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Study questionDoes parental fertility, measured by time to pregnancy (TTP), or use of medically assisted reproduction (MAR) affect pubertal development in the offspring?Summary answerNeither TTP nor type of MAR treatment had clinically relevant implications for mean age at achieving individual pubertal milestones or overall timing of puberty in boys and girls.What is known alreadyParental TTP and MAR have been associated with impaired semen quality in adult sons. Timing of puberty reflects earlier signals of reproductive health, but it remains unclear whether parental fertility or MAR affects pubertal development, especially in the growing generation of children conceived by IVF or ICSI.Study design, size, durationIn this study, 15 819 children born by mothers in the Danish National Birth Cohort from 2000 to 2003 participated in a nationwide puberty cohort (participation rate = 70%). Parental TTP and use of MAR were reported by mothers in early pregnancy and children's pubertal development data was self-recorded in web-based questionnaires from 11 years of age and 6 monthly throughout puberty (2012-2018).Participants/materials, setting, methodsPubertal development in children (of planned pregnancies, n = 13 285) born by untreated subfecund (TTP: 6-12 months) (n =2038), untreated severely subfeund (TTP: >12 months) (n = 1242), treated subfecund (n = 230) and treated severely subfecund (n = 1234) parents were compared to children born to more fertile parents (TTP: ≤5 months). We estimated mean monthly differences in mean age at achieving individual pubertal milestones (i.e. age at menarche, voice break, first ejaculation and Tanner stages 2, 3, 4 and 5 for breast or genital development and pubic hair growth) and a combined indicator of timing of puberty. Further, we compared mean age at achieving the individual pubertal milestones in children born by use of IVF or ICSI (n = 480) with children born by controlled ovarian stimulation or ovulation induction with or without intrauterine insemination (n = 902).Main results and the role of chanceWe found tendencies towards slightly later mean age at male pubertal timing and slightly earlier mean age at female pubertal timing among children born by untreated subfecund, treated subfecund, untreated severely subfecund and treated severely subfecund parents. There were no specific patterns with increasing TTP, use of MAR nor type of MAR treatment, and the magnitude of the mean differences for individual milestones and overall timing of puberty were small, i.e. 0.9 months (95% CI: -1.0; 2.8) for first ejaculation and -0.5 months (95% CI: -2.0; 1.0) months for age at menarche in boys and girls, respectively, born by treated severely subfecund parents when compared with children born by more fertile parents.Limitations, reasons for cautionNon-differential misclassification of the self-reported information on parental TTP and pubertal development in the offspring may serve as an alternative explanation of the findings, possibly biasing the estimates towards the null. The information on pubertal development was collected from around 11 years of age and onwards.Wider implications of the findingsThis study adds to the growing body of literature suggesting only limited harmful effects of parental subfecundity and MAR on offspring's long-term growth and development.Study funding/competing interest(s)This work was supported by the Danish Council for Independent Research [DFF 4183-00152]; and the Faculty of Health at Aarhus University. The authors have no financial relationships or competing interests to disclose.

Study Question: Is maternal age at menarche associated with pubertal development in sons and daughters?Summary Answer: Maternal age at menarche was associated with pubertal development in both sons and daughters.What Is Known Already: Studies have shown that age at menarche is greatly inherited from mother to daughter, but it remains largely unknown to what extent age at menarche in mothers is associated with timing of puberty in sons.Study Design, Size, Duration: In this population-based study we used data from the Puberty Cohort nested within the Danish National Birth Cohort. Live-born singletons aged 11 were followed from 2012 to 2016.Participants/materials, Setting, Methods: In total, 15 822 children (7697 sons and 8125 daughters) gave half-yearly information on puberty from the age of 11 years until full sexual maturity or 18 years of age through self-administrated questionnaires (participation rate 71%). Information on maternal age at menarche was reported by the mothers during pregnancy. Maternal age at menarche was used both as a continuous and as a categorical variable (earlier, same time or later than peers). A multivariable regression model for interval-censored data was used.Main Results and the Role Of Chance: Maternal age at menarche was positively associated with timing of genital development, pubic hair development, first ejaculation of semen, voice break, axillary hair development and acne in sons, and with timing of breast development, pubic hair development, menarche, axillary hair development and acne in daughters. In sons, the associations were of similar strength for all pubertal markers, whereas in daughters, the associations were strongest for breast development and menarche.Limitations, Reasons For Caution: Age at menarche was recalled during pregnancy. However, studies indicate that age at menarche is recalled moderately in adulthood. Information on puberty was self-reported, but inaccuracy of data would probably cause non-differential misclassification.Wider Implications Of the Findings: Early maternal age at menarche was associated with earlier pubertal development, and late maternal age at menarche was associated with later pubertal development in both sons and daughters. The largest effect-estimates were for the associations between maternal age at menarche and the daughters' age at menarche and age at breast development.Study Funding/competing Interest(s): The study was funded by the Danish Council for Independent Research (4183-00152). There are no competing interests.Trial Registeration Number: N/A. [ABSTRACT FROM AUTHOR]