Female Infertility and Neurodevelopmental Disorders in Children: associations and evidence for familial confounding in Denmark.

IMPORTANCE: Existing research suggests the impact of infertility on the risk of neurodevelopmental disorders in children, however, studies to date have failed to separate the impact of male and female infertility, often blurring the lines with proxies that encompass all forms of infertility. Moreover, while both health conditions co-occurring with infertility and genetic factors operating upstream have been suggested to influence the association between infertility and child outcomes, their roles and potential impact on observed associations remain unclear. OBJECTIVE: The objectives of this study are to investigate the relationship between female infertility and autism in the child, differentiating it from the effects of male and the couple infertility; consider the role of various maternal and birth factors in the association; and examine the effects of shared familial confounders on the association. DESIGN SETTING AND PARTICIPANTS: Danish population-based cohort study, including all singleton live births in Denmark 1998-2015, their parents and parents' siblings. The cohort was followed up until December 31, 2016. EXPOSURES: The exposure was a history of female infertility in the mother and the mother's sister. We examined four definitions of female infertility based on the ICD-10 codes derived from the Danish National Patient Register - any female infertility; specified female infertility; female exclusive infertility; and female or male infertility. MAIN OUTCOME AND MEASURES: The outcome was diagnosis of autism spectrum disorder (ASD) in the Danish Psychiatric Central Research Register or the national patient register. A multivariable Cox regression model was used to estimate the associations between female infertility and autism, accounting for child's sex, year of birth, maternal age, education level, chronic comorbidities, and pregnancy and birth complications. The effects of shared familial factors on the association were analyzed using exposure information from the child's maternal aunt. RESULTS: The cohort included 1,131,899 mother-child pairs, among which 18,374 children with ASD diagnosis. History of female infertility in the mother (all definitions) was significantly associated with autism in the child, with the association remaining robust after adjustment for covariates (HRadj=1.14 (95% CI, 1.03-1.26) for specified infertility). The diagnosis of infertility in a child's maternal aunt was also significantly linked to the child's autism risk, even after adjustment for maternal infertility (HRadj=1.10 (95% CI, 1.00-1.20). CONCLUSIONS AND RELEVANCE: in This population-based birth cohort study, we found a slightly higher risk of autism in children born to mothers with a history of infertility, with the association remaining consistent across various definitions of female infertility and robust to adjustments for demographic, child, and maternal factors. The study suggests for the first time that shared familial factors, possibly both genetic and non-genetic, could be influencing both female infertility and the risk of autism in children, indicating a need for further investigation into these familial effects.

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.

Analysis of peer reviewers' response to invitations by gender and geographical region: cohort study of manuscripts reviewed at 21 biomedical journals before and during covid-19 pandemic.

OBJECTIVES: To describe gender and geographical inequalities in invitations to review and the response to these invitations and to assess whether inequalities increased during the covid-19 pandemic. DESIGN: Retrospective cohort study. SETTING: 19 specialist medical journals and two large general medical journals from BMJ Publishing Group. POPULATION: Reviewers invited to review manuscripts submitted between 1 January 2018 and 31 May 2021. The cohort was followed up to 28 February 2022. MAIN OUTCOME MEASURES: Reviewer's agreement to review. RESULTS: A total of 257 025 reviewers were invited (38.6% (88 454/228 869) women), and 90 467 (35.2%) agreed to review. Invited reviewers were mainly (217 682; 84.7%) affiliated with high income countries: Europe (122 414; 47.6%), North America (66 931; 26.0%), Africa (25 735; 10.0%), Asia (22 693; 8.8%), Oceania (16 175; 6.3%), and South America (3076; 1.2%). Independent factors associated with agreement to review were gender (odds ratio 0.89, 95% confidence interval 0.87 to 0.92, for women compared with men), geographical affiliation (2.89, 2.73 to 3.06, for Asia; 3.32, 2.94 to 3.75 for South America; 1.35, 1.27 to 1.43, for Oceania; and 0.35, 0.33 to 0.37, for Africa compared with Europe), and country income (0.47, 0.45 to 0.49, for upper middle income; 5.12, 4.67 to 5.61, for lower middle income; and 4.66, 3.79 to 5.73, for low income compared with high income country). Agreement was also independently associated with editor's gender (0.96, 0.93 to 0.99, for women compared with men), last author's geographical affiliation (0.80, 0.78 to 0.83, for Asia; 0.89, 0.85 to 0.94, for Oceania compared with Europe), impact factor (1.78, 1.27 to 2.50, for >10 compared with <5), and type of peer review process (0.52, 0.35 to 0.77, for open compared with anonymised). During the first and second phases of the pandemic, agreement was lower than in the pre-pandemic period (P<0.001). The interaction between time periods and covid-19 related topic and reviewer's gender was non-significant. However, significant interaction was found between time periods and covid-19 related topic and reviewer's geographical affiliation. CONCLUSIONS: To reduce bias and improve diversity, editors need to identify and implement effective strategies and continually evaluate progress against these to ensure that more women and researchers from upper middle income and low income countries are involved in review.

