESULTS: There were 51 082 women who delivered during the pre-period and 63 964 during the post-period. The overall CS rate did not decrease (24.5% during the pre-period vs 25.1% during the post-period). There were no significant differences in CS rates for any group of the Ten Group Classification System after adjustment for maternity, maternal age and sociodemographic characteristics, nor did audit implementation decrease CS rate variability between maternity wards or within groups of the system. CONCLUSIONS: Implementation of an audit-and-feedback cycle using the Ten Group Classification System did not decrease either CS rates or variability between maternity wards.

Impact of maternal age on obstetric and neonatal morbidity: a retrospective cohort study.

BACKGROUND: Pregnancies in women over 35 years of age are becoming more frequent. The majority of studies point to an age of 35 as a provider of obstetric and neonatal complications. But several confounding factors are not taken into account and this results in contradictory results. METHODS: The objective was to quantify the strength of the association between maternal age and obstetric and neonatal morbidity. This observational study was based on systematic records of 9 years of pregnancies managed in the Obstetrics and Gynaecology Department of Antoine Béclère Hospital, Clamart, France. In all, 24,674 pregnancies were managed at Antoine Béclère Hospital between April 1, 2007 and December 31, 2015, including 23,291 singleton pregnancies. Maternal age was the age at the beginning of pregnancy, taken as a quantitative variable. The main outcome measure was a composite "unfavourable" pregnancy outcome that included miscarriage, induced abortion, in utero foetal death, stillborn or newborn infant weighing under 500 g or delivered before 24 weeks of gestational age. Obstetric and neonatal morbidity comprised hospitalisation during pregnancy for more than 1 day, pre-eclampsia, gestational diabetes requiring hospitalisation, caesarean delivery, preterm birth, small-for-gestational age, and newborn transfer to the paediatric unit or neonatal intensive care unit. RESULTS: Analyses were conducted among singleton pregnancies (n = 23,291) and were adjusted for obesity, assisted reproductive technology and geographical origin of the mother. Unfavourable pregnancy outcome rate tripled with age, from 5% among women aged 25 to 34 to 16% among those over 45. Women over 40 were twice as likely to be hospitalised as those aged 25 to 34. The caesarean section rate reached more than 40% among women over 40 and more than 60% in women over 45. The rate of newborn transfer to paediatric intensive care or a neonatal intensive care unit was doubled in women over 40 and small-for-gestational age was more frequent with age, reaching 34% in women over 45. CONCLUSIONS: The risk of maternal-foetal complications increases steadily with age and is particularly high after 35 years and closer monitoring appears to be necessary. These results provide additional evidence and information for public health decision-makers.

Infertility Treatment in France, 2008-2017: A Challenge of Growing Treatment Needs at Older Ages.

Objectives. To measure trends in infertility treatment use between 2008 and 2017 in France using data from the national health insurance system.Methods. Between 2008 and 2017, we observed a representative national sample of nearly 1% of all women aged 20 to 49 years who were affiliated with the main health insurance scheme in France (more than 100 000 women observed each year). We exhaustively recorded all health care reimbursed to these women.Results. Among women aged 20 to 49 years, 1.25% were treated for infertility each year. Logistic regression analysis showed a significant interaction between age and year of treatment use (P < .001). Over the decade, infertility treatment use increased by 23.9% among women aged 34 years or older, whereas among women younger than 34 years there was a nonsignificant variation.Conclusions. Women aged 34 years or older were increasingly treated for infertility between 2008 and 2017.Public Health Implications. Treatment efficiency decreases strongly with a woman's age, presenting a challenge for medical infertility care.

Cell-free fetal DNA versus maternal serum screening for trisomy 21 in pregnant women with and without assisted reproduction technology: a prospective interventional study.

PURPOSE: Cell-free DNA (cfDNA) as a primary screening test has been available for years but few studies have addressed this option in a prospective manner. The question is of interest after reports that maternal serum screening (MSS) is less accurate for pregnancies resulting from assisted reproduction technologies (ART) than for spontaneous pregnancies (SP). METHODS: A prospective interventional study was designed to address the performances of cfDNA compared with MSS in pregnancies with or without ART. Each patient was offered both MSS and cfDNA testing. The primary analysis cohort ultimately included 794 patients with a spontaneous pregnancy (SP) (n = 472) or pregnancy obtained after ART (n = 322). RESULTS: Overall, the false-positive rate and positive predictive value were 6.6% and 8.8% for MSS but 0% and 100% for cfDNA. MSS false-positive rate and positive predictive values were clearly poorer in the ART group (11.7% and 2.6%) than in the SP group (3.2% and 21.1%). The global rates of invasive procedures were 1.9% (15/794) with cfDNA but 8.4% (65/794) if MSS alone was proposed. CONCLUSION: cfDNA achieved better performance than MSS in both spontaneous and ART pregnancies, thus decreasing the number of invasive procedures. Our findings suggest that cfDNA should be considered for primary screening, especially in pregnancies obtained after ART.

