Recoverable intra-uterine device

Abstract

The disclosure relates to a retrievable intrauterine device which includes a recess suitable for containing one or more elements selected from the group that includes an embryo, male and/or female gametes, a fertilized oocyte, a non-fertilized ovule and a combination of the elements. The recess includes an inner wall made of a biocompatible polymer, the inner wall including at least one perforated portion having perforations with dimensions of between 1 pm and 10 pm, and an outer wall covering the inner wall, the outer wall being made of a biocompatible silicone elastomer and including at least one opening opposite said at least one perforated portion of the inner wall. The use of the device relates to the preimplantation development of gametes and/or embryos.

Claims

1. A recoverable intrauterine device comprising a housing adapted to comprise one or more of an embryo, male and/or female gametes, a fertilized oocyte, an unfertilized egg, or a combination thereof, wherein said housing comprises an inner wall made of a biocompatible polymer, said inner wall comprising at least one perforated portion having perforations of dimensions between 1 m and 10 m, and an outer wall covering said inner wall, the outer wall being made of a biocompatible silicone elastomer and comprising at least one opening facing said at least one perforated portion of said inner wall.

2. The recoverable intrauterine device of claim 1, wherein said perforations have dimensions between 2 m and 8 m.

3. The recoverable intrauterine device of claim 2, wherein the inner wall is made of polycarbonate.

4. The recoverable intrauterine device of claim 2, wherein said at least one perforated portion comprises from 1 million to 5 million perforations per cm.sup.2.

5. The recoverable intrauterine device of claim 2, wherein the inside wall has ends in a longitudinal direction and the housing is of elongate shape in the longitudinal direction, said outer wall extending beyond the ends of said inner wall in the longitudinal direction.

6. The recoverable intrauterine device of claim 2, wherein the perforations have substantially a circular shape of diameter between 2 m and 8 m.

7. The recoverable intrauterine device of claim 1, wherein the inner wall is made of polycarbonate.

8. The recoverable intrauterine device of claim 7, wherein said at least one perforated portion comprises from 1 million to 5 million perforations per cm.sup.2.

9. The recoverable intrauterine device of claim 7, wherein the perforations have substantially a circular shape of diameter between 1 m and 10 m.

10. The recoverable intrauterine device of claim 7, wherein the perforations have substantially a circular shape of diameter between 2 m and 8 m.

11. The recoverable intrauterine device of claim 1, wherein said inner wall comprising at least one perforated portion has 1 million to 5 million perforations per cm.sup.2.

12. The recoverable intrauterine device of claim 1, wherein the perforations have substantially a circular shape of diameter between 1 m and 10 m.

13. The recoverable intrauterine device of claim 1, wherein the inside wall has ends in a longitudinal direction and the housing is of elongate shape in the longitudinal direction, said outer wall extending beyond the ends of said inner wall in the longitudinal direction.

14. The recoverable intrauterine device of claim 13, further comprising at least one cap mounted at one end of the housing, said at least one cap being frictionally mounted at one of said ends of the inner wall of said housing and being partially covered by one end of the outer wall.

15. The recoverable intrauterine device of claim 14, wherein said housing is of elongated cylindrical shape.

16. The recoverable intrauterine device of claim 1, wherein said housing is of elongated cylindrical shape.

17. The recoverable intrauterine device of claim 16, wherein the outer wall comprises at least one opening extending in a longitudinal direction of the housing and on an angular sector of the housing between 80 and 120.

18. The recoverable intrauterine device of claim 17, wherein the inner wall comprises two perforated portions, diametrically opposed in said elongated cylindrical shape of the housing, and the outer wall comprises two openings respectively facing said two perforated portions of said inner wall.

19. The recoverable intrauterine device of claim 16, wherein the inner wall comprises two perforated portions, diametrically opposed in said elongated cylindrical shape of the housing, and the outer wall comprises two openings respectively facing said two perforated portions of said inner wall.

20. The recoverable intrauterine device of claim 1, wherein the inner wall and the outer wall are made of transparent material.

21. The recoverable intrauterine device of claim 1, wherein said device comprises at least one of male and/or female gametes, a fertilized oocyte, an unfertilized egg or a combination thereof.

22. The recoverable intrauterine device of claim 1, wherein said device contains one or more embryos.

23. The recoverable intrauterine device of claim 1, wherein the perforations have substantially a circular shape of diameter between 2 m and 8 m.

