EP2375992A1

EP2375992A1 - Device for detecting ovulation in female mammals, and method for detecting ovulation in female mammals using such a device

Info

Publication number: EP2375992A1
Application number: EP09768144A
Authority: EP
Inventors: Régine VINCI; Arnaud Vinci; Pascal Audoin
Original assignee: Effiance
Current assignee: Effiance
Priority date: 2008-11-05
Filing date: 2009-11-04
Publication date: 2011-10-19
Also published as: WO2010052428A1; FR2937852B1; FR2937852A1

Abstract

The invention relates to a device (1) for detecting ovulation in female mammals including at least one sensor (10) suitable for taking an in vivo measurement representing a chemical property of the cervical mucus, said property being representative of ovulation. The invention includes a second sensor (11) suitable for taking an in vivo measurement representing a physical property of the cervical mucus, said property being representative of ovulation. The property measured by means of the second sensor is the turbidity of the cervical mucus.

Description

DEVICE FOR DETECTING OVULATION IN A MAMMAL

FEMALE AND METHOD FOR DETECTING OVULATION IN A

FEMALE MAMMAL WITH THE USE OF SUCH A DEVICE

The invention relates to a device for detecting ovulation in a female mammal, and to a method for detecting ovulation in a female mammal using this device. Subsequently, by way of example, the detection device and the detection method are described in the case of the detection of ovulation in a woman. Ovulation is under the influence of hormones produced during the entire period during which a woman or a female mammal can procreate. These hormones, such as luteinizing hormone (LH) or follicle stimulating hormone (FSH), are secreted by the pituitary gland. These hormones have secretion peaks depending on the time of the cycle and cause the follicle to mature. This maturation is followed by the release of the egg. In other words, these hormones induce the release of the egg so that it is fertilized.

The detection of ovulation is of particular importance in determining either the fertility periods of the female or female mammal, or for indirect use as a contraceptive method.

It is possible to detect ovulation by ultrasound. This method, although very reliable, is extremely restrictive and can not be used in a private setting. There are also methods based on assays of various compounds present in saliva, methods that are unreliable. Another method is based on the evolution of the temperature curve. It is also unreliable since it depends on the physical and biological state of the female or female mammal, a feverish state that can distort the measurements. Moreover, because of the date of the temperature change, this method can only be used for contraceptive purposes. Indeed, the oocyte has a lifespan of about 8 hours and the temperature method provides a posteriori indication of ovulation. Other methods are based on blood or urine tests. These various methods are relatively cumbersome, restrictive and difficult to apply, for example for a woman, in a private setting.

It is therefore interesting to detect ovulation for a female mammal or a woman in a simple, fast, reliable and can be used in a private setting without requiring a hospital or medical environment.

WO-A-2007077405 discloses a probe measuring different parameters in the genital apparatus of a female mammal. These parameters are, in particular, the temperature and the concentration of hormones, such as progesterone. This probe is used with data storage and display devices, in particular on a remote display such as a computer screen. Such a device is particularly suitable for monitoring fertility periods in domestic animals such as cattle. The monitoring of the temperature, as indicated previously, is not satisfactory, in terms of reliability, to validate a detection of ovulation. There is also known a device marketed under the name of "DRAMINSKI electronic ovulation detector" allowing, in canines, to measure the resistivity of the vaginal mucosa during an ovulation cycle. Besides this method is also particularly suitable for animals, it is based on an electrical measurement dependent on the physiological state of the mucosa of the genital tract and not only the moment of the ovarian cycle.

Also known from WO-A-0074570, a device for measuring a physical characteristic of cervical mucus, the latter having variable physical characteristics during the ovarian cycle. In particular, this device combines a measurement, for example of temperature, with a measurement, in vitro, of the consistency of cervical mucus, that is to say a measurement of its viscosity. For this, the device requires taking samples of cervical mucus. Another physical parameter, namely the turbidity of the mucus, can also be taken into account by this device. The latter is relatively complex and does not allow a series of in vivo measurements, which limits its use in a private setting and outside a medical or biological environment. US-A-5,109,865 discloses a device for performing a representative measurement of the sodium ion concentration by a measurement of the impedance at the level of the vaginal mucosa.

WO-A-02/087446 discloses a method of determining ovulation by measuring the concentration of sodium ions in the cervical mucus. This measurement is performed by a conductance measurement associated with a measurement of pH or temperature.

