Device dedicated to medically assisted procreation

Abstract

A device (1) for the mobility of embryos in assisted reproduction technology, comprising (i) a developing plate (2) having at least one embryo development channel (3) suitable, in use, for housing a culture medium (ii) at least one pushing element (4) having a housing portion (5) of the embryo (E) arranged to slide in the embryo development channel (3) and defined by a retaining wall (12) in which a plurality of openings (13) are obtained to allow the crossing of the culture medium and holding of the embryo (E); and (iii) movement means (6, 16), suitable for moving the pushing element (4) to cause the sliding of the housing portion (5) in the embryo development channel (3) at a predetermined speed.

Description

[0001] "DEVICE DEDICATED TO MEDICALLY ASSISTED PROCREATION"

[0002] Cross-Reference to Related Applications

[0003] This Patent Application claims priority from Italian Patent Application No. 102024000012541 filed on May 31, 2024, the entire disclosure of which is incorporated herein by reference.

[0004] Technical Field

[0005] The present invention relates to a device dedicated to Medically Assisted Procreation and the features of which are capable of guaranteeing movement of the embryos during the incubation period .

[0006] Prior Art

[0007] As is known, in vivo fertilization occurs inside the ampulla of the Fallopian tube and, from that moment, the embryo is free and subjected to a passive movement that assists in cell division. In fact, after fertilization, the embryo starts its development phase assisted by the ciliated movement of the epithelium and by the contractions of the smooth musculature of the transoviduct / uterus .

[0008] The physiological movement that accompanies the embryo from fertilization up to the uterus (5\6 days after fertilization) guarantees that all the waste products of metabolism (catabolites) move away from the embryo itself. In this regard, it must be considered that the catabolites have a highly toxic effect for development of the embryo.

[0009] Up until now, IVF {in vitro fertilization) laboratories have used a static culture, which provides for the development of embryos in a microdrop of culture medium covered with mineral oil. The embryos remain in the microdrop for 5 days, or 120 hours, without any movement. As confirmed by extensive scientific literature, in these conditions, although the culture medium is rich in nutrients, an accumulation of waste products of the embryonic metabolism inevitably occurs, which can undermine cell division.

[0010] Many of the studies performed up until now have demonstrated that movement during the cell cultures has a beneficial influence on development, on the kinematics of cell division, on implanting and on the pregnancy rates of human, bovine and murine embryos.

[0011] For the above reasons, a part of the research is being concentrated on a fluid-dynamic culture as an alternative to a static culture.

[0012] US2021147773A1 describes a device for supporting the development of embryos comprising an inlet cavity, an outlet cavity and a closed culture chamber arranged between the inlet cavity and the outlet cavity. The device further comprises an inlet channel that fluidly couples the inlet cavity to the culture chamber and an outlet chamber and / or at least one outlet channel that fluidly couples the culture chamber to the outlet cavity. At least one among the outlet chamber and the outlet channel is sized to prevent the passage of the cell deposit through it.

[0013] Fluid-dynamic devices are currently far from being applied in medically assisted procreation techniques in terms of embryo culture .

[0014] A first disadvantage relates to the material. The Nunc culture plates / dishes that have always been used in medically assisted procreation centres are made from polystyrene (PS) , a biocompatible and non-toxic material, whereas the plates for fluid-dynamic circuits are made from PDMS, a silicone that, although defined as biocompatible, has proved to interfere with the metabolic processes of the embryos, also causing a delay in their development. In particular, the PDMS absorbs several hormones of the embryos and releases harmful substances into the culture medium in an uncontrolled manner, becoming potentially toxic .

[0015] Although experiments on the animal model have tested other types of materials, a problem nonetheless remains in relation to the extremely high costs of these devices. In fact, devices with an integrated fluid circuit currently require a sophisticated technology in a disposable bloc, which necessarily results in a cost that is too high for medically assisted procreation centres to sustain.

[0016] There was therefore a need to have a device for medically assisted procreation that guaranteed movement of the cell cultures without encountering the disadvantages of the prior art .

