Ava’s Research Ava is a research-driven digital health company
Active in all area’s of femtech, we develop science-based services for Ava’s users, and for Ava to become a companion for women throughout their whole reproductive age. Ava cooperates with international researchers in gynecology, obstetrics, reproductive endocrinology, computational science, machine learning, physiology, chronobiology, sensor technologies, data security and signal processing.
Past clinical trials
Changes of physiological data during the menstrual cycle- STUDY SCHEDULE
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March 2015 – April 2016
- SPONSOR
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Peter Stein, Ava AG
- PRINCIPAL INVESTIGATOR
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Prof. Dr. med. Brigitte Leeners
University Hospital Zurich / Department of Reproductive Endocrinology
Frauenklinikstrasse 10 / 8091 Zurich - STUDY CATEGORY
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Category A (minimal risk)
- BACKGROUND
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The scientific literature suggests that physiological parameters such as heart rate, respiratory rate, skin conductivity, sleep duration, sleep quality and skin perfusion are influenced by the menstrual cycle. The present study examines the extent to which such data correlate with the menstrual cycle to develop and validate an algorithm to identify the fertile days.
- OBJECTIVE(S)
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The aim of the study is to evaluate how physiological data measured with wrist-worn wearable correlates with the menstrual cycle.
- OUTCOME(S)
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The primary outcome is ovulation based on urinary reference measurements as a reference for an algorithm based on physiological parameters.
- STUDY DESIGN
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Prospective observational
- INCLUSION / EXCLUSION CRITERIA
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Inclusion
- Healthy, non-pregnant women between 20 and 40 years
- Regular cycles
- Written informed consent to participate in the study
Exclusion
- Health problems that could affect the menstrual cycle
- Taking medication or other substances that could affect the menstrual cycle or the measured physiological parameters
- Frequent changes in time zones
- Sleep disorders
- MEASUREMENTS AND PROCEDURES
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The present study examines the extent to which physiological data correlate with the menstrual cycle and ovulation identified by urine tests. For data recording, the participants wear CE-certified sensor bracelets and smart shirts during the night.
- NUMBER OF PARTICIPANTS
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T41 voluntarily participating women
- STUDY CENTER
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Single-Centre study, Clinic for Reproductive Endocrinology, University Hospital Zurich, Switzerland
- STUDY SCHEDULE
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January 2017 – April 2017
- SPONSOR
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Peter Stein, Ava AG
- PRINCIPAL INVESTIGATOR
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Prof. Dr. Björn Rasch
Kognitive Biopsychologie und Methoden, Departement für Psychologie
Universität Freiburg
Rue P.-A-de-Faucigny 2
CH-1701 Fribourg - STUDY CATEGORY
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Category A (minimal risk)
- BACKGROUND
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Sleep and cardiovascular parameters are dependent of gold standard laboratory methods that are measured in this study.
- OBJECTIVE(S)
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The aim of the study is to compare the sleep classification, pulse inter-beat-intervals and breathing rate measured at the wrist with gold standard EEG, ECG, and chest strap during sleep.
- OUTCOME(S)
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The primary outcome of the trial is the root mean squared error of the inter-beat-intervals measured with Ava at the wrist in comparison to the gold standard.
- STUDY DESIGN
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Validation Study
- INCLUSION / EXCLUSION CRITERIA
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Inclusion
- > 18 years
- Healthy
- Willingness to participate 4 nights
- MEASUREMENTS AND PROCEDURES
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Participants are sleeping 4 times in a sleep laboratory. Wrist-based parameters are measured with two Ava bracelets (one at each arm) continuously during sleep. Gold standard measurement are conducted through EEG (sleep), ECG (inter-beat-interval) and a chest belt (breathing rate).