US-A-5,240,010 discloses a method for measuring impedance in the cervical mucus, performed simultaneously with a temperature measurement. The invention proposes a probe making it possible to detect, by a series of in vivo measurements, the ovulation periods with an increased reliability compared to the existing one and easily usable in a private setting and based on measurements of two characteristics, a physical and chemical, representative of ovulation. For this purpose, the subject of the invention is a device for detecting ovulation in a female mammal, comprising at least one sensor, adapted to perform, in vivo, a measurement representative of a chemical characteristic of the cervical mucus, this characteristic being representative of ovulation, characterized in that it comprises a second sensor, adapted to perform, in vivo, a measurement representative of a physical characteristic of the cervical mucus, this characteristic being representative of ovulation and in that that the physical characteristic measured with the aid of the second sensor is the turbidity of the cervical mucus.

With such a device is measured, in vivo and indirectly on a given biological fluid, two characteristics, chemical and physical, reflecting ovulation.

According to advantageous but non-mandatory aspects of the invention, such a device may incorporate one or more of the following features:

- The chemical characteristic measured indirectly is the concentration of sodium chloride in the cervical mucus. At least one of the sensors is located at the end of a probe suitable for use in in vivo measurement.

The first sensor comprises an ion sensor, of the ISFET type.

The first sensor comprises two electrodes placed at one end of the probe.

- The end of the probe is configured as a fork.

- The forked end of the probe comprises at least two teeth equipped on at least their outer faces, the first sensor and on their internal faces, the second sensor. The second sensor comprises a transmitting diode and a receiving photodiode placed on the internal faces opposite the forked end of the probe.

- The values measured by at least one of the two sensors are displayed by switching on or blinking at least one LED on a display, the number of LEDs lit depending on the measured values of the chemical and / or physical characteristics.

- The probe is connected to a data storage module and / or a data processing module.

The invention also relates to a method for detecting ovulation in a female mammal using an ovulation detection device according to one of the preceding characteristics, characterized in that it comprises steps comprising at :

- a) introducing into the vagina, closer to the cervix, a probe constituting the device, - b) perform, at a given time, at least one representative measurement of a chemical characteristic of the cervical mucus,

c) comparing the value obtained with a predetermined value,

- d) deduce the date of ovulation.

According to advantageous but non-obligatory aspects of the invention, such a method may incorporate one or more of the following steps:

before step c), during step b), a measurement representative of a physical characteristic of the cervical mucus is also performed. during step c), the predetermined value is obtained either by learning, from the measurements previously made, or from a predefined value.

The invention will be better understood and other advantages thereof will appear more clearly on reading the following description of two embodiments of a device for detecting ovulation in a female mammal according to the invention. invention, given solely by way of example and with reference to the accompanying drawings in which:

FIG. 1 is a perspective view of a device according to a first embodiment of the invention,

FIG. 2 is a view similar to FIG. 1 of a device according to a second embodiment of the invention and

FIG. 3 is a view, on a larger scale, along the arrow III, of the end of the device of FIG. 2. As indicated above, ovulation is accompanied by a certain number of physiological modifications of which, in particular , a modification of the cervical mucus that is present in the genital apparatus of a female mammal. The cervical mucus sees its amount increase very strongly, about 10 to 30 times the normal amount in a woman, according to the Merck manual of diagnosis and therapy, (3 ^rd French edition, www.msdo.medcost.fr), and that of rapid way, globally concomitantly with the increase of the secretion of certain hormones. Cervical mucus has the usual function of ensuring the bacteriological safety of the uterus by forming a stopper avoiding microbial contamination. It also plays a dual role in the fertilization process. First, it promotes the passage of sperm to the egg. It also provides a role of temporary storage and filtration of these by blocking the passage of "unfit" sperm.

For this, during ovulation, in addition to a very large amount of secreted mucus, the composition and structure thereof vary. In particular, according to J. C. CZYBA and A. MONTELLA (human reproductive biology, SAURAMPS MEDICAL edition, 1993), there is a very significant increase in sodium chloride content in the mucus. It should be noted that cervical mucus is a basic liquid. This can be demonstrated by microscopic observation in which a fern leaf crystallization of the mucus is noted, crystallization characteristic of a significant presence of sodium chloride in a liquid. This concentration can reach about 1%. Such saline concentration promotes sperm survival and is accompanied by a significant variation in the turbidity of the cervical mucus, which becomes clear. This clarity reflects a looser structure of the mucus. This occurs before ovulation, as a viscous fluid, protein structure net, tight mesh. A looser structure promotes the passage of spermatozoa. We thus have, by the sodium chloride concentration and the turbidity, two characteristics, one chemical, the other physical, both relating to the same phenomenon interesting the same biological fluid, this phenomenon being representative of the ovulation because concomitant with the latter.

