Authors: G. Hatami Fard1, T. VerMilyea2, A.L. Schaffgotsch3, S. Ivanova4 1Impli Health, Research, London, United Kingdom 2Ovation Fertility Embryology, Austin, USA 3Impli Health, Management, London, United Kingdom 4Imperial College London, Mechanical Engineering, Hamlyn Centre, London, United Kingdom

Study question:
Is it possible to remotely monitor a patient’s hormone levels during an ART cycle using an unobtrusive and subcutaneously injectable biosensor for real-time monitoring?

Summary answer:
It is possible for in-situ remote continuous monitoring implantable devices to successfully measure patient blood hormone levels over a clinically relevant concentration range.

What is known already:
Worldwide 48.5 million couples suffer from infertility. In the UK, assisted reproductive treatments (ART) have increased by almost ten-fold in the last 20 years. Hormonal imbalances are the leading cause of female infertility and the success rate of ART tremendously depends on the accurate measurement of the levels of hormones, namely Luteinizing Hormone, Progesterone and Beta Estradiol. These hormone levels change and pulsate during each patient cycle, requiring women undergoing ART treatments to have a blood draw and endocrinology analysis every 2-3 days, making ART treatment highly invasive to a patient’s lifestyle and at a high cost.

Study design, size, duration:
In order to determine the feasibility and potential of the study question, a minimally invasive biosensor to monitor ART hormone levels in real time was developed. The biosensor was tested in vitro for the range of 1 pg/ml to 1 µg/ml in three analytical replicates. The resulting sensitivity of testing was measured in order to evaluate real-work applications.

Participants/materials, setting, methods:
A gold working electrode was utilized and activated using cyclic voltammetry. After activation, a self-assembled monolayer (Thiol-EDC-NHS), was formed on the gold surface, followed by the separate addition of anti-Progesterone4 and Beta-estradiol antibodies. After the addition of each layer, the Differential Pulse Voltammetry (DPV) of the gold electrode was measured. Based on the peak current, calibration curves were plotted and the sensitivity of the sensors was calculated. All electrochemical measurements were performed using CHI potentiostat.

Main results and the role of chance:
This electrochemical hormone biosensor technology) is based on the detection of Progesterone4 and Beta-estradiol biosensor electrodes which can continuously detect hormone levels with a limit of detection (LOD) and limit of quantification (LOQ) of 2.01 and 6.72 pg/ml, respectively. Further to this, the biosensor covers the detection of a wide range of hormone concentrations in the blood from 1 pg/ml to 1 µg/ml. The sensor was also characterised by microscopy techniques such as scanning electron microscope (SEM) and Raman microscopy. Next, the biosensors will be validated in-vivo by conducting animal trials allowing for the main parameters of the biosensors to be optimized according to the in-vivo study.

Limitations, reasons for caution:
This novel implantable biosensor technology requires more upcoming validation in animal models before then being tested clinically to order to assess its ability for widespread use.

Wider implications of the findings:
The development and implementation of an unobtrusive remote and continuous monitoring implantable system for hormonal concentrations monitoring that are vital for success in an ART procedure could transform the entirety of the process as well as positively influence patients’ access to care.