PARAMETERS

Technical Field

The present invention relates to a device for the measurement of endouterine parameters.

Background Art

It is well known that suboptimal chemical and physical factors in a patient’s uterus can impair gamete and embryo development, leading to a profound impact on their future development (Wale PL et ah, Hum Reprod Update, 2016, 22: 2-22).

The exact composition, variation and interdependent relationships of dissolved oxygen, pH and temperature within the female reproductive tract have only been partially investigated to date. Thus, the relevant concentrations of the various components and pH in commercially available culture media as well as the oxygen concentration and temperature currently used in incubators are very often based on extrapolated data mainly obtained from animal studies.

High, non-physiological oxygen concentrations may be negatively impacted by oxidative stress, thus contributing to defective embryo development with higher fragmentation rates.

At the same time, too low oxygen levels can impair embryogenesis, a process that involves many oxidative metabolic processes.

Other biophysical parameters, which might interact with dissolved oxygen levels, are also of primary importance in the embryo culture environment. pH is an important parameter for sperm binding and motility, ovocyte maturation and embryo development. In vitro, biological pH buffers can be used to be introduced into embryo culture media to help stabilize pH and minimize deleterious intracellular changes resulting from pH fluctuations in pre implantation human embryos.

However, the in vivo regulation of pH in luminal fluids within the reproductive tract is more complex. Clinically, in humans, abnormal acidity or alkalinity conditions within the reproductive tract are known to have an impact on reproduction, although attempts to address this issue have been of limited success to date.

As far as temperature is concerned, it is recognized that extreme variation in body temperature elicits an immune response, orchestrated through molecular networks of cytokines and microRNAs.

While embryos can demonstrate some degree of resilience to small changes in temperature, prolonged exposure in the culture to temperatures other than the optimal 37 degrees may reduce fertilization, implantation, and completed pregnancy rates.

Considering, therefore, the relevant role of the above mentioned chemical- physical parameters in the endouterine environment in order to obtain an efficient human reproduction, there is a need to develop an adequate technology which can allow the in vivo measurement of these parameters.

Description of the Invention

The main aim of the present invention is to devise a device for the measurement of endouterine parameters which allows effective and accurate detection of chemical and physical parameters inside a uterus.

Another object of the present invention is to devise a device for the measurement of endouterine parameters which allows for practical, in vivo detection of endouterine chemical-physical parameters.

A further object of the present invention is to devise a device for the measurement of endouterine parameters which allows rapid measurement and which is well tolerated by the patient during use.

Another object of the present invention is to devise a device for the measurement of endouterine parameters which allows overcoming the aforementioned drawbacks of the prior art within a simple, rational, easy and effective to use as well as affordable solution.

The aforementioned objects are achieved by the present device for the measurement of endouterine parameters having the characteristics of claim 1. Brief Description of the Drawings

Other characteristics and advantages of the present invention will become more apparent from the description of a preferred, but not exclusive, embodiment of a device for the measurement of endouterine parameters, illustrated by way of an indicative, yet non-limiting example, in the accompanying tables of drawings wherein:

Figure 1 is a schematic representation of the device for the measurement of endouterine parameters according to the invention.

Embodiments of the Invention

With particular reference to this figure, reference numeral 1 globally indicates a device for the measurement of endouterine parameters.

The device 1 according to the invention comprises: at least one catheter 2 provided with an ending portion 3 adapted to be inserted inside the uterus of a patient; and sensor means 7 associated with the ending portion 3 and configured to detect at least two characteristic chemical-physical parameters of the uterus selected from a group comprising: pH, tissue oxygenation and temperature. The catheter 2 extends along a longitudinal direction D and has a first ending portion 3 adapted to be inserted in the uterus and a second ending portion 4 adapted to be grasped by an operator for the placement of the device itself. Specifically, the device 1 is introduced into the uterine cavity through the cervical canal.

The catheter 2 is made of a flexible material.

In more detail, the catheter 2 is made of a polymeric material. For example, the catheter 2 may be made of a material selected from the list comprising: latex, silicone, fluorinated ethylene propylene (FEP), polyvinyl chloride (PVC), polyurethane (PU).

Conveniently, the catheter 2 has an outer diameter comprised between 2.3 mm and 2.7 mm.

Preferably, the catheter 2 has an outer diameter comprised between 2.45 mm and 2.55 mm.

The device 1 also comprises a stiletto element 5 internally associated with the catheter 2 and adapted to promote the insertion of the ending portion 3 inside the uterus.

The stiletto element 5 is of the type of a rod made of a rigid material which extends along the entire length of the catheter 2.

In more detail, the stiletto element 5 protrudes from the catheter 2 through the second ending portion 4 to allow it to be easily gripped.

The stiletto element 5 has a diameter comprised between 1.0 mm and 1.4 mm. Preferably, the stiletto element 5 has a diameter comprised between 1.15 mm and 1.25 mm.

The device 1 comprises at least one supporting body 6 of the sensor means 7. The supporting body 6 is arranged internally to the catheter 2.

In more detail, the supporting body 6 is arranged at the point where the first ending portion 3 is located.