It is therefore interesting to measure at least one of these two characteristics or, at the very least, to appreciate the variations as a function of time.

Cervical mucus is secreted regularly by the cervix over a period of time. It is therefore possible to measure at least one of these two characteristics. If one considers measuring both characteristics, it is interesting, to corroborate the measurements, to perform them in the same zone. For this, it is necessary to use two sensors located in the vicinity of one another. In addition, the measurements must be made almost simultaneously, otherwise they will not be representative of the characteristics of a defined area.

In all cases, that one or two characteristics are measured, it is advisable to use a device whose dimensions are sufficiently small for a comfortable use, from the anatomical point of view, and to avoid any contact of the sensor (s) ) with the vaginal wall, which could distort the measurements. It is also appropriate that the dimensions of this probe are not too low. In this case, we would have a one-off measure that would not be representative of what is happening at the level of the entire genital tract. Indeed, it is desired to measure at least one of these characteristics at a given point, so that the measurement is representative of the average composition of the cervical mucus. In the embodiment shown in Figure 1 schematically and simplified, a device 1 comprises a probe 2. The probe 2 has a mean diameter D close to 8 millimeters and a useful length L of about 120 millimeters.

In a non-illustrated embodiment, the body of the probe has dimensions such that it bears against the vaginal wall, while the end of the probe has small dimensions, thus avoiding contact with the sensor ( s) with the vaginal wall.

The device 1 comprises a probe 2, as shown in Figure 1, schematically and simplified. This device 1 comprises a handle 3, in the example it is shown in the form of a cylindrical handle 3. Alternatively, the handle 3 can adopt other shapes. This handle 3 is provided at one end with a button 4 for starting. Advantageously, there is an automatic shutdown of the device when the measurements have been made, with emission of a signal, sound and / or light. On this handle 3, a display device 5 by light emitting diodes (LED) 6 is provided. In this case, it is about ten diodes 6, same color or different colors. Alternatively, the number of diodes is different, i.e., less than or greater than ten. Depending on the values measured by the sensor (s), one or more LEDs 6 permanently light up or flash. The user can thus easily report, for example, on a calendar, in the case of a daily measurement, the number of diodes 6 lit which will enable him to detect a sudden change in the characteristics of the cervical mucus. For example, the device 2 can be calibrated so that all the diodes 6 are lit only when measuring a NaCl concentration at a predefined value. Such a predefined value corresponds, for example, to an average value obtained over several tests carried out with several women and incremented by a safety coefficient allowing determine a predefined value for a given population. In this case, we do not take into account the physiological particularities of each woman.

As a variant, in a preferred embodiment, the ignition of a certain number of diodes 6 is computationally computerized, by learning. For example, the ten diodes 6 light up when the measurement is equal to x times the measurement obtained on average during the previous n days, for measurements made in the same woman. For this purpose the device 1 is equipped with a data storage module and / or a data processing module, not illustrated. These modules are known per se and they are advantageously integrated, with a source of energy, in the handle 3. In a variant, these modules are offset with respect to the device 1. As a variant, only certain diodes 6, of a given color, light up when the predetermined value is reached.

In an embodiment not shown, the light display is accompanied by sound information. In a not shown embodiment, graphic information is associated with at least one, advantageously with each diode. This is, for example, a number, a letter or any other code. This information is taken into account by the user, instead of the number of lit diodes. As a variant, the display is remote for reading on a remote display, for example a computer screen which receives the information via a link, wired or wireless, which makes it possible to store and / or edit the data, a posteriori, and independently of the device 1.

In an embodiment not illustrated, the display is made in sound form.

The handle 3 is located at the end of the probe 2. This is, in the example, shown in a cylindrical tubular form. Alternatively, it may be of another form, closer to the anatomical constraints.

A collar, represented in the form of a disc 7, is mounted on the probe 2. The disc 7 is provided with a central orifice 8 allowing the insertion of the probe 2 into the disc 7. This is adapted for be moved in translation along the probe 1, while being easy to block, in a given position, by For example, the disk 7 is advantageously mounted hard on the probe 2.

