Infertility was associated with mental health, especially dysthymia and anxiety. The results differed by gender and the permanency of infertility. Gender-specific psychosocial support and follow-up for infertile people is warranted.

Reducing the number of transferred embryos would improve the health of in vitro fertilization children. Additional studies are needed to explain the poorer health of in vitro fertilization singletons, as well as follow-up studies to examine the health of in vitro fertilization children from 4 years onward.

No abstract

General cancer risk or risk of hormonal-related cancers in women was not increased by IVF. The differences in certain cancers suggest a healthy patient effect or may be partly caused by residual socio-economic differences. More large studies and reanalysis of existing studies are needed to evaluate cancer risk among infertile women by subgroups regarding the cause of infertility. When evaluating risk of cancer after drug exposure, dosage and the use of different medicaments should be taken into consideration.

Background Children born after medically assisted reproduction (MAR) are at higher risk of adverse birth outcomes than naturally conceived children. It is not known to what extent the excess risk should be attributed to harmful effects of the treatment or to pre-existing parental characteristics that confound the association. Methods We analysed birth weight, gestational age, risk of low birth weight, and risk of preterm birth among MAR-and naturally conceived children using Finnish population registers covering 65,634 children born in 1995-2000. First, we estimated the differences in birth outcomes by mode of conception in the general population using standard multivariate methods that controlled for observed factors (e.g., multiple birth, birth order, and parental socio-demographic characteristics). Second, we used a sibling-comparison approach that has not been used before in MAR research. We compared MAR-conceived children to their naturally conceived siblings, and thus controlled for all observed and unobserved factors shared by siblings. The latter analysis included 1245 children. Findings MAR-conceived children had worse outcomes than naturally conceived children for all outcomes, even after adjustments for observed child and parental characteristics (e.g., 60gr [95% CI:-34 to-86] lower birth weight; 2.2-percentage point [95% CI: 1•1 to 2•2] increased risk of preterm delivery). In the sibling comparison, the gap in birth outcomes was attenuated, such that the relationship between MAR and adverse birth outcomes was statistically and substantively weak for all outcomes (e.g., 31gr [95% CI:-22 to 85] lower birth weight; 1.6 percentage points [95% CI:-1•3% to 4•4%] increased risk of preterm delivery). Interpretation MAR-conceived children face an elevated risk of adverse birth outcomes. However, our results indicate that this increased risk is largely attributable to factors other than the MAR treatment itself. Funding European Research Council, the Academy of Finland, and the Signe and Ane Gyllenberg Foundation. Research in context Evidence before this study We searched for studies analysing the association between Medically Assisted Reproduction and birth outcomes within families who had at least one child conceived through MAR and one child conceived naturally, published in any language up until March 2018 (with no specified earliest date). We searched in PubMed and Google Scholar using relevant terms ("Medically Assisted Reproduction", "Assisted Reproductive Technology", "birth outcomes", "low birth weight", "preterm", "siblings", "within family"). We found only three studies that compared MAR-and naturally conceived children from the same families. These studies, which reported mixed findings, suffered from two major limitations. First, they relied on random-effects models, which are biased when unobserved random effects (e.g., measuring health) are correlated with observed covariates (e.g., maternal age, socioeconomic status). Second, they focused on children conceived through IVF only, and included chil...