[0017] Description of the Invention

[0018] The object of the present invention is a device for the development of embryos in assisted reproduction technology; said device being characterized by the fact of comprising (i) a developing plate having at least one embryo development channel, in which a culture medium for the embryo development is housed, (ii) at least one pushing element having a housing portion of the embryo arranged to slide in said embryo development channel and defined by a retaining wall, in which a plurality of openings are obtained to allow crossing of the culture medium and retaining of the embryo; and (iii) movement means connected to said pushing means to cause the sliding of said housing portion along said embryo development channel.

[0019] Preferably, said housing portion is defined by a "U"-shaped wall in which at least in the two vertical portions a plurality of openings is obtained to allow the culture medium to pass through it.

[0020] In this document, spatial references such as horizontal, vertical, upper, lower, refer to the device in its position in use, as shown in the drawings.

[0021] Preferably, said developing plate comprises a plurality of embryo development channels.

[0022] Preferably, said movement means comprise a mobile frame arranged to move along said at least one embryo development channel and in which one or more of said pushing elements are fixed.

[0023] Preferably, said pushing element includes said housing portion and a stem, to one end of which said housing portion is fixed; said stem being fixed to said mobile frame.

[0024] Preferably, said mobile frame has two ends which slidably engage two respective tracks which flank on opposite sides said at least one embryo development channel.

[0025] Preferably, said device comprises a command-and-control unit to control the movement of the movement means and to check the progress of the device operations.

[0026] Preferably, said command-and-control unit includes said two tracks engaged by sliding by the ends of the mobile frame.

[0027] A further object of the present invention is a method for developing fertilized embryos in the technique of assisted procreation; said method comprising:

[0028] - a housing step, in which an embryo is housed in a housing portion (5) defined by a retaining wall (12) , in which a plurality of openings (13) is obtained to allow crossing of a culture medium and to retain the embryo (E) and - a sliding step, in which said housing portion (5) is made to slide at a predetermined speed inside a single embryo development channel (3) in which a culture medium for embryo development is present.

[0029] Preferably, the sliding step lasts 5 or 6 days.

[0030] Brief Description of the Drawings

[0031] An illustrative and non-limiting embodiment is described below, with the assistance of the appended drawings, in which:

[0032] - Figure 1 is a perspective view of an embodiment of the device according to the present invention;

[0033] - Figure 2 is an exploded view of the device of Figure 1;

[0034] - Figure 3 is a perspective view of a detail of the device in use; and

[0035] Figure 4 is a detail of Figure 3.

[0036] Preferred Embodiment of the Invention

[0037] In Figures 1 and 2, the number 1 denotes, in its entirety, the device for assisted procreation according to the present invention .

[0038] The device 1 comprises (i) a developing plate 2 in which a plurality of embryo development channels 3 is obtained, (ii) a plurality of pushing elements 4, each of which has a housing portion 5 of a respective embryo E and that, in use, is arranged to slide inside a respective embryo development channel 3, (iii) a mobile frame 6 to which pushing elements 4 are fixed and is arranged to slide along the embryo development channels 3, and (iv) a command- and-control unit 7 adapted to control the movement of the mobile frame 6.

[0039] In particular, the developing plate 2 is made of polystyrene (PS) , a plastic tested to be compatible with the cell cultures and non-toxic, and has ten embryo development channels 3. The developing plate 2 has a length equal to 6.5 cm and a width equal to 5.5 cm.

[0040] The developing plate 2 is a disposable element of the device 1 and indicates the reference details of the relative patient. A time reference 8 is indicated along the ten embryo development channels 3, which correlates the sliding time of the in vitro development with the time of six days of in vivo development.

[0041] Each of the embryo development channels 3 has a length equal to 6 cm and a width comprised between 100 and 300 pm.

[0042] In use, the operator inserts around 1 ml of culture medium covered with around 2 ml of mineral oil for biological cultures into each of the embryo development channels. The culture medium for embryo development is formed of growth factors, amino acids, antioxidants, pyruvate, lactate and glucose that serve to allow growth of the embryo.