Description

(1) In the accompanying drawings, given by way of non-limiting example:

(2) FIG. 1 is a partial exploded perspective view of a recoverable intra-uterine device according to an embodiment of the invention;

(3) FIG. 2 is a view in longitudinal section on line II-II of the recoverable intra-uterine device of FIG. 1;

(4) FIG. 3 is a cross-section view on line III-III of FIG. 1; and

(5) FIG. 4 is a cross-section view diagrammatically illustrating the recoverable intra-uterine device according to an embodiment placed in a uterine cavity.

(6) A description will first of all be made with reference to FIGS. 1 to 3 of an example embodiment of a recoverable intra-uterine device.

(7) In general terms, the recoverable intra-uterine device comprises a housing 10 for containing various items employed in a process of medically assisted reproduction.

(8) In particular, the housing 10 is configured to contain diverse items according to the state of progression of the fertilization process, for example male gametes and/or female gametes, an unfertilized ovum, or a fertilized oocyte, or one or more embryos.

(9) It will be noted that the recoverable intra-uterine device is configured to contain one or other of these items according to the state of progression over time of the fertilization process.

(10) The housing 10 is particular in that it comprises a double wall formed from an inside wall 11 and from an external wall 12.

(11) The inside wall 11 is formed from a biocompatible polymer.

(12) As the inside wall 11 is adapted to form the inside cavity of the housing 10, it is important for the material used to be of medical quality and not to create conditions that are detrimental to the development of embryos.

(13) By way of example, the inside wall 11 may be formed of polycarbonate.

(14) Of course, other types of biocompatible polymer could be used, for example a polyimide.

(15) In order to allow exchanges with the intra-uterine environment, the inside wall 11 comprises at least one perforated part 13a, 13b.

(16) In this embodiment, and on a non-limiting basis, the housing is of cylindrical shape which is elongate in a longitudinal direction X.

(17) Thus, the inside wall 11 of the housing 10 also has an elongate cylindrical shape.

(18) In this embodiment, as clearly illustrated in FIG. 2, the inside wall 11 comprises two perforated parts 13a, 13b which are diametrically opposite in the elongate cylindrical shape of the inside wall 11.

(19) Of course, this embodiment is in no way limiting, and the inside wall could comprise a single perforated part or on the contrary, more than two perforated parts.

(20) The Applicant has found that the perforations should have sufficient dimensions to promote exchanges with the nutrients present in the uterine environment, but without attaining dimensions such that the items contained in the housing 10 can escape into the uterus uncontrollably or that detrimental cells can enter the housing 10.

(21) To that end, the perforations have dimensions comprised between 1 m and 10 m.

(22) The perforations may of course have various shapes.

(23) Whatever its shape, such a perforation will have dimensions comprised between 1 m and 10 m provided that a circle circumscribing that perforation has a diameter comprised between 1 m and 10 m.

(24) More particularly, perforations having dimensions comprised between 2 m and 8 m are preferred for the intended applications.

(25) As will appear below in the description of an embodiment of such a housing, the perforations may have a substantially circular shape of diameter comprised between 1 m and 10 m, and preferably between 2 m and 8 m.

(26) The perforations are preferably disposed randomly and evenly in the perforated part 13a, 13b.

(27) The density of these perforations must be sufficient in the perforated part 13a, 13b to create an adequate surface area for exchange with the intra-uterine environment.

(28) By way of example, the perforated part 13a, 13b comprises one million to five million perforations per cm.sup.2.

(29) The outside wall 12 is formed from a biocompatible silicone elastomer.

(30) Any type of silicone (or polymerized siloxane) taking the form of an elastomer may be used.

(31) Other types of biocompatible elastomer may be used, for example a polyurethane thermoplastic elastomer or an elastomer of HCE type obtained by a hot curing process (HCE: initialism of Heat Curable Elastomer).

(32) The outside wall 12 comprises at least one opening 14a, 14b for being positioned facing a perforated part 13a, 13b of the inside wall 11 when the outside wall 12 covers the inside wall 11.

(33) In this embodiment, as the housing 10 has an elongate cylindrical shape, the outside wall 12 also has the general shape of an elongate cylinder.

(34) On a non-limiting basis, in this embodiment in which the inside wall comprises two perforated parts 13a, 13b, the outside wall 12 comprises two openings 14a, 14b respectively facing the two perforated parts 13a, 13b of the inside wall 11.

(35) Of course, the number and disposition of the openings 14a, 14b in the outside wall 12 are inherently linked to the number and the disposition of the perforated parts 13a, 13b of the inside wall 11.

