WO2022082002A1

WO2022082002A1 - Devices, systems, and methods for physiological monitoring

Info

Publication number: WO2022082002A1
Application number: PCT/US2021/055222
Authority: WO
Inventors: Jeanna Tachiki RYAN; Joni AOKI; Young HONG; Kevin Marriott
Original assignee: Preov, Llc
Priority date: 2020-10-16
Filing date: 2021-10-15
Publication date: 2022-04-21

Abstract

A physiological monitoring system having an insertable device, a data communication unit, a power source, and a transceiver. The insertable device can optionally be an intravaginal ring. The insertable device has at least one sensing probe and/or sensor oriented to measure at least one physiological property. The data communication unit is configured to store and transmit collected physiological data that includes the at least one physiological property. The power source is electrically coupled to the sensing probe(s) and/or sensor(s) and the data communication unit. The transceiver is configured to wirelessly receive the collected physiological data from the data communication unit and to then transmit the collected physiological data to a remote computing device.

Description

DEVICES, SYSTEMS, AND METHODS FOR PHYSIOLOGICAL

MONITORING

CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims priority to and the benefit of the filing date of U.S. Provisional Patent Application No. 63/092,826, filed October 16, 2020, the entirety of which is hereby incorporated by reference herein.

FIELD

[0002] The present disclosure relates generally to using devices and systems to sense, measure, or determine physiological changes in various environments within a subject, including, for example, the intravaginal or cervical environment.

BACKGROUND

[0003] Women’s health and wellness is central to empowering women to lead healthy lives. At the core of most women’s human experience is the joy of having a child. Many women struggle with fertility and infertility during their journey to becoming pregnant. Timing intercourse properly during a woman’s menstrual cycle (e.g, within a period of time of 2-5 days before ovulation is expected) is critical to successfully becoming pregnant. Difficulties becoming pregnant for various reasons are widespread globally with the CDC estimating that over 12% of U.S. women between the ages of 15-44 years have trouble conceiving. Globally, 50 million couples are affected by some challenge relating to fertility and 10.5% of mothers with at least one live birth experience difficulty in having another child. Worldwide, there is expected to be an overall increase in difficulty to successfully conceive, significantly widening the market for fertility products. Fertility of the U.S. population is below a level sufficient to provide replacement for those native bom. There is also a declining birth rate in Britain, Western European countries, and Japan. Initially, decreased birth rates were beneficial to the economy. However, more recently, demographers and economists among developed countries are becoming more concerned with the low birth rates as population replacement has fallen below stability limits, which increases the danger of not being able to replace the aging workforce resulting in economic instability due to effects such as low tax revenue. Japan and France have already implemented profamily policies to increase birth rates. [0004] One big challenge for women trying to conceive a child is to accurately predict the “fertile window” during their menstrual cycle, which is a period of time before ovulation occurs during which sperm can fertilize a woman’s egg. Couples should time intercourse (or alternatively clinicians can release sperm into the woman’s vaginal cavity through other means like IUI, etc.) during the fertile period to optimize the chances of the woman becoming pregnant during a naturally occurring or medically- controlled menstrual cycle in which the egg is released from the woman’s ovar(ies). The fertile window is typically 2-5 days prior to a woman’s ovulation with the ideal period being 2 days. At least some of the challenges in accurately identifying a woman’s fertile window relate to variability in the fertile window amongst women and confusion about the complex physiological menstrual cycle process.

[0005] Many women choose to monitor their menstrual cycle in an effort to gain knowledge about the timing of their ovulation for fertility reasons and for other reasons such as birth control, health and wellness monitoring, pregnancy detection, and many other reasons. Specifically, women trying to conceive a child monitor their menstrual cycle to time intercourse during the fertile window to maximize their chances of becoming pregnant. However, less than 13% of women trying to conceive can accurately identify the day they ovulate (Zinaman et al. (2012), Curr Med Res Opin. 28 (5): 749-54). Tracking this information aids in conception planning through prediction of pending ovulation and may also be used to predict onset of menstruation to either achieve or avoid pregnancy. Current methods to track fertile periods can be heavily subjective, expensive, inconvenient, stressful, and time consuming.

[0006] Many women try tracking their Luteinizing Hormone (LH) level, basal body temperature (BBT), and viscosity of their cervical mucus, which are all biomarkers for detecting an imminent ovulation. Detecting LH levels is typically done with a urine test stick and provides only 12-24 hours’ notice before ovulation occurs, which is difficult for couples because little advanced planning can be done on such short notice, and the opportunity to take advantage of the full fertile window is lost. Estimating ovulation based on a woman’s BBT gives historical values of when ovulation occurred in the past because a decrease in BBT only occurs after the fertile window closes and typically 24 hours after ovulation occurs. BBT is useful for future estimates of when the women’s fertile window occurs during her cycle, but does not give women real-time or predictive control before the fertile window ends. Additionally, a woman’s BBT frequently fluctuates, and variable methods to obtain measurements of temperature can often lead to inaccurate results and analysis. Current methods of cervical mucus collection for ovulation detection require manual extraction and rely on individuals to visually analyze the mucus viscosity and texture. This method is highly subjective, may not be performed at the right time, may be uncomfortable or unacceptable for many women, and is too imprecise to serve as a reliable biomarker of imminent ovulation and many women do not wish to use this method. Regardless of the method used, monitoring the menstrual cycle continues to be a significant challenge in terms of reliability and convenience.

[0007] Women tracking their menstrual cycle seek products that are accurate and clearly communicate results. In addition, busier lifestyles have driven the need for devices that are convenient, discrete, time saving, and easy-to-use. The disclosed devices, systems, and method can allow the monitoring of cervical mucus without the user having to extract cervical mucus manually, collect a urine sample, or measure their body temperature repeatedly. With more technology capabilities available, women also seek products that can be synchronized with their smartphones and computers. Women trying to conceive would benefit greatly from receiving an accurate estimate of their fertile window within a reasonable period of time before ovulation occurs.

SUMMARY

[0008] A real-time menstrual cycle monitoring system can be used to monitor fertility. The menstrual cycle monitoring system can comprise an intravaginal body which includes both a hydration sensing probe(s) or sensor(s) oriented to measure bioelectrical impedance, resistance or conductance of cervical mucus or the vaginal and cervical environment, and a temperature sensor to monitor body temperature. A data communication unit stores and transmits collected fertility data. A power source can be electrically coupled to the hydration sensing probe(s) or sensor(s) and the data communication module.

[0009] The intravaginal sensor device may have a body in the shape of a ring, a torus, or a cylinder that may or may not be elongated. In one example, the intravaginal body can be an annular ring body sized to be oriented within the vagina, cervical environment or vaginal vault. In one example, the annular body is formed of polyurethane. Although the annular body can often be a single seamless body, in one example, the annular body includes a seam configured to provide access to the power source. Sections of the body may or may not be hollow to allow housing of any or all other components, including electrical.

[0010] The hydration sensing probe(s) or sensor(s) can include a complementary set of electrodes oriented in proximity to one another sufficient to measure bioelectrical impedance, resistance or conductance associated with cervical mucus, vaginal or cervical tissue or epithelium, or the cervical environment. In one example, the complementary set of electrodes have a gold electrode surface. In another example, the complementary set of electrodes are made of platinum-iridium. In yet another alternative, the hydration sensing probe(s) or sensor(s) further includes an antimicrobial coating.

[0011] The data communication unit further comprises a wireless transmitter configured to send the fertility data to a mobile device, computer or other platform. In this manner, the collected data can be immediately communicated to a user through a wireless data transfer. A mobile receiving device (e.g. a smartphone) can then use an associated tracking application which analyzes and displays fertility estimates based on the collected fertility data.

[0012] The temperature sensor can be configured to measure temperature and communicate the measured temperature to the data communication unit via radio frequency fields or Bluetooth. The temperature sensor may have measuring accuracy of ±0.1°C. However, these measurement ranges may be varied as desired for the application of the invention. Such data can supplement the calculation of fertility window estimates.

[0013] In various aspects, a physiological monitoring system includes an insertable device (e.g., intravaginal ring), a data communication unit, a power source, and a transceiver. The intravaginal ring can have at least one sensing probe and/or sensor oriented to measure at least one physiological property. The data communication unit can be configured to store and transmit collected physiological data that includes the at least one physiological property. The power source can be electrically coupled to the sensing probe(s) and/or sensor(s) and the data communication unit. The transceiver can be configured to wirelessly receive the collected physiological data from the data communication. The transceiver can be configured to transmit the collected physiological data to a remote computing device. Optionally, the data communication unit can be configured to wirelessly transmit the collected physiological data to the transceiver using a first transmission protocol (e.g., a wireless radiofrequency protocol), and the transceiver can be configured to transmit the collected physiological data to the remote computing device using a second transmission protocol (e.g., Bluetooth) that is different than the first transmission protocol.

[0014] Methods of using the disclosed physiological monitoring systems are also described.

[0015] There has thus been outlined, rather broadly, the more important features of the invention so that the detailed description thereof that follows may be better understood, and so that the present contribution to the art may be better appreciated. Other features of the present invention can become clearer from the following detailed description of the invention, taken with the accompanying drawings and claims, or may be learned by the practice of the invention.

BRIEF DESCRIPTION OF DRAWINGS

[0016] FIG. 1 is a graph showing timing of Ovulation in Relation to % Hydration of Cervical Mucus, Luteinizing Hormone (LH), and Basal Body Temperature (BBT). [0017] FIG. 2 is a bar graph illustrating fertility statistics.

[0018] FIG. 3 is a cervical mucus and fertility correlation algorithm according to one aspect of the disclosure.

[0019] FIG. 4A is a partially transparent front view of an exemplary menstrual cycle monitoring device as disclosed herein, with certain features of the data communication unit of the device being depicted.

[0020] FIG. 4B is an image providing a transparent front view of an exemplary menstrual cycle monitoring device as disclosed herein.

[0021] FIG. 5 A is a transparent front view of another exemplary menstrual cycle monitoring device as disclosed herein, with certain features of the sensor and the data communication unit of the device being depicted.

[0022] FIG. 5B is a non-transparent front view of the menstrual cycle monitoring device of FIG. 5 A.

[0023] FIG. 5C is a close-up perspective view of the electrodes of the menstrual cycle monitoring device of FIGS. 5A-5B.

[0024] FIG. 6 is a schematic diagram depicting components of an exemplary physiological monitoring system as disclosed herein.

[0025] FIG. 7 is a schematic diagram depicting an exemplary physiological monitoring system having an insertable device, a transceiver, and a remote computing device. [0026] FIG. 8 is a diagram illustrating components of an operating environment in which various aspects of the disclosure may be implemented.

[0027] FIG. 9 is a diagram illustrating components of an exemplary electrical subsystem for use with the physiological monitoring devices and systems as disclosed herein.

[0028] FIG. 10 is a schematic diagram depicting an exemplary environment for a remote computing device as disclosed herein.

[0029] FIG. 11 is a graph illustrating the inverse relationship of sodium content and measured electrical resistance of cervical mucus.

[0030] These drawings are provided to illustrate various aspects of the disclosure and are not intended to be limiting of the scope in terms of dimensions, materials, configurations, arrangements or proportions unless otherwise limited by the claims.

DETAILED DESCRIPTION

[0031] While these exemplary embodiments are described in sufficient detail to enable those skilled in the art to practice the invention, it should be understood that other embodiments may be realized and that various changes to the invention may be made without departing from the spirit and scope of the present invention. Thus, the following more detailed description of the embodiments of the present invention is not intended to limit the scope of the invention, as claimed, but is presented for purposes of illustration only and not limitation to describe the features and characteristics of the present invention, to set forth the best mode of operation of the invention, and to sufficiently enable one skilled in the art to practice the invention. Accordingly, the scope of the present invention is to be defined solely by the appended claims.

DEFINITIONS

[0032] In describing and claiming the present invention, the following terminology can be used.

[0033] The singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “an electrode” includes reference to one or more of such electrodes and reference to “a subject” refers to one or more such subjects. [0034] As used herein, the term “about” is used to provide flexibility and imprecision associated with a given term, metric or value. The degree of flexibility for a particular variable can be readily determined by one skilled in the art. However, unless otherwise enunciated, the term “about” generally connotes flexibility of less than 5%, and most often less than 1%, and in some cases less than 0.01%.

