ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This study compared the histology and growth phenotypes, epigenotypes and gene expression profiles of mouse embryos, embryonic livers, and placental tissue at differing gestational ages after exposure to IVF. They followed the growth and metabolic profiles (glucose, insulin, triglycerides, total cholesterol, HDL, LDL/VLDL) of offspring to age 12 weeks. Groups analysed by sex included those conceived naturally, by IVF, by IVF with TEBx (trophectoderm biopsy) and by IVF with both TEBx and vitrification (embryo cryopreservation). There were several differences when IVF+TEBx and IVF+TEBx+vitrification groups were compared to naturally conceived groups or those from IVF alone, with some sex dependence. TEBx/vitrification exacerbated the abnormal placental and fetal morphological and molecular phenotypes as well as adverse metabolic outcomes seen with IVF alone.

An estimated 9 million offspring have been born worldwide after assisted reproductive techniques (ART). Trophectoderm biopsy (TEBx) for preimplantation genetic testing is used to detect inherited genetic disorders and/or chromosome abnormalities in embryos. From the trophectoderm, 4-7 cells are removed for analysis. Some (but not all) studies show that TEBx may improve implantation rates and decrease miscarriages, but may not increase the number of live births particularly in younger women^1,2. Cryopreservation through vitrification for storing retrieved embryos is another common ART procedure.

Little is known about how such procedures affect the epigenome in humans because only data on the trophoblastic (placental) epigenome is accessible. Mice provide a good model because both trophoblasts and embryos can be sampled, they do not have infertility or subfertility that confounds the human data. Although their placentation differs in some respects, both mice and humans have a discoid placenta with hemochorial gas and nutrient exchange. With their large litter sizes, it is also possible to study whether there are sex differences in the impact of TEBx +/- vitrification. As well as good animal models, all routine medical information - including details of the specific ART procedures used for conception - should be carefully recorded not only in registries but in patients’ records, to allow us to better understand and monitor the impact of these procedures on health throughout the lifespan.

It should be noted that intracellular sperm injection (ICSI) was not used in their IVF procedures; this is another common ART method with potential consequences³ (see the next article by Ye et al.).

References: 1. Alteri A, Cermisoni GC, Pozzoni M, Gaeta G, Cavoretto PI, Vigan_OP. Obstetric, neonatal, and child health outcomes following embryo biopsy for preimplantation genetic testing. Hum Reprod Update 2023;29:291–306. doi: 10.1093/humupd/dmad001.2. Yan J, Qin Y, Zhao H, Sun Y, Gong F, Li R, Sun X, Ling X, Li H, Hao C et al. Live birth with or without preimplantation genetic testing for aneuploidy. N Engl J Med 2021;385:2047–2058. doi: 10.1056/NEJMoa2103613.3. Thompson JG, McLennan HJ, Heinrich SL, Inge MP, Gardner DK, Harvey AJ. A brief history of technical developments in intracytoplasmic sperm injection (ICSI). Dedicated to the memory of J.M. Cummins. Reprod Fertil Dev 2024 Jun:36:RD24047. doi: 10.1071/RD24047.