The effects of intrauterine insemination and single embryo transfer or modified natural cycle in vitro fertilization on offspring's health-Follow-up of a randomized clinical trial.

OBJECTIVE: Does ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction affect neurodevelopmental and physical health of the offspring? STUDY DESIGN: Infertile couples were randomly allocated to intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH), modified natural cycle in vitro fertilization (IVF-MNC) or single embryo transfer IVF (IVF-SET). We compared neurodevelopmental and physical health in childhood (4-7 years). We used age-appropriate questionnaires to assess behavioral problems (Child Behavior Check List (CBCL)) and executive functioning (Behavior Rating Inventory of Executive Function (BRIEF)). We measured body mass index Z-score, waist- and hip-circumference, body fat percentage, blood pressure Z-scores, pulse wave velocity, glucose, insulin, insulin resistance, total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides, and high sensitivity c-reactive protein. We compared groups by analysis of variance. RESULTS: We examined 191 (57%) of the 333 children born in the study at a mean age of 5.5 years (range 4.0-7.6 years). We found no statistically significant differences between randomization groups in children's neurodevelopmental or physical health indices (all p-values > 0.05). Comparing the outcomes between actual method of conception, including a naturally conceived group, also did not show statistically significant differences. CONCLUSIONS: Although this follow-up study was not powered on childhood outcomes and limited power due to attrition may have hampered detection of subtle effects, we found no indications of differences in neurodevelopmental and physical health between ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction. Future trials should be powered on child outcomes, and aim to optimize follow-up rates to provide answers that are more definitive.

Maternal obesity in pregnancy impacts offspring cardiometabolic health: Systematic review and meta-analysis of animal studies.

Obesity before and during pregnancy leads to reduced offspring cardiometabolic health. Here, we systematically reviewed animal experimental evidence of maternal obesity before and during pregnancy and offspring anthropometry and cardiometabolic health. We systematically searched Embase and Medline from inception until January 2018. Eligible publications compared offspring of mothers with obesity to mothers with a normal weight. We performed meta-analyses and subgroup analyses. We also examined methodological quality and publication bias. We screened 2543 publications and included 145 publications (N = 21 048 animals, five species). Essential methodological details were not reported in the majority of studies. We found evidence of publication bias for birth weight. Offspring of mothers with obesity had higher body weight (standardized mean difference (SMD) 0.76 [95% CI 0.60;0.93]), fat percentage (0.99 [0.64;1.35]), systolic blood pressure (1.33 [0.75;1.91]), triglycerides (0.64 [0.42;0.86], total cholesterol (0.46 [0.18;0.73]), glucose level (0.43 [0.24;0.63]), and insulin level (0.81 [0.61;1.02]) than offspring of control mothers, but similar birth weight. Sex, age, or species did not influence the effect of maternal obesity on offspring's cardiometabolic health. Obesity before and during pregnancy reduces offspring cardiometabolic health in animals. Future intervention studies should investigate whether reducing obesity prior to conception could prevent these detrimental programming effects and improve cardiometabolic health of future generations.