[0035] As used herein with respect to an identified property or circumstance, “substantially” refers to a degree of deviation that is sufficiently small so as to not measurably detract from the identified property or circumstance. The exact degree of deviation allowable may in some cases depend on the specific context.

[0036] As used herein, “adjacent” refers to the proximity of two structures or elements. Particularly, elements that are identified as being “adjacent” may be either abutting or connected. Such elements may also be near or close to each other without necessarily contacting each other. The exact degree of proximity may in some cases depend on the specific context.

[0037] As used herein, a plurality of items, structural elements, compositional elements, and/or materials may be presented in a common list for convenience. However, these lists should be construed as though each member of the list is individually identified as a separate and unique member. Thus, no individual member of such list should be construed as a de facto equivalent of any other member of the same list solely based on their presentation in a common group without indications to the contrary.

[0038] As used herein, the term “at least one of’ is intended to be synonymous with “one or more of.” For example, “at least one of A, B and C” explicitly includes only A, only B, only C, and combinations of each.

[0039] Concentrations, amounts, and other numerical data may be presented herein in a range format. It is to be understood that such range format is used merely for convenience and brevity and should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. For example, a numerical range of about 1 to about 4.5 should be interpreted to include not only the explicitly recited limits of 1 to about 4.5, but also to include individual numerals such as 2, 3, 4, and subranges such as 1 to 3, 2 to 4, etc. The same principle applies to ranges reciting only one numerical value, such as “less than about 4.5,” which should be interpreted to include all of the above-recited values and ranges. Further, such an interpretation should apply regardless of the breadth of the range or the characteristic being described.

[0040] Any steps recited in any method or process claims may be executed in any order and are not limited to the order presented in the claims. Means-plus-function or step-plus-function limitations will only be employed where for a specific claim limitation all of the following conditions are present in that limitation: a) “means for” or “step for” is expressly recited; and b) a corresponding function is expressly recited. The structure, material or acts that support the means-plus function are expressly recited in the description herein. Accordingly, the scope of the invention should be determined solely by the appended claims and their legal equivalents, rather than by the descriptions and examples given herein.

[0041] All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided herein can be different from the actual publication dates, which can require independent confirmation.

INTRODUCTION

[0042] To best support women to feel empowered and informed in their individual health and wellness, individual women need to have direct access to accurate, user- friendly, and convenient methods of monitoring their physiology. For example, women would benefit greatly if they had the ability to conveniently monitor various health conditions or parameters, including, for example, and without limitation, fertility, contraception, in vitro fertilization (IVF), pregnancy, hormone levels, menstrual cycles, gastrointestinal tract condition, blood glucose levels, cardiac condition or performance, or any other condition or parameter that can be monitored or detected using sensors.

[0043] There is a particular need for women to have access to accurate, user-friendly, and convenient methods of fertility monitoring. Current fertility monitoring options like LH urine strips and manual cervical fluid extraction and evaluation are ineffective in giving enough advanced notice, provide inaccurate or subjective data, or are simply undesirable to many women. These conventional options lead to lengthy periods of time during which women struggle with infertility possibly leading to frustration, relationship strain, and other personal and medical challenges for women experiencing infertility.

[0044] The surge in LH levels that triggers ovulation occurs in response to an increase in the levels of estrogen secreted by the woman’s ovar(ies). Scientific research has demonstrated that estrogen levels and the hydration of cervical mucus peak simultaneously, indicating pending ovulation as illustrated in FIG. 1. In addition, cervical mucus hydration increases several days prior to ovulation, and a woman’s hydration pattern remains consistent among menstrual cycles. Cervical mucus >97.5% water provides an environment conducive for sperm to survive in order to fertilize the egg. A small amount of sperm can live for up to 5 days, but the optimal timing of intercourse is around 2 days prior to ovulation. Therefore, predicting ovulation several days in advance gives women and couples time to plan ahead for their most fertile period.

[0045] Women would greatly benefit from a convenient physiological monitoring system that provides them with access to information concerning various physiological conditions or parameters of their bodies. For example, women would benefit from a convenient fertility monitoring system that gives them adequate advanced notice of ovulation that allows them to plan life around their fertile window, gives them objectively measured data to predict ovulation, has a user-friendly interface to manage their reproductive health and wellness, and gives them an option to involve companions or partners in the fertility tracking process. More generally, it is contemplated that individuals would greatly benefit from systems and methods that provide for more convenient and accurate transfer of data from an inserted device to an external (remote) computing device.

[0046] As further disclosed herein, it is contemplated that disclosed devices, systems, and methods can achieve one or more of these objectives. More generally, it is contemplated that the disclosed devices, systems, and methods can provide more convenient and/or more accurate or reliable transfer of data from an inserted device to an external (remote) computing device.

THE PHYSIOLOGICAL MONITORING SYSTEM

[0047] In various aspects, and with reference to FIGS. 4A-10, the disclosed physiological monitoring system can provide improvements in the transfer of data from an inserted device to a remote computing device. As used herein, the term “inserted device” refers to a device that is received within a portion of the body of a user, and the term “insertable device” refers to a device that is configured to be inserted within the portion of the body of the user. These definitions of “inserted” or “insertable” devices are intended to include, as non-limiting examples, an implant device that is fixedly secured within a portion of the body during use, as well as devices that are selectively inserted and removed from a portion of the body without the need for an operation or procedure to position or secure the device within the body. Within the specification, it should be understood that the terms “inserted device” and “insertable device” are generally used interchangeably when describing the functionality of the device. In particular embodiments, and as further disclosed herein, it is contemplated that the physiological monitoring system can include an inserted/insertable device and a transceiver that receives data from the inserted/insertable device and is configured to transmit the data to a remote computing device. In the following description, a fertility tracking and menstrual cycle monitoring system is disclosed as a particular example of the physiological monitoring system. However, it should be understood that the disclosed communication between the inserted/insertable device, the transceiver, and the remote computing device is applicable to any inserted/insertable device that includes one or more sensors for gathering physiological data of a human or animal subject. In the following description of the fertility monitoring system, the inserted device is described as being received within a portion of the vagina of a user. However, it should be understood that the inserted device, when used in other applications, can be inserted in other portions of the body. It should be further understood that the inserted device, when positioned within the vagina, can provide various physiological information other than fertility information.

[0048] In use, the inserted device 10 can provide physiological monitoring (e.g., fertility monitoring) through a connection between the inserted device and a user application. As further described herein, in some optional aspects, the inserted/insertable device 10 can include at least one sensor (optionally, a plurality of sensors) for detecting physiological characteristics of a user. For example, the inserted/insertable device 10 can comprise a temperature sensor 50 to detect the user’s basal body temperature (BBT) and a hydration sensor (or sensor assembly) 12 to detect physiological characteristics associated with a bioelectrical parameter of the user.

Other exemplary sensors that can be included within the inserted/insertable device 10 include, for example and without limitation, a chemical sensor, a flow sensor, a pressure sensor, a force sensor, a capacitance sensor, a field-effect transistor-based biosensor (BioFET), microelectromechanical systems (MEMS) based sensors, and the like. More generally, it is contemplated that the device 10 can comprise any sensor that is capable of measuring a parameter that can be used to determine or provide information related to a physiological condition of the user. The inserted/insertable device 10 can also include a data communication unit 20 (e.g., a wireless communication module) that transmits this sensed data to an external device, such as, for example, and without limitation, an intermediary transceiver, the user’s mobile device, or another external computing device, system, or server. Optionally, the external device(s) can transmit this user data to a back-end processor or algorithm for analysis. The processor and/or algorithm can analyze and compare the received data against empirical data, thresholds, or user-specific customized data to determine physiological condition data for the user. The processor and/or algorithm can transmit the user’s physiological condition data back to the user’s mobile or other device and instruct that user device to output the physiological condition data or other related information to the user through a user application. Optionally, the system can comprise a companion application that allows for sharing the determined physiological condition data with the computing devices of one or more individuals who are authorized to have access to the user’s physiological condition data. For example, it is contemplated that spouses, partners, physicians, health care providers, or other designated recipients can have access to the companion application.

Fertility Tracking Systems

[0049] As further described below, the disclosed physiological monitoring system 100 can overcome one or more of the barriers of conventional fertility tracking techniques by providing reliable and real-time information in an easy-to-use and convenient approach. The system 100 can be used by women trying to conceive and/or to prevent pregnancy and/or to monitor the menstrual cycle. As further explained herein, throughout the menstrual cycle, various hormones fluctuate in order for ovulation or release of an egg to occur. Hydration of cervical mucus changes depending on blood levels of estrogen and progesterone. As blood levels of estrogen increase, cervical mucus hydration increases. The surge in estrogen causes the LH surge, stimulating ovulation. The system 100 can help a woman predict her peak fertile period based on the hydration and/or ion levels of her cervical fluid, which can include cervical mucus and/or other fluids in the cervical environment.

The Intravaginal Ring

[0050] Optionally, in exemplary aspects, the inserted/insertable device 10 can be provided as an intravaginal ring, as shown in FIGS. 4A-5C. In these aspects, the intravaginal ring can comprise a temperature sensor 50 to detect the user’s basal body temperature (BBT) and a hydration sensor (or sensor assembly) 12 to detect physiological characteristics (e.g., at least one bioelectrical parameter) of the user’s vaginal tissue or vaginal environment. The inserted/insertable device 10 can be inserted into the vagina at or near the cervix following the last day of menstruation, and removed once ovulation has occurred. In exemplary aspects, the device 10 is not inserted into the cervix. In other exemplary aspects, at least a portion of the device 10 is positioned around the cervix. The number of days during which the device 10 is used (i.e., positioned within the vagina) may vary depending on the length of the user’s menstrual cycle, which can vary. It is contemplated that the average length of use (per period of insertion) can be about 7 to 14 days, however, it can be worn for up to 30 days or even 40 or 50 days in some cases. Typically, in healthy women, ovulation occurs during a two week period while a woman is using (optionally, wearing) the device 10. As further described herein, the device 10 can comprise a data communication unit 20 having a wireless communication module that transmits the sensed data to an external device, such as an intermediary transceiver (as further disclosed herein), a user’s mobile device, or another external computing device, system, or server. The external device can provide a processor and/or a fertility algorithm that transmit the user’s fertility data back to the user’s mobile or other device and instruct that user device to output fertility data or other related information to the user through a user application. The companion application, when provided, can allow for sharing the determined fertility data with the computing devices of one or more individuals who are authorized to have access to the user’s fertility data. For example, it is contemplated that spouses, partners, physicians, health care providers, or other designated recipients can have access to the companion application.

[0051] As previously explained, cervical fluid is a woman’s natural way of preparing for conception of a child and is important for the nourishment and survival of sperm that will ultimately fertilize a released egg that implants in the woman’s uterine lining to form an embryo that develops into a baby. The change in the hydration characteristics of the woman’s cervical fluid occurs days before ovulation occurs if detected accurately and precisely. In use, it is contemplated that the hydration sensor (or sensor assembly) 12 of the inserted/insertable device 10 can detect the change in the hydration characteristics of the woman’s cervical fluid within two to five days before ovulation actually occurs, thereby defining a fertile window within which release of sperm is optimal for fertilization of a released egg at ovulation.