Effect of Glyburide vs Subcutaneous Insulin on Perinatal Complications Among Women With Gestational Diabetes: A Randomized Clinical Trial.

Importance: Randomized trials have not focused on neonatal complications of glyburide for women with gestational diabetes. Objective: To compare oral glyburide vs subcutaneous insulin in prevention of perinatal complications in newborns of women with gestational diabetes. Design, Settings, and Participants: The Insulin Daonil trial (INDAO), a multicenter noninferiority randomized trial conducted between May 2012 and November 2016 (end of participant follow-up) in 13 tertiary care university hospitals in France including 914 women with singleton pregnancies and gestational diabetes diagnosed between 24 and 34 weeks of gestation. Interventions: Women who required pharmacologic treatment after 10 days of dietary intervention were randomly assigned to receive glyburide (n=460) or insulin (n=454). The starting dosage for glyburide was 2.5 mg orally once per day and could be increased if necessary 4 days later by 2.5 mg and thereafter by 5 mg every 4 days in 2 morning and evening doses, up to a maximum of 20 mg/d. The starting dosage for insulin was 4 IU to 20 IU given subcutaneously 1 to 4 times per day as necessary and increased according to self-measured blood glucose concentrations. Main Outcomes and Measures: The primary outcome was a composite criterion including macrosomia, neonatal hypoglycemia, and hyperbilirubinemia. The noninferiority margin was set at 7% based on a 1-sided 97.5% confidence interval. Results: Among the 914 patients who were randomized (mean age, 32.8 [SD, 5.2] years), 98% completed the trial. In a per-protocol analysis, 367 and 442 women and their neonates were analyzed in the glyburide and insulin groups, respectively. The frequency of the primary outcome was 27.6% in the glyburide group and 23.4% in the insulin group, a difference of 4.2% (1-sided 97.5% CI, -∞ to 10.5%; P=.19). Conclusion and Relevance: This study of women with gestational diabetes failed to show that use of glyburide compared with subcutaneous insulin does not result in a greater frequency of perinatal complications. These findings do not justify the use of glyburide as a first-line treatment. Trial Registration: clinicaltrials.gov Identifier: NCT01731431.

Statistical significance versus clinical relevance.

In March this year, the American Statistical Association (ASA) posted a statement on the correct use of P-values, in response to a growing concern that the P-value is commonly misused and misinterpreted. We aim to translate these warnings given by the ASA into a language more easily understood by clinicians and researchers without a deep background in statistics. Moreover, we intend to illustrate the limitations of P-values, even when used and interpreted correctly, and bring more attention to the clinical relevance of study findings using two recently reported studies as examples. We argue that P-values are often misinterpreted. A common mistake is saying that P < 0.05 means that the null hypothesis is false, and P ≥0.05 means that the null hypothesis is true. The correct interpretation of a P-value of 0.05 is that if the null hypothesis were indeed true, a similar or more extreme result would occur 5% of the times upon repeating the study in a similar sample. In other words, the P-value informs about the likelihood of the data given the null hypothesis and not the other way around. A possible alternative related to the P-value is the confidence interval (CI). It provides more information on the magnitude of an effect and the imprecision with which that effect was estimated. However, there is no magic bullet to replace P-values and stop erroneous interpretation of scientific results. Scientists and readers alike should make themselves familiar with the correct, nuanced interpretation of statistical tests, P-values and CIs.

Down syndrome maternal serum markers in oocyte donation and other assisted reproductive technologies.