This disc or flange 7 forms an adjustable stop preventing introduction beyond a certain position of the probe 2 in the vaginal cavity.

In the first embodiment illustrated in FIG. 1, the end 9 of the probe 2 is rounded and provided on its circular surface with two electrodes.

16,17 annular and parallel, with an insulating zone 18 between them. These electrodes are, for example, made of silver, titanium or a material suitable for use on a living being.

Such electrodes are known per se and form a first sensor 10 capable of making an electrical measurement.

The electrodes 16, 17 make it possible to measure a quantity related to the concentration of sodium chloride. Indeed, when this concentration increases, the mucus then behaving like an electrolyte, it is possible to detect an electromotive force of an electrochemical cell, the electrodes

16,17 behaving like an anode and a cathode. It is also possible, using an energy source located, for example, in the handle

3, passing a current of constant intensity through the electrodes 16, 17 and measuring a potential difference therebetween. The intensity of a current can also be measured when a constant voltage is applied between the electrodes 16, 17. In all cases, these three types of measurements reflect a change in the concentration of sodium chloride in the cervical mucus.

In another embodiment that is not illustrated, the end 9 of the probe 2 is equipped with chemical ion micro-sensors, for example of the EIS type.

(Electrolyte Insulator Semiconductor) or ISFET (Selective Ion Field Effect

Transistor). These micro-sensors measure, indirectly, an ionic concentration, for example Na + in the cervical mucus.

Such a measure depends only on the increase in the concentration of sodium chloride in the cervical mucus, an increase reflecting ovulation. This eliminates the measurement of a parameter that can vary independently of ovulation, which is the case, for example, with the measurement of the resistivity vaginal mucosa that may be influenced by anatomical and / or physiological parameters.

In a second embodiment illustrated in FIGS. 2 and 3, the free end 9 'of the probe is provided with two sensors 10' and 1 1 adapted to provide, respectively, a measurement of a chemical characteristic and a measurement of a physical characteristic of cervical mucus. For this, the end 9 'has, advantageously, a fork shape with at least two teeth 12, 13. Alternatively, the number of teeth is greater than two. On the end 9 ', that is to say on the inner faces 14, 14' and outer 15, 15 'of the teeth 12, 13, electrodes 16', 17 'are arranged. These electrodes 16 ', 17' are separated by an insulating zone 18 '. The assembly defines a first sensor 10 '. In a non-illustrated embodiment, the electrodes 16 ', 17' are arranged only on the outer faces 15, 15 'of the teeth 12, 13.

The internal faces 14, 14 'of the teeth 12, 13 comprise, facing one another, for one 14, an emitting diode 19 and, for the other 14', a receiving photodiode 20 or, variant, a phototransistor. The assembly, diode 19 and photodiode 20 form a second sensor 1 1. A flow of light passing through the cervical mucus present between the teeth 12, 13 when the probe 2 'is in measurement position is thus measured. A provision, at the same level of the probe 2 ', sensors 10' and 1 1, that is to say on one end 9 'of the probe, allows to validate, reciprocally, the two measurements since they relate to the same area. Measurements are performed in vivo and concomitantly on the physical and chemical characteristics of the cervical mucus. This limits the appearance of artifacts.

Advantageously, the end 9, 9 'of the probe is removable. Thus, it is easy to change the sensor (s) or perform cleaning operations when the end 9, 9 'is not suitable for a single use.

Hereinafter, a method of detecting ovulation in a female using a device 1, 1 'as described above is described, it being understood that such a method is also applicable in a female mammal. The user of such a device 1, 1 'performs at least once a day when she estimates that she is close to the ovulation period, a measure and this over several days so as to obtain a series of measures.

In a first step, the probe 2, 2 'is introduced into the vagina, closest to the cervix, so that the end 9, 9' bathes in the cervical mucus. For this, the position of the stop 7 is pre-set. Then, the sensor (s) 10, 10 ', 1 1 is or are turned on by operation of the button 4. The collected data are processed by the data processing module. As a variant, they are stored, before or after processing, on the data storage module. Depending on the measurement, a number of LEDs are lit. This number, or the associated graphical information, is noted. It corresponds to a measurement at time t. Advantageously, this number is plotted on a calendar as being the value measured at time t.

