P-565 Pharmacogenetic (PGx) Gene-Drug Association in IVF: clinical relevance of a panel test for ovarian stimulation
Authors: Lledo B , Ortiz J.A , Iervolino N , Bailen A , Morales R , Castillo J.C , Bernabeu A , Bernabeu R 
Published: June 2022

Abstract

Study question
Could the PGx approach be useful for increasing the number of mature oocytes after personalized COS?

Summary answer
There was an increase in the number of MII in the cycle after the PGx implementation compared to the previous cycle.

What is known already
Pharmacogenetics (PGx) is the study of variability in drug responses associated with genetic differences amongst individuals. There is a growing evidence-based indications for PGx testing, but the implications of PGx test results for individual patients poses the next challenge. An efficient controlled ovarian stimulation (COS) is essential for IVF, as its success is tightly related to the oocytes retrieved. PGx for COS may provide an alternative approach to predict ovarian response, as it may help to understand the unexpected response and design a personalized therapy. We evaluated the application and clinical impact of pharmacogenetic test for ovarian response to COS.

Study design, size, duration
We conducted an observational multicentric cohort study that evaluated the results of a PGx panel test and their implementation for personalized COS between June 2016 and November 2021. The primary outcome was the number of mature oocytes in the cycle after the PGx management compared with the previous cycle without PGx approach. PGx panel test includes the analysis of S680N in the FSHR gene and CAG repeats in exon 1 in AR gene.

Participants/materials, setting, methods
We included 228 patients who underwent PGx testing previous COS and a preceding COS without PGx approach. In total 549 cycles were included. For the cycle preceding to PGx test (C0-cycle), patients followed a COS protocol according to their clinical characteristic. For the cycle using PGx approach (C1-cycle) the gonadotrophin and doses were selected according to the polymorphism S680N in FSHR gene and an androgen pretreatment regarding to the number of repeats in AR gene.

Main results and the role of chance
Clinical characteristics of patients were measured. The median and IQR of age, AMH and number of antral follicle count of the patient included in the study were 39.1y [36.4-41.4], 0.72pmol/L [0.38-1.19] and 5 [4-8], respectively. These characteristics agree with the Bologna criteria for poor ovarian reserve. The mean duration of stimulation and total dose of gonadotrophins required were similar between C0 and C1 cycles (9.25 + 2.59 vs 9.15 + 3.68, p = 0.62; 2885 + 1383 vs 2645 + 1352, p = 0.16). Differences were shown in the female age 38.4 + 4.1y in C0 vs 39.1 + 4.1y in C1 (p &lt; 0.0001). Patients in C1 were older than their previous cycle C0. This difference is in favour of better ovarian stimulation outcome in the first cycle where patients were younger. Statistical differences were shown in MII yield (3.1 + 2.2 vs 4.2 + 3.2; p &lt; 0.001). Regarding the differences observed in the COS outcome among the different genotypes and PGx interventions, all the patients showed a clear benefit of PGx. On the other hand, for patients that carried a number of repeats lower than 22 and higher than 24 in AR gene and NN genotype for 680-FSHR, to which no PGx intervention has to be done according to the test result, no significances differences were reported (3.60 vs 4.22; p = 0.33).

Limitations, reasons for caution
A small sample size and the inherent limitations of an observational study. A clinical randomized trial will be necessary to draw firm conclusions. More research in the genes involved in ovarian function is warranted.

Wider implications of the findings
This project represents the first effort to investigate whether a PGx test could improve COS outcomes in POR cohort. Our results suggest that PGx test could benefit the process of controlled ovarian stimulation towards a true individualized approach in clinical practice.

Trial registration number
Not applicable