[0043] According to a variable with respect to what is shown in the figures, the device comprises a culture medium tank connected to the embryo development channels, in order to fill them automatically each time the old culture medium is removed. For example, automatic feeding of the embryo development channels can be obtained by means of a system of communicating jars.

[0044] Lastly, in the developing plate 2, on opposite sides to the plurality of embryo development channels 3, two grooves 9 are obtained that, as will be described below, cooperate in the movement of the pushing elements.

[0045] Each of the pushing elements 4 is formed of a stem 10 and of the housing portion 5 fixed to an end of the stem 10.

[0046] The pushing elements 4 are made of a malleable plastic resistant to the temperatures of the incubator (around 37 °C) .

[0047] The housing portion 5 has the function of housing the fertilized embryo E and holding it during the entire sliding inside the respective embryo development channel 3.

[0048] As shown in Figure 4, the housing portion 5 is defined by a U- shaped retaining wall 12, comprising two vertical portions 12a extending from opposite sides from a horizontal portion 12b.

[0049] At least in the two vertical portions 12a, a plurality of holes 13 is obtained that have the function of allowing the culture medium to cross said retaining wall 12, simultaneously holding the housed embryo. Such crossing guarantees that the waste products of metabolism (catabolites, indicated with black dots in Figure 4) also cross the retaining wall 12 and that, therefore, they move away from the embryo E, with the advantages described above.

[0050] In particular, the retaining wall 12 has a width equal to the one of the embryo development channels 3, i.e. comprised between

[0051] 100 and 300 pm.

[0052] Each of the pushing elements 4 is fixed to the mobile frame 6, which, substantially, has an overturned U shape and is formed of two uprights 14 and a beam 15, to which the stems 10 of the pushing elements 4 are fixed.

[0053] Each of the two uprights 14 has a free end 14a, that, in use, engages the movement means housed inside two respective tracks 16, which will be described below.

[0054] Lastly, the command-and-control unit 7 is the only reusable element of the device 1 and has the function of setting the movement of the mobile frame 6 and, therefore, of the pushing elements 4.

[0055] The command-and-control unit 7 also has the function of monitoring the progress of the operations, recording the state of progress of sliding of the embryos and, therefore, their development .

[0056] The command-and-control unit 7 comprises the two tracks 16 that are housed in the two respective grooves 9 obtained in the developing plate 2. Each of the tracks 16 comprises a respective slide (not shown, for simplicity) that, in use, is engaged by an end 14a of an upright 14 of the mobile frame 6.

[0057] Lastly, the command-and-control unit 7 comprises a display 17 as an interface with the operator for the process commands and for checks on the state of progress.

[0058] A procedure of use of the device of the present invention is described below.

[0059] The day before insemination (ICSI) , the developing plate 2 is mounted and prepared for pre-incubation at 37 °C.

[0060] In contrast with the static culture systems with microdrops of culture medium covered with mineral oil, the developing plate 2 is prepared by placing around 1 ml of culture medium covered with around 2 ml of mineral oil for biological cultures into each of the embryo development channels 3.

[0061] At this point, the command-and-control unit 7, in which the digital timer and the day of insemination is set, is connected. In particular, the tracks 16 are housed in the respective grooves 19.

[0062] Subsequently, the mobile frame 6 on which the pushing elements 4 have been fixed is mounted. In particular, the ends of the upright 14 are led to engage respective slides housed in the tracks 16.

[0063] The day after preparation of the device, insemination of the oocytes (ICSI) is performed. The operator takes the developing plate 2 from the incubator and houses the individual inseminated oocytes on the pushing elements 4, taking care to place them one by one in the respective housing portions 5 (as shown in Figure 3) .

[0064] Once the individual inseminated oocytes have been housed, the operator starts the time, so as to allow the start of slow sliding of the mobile frame 6 from day 1 to day 6 indicated in the time reference 8.