OBJECTIVE: Because maternal serum markers (pregnancy-associated plasma protein A, human chorionic gonadotropin free ß subunit, and alpha-fetoprotein) used for Down syndrome (DS) screening have been described as predictors of obstetrical complications and because assisted reproductive technology (ART) pregnancies are known to be at increased risk for obstetrical complications, it is unclear whether or not correction factors should be applied to the calculated risk of DS. The purpose of this study was to evaluate DS maternal serum markers in oocyte donation (OD) and ART pregnancies in comparison with natural pregnancies. METHOD: Multicenter retrospective 2010 to 2013 study in singleton pregnancies was used. First- and second-trimester DS screenings in 614 OD and 1921 ART pregnancies versus 7268 natural pregnancies are compared. RESULTS: There was a significant increase in hCGß in the OD group for both trimesters (first trimester: 1.28 MoM vs 1.02; P < .001 and second trimester: 1.32 MoM vs 1 MoM; P < .001). Pregnancy-associated plasma protein A was significantly lower in the ART group (0.92 and 1.02 MoM P < .001). CONCLUSION: Maternal serum markers for DS screening are significantly modified in ART and OD pregnancies. Because these markers are also markers for obstetrical complications, the rationale for applying correction factors is questionable.

Ovulatory status and menstrual cycle duration assessed by self-collection of urine on pH strips in a population-based sample of French women not using hormonal contraception.

BACKGROUND: Assessing menstrual cycle function in the general population using a non-invasive method is challenging, both in non-industrialized and industrialized countries. SUBJECTS AND METHODS: The Observatory of Fecundity in France (Obseff) recruited on a nationwide basis a random sample of 943 women aged 18-44 years with unprotected intercourse. A sub-study was set up to assess the characteristics of a menstrual cycle by using a non-invasive method adapted to the general population. Voluntary women were sent a collection kit by the post and requested to collect urine samples on pH strips, together with daily recording of reproductive-related information during a full menstrual cycle. A total of 48 women collected urine every day, whereas 160 women collected urine every other day. Immunoassays were used to measure pregnanediol-3-α-glucuronide, estrone-3-glucuronide and creatinine. Ovulation occurrence and follicular phase duration were estimated using ovulation detection algorithms, compared to a gold standard consisting of three external experts in reproductive medicine. RESULTS: Every other day urine collection gave consistent results in terms of ovulation detection with every day collection (intraclass coefficient of correlation, 0.84, 95% confidence interval, 0.76-0.98). The proportion of anovulatory menstrual cycles was 8%. The characteristics of the ovulatory cycles were length 28 (26-34), follicular phase 16 (12-23), luteal phase 13 (10-16) days median (10th-90th percentiles). DISCUSSION-CONCLUSION: Assessing menstrual cycle characteristics based on urine sample spot only collected every other day in population-based studies through a non-invasive, well accepted and cost-limited procedure not requiring any direct contact with the survey team appears feasible and accurate.

Seven out of 10 couples treated by IVF achieve parenthood following either treatment, natural conception or adoption.

The aim of this study was to explore the achievement of parenthood 8 years after starting IVF, considering multiple pathways to parenthood during and after IVF treatment. Medical data on 6507 couples who began IVF between 2000 and 2002 were obtained from the databases of eight French IVF centres. Information on long-term outcome was available for participants in the 2008-2010 postal survey. Multiple imputation methods were used to account for missing data. Eight years after starting IVF, 71% (95% CI 69 to 74) of treated couples had a child. This included 41% live births after IVF in the IVF centre, 7% live births after another treatment or after IVF in another centre, 12% live births after spontaneous conception and 11% adoptions. This study provides a longitudinal overview of paths to parenthood among couples successfully and unsuccessfully treated by IVF. These results should give hope to infertile couples as seven out of 10 couples finally became parents. However, IVF is not the only path to parenthood, and couples should be informed of the other possible avenues.

Congenital diaphragmatic hernia: does gestational age at diagnosis matter when evaluating morbidity and mortality?

OBJECTIVE: The objective of the investigation was to study the relationship between gestational age at diagnosis and mortality and morbidity in fetuses with an isolated congenital diaphragmatic hernia. STUDY DESIGN: Between January 2008 and November 2013, 377 live births with isolated congenital diaphragmatic hernia diagnosed antenatally at a known gestational age were recorded in the database of the French National Center for Rare Diseases. The primary outcome studied was mortality estimated at 28 days and at 6 months. The secondary outcome was morbidity evaluated by pulmonary arterial hypertension at 48 hours, oxygen therapy dependence at 28 days, oral disorders, enteral feeding, and prosthetic patch repair. Analyses were adjusted for the main factors of congenital diaphragmatic hernia severity (side of the hernia, thoracic herniation of the liver, gestational age at birth, lung-to-head ratio, and prenatal treatment by tracheal occlusion. RESULTS: Mortality rates at 28 days decreased significantly (P < .001) when gestational age at diagnosis increased: 61.1%, 39.2%, and 10.4% for a diagnosis in the first, second, and third trimester, respectively. Adjusted odds ratios were 3.12 [95% confidence interval, 1.86-5.25] and 0.35 [95% confidence interval, 0.18-0.66] for a diagnosis in the first and third trimesters, respectively, compared with a diagnosis in the second trimester. Similarly, morbidity decreased significantly when gestational age at diagnosis increased, and the trend remained significant after adjustment for the main factors of congenital diaphragmatic hernia severity (P < .001). CONCLUSION: Gestational age at diagnosis is an independent predictor of postnatal prognosis for children presenting an isolated congenital diaphragmatic hernia and should be taken into account when estimating postnatal morbidity and mortality.