[0052] Clinical studies show that the changes in cervical fluid characteristics detected by the disclosed inserted/insertable device 10 can serve as a reliable biomarker to predict the woman’s fertile window. More particularly, clinical studies have shown that the hydration percentage of cervical fluid has a temporal correlation with a woman’s ovulation in which the hydration characteristics predictably increase during a window of two to five days prior to ovulation. As mentioned above, the woman’s BBT noticeably increases after ovulation occurs and her LH levels spike within the preovulatory period. The LH level spike is timed closer to the day of ovulation than the change in the cervical fluid hydration percentage. Vaginal impedance in humans is lowest at one to two days prior to ovulation, with the lowest vaginal impedance value on the day of the preovulatory LH peak. A decrease in vaginal electrical resistance is closely associated with the LH peak and is significantly lower on ovulation day. Typically, as moistness of the vaginal cavity increases, electrical resistance declines. Vaginal conductivity increases with serum estrogen levels and decreases as serum progesterone increases. Clinical research indicates that changes in vaginal impedance, resistance and conductance are primarily due to changes in cervical mucus volume and ionic content, particularly sodium chloride (NaCl), and reflect the estrogemprogesterone ratio. When serum estrogen is unopposed by serum progesterone, cervical mucus has a greater hydration, and the overall concentration of ionizable materials remains constant per unit volume. Cervical mucus increases in hydration and volume as the blood serum estrogen levels rise, with both levels peaking at ovulation. When serum progesterone opposes serum estrogen, the cervical mucus dehydrates, resulting in the ionizable materials having a higher concentration per unit volume. Of note, a woman’s cervical mucus hydration pattern remains consistent from menstrual cycle to cycle even more so than changes in serum reproductive hormones. A study examining hydration of cervical mucus found cervical mucus water content to be at 92-94% during the pre-ovulatory and post-ovulatory phases, and at 97-98% around the time of ovulation. A significant increase in hydration was seen over a 1 day period that occurred about 3-4 days prior to the surge in LH, which occurs soon after the dramatic rise in estrogen. The environment most conducive for sperm to survive and fertilize the egg is at cervical mucus hydration levels of greater than 97.5%, which occurs about 2 days prior to ovulation. Clinical studies have found that although volume of mucus varied throughout the cycle, patterns in all women were similar.

[0053] The temperature sensor 50 of the inserted/insertable device 10 can measure the woman’s BBT, which is the temperature of the woman while fully at rest. For most women, the most accurate BBT measurement is taken immediately upon awakening from a night’s sleep before the woman sits up from a supine position. BBT increases when ovulation has occurred and is a confirming data point that validates the occurrence of ovulation during a woman’s menstrual cycle. It is contemplated that the combination of the measured hydration characteristics of the woman’s cervical fluid and the woman’s BBT can be used to predict and validate occurrence of ovulation. [0054] A sample chart tracking an expected progression of a woman’s BBT, percentage of hydration of cervical fluid, and LH levels during a portion of her menstrual cycle is shown in FIG. 1.

[0055] In further aspects, and as shown in FIGS 4A-5A and 6-9, the data communication unit 20 (e.g., wireless communication module) of the inserted/insertable device 10 can transmit the sensed data from the hydration sensor and optionally the temperature sensor to a remote device, such as a user’s phone or other personal computing device, an intermediary transceiver, a physician or other medical provider’s device, a companion’s device, or another computing device, network, or server. As shown, the remote device can transmit the sensed data to be processed by a fertility algorithm in any distributed processing architecture. For example, it is contemplated that the remote device can transmit the sensed cervical fluid data and the BBT data to a remote server for processing. Optionally, the fertility algorithm can reside on the remote server and be configured to process the sensed cervical fluid and temperature data to determine and identify a fertility window that corresponds to the optimal period of time for the woman to engage in intercourse prior to ovulation. The fertility algorithm can identify the woman’s fertile window and transmit an instruction to the user’s device to be output to the user (and, optionally, a companion and/or physician or other medical provider). [0056] In use, the system 100 and associated processing circuitry (which can execute a software application as further disclosed herein) can monitor and track hydration and/or ion levels of cervical mucus and/or the vaginal environment to predict the estrogen surge prior to the LH surge and pending ovulation. Hydration of cervical mucus can begin to increase greater than 2% from baseline 3-5 days prior to the peak in LH. A % hydration of cervical mucus greater than 97.5% can indicate ideal sperm penetrability. Two days prior to the peak in LH, the percentage (%) hydration of cervical mucus is expected to be around 98%. The disclosed processing circuitry, through the software application and a display as further disclosed herein, can display fertile days for timing of intercourse with a range of possible fertility to high fertility using one or more of a plurality of indicators, including but not limited to color, symbols, graphs, graphics, animations, or any other method(s). Typically, menstruation would be expected to start at around 14 days after ovulation and, depending on the individual’s cycle length, can also be indicated to the user by the disclosed processing circuitry, which can be configured to execute the software application.

[0057] As described further herein, when used for tracking fertility, the inserted/insertable device 10 can provide one or more bioelectrical measurements of the cervical fluid to determine a percentage of hydration of the cervical fluid. In exemplary aspects, the hydration sensor 12 (e.g., pair of electrodes) of the device 10 can measure the impedance value of the user’s cervical fluid during the period of time during which the user has the device inserted. FIG. 11 provides an example graph of a healthy woman’s electrical resistance values plotted over time as it relates to the day on which she experiences a sharp increase in LH levels, which indicates ovulation is imminent. As shown, the impedance value (charted as an electrical resistance value) sharply declines four to five days before the woman experiences an LH level peak, which occurs within one to two days before ovulation. The hydration sensor 12 (e.g., electrodes) can identify the sharp decrease in impedance value several days sooner than the LH peak occurs, thereby giving the woman more time to plan for timing intercourse to optimize the likelihood of conception.

[0058] In use, it is contemplated that the disclosed fertility tracking device and system can be precise and objective in the measurement of the hydration data for the cervical fluid and the basal body temperature data. It is further contemplated that the disclosed fertility device and system can be reliable by applying the predictive fertility window on precisely measured data, calendar data, empirical data, trends of previously tracked user data, or some combination of these data sources.

[0059] It is further contemplated that the disclosed device and system can be convenient for a woman because the intra-vaginal ring is designed to be positioned intra-vaginally at the completion of a woman’s menstruation and remains inserted until ovulation has occurred, thereby reducing the complexity of tracking fertility data for the woman during this critical conception time frame.

The Hydration Sensor Assembly

[0060] As described generally above and shown in FIGS. 4A-6, the inserted/insertable device (e.g., intravaginal ring) 10 can be integrated with a hydration and/or ion sensor assembly 12. The hydration and/or ion sensor(s) 12 may be composed of probe(s) and/or electrodes that are configured to measure the electrical impedance, resistivity and/or conductance of cervical mucus, the vaginal environment, and/or fluids and secretions near the cervix. The probe(s) and/or sensor(s) 12 can be at least partially embedded in the ring 10 and can optionally comprise a pair of electrodes 14, which can optionally be circumferentially spaced from one another about the ring 10. In exemplary configurations, the electrodes 14 can project from a surface of the ring body 16 as shown in FIGS. 4A-5C. A voltage can be applied between electrodes 14, and the drop in voltage can correspond to a measurement of the resistance of fluids, which may be converted to impedance. The electrodes 14 can comprise an excitation electrode and a return electrode that measures impedance across a known distance of cervical fluid. Electrical impedance is an extension of the concept of resistance and measures the opposition that a circuit presents to a current when a voltage is applied. Impedance possesses both magnitude and phase. In one specific example, and as shown schematically in FIG. 8, a sinusoidal strength current of 5 kHz can be passed through the cross-sectional area, which can determine extracellular fluid content based on the signal frequency and calculate and evaluate variations in hydration and/or ion levels. At low frequencies such as 5 kHz, current flows primarily through the extracellular water (ECW). An alternating current can be applied to measure electrical resistance and conductance of cervical mucus as they are related to the content of water and characteristic electrolytes, particularly sodium. As ovulation approaches, both the volume of water and sodium content in cervical mucus increase and the concurrent decrease in resistance can be objectively measured. [0061] Cervical mucus contains water, electrolytes, other ions, and other particles. When a current is passed through a fluid, it is able to conduct electrical current. At low frequencies at around or below 5 kHz, current from the electrodes 14 primarily passes through the extracellular fluid space (Weyer et al. (2012), Acta Polytecha. 52 (5): 120- 124), but begins to penetrate body tissues as frequency increases. A fixed or variable sinusoidal strength current can be passed through the cross-sectional area of the tissue in proximity to the device 10. As current is passed through the tissue, fluid and ion resistance or conductance can be determined based on the signal frequency as further disclosed herein, and this resistance or conductance can then be correlated with a corresponding variation in hydration levels as further disclosed herein.

[0062] In exemplary aspects, the hydration and/or ion sensor 12 can be in the form of a capacitor which includes electrodes 14 (optionally, parallel electrodes) that are made of or coated with a suitable conductor, e.g. nickel, gold, copper, platinum, titanium, cobalt, chromium, or alloys thereof. In exemplary aspects, the electrodes 14 can be gold-plated or plated with gold-copper alloy. In other aspects, the electrodes 14 can comprise platinum-iridium alloy, such as, for example, platinum-iridium 90-10. The hydration and/or ion sensor 12 can be operated at a suitable frequency such as 5 kHz. However, it is contemplated that any desired optimal sensor frequency can be used. For example, it is contemplated that a first frequency can be optimal for applications where measurements of cervical fluid are performed, and a second frequency can be optimal for other applications where measurements of tissue (e.g., vaginal and/or cervical epithelium/tissue) are performed. Probes and/or electrodes may be covered or made with an antimicrobial or hygienic coating such as pMTAC or pDA-g-pMTAC combo, silver, tin, copper, ZnO/Ti spray, DMDC-Q-g-EM hydrogel, platinum, titanium, alloys, stainless steel, cobalt or cobalt-based alloys, cobalt chromium, magnesium alloys, combinations or alloys thereof, or other material(s) that is biocompatible. It is contemplated that spectroscopy can also be used for cervical mucus and/or vaginal environment analysis. Estimates of hydration, percent water content, and/or other estimates can be generated from the data collected by the sensor 12. Other possible data collections concerning cervical mucus and/or the vaginal environment may include viscosity, pH, osmolarity, MUC 4 protein, MUC 5B protein, copper, iron protein: glycol ratio, IgA, IgG, Lactoferrin, Interleukin- 10 and/or other antimicrobial peptides.

Although the hydration sensor is described above as a pair of electrodes, it is contemplated that the hydration sensor can be configured to detect any bioelectrical characteristic of the cervical fluid to determine cervical fluid hydration levels or any combination of bioelectrical characteristics, such as electrical resistance, impedance, or conductance. Therefore, other structure and configurations of the hydration sensor are within the scope of this disclosure.

[0063] As further described herein, the hydration sensor 12 can measure impedance (or other bioelectrical) values of the cervical fluid over a time period. It is contemplated that this time period can be set according to a fertility schedule, such as a known, empirical, or user-specific estimation of the timing of ovulation. For example, the fertility schedule can be based on an expected number of days that ovulation occurs after menstruation ends based on historical data of the menstrual cycles of healthy women, the user-tracked menstrual cycle data, or a combination of both this information and other data. The fertility schedule can be set or programmed into firmware on the processing circuitry (chip of the data communication unit 20) of the inserted/insertable device 10 or can be customized from a default programmed fertility schedule based on user need or user data.

[0064] In exemplary aspects, the fertility schedule can correspond to the frequency and timing of the impedance (or other bioelectrical) measurements taken by the hydration sensor 12 and the temperature measurements of the temperature sensor 50. The fertility schedule occurs over a period of time, such as 10-14 days after menstruation ends. The frequency and timing of the impedance and temperature measurements can be periodic, manual, or a combination of both and can be adjusted (in a manual or automated fashion) after each menstrual cycle in which data is collected for the user.

[0065] In accordance with the fertility schedule, the hydration sensor 12 (and, optionally, the temperature sensor 50) can take multiple measurements over the defined period of time at intervals that are timed apart from each other by an interval time. The interval time can vary or can be similar or identical or a combination of the two. The output to the user can be fertility data that is based on a measurement from one or more of the measurements taken during the time period. In one optional example, impedance measurements can be taken at 6-8 hour intervals, and that impedance data can be averaged or filtered (e.g., a median or high/low filtering) over a 24 hour period of time. Alternatively, in other aspects, it is contemplated that the device 10 can be configured to determine a real-time value for the user’s impedance and BBT if the user is fully at rest (or the most recent BBT, if the user is not fully at rest). The fertile window output to the user can be based on the data processed over a time period, such as for example, 24 hours. Additionally, or alternatively, it is contemplated that the fertile window output can be based on a real-time receipt and analysis of data. Thus, in some aspects, it is contemplated that the user can be provided with either a real-time fertile window output or a fertile window output that is based on historical data over a longer time period.

[0066] In use, it is contemplated that the convenient collection and trending of the user’s data over time can offer a reliable and user-friendly option for users that prefer to manually track and process this data without the benefit of precision data collection, processing, and trending.