(36) In the embodiment described with reference to FIGS. 1 to 3, the outside wall 12 comprises two openings 14a, 14b which each extend in the longitudinal direction X of the housing 10.

(37) As clearly illustrated in FIG. 3, the two openings 14a, 14b are diametrically opposite in the elongate cylindrical shape of the outside wall 12.

(38) Each opening 14a, 14b extends over an angular sector a of the housing 10 comprised between 80 and 120.

(39) Preferably, when the outside wall 12 comprises two openings 14a, 14b, the angular sector a of each of the openings is comprised between 80 and 90.

(40) In this embodiment, two openings 14a, 14b having an angular sector a of the same value have been illustrated by way of example.

(41) Of course, the invention is not limited to this embodiment and the openings of the outside wall 12 can have angular sectors of different values.

(42) In particular, an embodiment can be preferred in which the sum of the angular sectors a of the openings provided in the outside wall 12 remains less than 180 such that the outside wall 12 can maintain sufficient rigidity in the length of the housing 10, in particular to enable holding of the closure system.

(43) Similarly, the length in the longitudinal direction X of each opening 14a, 14b is comprised between a quarter and half of the length of the outside wall 12 of the housing 10, and preferably substantially equal to one third of that length.

(44) Preferably, the biocompatible polymer used to produce the inside wall 11 and the biocompatible silicone elastomer used to produce the outside wall 12 are transparent materials, enabling the biologist and/or the physician to observe the inside of the capsule when it is manipulated.

(45) On a non-limiting basis, a dimensional example of a housing 10 of a recoverable intra-uterine device will be given.

(46) The inside wall 11 may have an inside diameter of 350 m and an outside diameter of 500 m.

(47) The thickness of the inside wall 11 is thus substantially equal to 100 m.

(48) The length in the longitudinal direction X of the inside wall 11 is comprised between 4 mm and 6 mm in length.

(49) Correspondingly, the outside wall 12 has an inside diameter comprised between 300 m and 500 m and preferably equal to 430 m.

(50) The outside diameter of the outside wall 12 is comprised between 700 m and 800 m and is preferably equal to 800 m.

(51) The thickness of the outside wall 12 is thus comprised between 200 m and 400 m.

(52) The length in the longitudinal direction X of the outside wall 12 is comprised between 7 mm and 8 mm.

(53) The windows 14a, 14b thus extend in the longitudinal direction X over a length comprised between 2 mm and 3 mm, and preferably have a length equal to 2.8 mm.

(54) The angular sector of each opening 14a, 14b is substantially equal to 80.

(55) Independently of the specific dimensions indicated above, the housing has an elongate form in the longitudinal direction X, the outside wall 12 extending beyond the ends of the inside wall 11 in the longitudinal direction X.

(56) A housing 10 is thus obtained with an outside wall 12 forming a protective cage around the inside wall 11.

(57) A description will now be given by way of non-limiting example of a method of producing such a double-walled housing 10.

(58) A cylindrical tube of silicone elastomer is employed cut to length to form the outside wall 12.

(59) The openings 14a, 14b may be produced for example by cutting with a laser or for instance by cutting with a water jet under pressure.

(60) Perforations are made over a tubular portion of polymer, such as polycarbonate to constitute the inside wall 11.

(61) The inside wall 11 is cut to length, then inserted into the outside wall 12.

(62) The perforated parts of the inside wall 11 appear exposed through the openings 14a, 14b of the outside wall 12.

(63) To that end, track etching technology may for example be employed which is known for the production of porous polymer membranes.

(64) In its principle, this track etching technology consists in irradiating the surface of the polymer forming the inside wall 11 by high energy heavy ions.

(65) The bombardment by high energy heavy ions induces the formation of tracks by locally degrading the surface of the polymer.

(66) The tracks are then revealed in the form of perforations (or pores) by selective chemical attack.

(67) It is by way of example possible to use a caustic soda based chemical bath to create the perforations within the thickness of the inside wall 11.

(68) Perforations are thus obtained which are randomly and evenly distributed over the perforated part 13a, 13b of the inside wall 11.

(69) By way of non-limiting example, it is possible to obtain perforations in an inside wall 11 of polycarbonate which have a size substantially equal to 3.2 m.

(70) A housing 10 is thus obtained formed from a double wall, taking the general shape of an elongate cylinder open at both its ends.

(71) In order to obturate the housing, the intra-uterine device comprises at least one plug mounted at an end of the housing 10.

