Abstract
SummaryAdvancing age has a negative impact on female fertility. As implantation rates decline during the normal maternal life course, age-related, embryonic factors are altered and our inability to monitor these factors in an unbiased genome-wide manner in vivo has severely limited our understanding of early human embryo development and implantation. Our high-throughput methodology uses trophectoderm samples representing the full spectrum of maternal reproductive ages with embryo implantation potential examined in relation to trophectoderm transcriptome dynamics and reproductive maternal age. Potential embryo-endometrial interactions were tested using trophectoderm sampled from young women, with the receptive uterine environment representing the most ‘fertile’ environment for successful embryo implantation. Potential roles for extracellular exosomes, embryonic metabolism and regulation of apoptosis were revealed. These biomarkers are consistent with embryo-endometrial crosstalk/developmental competency, serving as a mediator for successful implantation. Our data opens the door to developing a diagnostic test for predicting implantation success in women undergoing fertility treatment.
Highlights
In recent years, maternal age, which heavily influences reproductive success rates, has been rising worldwide (Schmidt et al, 2012)
As implantation rates decline during the normal maternal life course, age-related, embryonic factors are altered and our inability to monitor these factors in an unbiased genomewide manner in vivo has severely limited our understanding of early human embryo development and implantation
Our high-throughput methodology uses trophectoderm samples representing the full spectrum of maternal reproductive ages with embryo implantation potential examined in relation to trophectoderm transcriptome dynamics and reproductive maternal age
Summary
Maternal age, which heavily influences reproductive success rates, has been rising worldwide (Schmidt et al, 2012). Decreased live birth rates are correspondingly observed in women over 35 years, even when euploid embryos are transferred during ART procedures (Scott et al, 2012). Implantation and pregnancy rates are reduced for women over the age of 40 (Harton et al, 2013). These results suggest that in addition to the known risk of increased developmentally lethal aneuploidy (Irani et al, 2019), other poorly understood age-related factors must impact implantation and inevitably, pregnancy
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