Exemplary Ring Configurations

[0067] With reference to FIGS. 4A-5C, the inserted/insertable device 10 can be made of flexible, selectively deformable material, which may include plastic or other material or polymer such as medical-grade polyurethane, silicone, ethyl vinyl acetate, or other biocompatible polymer. In exemplary aspects, the inserted/insertable device 10 can comprise medical-grade silicone. Although numerous materials can be used for the device body 16, it is contemplated that preferred materials are non-conductive and biocompatible while also exhibiting great tensile strength, excellent elongation, superior flexibility, versatility, low compression set and a desired durometer range (dry hardness) of 35 to 45 Shore A, when measured in accordance with ASTM D2240-05. It is contemplated that a preferred swollen hardness range can be 30 to 90 Shore A. In use, the material can have a surface or implant contact of more than 24 hours and 30 days. The power source 40, communication hardware 26, and other components can be fully enclosed within the intravaginal ring core and completely covered by such materials to prevent exposure to bodily tissue or fluids. In further aspects, it is contemplated that the materials of the hydration sensors can also provide biocompatibility, inertness within the body, and bio-robustness.

[0068] The core (i.e., the interior of the ring body 16) may or may not be hollow depending on the internal contents, which can include at least one battery, wiring, or other necessary contents to power the device and allow the device to communicate data to a remote device (referred to collectively as power source 40). In exemplary aspects, it is contemplated that the power source 40 (e.g., battery) can have a life or duration of at least 35 days or from 35 to 40 days. Optionally, the device 10 can generally have an outside diameter between 55 mm and 65 mm but may reach up to 120 mm. In some exemplary aspects, the outside (outer) diameter is less than 65 mm. Optionally, the device 10 can generally have an inner diameter of 45 mm but may range between 34 mm to 65 mm or from 35 mm to 56 mm. Optionally, in further aspects, the cross- sectional diameter (or thickness) of the ring body 16 can range from 6 mm to 30 mm. In exemplary aspects, as shown in FIGS. 5A-5B, the outer and inner diameters of the device 10 and the cross-sectional diameter of the ring body 16 can be vary (e.g., within the above ranges) along the circumference of the device. Optionally, pliability or flexibility of the device 10 can generally be between 0.01 to 3.00 Newtons. Optionally, tensile strength can be at least 500 psi but can range between 115 to 5400 psi. The device 10 can optionally have a twist angle of up to 55 degrees and be configured to return to its original diameter and elasticity. The cross-sectional diameter of a portion of the ring body 16 can optionally be about 10 mm but can vary between 4 mm to 20 mm. In exemplary aspects, the cross-sectional diameter of the ring body 16 is at least 4 mm. The compression resistance can optionally be 55% to 85% of its original diameter and elasticity (after repeated vertical compression using a 129 g mass). The ring body 16 can optionally be a single continuous piece or, alternatively, broken at one or more seams (not shown) and/or at the location(s) of the batter(ies) to allow removal of the batter(ies) or other components for proper disposal.

[0069] Under normal conditions of use, the batter(ies) 40 can be hermetically sealed within the core of the ring body 16. The batter(ies) 40 and communication hardware components 26 can typically be fully enclosed within the intravaginal ring core and completely covered by medical grade polyurethane, thereby preventing exposure to bodily tissue or fluids. At low frequencies below approximately 10 kHz, it is contemplated that current will not pass across the cell membrane due to the capacitive nature of the bilipid membrane structure.

[0070] At least one miniaturized electric cell of a plurality of such cells can be interconnected to a miniature battery 40 which is enclosed within the body of the device 10 (e.g., annular ring member). For example, button cell batteries can be suitable such as, but not limited to, SR626W or equivalent Energizer 377/376. In one specific example, a zinc cathode (negative electrode), a silver oxide anode (positive electrode), and an alkaline electrolyte can be used. Typically, such cells can provide amperage: 28 mAh (to 1.2 volts), impedance (40 Hz): 15-30 ohms, battery duration 35 days or 840 hours, and silver oxide cells have 90% service maintenance after 1-year storage at 21°C. A boost convertor may be used with single 1.5 V batteries; this may be adequate to power the measurement electronics as well. If not, then a separate boost converter may be incorporated.

[0071] As described above, the electrodes 14 of the device 10 can be spaced apart by a certain distance, which may generally range between about 1 mm and about 5 mm but may reach up to 65 mm from one another.

[0072] In exemplary aspects, the device 10 (intravaginal ring) can have a shape that can effectively surround the cervix and measure cervical fluid quality by electrical properties as further disclosed herein. As shown in FIGS. 5A-5B, the ring body 16 can have a complex shape, with both a variable diameter of the device and a variable thickness of the ring body depending on the location along the circumference of the ring body where the measurements are performed. Optionally, the electrical components of the device can be populated on a single side of the ring body 16. In exemplary aspects, the portions of the ring body 16 where electrical components are housed can have a generally greater thickness than adjoining portions of the ring body. For example, in some optional aspects, and as shown in FIG. 5B, the ring body 16 can comprise first and second housing portions 18 that receive respective electrical components, with the housing portions 18 positioned on opposing sides of the device. In these aspects, the electrical components within the respective housing portions can be electrically connected through at least one cable 15 (e.g., a flex cable) that passes through a reduced-thickness portion 19 of the ring body 16 that is positioned between the first and second housing portions 18. It is contemplated that reduced-thickness portion 19 can define a recessed section of the inner diameter of the device, thereby providing for an increased inner diameter of the device relative to an axis that is generally perpendicular to the inner diameter defined by the two housing portions 18. Because the body is inserted near the woman’s sensitive cervical and vaginal tissue, the ring body 16 can be designed to be smooth and biocompatible. In some aspects, it is contemplated that the ring body 16 can have indents, cavities, or contours to prevent edges or surfaces of the ring from irritating the vaginal or cervical tissue that the device contacts. For example, it is contemplated that the ring body 16 can define a recessed surface that defines one or more openings through which respective electrodes project, thereby limiting or preventing direct tissue contact and irritation or discomfort. In exemplary aspects, it is contemplated that the shape, dimensions, and materials of the ring body can allow a user to selectively compress the ring (or otherwise reduce the operative diameter of the ring body) to permit easy and/or efficient insertion within the vagina, either manually or with an applicator.

[0073] In exemplary aspects, it is contemplated that the device 10 can have a weight of less than 0.5 oz (14 grams).

[0074] Optionally, in some aspects, the inserted/insertable device 10 can be disposable after each period of use. In these aspects, it is contemplated that a plurality of inserted/insertable devices 10 can be sold and/or packaged together as a kit. Alternatively, in other aspects, it is contemplated that the inserted/insertable device 10 can be reusable. In these aspects, it is contemplated that the reusable device 10 can comprise one or more of: a rechargeable battery; one or more batteries that utilize wireless charging, such as magnetic charging or wireless power transfer; or other power supply technology that supports harvesting of energy and/or transformation of humangenerated energy to power the device, thereby retaining the integrity of the inserted/insertable device.

Data Collection and Transmission

[0075] As shown in FIGS. 6-7 and 10, real time data from the sensors (e.g., the hydration sensor 12) can be collected and translated to an external (remote) computing device 200 via a data communication unit 20, which can include Bluetooth, radiofrequency identification (RFID), telemetry or other wired or wireless technology. In these aspects, it is contemplated that the data communication unit 20 can comprise a wireless transmitter 22 and a wireless receiver 24. Optionally, it is contemplated that the wireless transmitter 22 and the wireless receiver 24 can be provided as a single component (e.g., a wireless radio or transceiver). In further exemplary aspects, it is contemplated that the data communication unit 20 can comprise communication hardware 26, such as, for example, Bluetooth hardware or radio-frequency transmission hardware as is known in the art. In still further aspects, the data communication unit 20 can be communicatively coupled to a microcontroller 30, which can, in turn, be communicatively coupled to the hydration sensors 12/electrodes 14 and the temperature sensor 50 as disclosed herein. In some aspects, it is contemplated that the microcontroller can receive fertility data from the hydration and temperature sensors 12, 50 and then direct the transmitter to transmit the fertility data to the processor 1003 of the remote computing device 200. Alternatively, in other aspects, the microcontroller can receive fertility data from the hydration and temperature sensors 12, 50 and then direct the transmitter to transmit the fertility data to an intermediary transceiver 150, which can be positioned external to the user and have receiver hardware for receiving the data from the data communication unit 20 and transmitter hardware for transmitting the data to the remote computing device 200. The data can be integrated with a software application accessible by the remote computing device 200 (e.g., a computer, smartphone, smart watch, tablet, or other mobile device or other software application device) for data storage, analysis and/or menstrual cycle tracking. The software application, when executed by a processor 1003 of the remote computing device 200, can aid the user in identifying the most fertile days of their menstrual cycle and provide information regarding the individual’s menstrual cycle, including, for example and without limitation, an estimated time of ovulation. In operation, it is contemplated that the wireless transmitter 22 of the data communication unit 20 can transmit fertility data to the receiver hardware 152 of the transceiver 150 and/or the processor 1003 of the remote computing device 200, while the wireless receiver 24 of the data communication unit 20 can receive remote instructions from the transmitter hardware 154 of the transceiver 150 and/or the processor 1003 of the remote computing device 200. Optionally, the microcontroller 30 can receive data from the electrodes 14 and/or temperature sensor 50 and then cause the data communication unit 20 (e.g., the wireless transmitter 22) to transmit the data to the transceiver 150 and/or the remote computing device 200.

[0076] The device 10 can be connected to a current source and to an amplifier. In some exemplary aspects, and with reference to FIG. 8, it is contemplated that during impedance measurements, the microcontroller 30 can generate a square wave using a pulse width modulation peripheral. This signal can be passed to a capacitor filter integrated circuit 74 to generate a sine wave. The sine wave can be fed to a trans conductance amplifier 76 which converts the voltage signal to the desired current, which is then applied to the excitation electrode (or excitation probe) through a suitable AC coupling capacitor (which blocks any DC component of the signal). The resulting voltage can be sensed by a high impedance differential or instrumentation amplifier 78, and the sensed voltage can be applied to a peak detector circuit 80, which can convert the AC to a DC peak value that is then measured using the Analog-to-Digital Converter peripheral in the microcontroller 30 of the data communication unit 20.

[0077] As mentioned above, the system 100 can optionally comprise a transceiver 150 that receives data from the data communication unit 20 of the device 10 and is configured to transmit the data to a remote device 200, which can either comprise a back-end server or transmit the data to a back-end server for processing. In various aspects, it is contemplated that the arrangement and combination of the disclosed circuit components can be configured to provide optimal transmission of wireless signals from the inserted device through the tissue of the user and then to the transceiver 150 (and from the transceiver to the inserted device in some aspects).

[0078] In exemplary aspects, the wireless transmitter 22 of the data communication unit 20 can transmit data to the transceiver 150 on a mid- or high power radio frequency (RF) communication frequency band. In further exemplary aspects, the transceiver 150 can be configured to transmit data to the remote device 200 using a higher-frequency transmission protocol, such as Bluetooth, Bluetooth Low Energy (BLE), or Wi-Fi® (a registered trademark of the Wi-Fi Alliance). It is contemplated that the lower frequency signals provided by RF communication can improve penetration through body tissue in order to permit transmission to the transceiver 150. Optionally, the receiver 152 of the transceiver 150 and/or the transmitter 22 of the data communication unit 20 can comprise or be in communication with wire loops (e.g., magnetic loop antennas) that provide or receive communication through magnetic fields rather than through electromagnetic radiation.