Medical factors associated with early IVF discontinuation.

Even when IVF is reimbursed by the social insurance system, as in France, high discontinuation rates have been reported and some patients drop out as soon as the first failed IVF cycle. This study aims to investigate medical factors associated with treatment discontinuation in an IVF centre after the first unsuccessful cycle. The study included 5135 couples recruited in eight French IVF centres and who had had an unsuccessful first IVF cycle in these centres in 2000-2002 (i.e. no live birth). Of these couples with a first failed IVF, 1337 did not have a second IVF in the centre (26%, 'early discontinuation group') and 3798 continued treatment with a second IVF in the centre. The characteristics of couples who discontinued IVF treatment were compared with those who continued using logistic regressions. Older women, women with duration of infertility >5years, with female factor or unexplained infertility, with 0 or 1 oocyte retrieved and no embryo transfer during the first IVF were more likely to discontinue treatment early. Risk of early discontinuation was associated with medical factors that are also well known to be associated with impaired chance of successful IVF. Even when IVF is reimbursed by the social insurance system, as in France, high discontinuation rates have been reported and some patients drop out as soon as the first failed IVF cycle. This study aims to investigate medical factors associated with treatment discontinuation in an IVF centre after the first unsuccessful cycle. The study included 5135 couples recruited in eight French IVF centres who had had an unsuccessful first IVF cycle in these centres in 2000-2002 (i.e. who remained childless after a first cycle). Of these couples with a first failed IVF, 1337 did not have a second IVF in the centre and 3798 continued treatment with a second IVF in the centre. The characteristics of couples who discontinued IVF treatment were compared with those who continued. After a first failed IVF cycle, more than one-quarter (26%) of couples discontinued IVF treatment. Older women, women with duration of infertility >5years, with female factor or unexplained infertility, with 0 or 1 oocyte retrieved and with no embryo transfer during the first IVF were more likely to discontinue treatment early. The risk of early discontinuation was associated with medical factors that are also well known to be associated with impaired chance of success during IVF treatment. A next step would be to examine whether the early discontinuation results from a decision of the couple themselves, from medical, psychological and/or social staff counselling or from some combination of all of these factors.

Stability of procalcitonin at room temperature.

BACKGROUND: The aim was to assess procalcitonin (PCT) stability after two days of storage at room temperature. METHODS: Samples were collected from febrile children aged 7 to 92 days and were rapidly frozen after sampling. PCT levels were measured twice after thawing: immediately (named y) and 48 hours later after storage at room temperature (named x). PCT values were described with medians and interquartile ranges or by categorizing them into classes with thresholds 0.25, 0.5, and 2 ng/mL. The relationship between x and y PCT levels was analyzed using fractional polynomials in order to predict the PCT value immediately after thawing (named y') from x. RESULTS: A significant decrease in PCT values was observed after 48 hours of storage at room temperature, either in median, 30% lowering (p < 0.001), or as categorical variable (p < 0.001). The relationship between x and y can be accurately modeled with a simple linear model: y = 1.37 x (R2 = 0.99). The median of the predicted PCT values y' was quantitatively very close to the median of y and the distributions of y and y' across categories were very similar and not statistically different. CONCLUSIONS: PCT levels noticeably decrease after 48 hours of storage at room temperature. It is possible to pre- dict accurately effective PCT values from the values after 48 hours of storage at room temperature with a simple statistical model.

Clinical predictors of radiographic abnormalities among infants with bronchiolitis in a paediatric emergency department.

