P-696 Continuous monitoring of female hormones as a tool to improve IVF treatment’s efficacy
Authors: Moinipoor Z , Anastasova S , VerMilyea M , Gil B , Fard G , Schaffgotsch A  L , Owen B 
Published: July 2024

Abstract

Study question
Is it possible to employ an unobtrusive and injectable biosensor for real-time remote monitoring of patient’s hormone levels (LH, P4, E2) during an ART cycle?

Summary answer
In-situ implantable biosensors can effectively monitor clinically relevant hormone levels in real-time to improve ART cycle.

What is known already
Worldwide 48.5 million couples suffer from infertility. Hormonal imbalances can impede pregnancy by compromising the intricate processes of the reproductive system, affecting ovulation, egg quality, fallopian tube function, and endometrial receptivity. In the UK, assisted reproductive treatments (ART) have surged ten-fold in the last 20 years. ART success tremendously depends on the accurate measurement of hormone levels, namely Luteinizing Hormone (LH), oestradiol (E2), and progesterone (P4). These hormone levels change and pulsate during each patient cycle, requiring women to undergo a blood draw and endocrinology analysis every 2-3 days, making ART treatment a highly invasive and time consuming method.

Study design, size, duration
In order to determine the feasibility of the study question, Impli designed a minimally invasive implantable biosensor to continuously monitor essential hormones for women’s fertility such as LH, P4 and E2 in order to enhance the quality of treatment and improve the ART experience. An implantable electrochemical aptamer-based biosensors has been developed using cutting-edge electronics and electrochemical technologies. This minimally invasive biosensor allows patients to monitor their hormone levels in real-time during ART without venipuncture.

Participants/materials, setting, methods
The implantable biosensor contains the biorecognition interface, designed using the DNA-based aptamers coupled to the detection gold working electrodes. When the biosensor is in touch with the sample, hormones bind to the respective aptamers, which leads to changes in the electrical properties of the gold electrode. The changes are then monitored and calibrated through sensitive electrochemical techniques such as differential pulse voltammetry (DPV), using CHI potentiostat.

Main results and the role of chance
The biosensor was tested in vitro in artificial interstitial fluid (ISF) containing the range of 1 pg/ml to 1 µg/ml of hormones yielding a limit of detection (LOD) of 0.46 pg/ml, 1.15 pg/ml, and 0.58 pg/ml for E2, P4 and LH, respectively. Our data was validated using ELISA assays. A notably high linear correlation coefficient (R2) of approximately 0.9 was observed between the signals obtained from the ELISA and the biosensors, confirming the reliability of the aptamer biosensors for hormone analysis. The stability of the biosensor was also investigated over one week. The DPV technique was employed to assess the cross-reactivity of potential interferences with each biosensor. The results revealed that each biosensor exhibited notable selectivity towards its respective analyte over other interferences, at significantly higher concentrations. The biosensor was also characterised by microscopy techniques such as SEM and Raman analysis.

Limitations, reasons for caution
This novel implantable biosensor technology requires further upcoming validation in animal models to assess its ability for widespread use. Once validated, the appropriate human clinical trials will be undertaken.

Wider implications of the findings
The development and implementation of an unobtrusive implantable remote and continuous monitoring system, capturing hormone concentrations that are vital for success in an ART procedure, could transform the industry and positively influence patient’s access to care and the patient journey.

Trial registration number
No clinical trial