[0079] In exemplary aspects, the wireless transmitter 22 of the data communication unit 20 of the device 10 can be provided as a component of the microcontroller structure 30. For example, in some aspects, the microcontroller 30 can comprise a microcontroller that includes a transmitter that is capable of supporting a variety of transmission frequencies. The frequencies used can be in the industry, scientific, and medical (ISM) bands and/or short-range device (SRD) bands. In exemplary aspects, the transmitter can support transmission frequencies in the range of about 300 MHz to about 600 MHz, or about 350 MHz to about 600 MHz, or from about 400 MHz to about 550 MHz, or less than 1 GHz (e.g., frequencies selected from the 315-, 433-, 470-, 500-, 779-, 868-, 915-, and 920-MHz ISM and SRD bands). It is contemplated that the frequency (or frequencies) can be selected based on penetration of muscle and other tissues. For example, relatively low frequencies can have higher penetration rates than relatively high frequencies. As a specific example, it is contemplated that 2.4GHz radios (including conventional Bluetooth radios) can have difficulty transmitting through muscle and similar tissues. It is contemplated that the transmission frequencies in the examples and ranges disclosed herein (e.g., below 1GHz) can provide improved transmission through tissue of the user. Advantageously, the 433 MHz-frequency band is allowed for unlicensed use in Europe and can be used with the disclosed devices and systems. More generally, it is contemplated that specific frequency band selected for a given transmitter can be determined based on the regulatory requirements or standards of a particular geographic region (e.g., country) where the device or system including the transmitter is to be used. Optionally, the microcontroller 30 can be provided as a radio chip that has the flexibility to work at a variety of frequencies. For example, the microcontroller 30 can be a CC1310 transceiver/ microcontroller (TEXAS INSTRUMENTS), which includes a transmitter capable of transmissions at 433MHz and other frequency bands. In exemplary aspects, it is contemplated that the transmitter can use frequency shift keying (FSK) modulation to encode data.

[0080] In further aspects, the receiver 152 of the transceiver 150 can likewise be configured to support receipt of transmission frequencies in the range of about 300 MHz to about 600 MHz, or about 350 MHz to about 600 MHz, or from about 400 MHz to about 550 MHz (e.g., frequencies selected from the 315-, 433-, 470-, 500-, 779-, 868- , 915-, and 920-MHz ISM and SRD bands). Optionally, the receiver 152 of the transceiver 150 can be a component of a CC1350 transceiver/microcontroller (TEXAS INSTRUMENTS), which also incorporates a BLE transceiver that can function as the transmitter 154 of the transceiver 150. Thus, it is contemplated that the transceiver 150 can provide the dual functionality of supporting the same range of frequencies (under a first wireless transmission protocol, for example, radiofrequency) as the transmitter 22 of the data communication unit 20 of the device 10, while also having the ability to transmit data to a remote computing device 200 using a different range of transmission frequencies (under a second wireless transmission protocol, for example, Bluetooth or Bluetooth Low Energy). It is further contemplated that the transceiver 150 can comprise a single chip that both receives the lower frequency transmissions from the data communication unit 20 and sends that data to a Bluetooth-enabled remote device 200. To accomplish this, it is contemplated that the transceiver 150 can comprise two radios within a single package: one radio for a lower frequency band (e.g., a Sub-lGHz ISM radio) to match the frequency and modulation of the sensor radio transmission, and a second radio for a higher frequency band (e.g., a 2.4 GHz BLE radio) that supports communication with BLE (e.g., version 4.2) compatible radios. In use, it is contemplated that the transceiver 150 can be configured to manage radio interfaces as well as data storage. In further exemplary aspects, it is contemplated that the hardware of the data communication unit 20 and the transceiver 150 can further comprise high resolution analog-to-digital converters (12-bit).

[0081] In exemplary aspects, the power source 40 can comprise at least one battery (optionally, a plurality of batteries, such as, for example, two batteries). Optionally, in some aspects, the plurality of batteries can comprise at least four batteries to account for the high discharge rates of the system. It is contemplated that by powering the transceiver 150 by at least one battery, the portability of the system can be improved. [0082] In further exemplary aspects, the transmitter 22 of the data communication unit 20 can comprise or be communicatively coupled to an antenna 25, which can optionally extend circumferentially within the interior of the ring body 16 (optionally, through the entire circumference of the ring body). Optionally, the antenna 25 can be provided as an embedded circular wire that is driven by the transmitter 22 to generate a transmission signal (e.g., a 433 MHz RF signal) to be received by the transceiver 150. The antenna can be configured (e.g., sized) based on the particular frequency band used. Thus, it is contemplated that each antenna can be configured for use with a particular frequency band. An impedance matching network can transform the output impedance of an RF port of the transmitter 22 to the impedance presented by the loop antenna 25, thereby allowing for maximum RF transmission power. The transceiver 150 can receive the signal (e.g., 433 MHz signal) from the data communication unit 20 with the vaginal electrical resistance (VER) or other bioelectrical data and temperature data (or other physiological data) from the device 10, and then transmit that data via Bluetooth or other protocol to the remote computing device 200. It is contemplated that each radio can have a separate antenna and impedance matching network to maximize the performance of the radios while maintaining a compact size.

[0083] In exemplary aspects, it is contemplated that the transceiver 150 can have a maximum dimension of less than 8 inches or more preferably, less than six inches. Optionally, in these aspects, it is contemplated that the maximum dimension of the transceiver 150 can be six inches or smaller, four inches or smaller, or three inches or smaller. In one exemplary aspect, a housing of the transceiver 150 can have dimensions of about six inches by about 2.5 inches by about one inch. Optionally, it is contemplated that the dimensions of the housing of the transceiver 150 can be determined at least in part by the battery /batteries used. Optionally, the transceiver 150 can have dimensions that are sufficient to house a plurality of replaceable batteries (e.g., four AA batteries or four AAA batteries). Optionally, it is contemplated that the battery storage can be sufficient to operate the transceiver for at least 14 days. In further optional aspects, it is contemplated that the battery can be rechargeable. In this way, the device can charged daily, so a smaller battery /battery pack can be used, thereby allowing for a smaller housing size. In further optional aspects, it is contemplated that the dimensions of the housing of the transceiver 150 can be determined at least in part by the antenna. For example, in some aspects, the transceiver can be configured to receive signals on the order of 433 MHz. Accordingly, a suitable antenna can be a significant fraction of the wavelength of the signal. For a classic dipole antenna, the antenna can have a length of about 13 inches. In further aspects, it is contemplated that an antenna having a length of six inches or less (e.g., about 5-6 inches) can be used. Accordingly, the housing can be configured to house an antenna having such a length. In some aspects, it is contemplated that the housing of the transceiver 150 can be configured to mechanically couple to a mobile phone or tablet of a user. For example, it is contemplated that the transceiver 150 can comprise a clip, a sleeve, adhesive strip, or other fastener that is configured to couple (e.g., attach, mount, or otherwise secure) the transceiver to a case or housing of a mobile phone or tablet. In exemplary aspects, the transceiver can be selectively decoupled from the mobile phone or tablet through the use of a releasable or removable fastener or other connection. Additionally, or alternatively, it is contemplated that the transceiver 150 can be positioned in proximity to the phone or other mobile device of the user (e.g., on a nightstand, on a table or desk, on a vehicle console) so that the device 10 is positioned within transmission range of the transceiver 150 when data needs to be transmitted from the device 10 to the transceiver 150. It is contemplated that the positioning of the device 10 within the transmission range can be particularly advantageous while the user is sleeping. Optionally, in exemplary aspects, it is contemplated that the transmission range of the transceiver can be at least four inches or at least two feet. In these aspects, it is further contemplated that the transmission range can be up to 10 feet or up to 15 feet.

[0084] As further described below, and with reference to FIG. 9, it is contemplated that the electrical components of the inserted/insertable device 10 can be divided among a plurality of subcircuits or subsections, including, for example, the data communication unit (low-frequency transceiver/microcontroller), an RF Antenna and impedance matching network, a step-down switching converter, power domain switches, impedance measurement, temperature measurement, magnetoresistive-based power latching, non-volatile memory storage, and a programming interface. [0085] In exemplary aspects, the data communication unit 20 can be electrically coupled to a step-down switching converter (a buck switching regulator) 64 that is configured to convert the voltage provided by the batteries 40 (e.g., a voltage of 2.5 V to 3.1 V) to an output voltage of 1.8V, which can power the microcontroller 30 of the data communication unit (optionally, including a transceiver), the temperature sensor 50, and an external memory (e.g., EEPROM) 72. Although specific voltage values are provided above, it is contemplated that the voltage provided by the batteries can be converted to other output voltages, depending upon the particular components of the electrical system of the device 10. In exemplary aspects, the step-down switching converter 64 can be a TPS62740 switching voltage converter (TEXAS INSTRUMENTS) or other suitable switching converter that provides low quiescent operating current, efficiency, and a small profile/package size.

[0086] In further aspects, the electrical system of the device 10 can comprise a plurality of switches that are controlled by the microcontroller 30 of the data communication unit 20. In use, it is contemplated that a first switch 68 can provide 1.8 V power (or other lower power output, after the step-down conversion) and a second switch 66 can provide power directly from the batteries to various subcircuits. In exemplary aspects, the switch-enabled 1.8 V domain can provide power to the temperature sensor 50 and to the external memory 72. In further aspects, the battery-voltage domain (of 2.5 V - 3.1 V) can provide power to the impedance measurement subcircuit as described further herein.

[0087] The impedance measurement subcircuit can itself be divided into various subportions. First, a low pass filter can receive a signal (e.g., a 5kHz square wave signal) from the microcontroller 30 and transform the signal to a selected output (e.g., a sinusoidal output). At least one current pump 76 (optionally, two current pumps or opamps) can buffer the signal and drive a constant current through the impedance measurement electrodes 14. The impedance measurement circuitry can further comprise a bandpass amplifier/filter 78 (e.g., a 5kHz center frequency bandpass filter) that receives the signal from one of the electrodes. At least one additional pump (e.g., two additional pumps or opamps) can be used to implement a peak detection circuit 80. A final pump/amplifier 82 (e.g., an opamp) can provide the capability of changing amplifier gain.

[0088] A temperature measurement subcircuit can be provided by the temperature sensor 50, which can communicate with the microcontroller 30 (optionally, over an I2C communication interface). In exemplary aspects, the temperature sensor 50 can be powered by the 1.8 V supply domain as discussed above.

[0089] A magnetoresistive-based power latching subcircuit can comprise a magnetoresistive sensor 60 that can be directly powered by the batteries 40. An example of such a magnetoresistive sensor 60 is an RR121-1B13-312 magnetic switch (COTO TECHNOLOGY). An external magnet can be positioned in proximity to the magnetoresistive sensor prior to use of the device. In response to removal of the external magnet, the output voltage level of the magnetoresistive sensor 60 can transition from 0V to the voltage level of the batteries, thereby activating a load switch 62 that allows the battery voltage to connect to the rest of the electrical system, thereby turning on the device. Thus, the device will remain powered off until the magnet is moved away from the device by a sufficient distance to change the output voltage level of the sensor 60. In use, it is contemplated that the inserted/insertable device (e.g., intravaginal ring) 10 can be activated by the user in response to removal of an external magnet that is coupled to the device prior to initial use. In exemplary aspects, the external magnet can be a strong earth magnet (e.g., a high-grade neodymium disc magnet). In further aspects, a package design of the device 10 can be configured to support the external magnet in proximity to the magnetoresistive sensor to supply sufficient magnetic force to prevent transition of the voltage level until the external magnet is removed by the user. It is contemplated that the packaging of the device in this manner can ensure that the device is not drained of battery power prior to use. In exemplary aspects, the magnet can be associated with the product packaging such that removal of the product packaging causes the change in the output voltage of the sensor 60, thereby turning on the device.

[0090] Optionally, as discussed above, the electrical system can further comprise nonvolatile storage memory 72, such as, for example, and without limitation an EEPROM. The memory 72 can optionally operate at 1.8V and communicate with the microcontroller 30. In exemplary aspects, the memory 72 can store measurement data for later transmission to the transceiver 150 and/or another remote device. For example, the memory 72 can store measurements for 24 hours. In exemplary aspects, it is contemplated that the transceiver 150 can transmit all stored measurements at each transmittal of measured data. In some exemplary aspects, the transceiver 150 can be configured to store 14 days, or at least 14 days, of measured data. It is contemplated that the non-volatile memory 72 can be configured to store data even if power is removed from the transceiver.

[0091] In further aspects, the electrical system of the device 10 can comprise a programming interface 70 that supports the downloading of program data to the microcontroller. Additionally, or alternatively, it is contemplated that such program data can be transmitted to the microcontroller through a remote computing device 200 and/or the transceiver 150. Optionally, a trigger signal can cause the insertable device 10 to transmit data to the transceiver. The trigger signal can be, for example, a user opening an application on a smartphone for embodiments in which the transceiver is associated with the smartphone. In this way, the necessary proximity between the insertable device 10 and the transceiver can be ensured, thereby eliminating power use when the transceiver is too far from the insertable device 10.