BACKGROUND: Acute viral respiratory exacerbation is one of the most common conditions encountered in a paediatric emergency department (PED) during winter months. We aimed at defining clinical predictors of chest radiography prescription and radiographic abnormalities, among infants with bronchiolitis in a paediatric emergency department. METHODS: We conducted a prospective cohort study of children less than 2 years of age with clinical bronchiolitis, who presented for evaluation at the paediatric emergency department of an urban general hospital in France. Detailed information regarding historical features, examination findings, and management were collected. Clinical predictors of interest were explored in multivariate logistic regression models. RESULTS: Among 410 chest radiographs blindly interpreted by two experts, 40 (9.7%) were considered as abnormal. Clinical predictors of chest radiography achievement were age (under three months), feeding difficulties, fever over 38°C, hypoxia under than 95% of oxygen saturation, respiratory distress, crackles, and bronchitis rales. Clinical predictors of radiographic abnormalities were fever and close to significance hypoxia and conjunctivitis. CONCLUSION: Our study provides arguments for reducing chest radiographs in infants with bronchiolitis. For infants with clinical factors such as age less than three months, feeding difficulties, respiratory distress without hypoxia, isolated crackles or bronchitis rales, careful clinical follow-up should be provided instead of chest radiography.

Contraceptive Use Measured in a National Population-Based Approach: Cross-Sectional Study of Administrative Versus Survey Data.

BACKGROUND: Prescribed contraception is used worldwide by over 400 million women of reproductive age. Monitoring contraceptive use is a major public health issue that usually relies on population-based surveys. However, these surveys are conducted on average every 6 years and do not allow close follow-up of contraceptive use. Moreover, their sample size is often too limited for the study of specific population subgroups such as people with low income. Health administrative data could be an innovative and less costly source to study contraceptive use. OBJECTIVE: We aimed to explore the potential of health administrative data to study prescribed contraceptive use and compare these data with observations based on survey data. METHODS: We selected all women aged 15-49 years, covered by French health insurance and living in France, in the health administrative database, which covers 98% of the resident population (n=14,788,124), and in the last French population-based representative survey, the Health Barometer Survey, conducted in 2016 (n=4285). In health administrative data, contraceptive use was recorded with detailed information on the product delivered, whereas in the survey, it was self-declared by the women. In both sources, the prevalence of contraceptive use was estimated globally for all prescribed contraceptives and by type of contraceptive: oral contraceptives, intrauterine devices (IUDs), and implants. Prevalences were analyzed by age. RESULTS: There were more low-income women in health administrative data than in the population-based survey (1,576,066/14,770,256, 11% vs 188/4285, 7%, respectively; P<.001). In health administrative data, 47.6% (7034,710/14,770,256; 95% CI 47.6%-47.7%) of women aged 15-49 years used a prescribed contraceptive versus 50.5% (2297/4285; 95% CI 49.1%-52.0%) in the population-based survey. Considering prevalences by the type of contraceptive in health administrative data versus survey data, they were 26.9% (95% CI 26.9%-26.9%) versus 27.7% (95% CI 26.4%-29.0%) for oral contraceptives, 17.7% (95% CI 17.7%-17.8%) versus 19.6% (95% CI 18.5%-20.8%) for IUDs, and 3% (95% CI 3.0%-3.0%) versus 3.2% (95% CI 2.7%-3.7%) for implants. In both sources, the same overall tendency in prevalence was observed for these 3 contraceptives. Implants remained little used at all ages, oral contraceptives were highly used among young women, whereas IUD use was low among young women. CONCLUSIONS: Compared with survey data, health administrative data exhibited the same overall tendencies for oral contraceptives, IUDs, and implants. One of the main strengths of health administrative data is the high quality of information on contraceptive use and the large number of observations, allowing studies of subgroups of population. Health administrative data therefore appear as a promising new source to monitor contraception in a population-based approach. They could open new perspectives for research and be a valuable new asset to guide public policies on reproductive and sexual health.

Impact of oxygen tension during in vitro maturation: a sibling-oocyte prospective double-blinded study.

