P–565 Does length really matter? The impact of lifestyle on granulosa cell telomeres length and IVF outcome
Authors: Limonad O , Hantisteanu S , Meise. Sharon S , Haggiag N , Estrada D , Michaeli M , Shalom-Paz E 
Published: August 2021

Abstract

Study question
Is the relative telomere length in granulosa cells associated with an abnormal metabolic profile of IVF patients and treatment outcome?

Summary answer
Longer telomeres and higher pregnancy rates have been observed in women with higher follicular fluid glucose levels.

What is known already
Telomeres may serve as a biomarker of cell senescence; their length varies depending on two factors: genetic predisposition and shortening processes related to cell division. In several studies, telomere shortening in granulosa cells has been shown to be correlated with ovarian aging. However, these findings are still limited in applicability, and more research is required to define the factors involved.

Study design, size, duration
Women undergoing IVF participated in a prospective cohort study between 2018 and 2019. Peripheral blood was obtained on the day of oocyte retrieval. Pooled samples of follicular fluid were collected for a comprehensive telomere length analysis in granulosa and cumulus cells by quantitative PCR (qPCR).

Participants/materials, setting, methods
DNA was extracted from granulosa cells and assessed for relative telomere length by monochrome multiplex quantitative PCR (qPCR). Telomere length was then analyzed relative to a single copy gene (36B4) to evaluate possible metabolic profile’s impact on telomere length and treatment outcome. Hormonal profile, chemistry, and inflammation factors were analyzed in the follicular fluid and serum.

Main results and the role of chance
Out of forty-nine women recruited for the study, forty-one cases were eligible for a comprehensive analysis. Follicular fluid CRP and triglyceride levels in BMI-based analysis were significantly lower in women with BMI &lt;25 compared to those with BMI &gt;30 (0.5 (0.2–1.5) vs. 6.6 (3.6–10.6); p &lt; 0.0001 and 21.04 ± 8.04 vs. 28.18 ± 8.97; p = 0.011, respectively). Interestingly, a significant correlation between the relative lengths of telomeres and pregnancy rate was observed (p &lt; 0.001), with a higher pregnancy rate in women with longer telomeres (88%) than in women with shorter telomeres (38%). Relatively longer telomeres (0.96 (0.94–0.99) vs. 0.91 (0.82–0.95), p = 0.02) and higher levels of follicular fluid glucose (63±11.12 vs. 50.67±15.69, p = 0.006) were observed in those who conceived. No statistically significant differences were detected in the levels of the other hormones measured in the blood or follicular fluid on the day of oocyte retrieval or other clinical parameters, including follicle size and number, embryo quality, and the number of OHSS cases.

Limitations, reasons for caution
As a preliminary study, there were few participants. Further implications can be reached by increasing the sample size, but telomerase activity evaluation is required to confirm telomere length measurements without question. Whether short telomeres associate with infertility as a cause or consequence of BMI warrant more research.
Wider implications of the findings: The relative length of telomeres in granulosa cells at the time of oocyte retrieval may serve as a predictive biomarker for oocyte competence and subsequent pregnancy. Moreover, healthy lifestyle behavior is recommended.

Trial registration number
Not applicable