[0092] In exemplary aspects, the transceiver 150 can be reusable. So, although the device 10 can be replaced at a regular sequence (for example, from month to month), the user can use each replacement device with the same transceiver 150. In some exemplary aspects, it is contemplated that the transceiver 150 can be sold or packaged as a kit that further comprises a plurality of devices 10 (e.g., intravaginal rings).

[0093] In further exemplary aspects, it is contemplated that the electrical system of the device 10 can comprise firmware that has over-the-air transmission/download capabilities. It is contemplated that the firmware can gather impedance and temperature measurements and periodically transmit that stored data to the remote transceiver unit 150. It is further contemplated that the transceiver 150 can comprise firmware with over-the-air transmission/download capabilities.

Data Processing

[0094] In use, the device (e.g., ring) 10 can be manually inserted into the vagina close to the cervix at the end of the menstruation period, which is usually around Day 7 of the menstrual cycle for most users. The device 10 may be worn until the day of ovulation and/or the start of menstruation, which is around Days 14 and 28, respectively, of the menstrual cycle for many users. Cervical mucus changes in response to changes in estrogen, progesterone, and/or other biomarkers and their ratio, which change once implantation (of sperm) has occurred. In one alternative aspect, the device 10 may be used to measure hydration, change in rheological properties, volume, viscosity, and/or conductance of cervical mucus and/or the vaginal environment, and/or early pregnancy factor in cervical mucus to indicate early pregnancy soon after implantation, which may occur anywhere from seven to twelve days after ovulation.

[0095] This device 10 can provide a reliable, convenient and easy-to-use tool for women and couples trying to conceive, prevent pregnancy, or track the menstrual cycle. In use, it is contemplated that the sensor-integrated intravaginal ring can provide real time objective measurements of cervical mucus and the vaginal or cervical environment. In order to increase chances of conceiving or preventing pregnancy, this information can be integrated into a software application to help users track their ovulation window (most fertile days) and menstrual cycle.

[0096] As previously mentioned, the device (e.g., ring) 10 has wireless communication capabilities to present real-time and quantitative measurements of the impedance, resistance, and/or conductance of cervical mucus and/or the vaginal environment. Optionally, such quantitative measurements can be correlated to a percent water content or other easy to understand measurement that is displayed to the user. The impedance, resistance, or conductance data gathered from the probe(s) and or sensor(s) 12 can be collected automatically and wirelessly transmitted to an external software application with an algorithm to chart the user’s menstrual cycle, e.g. typically in a calendar, graph and/or other format(s). Optionally, as further described herein, the data can be transmitted to the transceiver 150, which then transmits the data to a remote device that is configured to execute the external software application. The calendar can be accessed through the user’s smartphone, smart watch, tablet, computer and/or other software application device (i.e., a remote computing device 200). Through monitoring of cervical mucus and the vaginal environment, the disclosed system 100 provides more advanced notice of pending ovulation compared to commonly used fertility monitors. Advance notice can be up to 5 days’ notice (e.g., up to 48, 72, 96, or 120 hours in advance).

[0097] As further disclosed herein, once the device is positioned within a user, the sensors of the device can transmit VER (or other bioelectrical data) and temperature data to the transceiver 150, which will then transmit the data to a remote device (e.g., the user’s remote device) at regular intervals. The user’s application, which is executed by the user’s device, can present the sensor data to the user and notify the user of times of peak fertility. Optionally, the user’s remote device can store the data. Additionally, or alternatively, a remote server or other remote device can store the data, and the data can be retrieved using the user’s remote device. [0098] In exemplary aspects, it is contemplated that the device 10 can be configured to measure and store temperature data at least once per hour. However, any selected frequency of temperature measurement can be used. In further optional aspects, it is contemplated that the device 10 can be configured to measure and store impedance and/or resistance and/or conductance data at least once every six hours. However, any selected frequency of measurement of bioelectrical properties can be used. In still further optional aspects, the device 10 can be configured to transmit the collected data to the transceiver 150 at least once every six hours. However, it is contemplated that any selected frequency of transmission of the collected data to the transceiver can be used. In still further optional aspects, the batteries 40 of the device 10 can have at least 14 days of operational life.

[0099] Optionally, as further disclosed herein, the hydration sensor 12 can be a pair of probes 14 (e.g., electrode probes) installed on one end, two ends, or at any other points throughout the device 10 with an interdigital (e.g., circumferential) spacing of up to 6 mm. Bioelectrical impedance at frequencies of 1-5 kHz has been used to estimate extracellular fluid volume. This device 10 can conduct a frequency of 5 kHz to estimate extracellular fluid volume and analyze this data in an algorithm to evaluate variations in hydration throughout the cycle period. Bioelectric Impedance Analysis (BIA) is the most used and is one of the earliest proposed methods for the estimation of body compartments. BIA, which is based on the inverse proportion between assessed impedance and total body water (TBW), represents the conductive path of the electric current. BIA can estimate water content by using the electrical properties of living tissue. Tissue impedance is proportional to the fluid content when an alternating electrical current is applied and cells acts as capacitors due to the polarity of cell membranes. Cell membrane impedance depends on the frequency of the applied current. At low frequencies, conductance is governed primarily by extracellular water (ECW) as current does not flow through a capacitor but instead flows freely through the ECW. Additionally, conductance and measured impedance of fluids are significantly affected by the concentration of ionic species within a cell. The cyclic variation in the resistance and impedance of cervical mucus can be attributed to the characteristic increase and decrease in the concentration of water and electrolytes such as sodium and chloride in cervical mucus that occur during the menstrual cycle. Specifically, water content of cervical mucus is maximal and thus resistance is minimal at ovulation. The method of measuring the approaching ovulation can be obtained by monitoring changes in cervical mucus secretion and of its impedance by the electrodes as described above. Thus, as measured resistance decreases at or below a threshold value or at or above a threshold rate, the processing circuitry disclosed herein can be configured to provide an output indicative of approaching ovulation.

[0100] Body Area Sensor Networks (BASNs) can include signals collected by sensors which relay them to the sink node and are connected to a central interface device. The communications between sensor nodes usually employ wireless technologies, including, for example Bluetooth or RF transmission protocols. BIA is considered safe. Currents at a frequency of 50 kHz are reported to be unlikely to stimulate electrically excitable tissues, such as nerves or cardiac muscle, and relatively small current magnitudes are involved (<1 mA), less than the threshold of perception. Furthermore, the use of batteries or low-voltage power sources greatly diminishes risks from macroshock.

[0101] In order to begin use of the device, the user will need to successfully complete a series of steps. After removing the device from product packaging, the user will need to activate the battery (or other power source) 40 prior to use. Such activation can occur using conventional magnetic activation processes as further disclosed herein, or by the removal of pull tabs, to permit formation of a closed circuit in the manner known in the art. The user can then hold the device between a thumb and index finger and gently push the sides of the device together to selectively shape the device for insertion into the vagina. The device can then be inserted into the vagina and gently pushed upwards with the index finger until the device reaches the cervix. In use, as further disclosed herein, the device can measure cervical mucus impedance, resistance, or conductance until the device is removed from the cervical environment. Once the user is ready to remove the device, the device can be removed by inserting the thumb and index finger into the vagina and pulling out the device.

[0102] In use, it is contemplated that the device 10 can be worn during or removed prior to intercourse. It is further contemplated that the device 10 can be removed during menstruation and comfortably worn as long as the ring has been inserted far enough and as close to the cervix as possible. Data from the cervical ring can be communicated to a user-friendly software application accessible by remote computing device 200 or website for analysis and interpretation.

[0103] In use, the disclosed transceiver 150 can provide effective and efficient wireless transmission between an inserted medical device (e.g., an intravaginal implant) and an external device. Thus, it is contemplated that the disclosed transceiver 150 can be used with other inserted devices that collect physiological data to be processed external to the user.

[0104] Default manufacturer settings for measuring impedance, resistance or conductance can be at any fixed interval, including every 15 or 30 minutes (resulting in 48-96 readings per day), every 1-2 hours (resulting in 12-24 readings per day), or every 3-6 hours (resulting in 4-8 readings per day). However, the user may or may not adjust these measurement settings to as frequent as every hour to as infrequent as no measurements (e.g. and rely on a manual request to the device, through the wireless receiver and microcontroller, to take a reading). Optionally, the measurement settings can be adjusted to modify the frequency of impedance, resistance or conductance measurements throughout the day and/or to have a variable interval. For example, it is contemplated that impedance, resistance or conductance measurements can be taken at one interval (e.g., every 30 minutes) during certain hours or times of day and taken at a second interval (e.g., every 3 hours during certain hours or times of day). The user may or may not also take a reading at any point they request through the software application interface. Once impedance, resistance or conductance measurements indicate that cervical mucus hydration has exceeded a hydration threshold (e.g., increasing by an absolute value of >2% or reaching >97% hydration), the processor (through the software application) can provide an output to the user (e.g., a visual output on a display) that is indicative of pending ovulation. Optionally, the device 10 can be configured to perform measurements in a continuous, automated fashion at the intervals discussed above. Optionally, the device 10 can permit user-initiated (on-demand) measurements; however, it is understood that the device need not permit such user- initiated measurements.

[0105] Monitoring cervical mucus is a highly effective method, but unlike conventional methods of monitoring cervical mucus, the disclosed device 10 is intended to remain in the vagina for an extended period of time (e.g., 14 days or more) to specifically measure and/or determine the hydration of cervical mucus as one of its fertility biomarkers. The sharp increase in hydration of cervical mucus indicates pending ovulation, and it also provides an optimal environment for sperm penetrability. Additionally, the disclosed system provides women and couples with more advanced notice of pending ovulation, which is crucial for planning around the brief fertile window.

[0106] In use, it is contemplated that users of the device 10 do not need to manually upload or interpret data, as the wireless capabilities of the device allow for automatic communication with cell phones, mobile devices (e.g., tablets, smart watches) and/or other computer applications but may manually input information. The disclosed system provides personalized menstrual cycle information giving women and couples more time to plan and time intercourse as the disclosed system predicts ovulation up to 5 days prior. In contrast, conventional monitoring of other biomarkers like peak LH in the urine or basal body temperature identifies ovulation less than 24 hours in advance as can be seen in FIG. 1.

[0107] Normal internal body temperature is maintained between 36.5-37.5°C (97.7- 99.5°F), while relative humidity inside the body is 100%. Silver oxide, zinc alkaline, and other batteries having good resistance to shock and vibration can be adequate for the disclosed device and system.

[0108] Furthermore, the cervix is a firm, cylindrical structure situated at the lower pole of the uterine corpus. The non-pregnant cervix is about 25 mm in length, with an anteroposterior diameter ranging between 20-25 mm and a transverse diameter of 25-30 mm. Considerable variations may exist depending on age, parity and stage of menstrual cycle. Notably, the main product of the human cervix is cervical mucus, which is manufactured and secreted by the columnar cells in the cervix throughout the menstrual cycle and is regulated by estrogen and progesterone. The cervical mucus that is produced during ovulation has a stretchy and stringy consistency. Following ovulation, mucus reduces in fluidity and volume and becomes viscous. These changes can be correlated with changes in hydration and ion levels. Cervical mucus displays characteristic changes in water and electrolyte content throughout the menstrual cycle. As shown in FIG. 11, sodium content increases and measured electrical resistance of cervical mucus decreases during the 5 days leading up to ovulation (Day 0), which is when luteinizing hormone (LH) also reaches maximal levels. As sodium concentration and/or content increases, the electrical resistance decreases. Thus, it is contemplated that the water content and/or viscosity changes of cervical mucus and/or hydration changes to the cervical and/or vaginal epithelium that occur leading up to ovulation also contribute to this electrical resistance pattern. Accordingly, as the resistance of cervical mucus changes, it is understood that a corresponding change to the hydration of the cervical mucus also occurs. In exemplary aspects, it is contemplated that the disclosed processing circuitry, through a software application, can monitor recorded fertility data to determine when measured resistance, impedance, or conductance exceeds a threshold value that corresponds to a change in cervical mucus hydration that is indicative of fertility.

[0109] As further disclosed herein, the device (e.g., ring) 10 can optionally communicate with the user’s accessory interface using low-data-rate, low-power, and low-complexity short-range radio frequency (RF) transmissions in a wireless personal area network (WPAN).

