P-175 Human cumulus cell telomere length and its association with assisted reproduction outcomes
Authors: Kumar K , Nesbeth L , Venturas M , Needleman D , Racowsky C , Wells D 
Published: June 2023

Abstract

Study question
Is there any relationship between the relative telomere length (RTL) within cumulus cells (CCs) and the outcome of assisted reproductive treatment using the corresponding oocyte?

Summary answer
Lower RTLs in CCs were significantly associated with embryos chosen for transfer or cryopreservation. In contrast, embryos considered non-viable (discarded) tended to have higher RTLs.

What is known already
Cumulus cells fulfil vital roles in support of oocyte development, including the transduction of external signals and the provision of resources via transzonal projections. Given their essential role in the acquisition of oocyte developmental competence, the biology of CCs is of clinical relevance. Telomeres are specialised structures protecting the ends of chromosomes, composed of repetitive DNA sequences and associated proteins. Telomeres shorten with each mitotic division, as well as due to oxidative damage, eventually reaching a critical threshold at which point cellular senescence occurs. Currently, published data on CCs telomere length and relationship with oocyte potential are conflicting.

Study design, size, duration
The study involved 182 human CC samples collected from 52 IVF patients. Quantitative PCR (qPCR) was used to measure the relative telomere length in each of the CC samples. Telomere lengths were assessed for associations with various patient characteristics (e.g. age, body mass index, infertility diagnosis). Additionally, potential relationships with clinically relevant oocyte/embryo features were investigated (fertilisation; development/morphology), as well as the eventual fate of the associated embryo (transferred; cryopreserved for potential future use; discarded).

Participants/materials, setting, methods
Real-time quantitative PCR was carried out using PCR primers specific for the telomere repeat. A single-copy gene was also amplified from each CC sample. Quantification of this gene was used for normalisation of the telomere data, allowing control for variation in the number of cumulus cells in each sample. Associations between RTL in CCs and patient, embryonic, and clinical factors were assessed using various statistical methods, with P-values &lt;0.05 considered significant.

Main results and the role of chance
No associations were identified between RTL and any patient characteristics, except for BMI. The amount of CC telomeric DNA tended to be greater for patients with higher BMI (P = 0.002). When considering links between RTL and oocyte or embryonic factors, a significant relationship was detected between the quantity of telomeric DNA in CCs and whether the corresponding embryo was considered non-viable (discarded) or whether it was transferred or cryopreserved (P = 0.019). This finding raises the possibility that measurement of RTL in CCs could provide a pre-conception, non-invasive assessment of oocyte quality. In the context of fertility preservation, RTL measurement could assist in evaluating a cohort of oocytes, indicating whether the cryopreserved eggs are likely to be sufficient or whether additional cycles to generate more would be advisable. If future studies confirm that CC RTL has a strong predictive value, the possibility of limiting fertilisation to oocytes considered to have high likelihood of viability could also be considered for routine IVF cycles. It is unclear why shorter CC telomeres might be associated with oocytes of superior potential, but one possibility is that the cells may have undergone a greater proliferation (more mitoses), resulting in a more extensive cumulus mass supporting the enclosed oocyte.

Limitations, reasons for caution
Before drawing definitive conclusions, confirmation of the findings within a larger, independent data set is necessary. Even if confirmed, determination of the true clinical value of telomere assessment will require further, appropriately designed studies. The current study was not powered to evaluate relationships between CC telomere lengths and IVF outcomes.

Wider implications of the findings
Currently, simplistic morphological evaluation is the only method for assessing oocyte competence prior to fertilisation. If CCs telomere measurement is confirmed to have predictive value, a preconception test of oocyte potential could be offered. This would be extremely valuable for patients cryopreserving oocytes for fertility preservation and for donor banks.

Trial registration number
NA