Abstract
Abstract Study question Are early reproductive outcomes of individuals conceived with IVF different from the general population or from spontaneously conceived individuals born to couples with infertility? Summary answer The first birth cohorts from IVF were more likely to experience infertility and use assisted reproduction also when accounting for parental factors and infertility What is known already In-vitro fertilisation has helped countless couples overcome involuntary childlessness, but little is yet known of the reproductive outcomes of their offspring. Deviations could occur as a result of the transmission of, or reaction to, parental traits and behaviors, or adverse effects of the procedures. A few small studies of young adults conceived with intra-cytoplasmic sperm injection due to male factor infertility have indicated lower sperm quantity (but not quality) compared to spontaneously conceived males, and no differences in reproductive hormones or antral follicle count in females. Study design, size, duration This nation-wide cohort study considered all individuals in the Swedish Medical Birth Register, born between 1985 and 1996 (N = 1,291,795). Linkage of population-registers allowed prospective follow-up of potential reproductive outcomes, migration from Sweden or death, until the end of 2017. Participants/materials, setting, methods Parental infertility and IVF use was identified from maternal self-report and IVF-clinic reporting to the Medical Birth Register, which was also used for outcome ascertainment, along with registers over family relations, outpatient specialist care, and assisted reproduction. Individuals conceived with IVF were compared to spontaneously conceived individuals of the same age. Comparisons were also adjusted for parents’ age, education and country of origin and further restricted to only concern individuals whose parents experienced infertility. Main results and the role of chance Compared to spontaneously conceived of the same age, individuals conceived with IVF were less likely to have had any biological children across all studied birth cohorts (Hazard ratio (HR) 0.67 95% Confidence interval (CI) 0.62–0.74 overall), but adjustment for parental factors and comparison to individuals with parental infertility attenuated the differences to the null. Among individuals followed until at least age 30, those that had been conceived with IVF were more likely to have received a diagnosis of infertility (HR 2.03, 95% CI 1.15–3.58), also after adjustment for parental factors (HR 2.08, 95% CI 1.18–3.66) and restriction with respect to parental infertility (HR 1.82, 95% CI 1.03–3.24). While there was no substantial difference in mean age, the first recorded birth was more likely to have been preceded by infertility and IVF assistance when individuals had been conceived with IVF themselves (Odds ratio (OR) 2.89, 95% CI 1.47–5.66 and OR 3.83, 95% CI 1.48-9.93 respectively in adjusted comparison to individuals with parental infertility). Corresponding elevated risks were not observed in any of the birth cohorts for which follow-up did not extend beyond their 20s (born 1988-1996). Limitations, reasons for caution Since not even the first IVF birth cohorts have completed their expected reproductive period, these findings merely represent an indication of the early reproductive outcome of the first generation conceived with IVF in Sweden. Information on type and severity of parental infertility was not available. Wider implications of the findings Finding the earliest birth cohorts conceived with IVF at elevated risk of infertility and of using IVF for their first birth, also when accounting for parental infertility, stresses the need for further monitoring as more cohorts enter and pass through the expected reproductive period. Trial registration number Not applicable
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