[0110] The device can be optimized for fertility and menstrual cycle monitoring. A menstrual cycle algorithm programmed into a software application can analyze the data from the vaginal ring and deliver easily understandable information through a user- friendly interface to help the user identify their most fertile days. FIG. 3 illustrates one example algorithm. Hydration of cervical mucus can be monitored once every 6 hours when default settings are used, but could be measured more often or less often depending on how the firmware is programmed. Information on the user’s menstrual cycle can be presented to the user on a display in a format such as a calendar or graph. Hydration of cervical mucus begins to gradually increase at about 5 days prior to ovulation and indicates the concurrent increase in serum estrogen. Optionally, in exemplary aspects, fertile cervical mucus can be identified either when percent hydration increases at a rate greater than 2% within a 24-hour period or when hydration is greater than 97%. The fertile period can end when hydration decreases by greater than 2%, which indicates ovulation has occurred. Optionally, in exemplary aspects, it is contemplated that a decrease in resistance and/or impedance of greater than 5% during a 24-hour period (or other threshold decrease (i. e. , percentage decrease or decrease below a specific resistance or impedance value)) can be indicative of or correspond to a greater than 2% increase in percent hydration, thereby causing the processor, through the software application, to provide an output to a user (optionally, through the display device) indicative of a period of fertility. See Fernando et al. (1987), Fertility and Sterility. 47 (3): 409-415. It is further contemplated that an increase in conductance and/or ion (e.g., sodium) levels above a selected threshold increase (i.e., percentage increase or increase below a specific conductance or ion level) can be indicative of or correspond to a greater than 2% increase in percent hydration, thereby causing the processor, through the software application, to provide an output to a user (optionally, through the display device) indicative of a period of fertility. Although specific threshold values are disclosed herein, it is understood that the precise correlation between the decrease in resistance and/or impedance and the increase in percent hydration can vary significantly depending upon the specific user. Thus, exemplary thresholds that can trigger the signaling of a fertile period can include, for example and without limitation, a decrease in resistance and/or impedance of at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, or at least 10% during a 24-hour period (in comparison to the measured or baseline resistance and/or impedance at the beginning of the 24-hour period). Similarly, it is understood that the precise correlation between the increase in conductance and/or sodium (or other ion) levels and the increase in percent hydration can vary significantly depending upon the specific user. Thus, other exemplary thresholds that can trigger the signaling of a fertile period can include, for example and without limitation, an increase in conductance and/or sodium (or other ion) levels of at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, or at least 10% during a 24-hour period (in comparison to the measured or baseline resistance and/or impedance at the beginning of the 24-hour period). The expected start of the menstrual cycle is about 14 days after ovulation in a 28-day menstrual cycle (period). The specific algorithms disclosed herein are merely exemplary, and it is specifically contemplated that other algorithms may be used. No concurrent use of other intrauterine, vaginal, or cervical devices is needed or recommended when using this device.

[OHl] As a general guideline, the device can be a monthly-use (i.e., useable during a 30-day period), disposable, and highly portable fertility device. The device, in one example, can comprise an electrified annular cervical ring fabricated of medical -grade, flexible, soft, opaque material (e.g., silicone). In exemplary aspects, the internal diameter of the ring can be shaped to match that of the cervix and can have an external diameter that is large enough to wedge the ring against the pelvic floor.

[0112] Hydration can most often be monitored once every 15 or 30 minutes, every 1-2 hours, or every 3-6 hours when default settings are used, but can be measured more often or less often as further disclosed herein. Measurements may or may not be requested by the user through the software application as desired. The device can also detect/indicate real-time cervical mucus hydration changes from baseline.

[0113] In exemplary aspects, a remote device 200 of the system 100 can execute a back-end fertility tracking algorithm that receives and processes the data collected by the device 10 (e.g., intravaginal ring) to determine fertility data that is useful to the user and, optionally, a “companion” of the user. For example, as shown in FIGS. 6-7 and 10, the below block diagram shows an example relationship between a back-end server on which the fertility tracking algorithm resides and the various external devices that can communicate with it. The intra-vaginal ring discussed above can sense the impedance and temperature data and transmit the data to either an intermediary transceiver or a user’s mobile device or computer as further disclosed herein. The intermediary transceiver can transmit the data to the user’s mobile device or computer or directly to the remote server on which the fertility tracking algorithm resides. Regardless of the device from which the remote server receives the impedance and temperature data, the remote server(s) receives that data and generates fertility data relevant to the user and, optionally, stores the user data.

[0114] In exemplary aspects, the fertility algorithm, which can reside on a remote server or within an external device, can process the sensed cervical fluid and temperature data to determine a fertility window that identifies for the user the optimal period of time to engage in intercourse prior to ovulation. The fertility algorithm can identify the woman’s fertile window and transmit an instruction back to the user’s device to be output to the user and optionally a companion.

[0115] In exemplary aspects, the disclosed systems and methods can become smarter and more precise over time as they build on data from individual users and data gleaned from a group of users (which would be anonymous to protect private healthcare data). It is contemplated that the systems and methods can be developed to give real-time fertility (or other physiological) output based on all sources of data, individual tracked data, researched data, trends, group data, and the like. In exemplary aspects, the method can be designed to output any fertility or other data that can be determined based on the measurements of the disclosed device 10. For example, when the device 10 is configured to measure the impedance value and the basal body temperature as disclosed herein, the fertility window can be determined as discussed above. Additionally, or alternatively, in other aspects, the device can include one or more sensors that are capable of sensing parameters that are indicative of one or more of the following physiological characteristics, which can be determined and/or shared with the user: contraception information, pregnancy detection, pregnancy test timing, sleep patterns, pulse, perimenopausal information, infectious disease susceptibility, medical data related to menstrual cycles such as migraine data, labor indicators, metabolic rate, movement or activity tracking, and other physiological parameter tracking that can be based on the data collected by the device. Thus, in exemplary aspects, it is contemplated that the device can comprise any sensor that is configured to detect a parameter within the vagina (or other area within the body) that is indicative of one or more physiological conditions of the user. More generally, it is contemplated that while the device is inserted, the device can provide one or more wireless outputs to a transceiver that are indicative of one or more physiological parameters or conditions of the user.

[0116] In various aspects, it is contemplated that the disclosed system can be configured to make predictions, give estimates, diagnose, track, store, or otherwise manipulate the impedance and temperature data of the system.

User Application

[0117] As further disclosed herein, the disclosed system 100 can comprise a user application that is executed by a remote computing device to provide one or more outputs to a user. The core data the user application outputs is the user’s fertility window. The fertile window can be calculated by the above-described fertility tracking algorithm based on the data measured by the device 10. The user application can be designed to display visual, audible, and/or tactile outputs to the user. In some aspects, the user application can primarily or exclusively provide or display fertility data.

[0118] Optionally, in exemplary aspects, the user application can have a user interface that shows the user the most notable user fertility data, which is the fertility window. The fertility window can optionally be shown in a dial format, noting specific days on which the fertile window begins, how long it will last, and when it ends. The fertility data can also include markers on the dial, such as timing of intercourse, ovulation day, menstruation tracking, and a real-time indicator of the user’s current time in her menstrual cycle.

[0119] The Computing System

[0120] FIG. 10 shows an exemplary computing system 1000 that can be used to receive fertility data and/or control operation of various aspects of the disclosed system 100, including the timing of fertility data measurements and the processing of the fertility data. Computing system 1000 can include remote computing device 200 and a display 1011 in electronic communication with the remote computing device, which can be any conventional computing device, such as, for example and without limitation, a personal computer, computing station (e.g., workstation), portable computer (e.g., laptop, mobile phone, tablet device), smart device (e.g., smartphone, smart watch, activity tracker, smart apparel, smart accessory), security and/or monitoring device, a server, a router, a network computer, a peer device, edge device or other common network node, and so on. In some optional embodiments, a smart phone, tablet, or computer (i.e., a laptop or desktop computer) can comprise both the computing device 200 and the display 1011. Alternatively, it is contemplated that the display 1011 can be provided as a separate component from the computing device 200.

[0121] The remote computing device 200 may comprise one or more processors 1003, a system memory 1012, and a bus 1013 that couples various components of the computing device 200 including the one or more processors 1003 to the system memory 1012. In the case of multiple processors 1003, the computing device 200 may utilize parallel computing.

[0122] The bus 1013 may comprise one or more of several possible types of bus structures, such as a memory bus, memory controller, a peripheral bus, an accelerated graphics port, and a processor or local bus using any of a variety of bus architectures. [0123] The computing device 200 may operate on and/or comprise a variety of computer readable media (e.g., non-transitory). Computer readable media may be any available media that is accessible by the computing device 200 and comprises, non- transitory, volatile and/or non-volatile media, removable and non-removable media. The system memory 1012 has computer readable media in the form of volatile memory, such as random access memory (RAM), and/or non-volatile memory, such as read only memory (ROM). The system memory 1012 may store data such as fertility data 1007 and/or program modules such as operating system 1005 and device/fertility software 1006 that are accessible to and/or are operated on by the one or more processors 1003. [0124] The computing device 200 may also comprise other removable/non-removable, volatile/non-volatile computer storage media. A mass storage device 1004 may provide non-volatile storage of computer code, computer readable instructions, data structures, program modules, and other data for the computing device 200. The mass storage device 1004 may be a hard disk, a removable magnetic disk, a removable optical disk, magnetic cassettes or other magnetic storage devices, flash memory cards, CD-ROM, digital versatile disks (DVD) or other optical storage, random access memories (RAM), read only memories (ROM), electrically erasable programmable read-only memory (EEPROM), and the like.

[0125] Any number of program modules may be stored on the mass storage device 1004. An operating system 1005 and the device/fertility software 1006 may be stored on the mass storage device 1004. One or more of the operating system 1005 and the device/fertility software 1006 (or some combination thereof) may comprise program modules and the device/fertility software 1006. Fertility data 1007 may also be stored on the mass storage device 1004. The fertility data 1007 may be stored in any of one or more databases known in the art. The databases may be centralized or distributed across multiple locations within the network 1015. Thus, it is contemplated that the databases can be provided in a computing device 200 or in a remote computing device that is communicatively coupled to the computing device 200.

[0126] A user may enter commands and information into the computing device 200 via an input device (not shown). Such input devices comprise, but are not limited to, a keyboard, pointing device (e.g., a computer mouse, remote control), a microphone, a joystick, a scanner, tactile input devices such as gloves, and other body coverings, motion sensor, and the like These and other input devices may be connected to the one or more processors 1003 via a human machine interface 1002 that is coupled to the bus 1013, but may be connected by other interface and bus structures, such as a parallel port, game port, an IEEE 1394 Port (also known as a Firewire port), a serial port, network adapter 1008, and/or a universal serial bus (USB).

[0127] A display 1011 may also be connected to the bus 1013 via an interface, such as a display adapter 1009. It is contemplated that the computing device 200 may have more than one display adapter 1009 and the computing device 200 may have more than one display 1011. A display 1011 may be a monitor, an LCD (Liquid Crystal Display), light emitting diode (LED) display, television, smart lens, smart glass, and/ or a projector. In addition to the display 1011, other output peripheral devices may comprise components such as speakers (not shown) and a printer (not shown) which may be connected to the computing device 200 via Input/Output Interface 1010. Any step and/or result of the methods may be output (or caused to be output) in any form to an output device. Such output may be any form of visual representation, including, but not limited to, textual, graphical, animation, audio, tactile, and the like. The display 1011 and computing device 200 may be part of one device, or separate devices.

[0128] Optionally, the computing device 200 can operate in a networked environment using logical connections to one or more remote computing devices 1014a, b,c (i.e., computing devices that are remote from computing device 200). A remote computing device 1014a, b,c may be a personal computer, computing station (e.g., workstation), portable computer (e.g., laptop, mobile phone, tablet device), smart device (e.g., smartphone, smart watch, activity tracker, smart apparel, smart accessory), security and/or monitoring device, a server, a router, a network computer, a peer device, edge device or other common network node, and so on. Logical connections between the computing device 200 and a remote computing device 1014a, b,c may be made via a network 1015, such as a local area network (LAN) and/or a general wide area network (WAN). Optionally, the remote computing device 1014 can comprise fertility software that, when executed, can determine a fertility window or other useful physiological parameters of a user. Such network connections may be through a network adapter 1008. A network adapter 1008 may be implemented in both wired and wireless environments. Such networking environments are conventional and commonplace in dwellings, offices, enterprise-wide computer networks, intranets, and the Internet. In further exemplary aspects, it is contemplated that the computing device 200 can be in communication with the remote computing devices 1014a, b,c through a Cloud-based network. In exemplary aspects, it is contemplated that data from computing device 200 can be transmitted wirelessly to other remote computing devices 1014a, b,c for use by clinicians or other individuals involved with the health care of the device user.