[0065] During development, the embryos are free to move inside the housing portion 5, imitating the passive movement that occurs in nature in the maternal oviduct. Thanks to the perforated retaining wall 12, during sliding the waste products of metabolism will not remain around the embryos, thus facilitating their morphokinetic development.

[0066] At the end of the 5-6 days of embryo culture and therefore at the end of the procedures, the device is taken apart and both the developing plates 2 and the pushing elements 4 and the mobile frame 6 are discarded, whereas the command-and-control unit 7 is simply reset to zero in order to be reused for a subsequent culture .

[0067] The advantages for mobility of the embryos in the period of development and for the possibility of manufacturing the disposable parts in polystyrene (PS) , which is biocompatible and non-toxic for the embryos, are clear from the above description. Furthermore, since the disposable parts do not have electronic components, the device of the present invention has both a low environmental and financial impact. In fact, unlike disposable plates with integrated circuits (made from the same materials as mobile telephones (PDMS) ) , the device uses a command-and- control unit that, insofar as concerns the electronics, is not disposable, but reusable, with an environmental and financial impact that is certainly low.

[0068] Lastly, for operators the device of the present invention is a new system for control of cell cultures that provides the precise date and time of cleavage (cell division) that can be recorded in the traceability managing system required by the control agencies (CNT Centro Nazionale Trapianti - Italian National Transplant Centre) .

Claims

CLAIMS1. Device (1) for the development of embryos in assisted reproduction technology; said device being characterized by the fact of comprising (i) a developing plate (2) having at least one embryo development channel (3) in which a culture medium for the embryo development is housed, (ii) at least one pushing element (4) having a housing portion (11) of the embryo (E) arranged to slide in said embryo development channel (3) and defined by a retaining wall (12) in which a plurality of openings (13) are obtained to allow the crossing of the culture medium and holding of the embryo (E) ; and (iii) movement means (6, 16) connected to said pushing means (4) to cause the sliding of said housing portion (5) along said embryo development channel (3) .

2. Device according to claim 1, characterized in that said housing portion (5) is defined by a "U"-shaped wall (12) in which at least in the two vertical portions (12a) a plurality of openings (13) is obtained to allow the cultivation medium to pass through it.

3. Device according to claim 1 or 2, characterized in that said developing plate (2) includes a plurality of embryo development channels ( 3 ) .

4. Device according to one of the previous claims, characterized in that said movement means comprise a mobile frame (6) arranged to move along said at least one embryo development channel (3) and in which one or more of said pushing elements (4) are fixed.

5. Device according to claim 4, characterized in that said pushing element (4) includes said housing portion (5) and a stem (10) , to one end of which said housing portion (5) is fixed; said stem (10) being fixed to said mobile frame (6) .

6. Device according to claim 4 or 5, characterized in that said mobile frame has two ends (14a) which slidably engage two respective tracks (16) which flank on opposite sides said at least one embryo development channel (3) .

7. Device according to any of the previous claims, characterized in that it includes a command-and-control unit (7) to control the movement of the movement means (6) and to check the progress of the device operations.

8. Device according to claims 6 and 7, characterized in that said command-and-control unit (7) includes said two tracks (16) engaged by sliding from the ends (14a) of the mobile frame (6) .

9. Device according to one of the previous claims, characterized in that said developing plate (2) is made of polystyrene.

10. Method for developing fertilized embryos in the technique of assisted procreation; said method comprising:- a housing step, in which a non-frozen embryo is housed in a housing portion (5) defined by a retaining wall (12) , in which a plurality of openings (13) is obtained to allow crossing of a culture medium and to retain the embryo (E) and- a sliding step, in which said housing portion (5) is made to slide at a predetermined speed inside a single embryo development channel (3) in which a culture medium for embryo development is present.

11. The method according to claim 10, characterized in that said housing portion (5) is fixed to an end of a pushing element (4) , which is moved by movement means (6, 16) in order to obtain sliding of said housing portion (5) along said embryo development channel (3) at a pre-set speed.

12. The method according to claim 10 or 11, characterized inthat said sliding step lasts 5 or 6 days.

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