Female authorship of covid-19 research in manuscripts submitted to 11 biomedical journals: cross sectional study.

OBJECTIVE: To describe prominent authorship positions held by women and the overall percentage of women co-authoring manuscripts submitted during the covid-19 pandemic compared with the previous two years. DESIGN: Cross sectional study. SETTING: Nine specialist and two large general medical journals. POPULATION: Authors of research manuscripts submitted between 1 January 2018 and 31 May 2021. MAIN OUTCOME MEASURES: Primary outcome: first author's gender. SECONDARY OUTCOMES: last and corresponding authors' gender; number (percentage) of women on authorship byline in "pre-pandemic" period (1 January 2018 to 31 December 2019) and in "covid-19" and "non-covid-19" manuscripts during pandemic. RESULTS: A total of 63 259 manuscripts were included. The number of female first, last, and corresponding authors respectively were 1313 (37.1%), 996 (27.9%), and 1119 (31.1%) for covid-19 manuscripts (lowest values in Jan-May 2020: 230 (29.4%), 165 (21.1%), and 185 (22.9%)), compared with 8583 (44.9%), 6118 (31.2%), and 7273 (37.3%) for pandemic non-covid-19 manuscripts and 12 724 (46.0%), 8923 (31.4%), and 10 981 (38.9%) for pre-pandemic manuscripts. The adjusted odds ratio of having a female first author in covid-19 manuscripts was <1.00 in all groups (P<0.001) compared with pre-pandemic (lowest in Jan-May 2020: 0.55, 98.75% confidence interval 0.43 to 0.70). The adjusted odds ratio of having a woman as last or corresponding author was significantly lower for covid-19 manuscripts in all time periods (except for the two most recent periods for last author) compared with pre-pandemic (lowest values in Jan-May 2020: 0.74 (0.57 to 0.97) for last and 0.61 (0.49 to 0.77) for corresponding author). The odds ratios for pandemic non-covid-19 manuscripts were not significantly different compared with pre-pandemic manuscripts. The median percentage of female authors on the byline was lower for covid-19 manuscripts (28.6% in Jan-May 2020) compared with pre-pandemic (36.4%) and non-covid-19 pandemic manuscripts (33.3% in Jan-May 2020). Gender disparities in all prominent authorship positions and the proportion of women authors on the byline narrowed in the most recent period (Feb-May 2021) compared with the early pandemic period (Jan-May 2020) and were very similar to values observed for pre-pandemic manuscripts. CONCLUSIONS: Women have been underrepresented as co-authors and in prominent authorship positions in covid-19 research, and this gender disparity needs to be corrected by those involved in academic promotion and awarding of research grants. Women attained some prominent authorship positions equally or more frequently than before the pandemic on non-covid-19 related manuscripts submitted at some time points during the pandemic.

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.