Optionally, in these aspects, the computing device 200 can allow a user to selectively upload fertility data to a Cloud storage unit, from which the remote computing devices 1014a, b,c can securely access a user’s fertility information. In further aspects, it is contemplated that the fertility data can be provided as a report or dataset that can be downloaded by a clinician for use in providing further advice or treatment to the user. [0129] Application programs and other executable program components such as the operating system 1005 are shown herein as discrete blocks, although it is recognized that such programs and components may reside at various times in different storage components of the computing device 200, and are executed by the one or more processors 1003 of the computing device 200. An implementation of the device/fertility software 1006 may be stored on or sent across some form of computer readable media. Any of the disclosed methods may be performed by processor-executable instructions embodied on computer readable media.

Exemplary Aspects

[0130] In view of the described products, systems, and methods and variations thereof, herein below are described certain more particularly described aspects of the invention. These particularly recited aspects should not however be interpreted to have any limiting effect on any different claims containing different or more general teachings described herein, or that the “particular” aspects are somehow limited in some way other than the inherent meanings of the language literally used therein.

[0131] Aspect 1: A physiological monitoring system comprising: a) an intravaginal ring having at least one sensing probe and/or sensor oriented to measure at least one physiological property; b) a data communication unit that is configured to store and transmit collected physiological data that includes the at least one physiological property; c) a power source electrically coupled to the sensing probe(s) and/or sensor(s) and the data communication unit; and d) a transceiver that is configured to wirelessly receive the collected physiological data from the data communication unit, wherein the transceiver is configured to transmit the collected physiological data to a remote computing device.

[0132] Aspect 2: The physiological monitoring system of aspect 1, wherein the data communication unit is configured to wirelessly transmit the collected physiological data to the transceiver using a first transmission protocol, and wherein the transceiver is configured to transmit the collected physiological data to the remote computing device using a second transmission protocol that is different than the first transmission protocol.

[0133] Aspect 3: The physiological monitoring system of aspect 2, wherein the first transmission protocol is a wireless radiofrequency protocol.

[0134] Aspect 4: The physiological monitoring system of aspect 2 or aspect 3, wherein the second transmission protocol has a higher frequency than the first transmission protocol.

[0135] Aspect 5: The physiological monitoring system of any one of aspects 1-4, further comprising the remote computing device.

[0136] Aspect 6: The physiological monitoring system of aspect 5, wherein the remote computing device is selected from the group consisting of a smart phone, a tablet, a smart watch, and a computer. [0137] Aspect 7: The physiological monitoring system of any one of the preceding aspects, wherein the at least one physiological property comprises bioelectrical impedance, resistance or conductance.

[0138] Aspect 8: The physiological monitoring system of any one of the preceding aspects, wherein the intravaginal ring comprises a temperature sensor configured to measure body temperature and communicate the measured body temperature to the data communication unit.

[0139] Aspect 9: The physiological monitoring system of any one of the preceding aspects, wherein the intravaginal ring further comprises an annular body sized to be oriented in a vaginal vault and/or a vaginal environment.

[0140] Aspect 10: The physiological monitoring system of any one of the preceding aspects, wherein the sensing probe(s) and/or sensor(s) comprise a complementary set of electrodes.

[0141] Aspect 11: The physiological monitoring system of any one of the preceding aspects, wherein the data communication unit comprises a wireless transmitter configured to send the collected physiological data to the remote computing device. [0142] Aspect 12: The physiological monitoring system of aspect 7 or aspect 8, wherein the remote computing device has a processor that is configured to execute a tracking application that analyzes and displays fertility estimates based on the fertility data.

[0143] Aspect 13: The physiological monitoring system of aspect 12, wherein the tracking application of the remote computing device is configured to determine hydration based upon the fertility data.

[0144] Aspect 14: The physiological monitoring system of aspect 12 or aspect 13, wherein the tracking application is configured to correlate the measured bioelectrical impedance, resistance, and/or conductance of the collected fertility data with a corresponding hydration of cervical mucus.

[0145] Aspect 15: The physiological monitoring system of any one of the preceding aspects, wherein the sensing probe(s) and/or sensor(s) of the device comprises a sensor configured to measure bioelectrical resistance.

[0146] Aspect 16: The physiological monitoring system of any one of the preceding aspects, wherein the sensing probe(s) and/or sensor(s) of the device comprises a sensor configured to measure bioelectrical conductance. [0147] Aspect 17: The physiological monitoring system of any one of the preceding aspects, wherein the probe(s) and/or sensor(s) of the device comprises a sensor configured to measure bioelectrical impedance.

[0148] Aspect 18: The physiological monitoring system of aspect 11, wherein the wireless transmitter of the data communication unit is communicatively coupled to an antenna that extends circumferentially within an interior of the intravaginal ring.

[0149] Aspect 19: The physiological monitoring system of any one of the preceding aspects, wherein the transceiver is physically coupled to a mobile phone.

[0150] Aspect 20: A method comprising: e) using the system of any one of the preceding aspects;

1) orienting the intravaginal ring such that the at least one sensing probe(s) and/or sensor(s) is in fluid communication with cervical fluid of a subject; and g) using the data communication unit of the device to transmit physiological data of the subject to the transceiver; and h) using the transceiver to transmit the physiological data of the subject to the remote computing device.

[0151] Aspect 21 : The method of aspect 20, further comprising, using a processor of the remote computing device to analyze and display fertility estimates based on the physiological data.

[0152] Aspect 22: The method of aspect 21, wherein the processor of the remote computing device is configured to determine hydration based upon the physiological data.

[0153] Aspect 23: A physiological monitoring system comprising; i) an insertable device having at least one sensing probe and/or sensor oriented to measure at least one physiological property; j) a data communication unit that is configured to store and transmit collected physiological data that includes the at least one physiological property; k) a power source electrically coupled to the sensing probe(s) and/or sensor(s) and the data communication unit; and 1) a transceiver that is configured to wirelessly receive the collected physiological data from the data communication unit using a first transmission protocol, wherein the transceiver is configured to transmit the collected physiological data to a remote computing device using a second transmission protocol that is different than the first transmission protocol.

[0154] Aspect 24: The physiological monitoring system of aspect 23, wherein the first transmission protocol is a wireless radiofrequency protocol.

[0155] Aspect 25: The physiological monitoring system of aspect 23 or aspect 24, wherein the second transmission protocol is a Bluetooth protocol.

[0156] Aspect 26: The physiological monitoring system of any one of aspects 23-25, further comprising the remote computing device.

[0157] Aspect 27: The physiological monitoring system of aspect 26, wherein the remote computing device is selected from the group consisting of a smart phone, a tablet, a smart watch, and a computer.

[0158] Aspect 28: The physiological monitoring system of any one of aspects 23-27, wherein the transceiver is physically coupled to a mobile phone.

[0159] The foregoing detailed description describes the invention with reference to specific exemplary embodiments. However, it can be appreciated that various modifications and changes can be made without departing from the scope of the present invention as set forth in the appended claims. The detailed description and accompanying drawings are to be regarded as merely illustrative, rather than as restrictive, and all such modifications or changes, if any, are intended to fall within the scope of the present invention as described and set forth herein.

Claims

47

What is claimed is:

1. A physiological monitoring system comprising: a) an intravaginal ring having at least one sensing probe and/or sensor oriented to measure at least one physiological property; b) a data communication unit that is configured to store and transmit collected physiological data that includes the at least one physiological property; c) a power source electrically coupled to the sensing probe(s) and/or sensor(s) and the data communication unit; and d) a transceiver that is configured to wirelessly receive the collected physiological data from the data communication unit, wherein the transceiver is configured to transmit the collected physiological data to a remote computing device.

2. The physiological monitoring system of claim 1, wherein the data communication unit is configured to wirelessly transmit the collected physiological data to the transceiver using a first transmission protocol, and wherein the transceiver is configured to transmit the collected physiological data to the remote computing device using a second transmission protocol that is different than the first transmission protocol.

3. The physiological monitoring system of claim 2, wherein the first transmission protocol is a wireless radiofrequency protocol.

4. The physiological monitoring system of claim 2, wherein the second transmission protocol has a higher frequency than the first transmission protocol.

5. The physiological monitoring system of claim 1, further comprising the remote computing device.

6. The physiological monitoring system of claim 5, wherein the remote computing device is selected from the group consisting of a smart phone, a tablet, a smart watch, and a computer. 48 The physiological monitoring system of claim 1, wherein the at least one physiological property comprises bioelectrical impedance, resistance or conductance. The physiological monitoring system of claim 1, wherein the intravaginal ring comprises a temperature sensor configured to measure body temperature and communicate the measured body temperature to the data communication unit. The physiological monitoring system of claim 1, wherein the intravaginal ring further comprises an annular body sized to be oriented in a vaginal vault and/or a vaginal environment. The physiological monitoring system of claim 1, wherein the sensing probe(s) and/or sensor(s) comprise a complementary set of electrodes. The physiological monitoring system of claim 1, wherein the data communication unit comprises a wireless transmitter configured to send the collected physiological data to the remote computing device. The physiological monitoring system of claim 7, wherein the remote computing device has a processor that is configured to execute a tracking application that analyzes and displays fertility estimates based on the fertility data. The physiological monitoring system of claim 12, wherein the tracking application of the remote computing device is configured to determine hydration based upon the fertility data. The physiological monitoring system of claim 12, wherein the tracking application is configured to correlate the measured bioelectrical impedance, resistance, and/or conductance of the collected fertility data with a corresponding hydration of cervical mucus. The physiological monitoring system of claim 1, wherein the sensing probe(s) and/or sensor(s) of the device comprises a sensor configured to measure bioelectrical resistance. The physiological monitoring system of claim 1, wherein the sensing probe(s) and/or sensor(s) of the device comprises a sensor configured to measure bioelectrical conductance. 49 The physiological monitoring system of claim 1, wherein the probe(s) and/or sensor(s) of the device comprises a sensor configured to measure bioelectrical impedance. The physiological monitoring system of claim 11, wherein the wireless transmitter of the data communication unit is communicatively coupled to an antenna that extends circumferentially within an interior of the intravaginal ring. The physiological monitoring system of claim 1, wherein the transceiver is physically coupled to a mobile phone. A method comprising: a) using the system of any one of the preceding claims; b) orienting the intravaginal ring such that the at least one sensing probe(s) and/or sensor(s) is in fluid communication with cervical fluid of a subject; and c) using the data communication unit of the device to transmit physiological data of the subject to the transceiver; and d) using the transceiver to transmit the physiological data of the subject to the remote computing device. The method of claim 20, further comprising using a processor of the remote computing device to analyze and display fertility estimates based on the physiological data. The method of claim 21, wherein the processor of the remote computing device is configured to determine hydration based upon the physiological data. A physiological monitoring system comprising; a) an insertable device having at least one sensing probe and/or sensor oriented to measure at least one physiological property; b) a data communication unit that is configured to store and transmit collected physiological data that includes the at least one physiological property; c) a power source electrically coupled to the sensing probe(s) and/or sensor(s) and the data communication unit; and 50 d) a transceiver that is configured to wirelessly receive the collected physiological data from the data communication unit using a first transmission protocol, wherein the transceiver is configured to transmit the collected physiological data to a remote computing device using a second transmission protocol that is different than the first transmission protocol.

24. The physiological monitoring system of claim 23, wherein the first transmission protocol is a wireless radiofrequency protocol.

25. The physiological monitoring system of claim 24, wherein the second transmission protocol is a Bluetooth protocol.

26. The physiological monitoring system of claim 23, further comprising the remote computing device.

27. The physiological monitoring system of claim 26, wherein the remote computing device is selected from the group consisting of a smart phone, a tablet, a smart watch, and a computer.

28. The physiological monitoring system of any one of claims 23-27, wherein the transceiver is physically coupled to a mobile phone.