These steps are repeated later, at a time t + n. The value obtained at time t + n is also reported on the calendar and compared with the value obtained at time t. The measurements are regularly carried out until a significant and significant variation in the number of LEDs lit is detected between a time t '+ n and a time t'. Such variation reflects a large and rapid change in NaCl concentration and / or turbidity of the cervical mucus. In other words, this variation provides an indication of the imminence of ovulation. The user, by comparison with several series of measurements made over several ovulatory periods, can deduce, from time t '+ n, an ovulation date.

With a device 1, equipped with at least one sensor 10, 10 ', 1 1 is obtained information relating to the imminence or absence of ovulation. Indeed, in trials involving 4 women, 6 measurements were made using the sensor 10 over a dozen cycles. Measurements indicated ovulation within 12 hours. These measurements, made every 24 hours, were based on a measurement of a current, a voltage being applied between the electrodes.

For example, in one of the four women, a three- ^fold variation was observed between the measurements taken between the 2 ^nd and the 3 ^rd day. after the rules. Ovulation within 12 hours was confirmed by ultrasound. Similarly, all the data collected during the tests performed on the four women were validated by ultrasound.

Alternatively, other physical characteristics of the cervical mucus can be measured. It is, for example, to appreciate the structural change of this one by the variation of the propagation not of a luminous electromagnetic radiation in the mucus, but by the speed of propagation, of a sound wave. This speed varies in fact according to the nature of the medium through, so depending on the structure and / or the viscosity of the cervical mucus. Such a device 1, 1 'is easily used privately by a woman and a double measurement, on the same fluid, allows increased reliability compared to known devices, while allowing optimal prediction of the ovulation period. Such a device is particularly intended for human use, nevertheless it is easily applicable to any female mammal.

Claims

1. Device (1; 1 ') for detecting ovulation in a female mammal, comprising at least one sensor (10; 10') adapted to perform, in vivo, a measurement representative of a chemical characteristic of the cervical mucus, this characteristic being representative of ovulation, characterized in that it comprises a second sensor (1 1), adapted to perform, in vivo, a measurement representative of a physical characteristic of the cervical mucus, this characteristic being representative of the ovulation and in that the physical characteristic measured with the aid of the second sensor (1 1) is the turbidity of the cervical mucus.

2. Device according to claim 1, characterized in that the indirectly measured chemical characteristic is the concentration of sodium chloride in the cervical mucus.

3. Device according to one of the preceding claims, characterized in that at least one of the sensors (10; 10 ', 1 1) is located at the end (9; 9') of a probe (2; ') suitable for use in vivo measurement.

4. Device according to claim 3, characterized in that the first sensor comprises an ion sensor, ISFET type.

5. Device according to claim 3, characterized in that the first sensor (10; 10 ') comprises two electrodes (16, 17; 16', 17 ') placed at one end (9; 9') of the probe (1 1 ').

6. Device according to claim 3, characterized in that the end (9 ') is configured fork.

7. Device according to claim 6, characterized in that the forked end (9 ') of the probe (2') comprises at least two teeth (12, 13) equipped on at least their outer faces (15, 15 '). ) of the first sensor (10 ') and, on their inner faces (14, 14'), the second sensor (1 1).

8. Device according to claim 7, characterized in that the second sensor (1 1) comprises an emitter diode (19) and a receiving photodiode (20) placed on the internal faces (14, 14 ') facing the forked end (9') of the probe (2 ').

9. Device according to one of the preceding claims, characterized in that the values measured by at least one of the two sensors (10; 10 ', 1 1), are displayed by ignition or blinking of at least one LED (6) on a display (5), the number of LEDs (6) lit depends on the measured values of the chemical and / or physical characteristics.

10. Device according to one of the preceding claims, characterized in that the probe (2; 2 ') is connected to a data storage module and / or to a data processing module.

1 1. Method for detecting ovulation in a female mammal using an ovulation detection device (1; 1 ') according to one of the preceding claims, characterized in that it comprises steps comprising to: - a) introducing into the vagina, closer to the cervix, a probe (2, 2 ') constituting the device (1, 1'), b) performing, at a given instant, at least one representative measure of a chemical characteristic of the cervical mucus, c) comparing the value obtained with a predetermined value, - d) deducing the date of ovulation.

12. The method of claim 1 1, characterized in that, before step c), during step b), a measurement representative of a physical characteristic of the cervical mucus is also performed.

13. Method according to one of claims 1 1 or 12, characterized in that, in step c), the predetermined value is obtained either by learning, from the measurements previously made, or from a value predefined.