(72) In this embodiment, the intra-uterine device comprises two plugs 20, 21 respectively mounted at the distal and proximal ends of the housing 10.

(73) The plugs 20, 21 may for example be produced from titanium.

(74) As clearly illustrated in FIG. 2, each plug 20, 21 is mounted by friction at an end of the inside wall 11.

(75) For this purpose, each plug 20, 21 comprises a first frusto-conical part 20a, 21a of which the outside diameter is, at its small base, slightly less than the inside diameter of the inside wall 11. The first frusto-conical part 20a, 21a widens to attain, at its larger base, an outside diameter slightly greater than the inside diameter of the inside wall 11.

(76) Each first frusto-conical portion 20a, 21a is extended by a second frusto-conical portion 20b, 21b widening from the first frusto-conical portion 20a, 21a.

(77) The second frusto-conical portion 20b, 21b is configured to be covered by one end of the outside wall 12 which extends beyond the ends of the inside wall 11, to an extender of the plug 20c, 21c.

(78) The wider diameter of each plug 20, 21, and here the wide base of the second frusto-conical part 20b, 21b, has a dimension slightly greater than the inside diameter of the outside wall 12 such that the mounting of the plug 20, 21 is achieved by slight deformation of the outside wall 12 of the housing, providing perfect sealing for the mounting of the plug.

(79) The distal plug 20 further comprises a first extender 20c having for example the shape of a nail head, enabling the physician or biologist to manipulate the distal plug 20 to enable the closing or the opening of the housing 10.

(80) The proximal plug 21 is extended by a second extender 21c, forming a fastening stem 21c configured to be inserted by force into a connector 30 (partially illustrated in FIGS. 1 and 2).

(81) Such a connector is described in particular in document FR 2 903 879 A1 and does not need to be described here in detail.

(82) Only the essential parts of this connector are reviewed below with reference to FIG. 4.

(83) Such a connector is configured for mounting a stabilizing arm, useful for holding the intra-uterine device in position in the uterus, as well as for the mounting of a removal thread.

(84) As clearly illustrated in FIG. 4, the connector 30 comprises a cylindrical tube extending to the proximal end of the housing 10.

(85) The cylindrical tube of the connector 30 is for example of silicone elastomer and is mounted by force at its distal end on the fastening stem 21c joined to the proximal plug 21.

(86) A stabilizing arm 31 is fastened at the proximal end of the cylindrical tube of the connector 30.

(87) In general terms, the stabilizing arm 31 can adopt a folded position, thus extending in the longitudinal direction X of the housing 10 and of the connector 30, and an extended position such as illustrated in FIG. 4 in which, by a spring effect, the stabilizing arm 31 unfolds, one end 31a of the arm coming locally into contact with the uterus u.

(88) The stabilizing arm 31 can for example be formed of steel and may have at its end 31a a protective sleeve of silicone elastomer.

(89) Furthermore, a removal thread 32 of nylon to enable the removal of the device from the uterus by pulling is fastened to the proximal end of the cylindrical tube of the connector 30.

(90) The principle of use and of putting in place the intra-uterine device is similar to that described in document FR 2 903 879 A1

(91) As clearly illustrated in FIG. 4, the intra-uterine device is inserted through the body's passages into the uterus by means of a transfer catheter (not shown).

(92) The transfer catheter is next withdrawn enabling the stabilizing arm 31 to extend and hold the intra-uterine device in place for a few hours or a few days, enabling preimplantation development of the embryo in the intra-uterine environment.

(93) Thanks to the porosity of the inside wall 11 of the housing 10, at the location of the perforated parts 13a, 13b, exchanges between the gametes and/or embryos contained in the intra-uterine device and the uterine fluids are promoted and enable optimal development of the embryo.

(94) To that end, the intra-uterine device is placed in the uterus u near the fundus f and the end 31a of the stabilizing arm 31 comes into contact only with a very small portion of the endometrial wall at the location of the cervical canal i.

(95) Thus, the endometrial layer that lines the uterine cavity at the fundus f, the corpus p and the cervical canal i have very little contact with the intra-uterine device, avoiding any deterioration of the endometrium which could be detrimental to the later reimplantation of the embryo.

(96) Furthermore, the removal thread 32 extends through the cervix c to emerge in the vagina v and enable easy extraction of the device by the practitioner, simply by pulling.

(97) Of course, the invention is not limited to the embodiments described above and numerous modifications may be made to those examples without departing from the scope of the invention.