Increased CASP8 expression linked to better IVF outcomes for older women

Increased CASP8 expression linked to better IVF outcomes for older women | Image Credit: © phonlamaiphoto - © phonlamaiphoto - stock.adobe.com.

There is an association between increased CASP8 expression and successful implantation outcomes in patients with advanced maternal age (AMA), according to a recent study presented at the American College of Obstetricians and Gynecologists 2024 Annual Clinical & Scientific Meeting in San Francisco, California, from May 17 to May 19, 2024.¹

AMA is defined as maternal age of 35 years or older and has been linked to increased risk of ovarian reserve decline and reduced live birth rates following 1 in vitro fertilization (IVF) cycle. Current guidelines suggest patients with AMA receive preimplantation genetic testing for aneuploidy (PGT-A).

Activity from the CASP8 gene has been historically associated with various outcomes in female-related health outcomes; research has shown polymorphism of the gene may be associated with reduced risk of breast cancer,² as well as reduced risk of carcinogenesis and delayed age of epithelial ovarian cancer onset.³

While genetic testing for PGT-A is recommended to improve live birth outcomes, data has indicated standard IVF practices are noninferior to this method. This indicates a need to determine additional biomarkers that can help doctors select the most viable embryo.¹

Investigators conducted a study to determine biomarkers for choosing the most viable embryo. Day 5 IVF embryos receiving PGT-A were evaluated through collection of blastocoel fluid-conditioned media.

After obtaining blastocoel fluid samples from 4 groups categorized by implantation status and maternal age, investigators purified RNA and synthesized cDNA. Expressions of CASP3, CASP7, CASP8, and BCL2L12 levels were evaluated across 64 embryos using RT-qPCR.

Among patients aged under 35 years, IVF embryos with positive implantation outcomes often had increased CASP3 and CASP7 expression in media. Additionally, IVF embryos from AMA patients had increased CASP8 expression in media regardless of implantation status.

These results indicated an association between higher CASP8 expression and improved implantation outcomes among AMA patients. Investigators concluded, “CASP8 could be activated in preimplantation embryos as an aging response as found in AMA samples.”

Reference

1. ^{Archer HC, Thao Nguyen D, Petyak E, et al. Intrinsic and extrinsic apoptotic activation may dictate IVF outcomes in women of advanced maternal age. Poster presented at: The American College of Obstetricians and Gynecologists 2024 Annual Clinical & Scientific Meeting. San Francisco, CA. May 17-19, 2024.}
2. ^{MacPherson G, Healey CS, Teare MD, et al. Association of a common variant of the CASP8 gene with reduced risk of breast cancer. J Natl Cancer Inst. 2004;96(24):1866-1869. doi:10.1093/jnci/dji001}
3. ^{Ma X, Zhang J, Liu S, Huang Y, Chen B, Wang D. Polymorphisms in the CASP8 gene and the risk of epithelial ovarian cancer. Gynecol Oncol. 2011;122(3):554-559. doi:10.1016/j.ygyno.2011.05.031}