The supporting body 6 has a substantially cylindrical conformation and has a diameter comprised between 1.4 mm and 1.6 mm.

Preferably, the supporting body 6 has a diameter comprised between 1.5 mm and 1.55 mm.

Advantageously, the sensor means 7 comprise at least one pH sensor 8 adapted to detect at least one pH parameter.

The pH level inside the human body represents the amount of free protons inside aqueous body fluids. It is defined as the negative log of hydrogen ion activity. The pH in the female reproductive tract has been studied in numerous studies. Lower pH levels are found inside the cervix and the vaginal canal than inside the uterus and fallopian tubes.

From animal studies, uterine pH is estimated to be comprised between 7.0 and

8.0.

The pH sensor 8 is selected from the group comprising: glass micro-electrode, ion-sensitive field-effect transistor and an ion-sensitive metal electrode.

Glass micro-electrodes comprise an ion-sensitive glass membrane, which defines the exterior of the electrode itself. The inside of the probe contains a silver chloride reference electrode in a fixed pH solution and saturated potassium chloride to maintain the potential stable. Ions inside the solution under test are exchanged with the glass, thus causing a difference in potential between the glass itself and the internal electrode.

Ion- sensitive field-effect transistors and ion- sensitive metal electrodes are based on the principle that ions interacting with the metal surface cause a change in the surface potential. Similarly to the glass micro-electrodes, this potential is referred to an internal reference electrode.

Preferably, the sensor means 7 comprise at least one oxygenation sensor 9 adapted to detect a tissue oxygenation parameter.

The degree of oxygenation inside tissues is defined by the partial pressure (p02). In a liquid, this external partial pressure causes oxygen to dissolve inside the liquid. Unlike p02 which represents partial pressure in mmHg, dissolved oxygen is a measure of concentration, that is, the amount of dissolved oxygen molecules in the liquid (mg/L). Dissolved oxygen depends on several key physical factors, such as salinity, temperature, and pH, as well as external pressures.

When oxygenated blood reaches the female reproductive tract, a pressure gradient is generated between the blood and the tissue. An increase in the concentration of carbon dioxide in the blood ensures that oxygen unbinds from hemoglobin. A diffusion flow of oxygen into the tissue and into the cellular components of the reproductive tract occurs because of the difference in p02. The oxygenation sensor 9 is selected from the group comprising: fiber optic oximeter, fluorescence optical sensor, polarographic sensor and galvanic sensor. The fiber optic oximeter uses two wavelengths to measure the concentration of hemoglobin (Hb) and oxyhemoglobin (Hb02). In particular, wavelengths of 660 nm and 805 nm are used, where 805 nm is the isosbestic point, i.e., the point at which the values of the extinction coefficients are equal for Hb and Hb02. The fiber optic oximeter measures absorbance directly from the light reflected by the sample.

The optical fluorescence sensor is a chemical sensor that is based on a fluorescent signal. This can be intensity or decay time dependent. Basically, an oxygen- sensitive fluorescent dye is embedded in a polymeric membrane, which is placed in contact with the tissue under test. The intensity of the fluorescent signal is measured upon excitation by means of a light source. When oxygen interacts with the dye, the fluorescence is turned off.

The polarographic sensor and the galvanic sensor are based on a reaction which occurs at the interface between an electrode and the solution under test. Through the application of a polarization potential, applied (for the polarographic sensor) or self-polarized (for the galvanic sensor), oxygen is reduced locally on the electrode surface.

Conveniently, the sensor means 7 comprise at least one temperature sensor 10 adapted to detect a temperature parameter.

The temperature sensor 10 is selected from the group comprising: thermistor, thermocouple and infrared thermograph.

A thermistor is a temperature- sensitive resistor, wherein the resistance of a metal oxide changes with temperature.

Thermocouples consist of two different metals which create a difference in potential along the metal-to-metal junction based on the thermoelectric effect. The infrared thermograph is provided with a thermal imaging camera which detects radiation in the infrared range of the electromagnetic spectrum and performs measurements related to the emission of this radiation. This instrument is able to detect the temperatures of the analyzed target by measuring the intensity of infrared radiation emitted by the target under test. Conveniently, the device 1 comprises transmission means 11 operatively connected to the sensor means 7 and configured to transmit the chemical- physical parameters to an external electronic unit U.

In the embodiment shown in the figure, the transmission means 11 comprise a wired electronic connection.

It cannot however be ruled out that the transmission means 11 may comprise a wireless transmission device. For example, the transmission means 11 may comprise a Wi-Fi device or a radio wave emitting device.

It has in practice been ascertained that the described invention achieves the intended objects, and in particular the fact is emphasized that the device for the measurement of endouterine parameters according to the invention allows effective and accurate detection of chemical-physical parameters inside a uterus, due to the presence of the sensor means.

In addition, the present device allows for practical, in vivo detection of the aforementioned endouterine chemical-physical parameters.

Finally, the present device for the measurement of endouterine parameters allows for rapid measurement and its small size makes it well tolerated by the patient during use.