- NUMBER OF PARTICIPANTS
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10
- STUDY CENTER
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Single center
Kognitive Biopsychologie und Methoden, Departement für Psychologie / Universität Freiburg
Rue P.-A-de-Faucigny 2 / CH-1701 Fribourg
Ongoing clinical trials
Physiological parameters during menstrual cycle and pregnancy(Use of physiological parameters measured non-invasively during sleep through a wearable medical device to predict menstrual cycle dynamics as well as pregnancy complications in women living in Switzerland)
- STUDY SCHEDULE
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September 2016 – 2019 (expected)
- SPONSOR / PRINCIPAL INVESTIGATOR
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Prof. Dr. med. Brigitte Leeners
University Hospital Zurich / Department of Reproductive Endocrinology
Frauenklinikstrasse 10 / 8091 Zurich - STUDY CATEGORY
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Category A (minimal risk)
- BACKGROUND
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Several physiological parameters are affected by hormonal changes driven by the menstrual cycle. Besides the well-known changes in body temperature , these changes also influence cardiovascular parameters, such as heart rate 1 2 , heart rate variability and skin blood flow . Additionally, De Zambotti et al. showed changes in the length of different 3 4 5 sleep phases whereas skin properties are affected by menstrual cycle , too. New technologies in the wearable sensor 6 area allow for measuring this data highly convenient and non-invasively by wearing a sensor bracelet. The measured physiological data could help to better predict the fertile window of a women, to recognize pregnancy early on and to monitor pregnancy. Finally, these data could be used to improve fertility treatments to achieve a pregnancy in infertile couples, affecting nearly 20% of Swiss population.
1 Baker FC, Waner JI, Vieira EF, Taylor SR, Driver HS, Mitchell D. Sleep and 24-hour body temperatures: A comparison in young men, naturally cycling women and women taking hormonal contraceptives. J Physiol. 2001;530(3):565-574. doi:10.1111/j.1469-7793.2001.0565k.x.
2 Moran VH, Leathard HL, Coley J. Cardiovascular functioning during the menstrual cycle. Clin Physiol. 2000;20(6):496-504. doi:10.1046/j.1365-2281.2000.00285.x.
3 Sato N, Miyake S, Akatsu J, Kumashiro M. Power Spectral Analysis of Heart Rate Variability in Healthy Young Women During the Normal Menstrual Cycle. Psychosom Med. 1995;57:331-335.
4 Frascarolo P, Schutz Y, Jéquier E. Decreased thermal conductance during the luteal phase of the menstrual cycle in women. J Appl Physiol. 1990;69(6):2029-2033.
5 De Zambotti M, Nicholas CL, Colrain IM, Trinder J a., Baker FC. Autonomic regulation across phases of the menstrual cycle and sleep stages in women with premenstrual syndrome and healthy controls. Psychoneuroendocrinology. 2013;38(11):2618-2627. doi:10.1016/j.psyneuen.2013.06.005.
6 Eisenbeiss C, Welzel J, Schmeller W. The influence of female sex hormones on skin thickness: Evaluation using 20 MHz sonography. Br J Dermatol. 1998;139(3):462-467. doi:10.1046/j.1365-2133.1998.02410.x.
- OBJECTIVE(S)
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The aim of the study is to evaluate how physiological data measured with a medical wrist-worn wearable correlates with the menstrual cycle (e.g. hormones, ovulation) and pregnancy.
Based on this data, algorithms will be developed:- to predict ovulation which will be especially helpful for women who want to conceive to inform them about their fertile days (primary objective),
- recognize pregnancy,
- and monitor pregnancy.
- OUTCOME(S)
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The primary outcome is ovulation based on urinary reference measurements.
The main secondary outcomes are:- hormonal levels measured by saliva tests for a sub-group of women,
- collected physiological data during pregnancy,
- a positive pregnancy indication through urinary hCG tests,
- and the detection of ovulation by ultrasonography.
- STUDY DESIGN
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Prospective observational
- INCLUSION / EXCLUSION CRITERIA
-
Inclusion
- Healthy, non-pregnant women between 20 and 40 years who are trying to conceive
- Regular cycles
- Written informed consent to participate in the study
Exclusion
- Health problems that could affect the menstrual cycle
- Taking medication or other substances that could affect the menstrual cycle or the measured physiological parameters
- Frequent changes in time zones
- Sleep disorders
- Unsuccessfully trying to conceive for > 12 months
- MEASUREMENTS AND PROCEDURES
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Measurements up to 9 months till conception as well as during pregnancy.
The study includes examinations of the menstrual cycle within three groups. All women are examined by an electronic bracelet every day during sleep at home to measure skin temperature, ambient temperature, pulse rate, pulse rate variability, respiration rate, skin conductance response, sleep duration/quality and skin perfusion in combination with electronic diaries to enter daily activities in an online survey including questions about the night, the day before and the occurrence of positive ovulation/pregnancy tests based on the Advanced Fertility Monitor of Clearblue. In one subgroup additional hormonal saliva measurements are performed. The second subgroup includes ultrasound measurements of the ovaries/growing follicles.