OBJECTIVE: To determine whether oxygen (O2) tension (20% vs. 5%) has an impact on oocyte maturation rates and morphology during in vitro maturation (IVM). DESIGN: A prospective, observational, monocentric, sibling-oocyte study. SETTING: University Hospital. PATIENTS: A total of 143 patients who underwent IVM for fertility preservation purposes from November 2016 to April 2021 were analyzed. Patients were included when ≥2 cumulus-oocyte complexes (COCs) were retrieved. The cohort of COCs obtained for each patient was randomly split into two groups: group 20% O2 and group 5% O2. INTERVENTION: Cumulus-oocyte complexes were incubated for 48 hours either under 5% O2 or 20% O2. After 24 and 48 hours of culture, every oocyte was assessed for maturity and morphology, to estimate oocyte quality. Morphology was evaluated considering six parameters (shape, size, ooplasm, perivitelline space, zona pellucida, and polar body characteristics), giving a total oocyte score ranging from -6 to +6. MAIN OUTCOME MEASURES: Maturation rates and total oocyte scores were compared using paired-sample analysis between group 20% O2 and group 5% O2. RESULTS: Patient median age was 31.4 [28.1-35.2] years-old. The mean serum antimüllerian hormone levels and antral follicle count were 3.2 ± 2.3 ng/mL and 27.2 ± 16.0 follicles, respectively. A mean of 10.7 COCs per cycle were retrieved, leading to 6.1 ± 2.4 metaphase II oocytes vitrified (total maturation rate = 57.3%; 991 metaphase II oocytes/1,728 COCs). A total of 864 COCs were included in each group. Oocyte maturation rates were not different between the two groups (group 20% O2: 56.82% vs. group 5% O2: 57.87%, respectively). Regarding oocyte morphology, the mean total oocyte score was significantly higher in group 5% O2 compared with group 20% O2 (3.44 ± 1.26 vs. 3.16 ± 1.32, P=.014). CONCLUSION: As culture under low O2 tension (5% O2) improves oocyte morphology IVM, our results suggest that culture under hypoxia should be standardized. Additional studies are warranted to assess the impact of O2 tension on oocyte maturation and the benefit of IVM under low O2 tension for embryo culture after utilization of frozen material.

Fertility after ectopic pregnancy: the DEMETER randomized trial.

STUDY QUESTION: Does treatment for the resolution of ectopic pregnancy (EP) affect subsequent spontaneous fertility [occurrence of an intrauterine pregnancy (IUP)]? SUMMARY ANSWER: There is no significant difference in 2 years subsequent fertility neither between methotrexate and conservative surgery for less active EP nor between conservative and radical surgery for the most active EP. WHAT IS KNOWN ALREADY: No randomized trial has compared radical and conservative surgery treatments. A recent review of the Cochrane database did not conclude about fertility due to insufficient data. Prospective studies from EP registries in two regions of France (Auvergne and Greater Lille) have suggested that fertility is similar after medical treatment and conservative surgery and lower after radical surgery. STUDY DESIGN, SIZE, DURATION: This randomized controlled trial included all women with an ultrasound-confirmed EP. Women were divided into two arms according to the activity of the EP (defined by Fernandez's score). In arm 1 (less active ectopic pregnancies, i.e. Fernandez's score <13 and no haemodynamic failure), medical treatment was considered practicable, and women were randomly allocated to conservative surgery with a systematic post-operative i.m. methotrexate injection within 24 h or to an i.m. methotrexate injection alone. In arm 2 (active ectopic pregnancies), medical treatment was considered impracticable, and, thus, all women had to undergo surgery; they were randomly allocated to either a radical or conservative procedure, the latter including a post-operative methotrexate injection. Sample sizes (n = 210 in arm 1 and n = 230 in arm 2) were computed to provide a statistical power of 80% to detect a 20% difference in subsequent cumulative fertility rates between treatments in each arm. The total duration of the trial was 5 years. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: The trial took place in 17 centres in France from 2005 to 2009. Two hundred and seven women were included in arm 1 and 199 in arm 2. Cumulative fertility curves were drawn with the Kaplan-Meier method and compared with the log-rank test. Hazard ratios (HRs) were computed with the Cox model. Analysis was performed according to the intention-to-treat principle. MAIN RESULTS: Arm 1: cumulative fertility curves were not significantly different between medical treatment and conservative surgery. HR was 0.85 (0.59-1.22) P = 0.37. The 2-year rates of IUP were 67% after medical treatment and 71% after conservative surgery. Arm 2: cumulative fertility curves were not significantly different between conservative and radical surgery. HR was 1.06 (0.69-1.63) P = 0.78. The 2-year rates of IUP were 70% after conservative surgery and 64% after radical surgery. LIMITATIONS, REASONS FOR CAUTION: Inclusion in this trial was more difficult than expected, especially in arm 2 in which women were reluctant to radical surgery. In consequence, the sample size was slightly lower than planned. However, due to a lower proportion of lost to follow-up than expected (10% instead of 15%), the statistical power remained very close to 80%. WIDER IMPLICATIONS OF THE FINDINGS: As it is a multicentre randomized trial, the results may be generalized with satisfactory confidence. The results of this trial invite gynaecologists to reconsider the management of EP and to modify balance between considerations of initial recovery and preservation of fertility. TRIAL REGISTRATION NUMBER: NCT00137982 on the WHO International Clinical Trials Registry Platform.