O-073 CD163 in follicular fluids can be the novel marker to predict clinical outcome of oocyte
Authors: Ijuin A , Hayama T , Sueyoshi S , Toda M , Hamada H , Miyakoshi A , Saito M , Tochihara S , Oike Y , Ueno H , Takeshima T , Sakakibara H , Yumura Y , Miyagi E , Murase M 
Published: July 2024

Abstract

Study question
Can we find novel marker in follicular fluid at the oocyte retrieval to evaluate oocyte condition besides karyotype by proteomics?

Summary answer
We found significant higher concentration of CD163 in the follicle fluids, from those oocytes resulted in pregnancy or live birth.

What is known already
Although preimplantation genetic testing for aneuploidy (PGT-A) is effective for embryo selection, only karyotype is considered in PGT-A. If we can evaluate other conditions of oocytes besides karyotype, the pregnancy rate can be improved. In addition to changes in the oocyte per se, factors affecting the quality of oocytes, such as ageing, change the microenvironment surrounding the oocyte. For example, it has been reported that the follicle itself becomes more fibrotic with age, resulting in increased oxidative stress, and that the concentration of cytokines, amino acids, fatty acids, and other substances in the follicle also changes.

Study design, size, duration
Proteomic analyses were performed on follicular fluid collected at the oocyte retrieval, and the proteins showed differences in relation to clinical outcome. We focused on one of those candidates, CD163, and evaluated the concentration by ELISA and checked for possible relevance to clinical outcome of the oocytes derived from each follicles. We also investigated the effect of this protein on oocyte maturation.

Participants/materials, setting, methods
Under the ethical review of Yokohama City University and informed consent with patients in Reproduction center of Yokohama City University Medical Center, we aspirated human follicular fluids individually at the oocyte retrieval. The oocytes were retrieved from the follicular fluid and remained fluid was cryopreserved for further analysis. We followed clinical outcome of oocyte from each follicle, compared the concentration of the protein in each follicle.

Main results and the role of chance
Proteomic analysis revealed CD163 in follicular fluids seemed to have relation with the clinical outcome. We collected 120 follicular fluid samples from 93 patients from 2017 to 2021, and evaluated the concentration of CD163 of them. Follicles which had contained oocytes derived are cryopreserved or fresh embryo transferred had higher than other follicles; 140.6 ± 73.1 vs 95.2 ± 30.7 ng/ml (mean ± SD, p &lt; 0.01). Similarly, follicles, which had contained oocytes led to clinical pregnant and live birth after single embryo transfer, had higher concentrations of CD163; 140.5 ± 71.8 vs 101.6 ± 38.4 ng/ml (pregnant vs not pregnant, mean ± SD, p &lt; 0.01), 138.7 ± 74.1 vs 109.2 ± 45.3 ng/ml (live birth vs not live birth, mean ± SD, p &lt; 0.01). These results suggest that CD163 concentration in follicular fluid might be a novel marker of the clinical outcome.

Limitations, reasons for caution
Although we tried to investigate the relationship of CD163 and oocyte maturation, unfortunately we have not yet been able to clarify them. However, we believe that CD163 may act as an indirect marker representing other factors directly involved in oocyte maturation and development. We would like to investigate this further.

Wider implications of the findings
When CD163 concentration in follicular fluids is evaluated, we might be able to predict the clinical outcome of each oocyte at the day of oocyte retrieval. This may contribute to further improvement of pregnancy rate without invasion to embryo.

Trial registration number
the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant-in-Aid for Scientific Research C (Grant Number 22K07920)