- NUMBER OF PARTICIPANTS
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Up to 430 voluntarily participating women
- STUDY CENTER
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Single-Centre study, Clinic for Reproductive Endocrinology, University Hospital Zurich, Switzerland
Future research
FOLLOWING RESEARCH TOPICS ARE OF SPECIAL INTEREST TO AVA
- Fertility, infertility and fertility treatments
- Natural birth control / contraception
- Reproductive Endocrinology
- Preeclampsia
- Other hypo- and hypertensive disease patterns in
gynecology and obstetrics - General gynecology and obstetrics
Scientific publications
- Leeners, B., Stein, P. (2016, June). Digital Women’s Health based on Wearables and Big Data (supported by Bayer Healthcare), Symposium conducted at the Annual Meeting of Swiss Society of Gynecology and Obstetrics (SGGG), Interlaken, Switzerland.
- Stein, P., Falco, L., Kuebler, F., Annaheim, S., Lemkaddem, A., Delgado-Gonzalo, R., Verjus, C., Leeners, B. (2016, October), Digital Women’s Health based on Wearables and Big Data, Poster presented at the Annual Meeting of American Society of Reproductive Medicine (ASRM), Salt Lake City, UT, USA.
- Stein, P., Falco, L., Kuebler, F., Annaheim, S., Lemkaddem, A., Delgado-Gonzalo, R., Verjus, C., Leeners, B. (2016, October), Digital women’s health based on wearables and big data – new findings in physiological changes throughout the menstrual cycle, Poster presented at the Annual Meeting of Germany Society of Gynecology and Obstetrics (DGGG), Stuttgart, Germany.
- Shilaih, M., De Clerck, V., Falco, L., Kuebler, F., and Leeners, B. (2017, May). Pulse Rate Measurement During Sleep Using Wearable Sensors, and its Correlation with the Menstrual Cycle Phases, A Prospective Observational Study, Scientific Reports.
- Shilaih, M., Annaheim, S., De Clerck, V., Falco, L., Kuebler, F., and Leeners, B. (2016, November). The continuous measurement of wrist skin temperature during the night as an alternative method to detect the basal body temperature shift in the luteal phase of the menstrual cycle, In preparation
- Shilaih M, de Clerck V, Falco L, Kübler F, Leeners B. Pulse Rate Measurement During Sleep Using Wearable Sensors, and its Correlation with the Menstrual Cycle Phases, A Prospective Observational Study. Scientific reports. 2017 May 2;7(1):1294.
- Shilaih M, Falco L, Kuebler F, Leeners B. Wrist worn wearable sensors capture the physiological changes associated with early pregnancy. Fertility and Sterility. 2017 Sep 30;108(3):e379. Poster presented at the Annual Meeting of American Society of Reproductive Medicine (ASRM), San Antonio, TX, USA.
- Shilaih M, Goodale BM, Falco L, Kübler F, De Clerck V, Leeners B. Modern fertility awareness methods: Wrist wearables capture the changes of temperature associated with the menstrual cycle. Bioscience reports. 2017 Nov 24:BSR20171279.
- Renevey, P., Delgado-Gonzalo, R., Verjus, C., Solà, J., Combertaldi, S., Rasch, B., Leeners, B., Dammeier, F., Kübler, F. (2018, March). Respiratory and Cardiac Functions Monitoring During Night Using a Wrist-worn Optical Device, Poster presented at IEEE Biomedical and Health Informatics Conference, Las Vegas, NV, USA.
- M. Shilaih, B. Goodale, L. Falco, F. Kuebler, F. Dammeier, B. Leeners; Capturing the physiological characteristics of early pregnancy using wrist worn wearables, ESHRE July 2018, Poster presentation (P-476) at the European Society of Human Reproduction and Embryology.
Clinical and research cooperations
Ava is Interested in clinical and research cooperation in gynecology, obstetrics and adjacent fields.
For cooperating researchers, Ava can provide fully anonymized data including
- Raw data of all physiological signals
- User entered daily survey information for environmental and behavioral parameters
- Demographic data of participants
- Processed data of ovulation, fertile days and other outcomes
- User entered data into the App e.g. menstruation and symptoms
Please contact us if you are interested in a research or clinical cooperation:
Maureen Cronin, Chief Medical Officer, maureen.cronin@avawomen.com.
Ava abides by the highest security standard both in the EU and the United States, and has region specific servers for storing the data. The users’ data is stored anonymously with their id and registration info separately stored.
Additional information about Ava can be found here: