Abstract:
The recoverable intra-uterine system comprises a housing capable of containing one or a plurality of elements selected from among the group comprising an embryo, male and/or female gametes, a fertilized oocyte, and unfertilized ovum and a combination of these elements, the housing having along an axis a distal end and a proximal end, and a device for holding the recoverable intra-uterine device in the uterus. The holding device is arranged at the proximal end of the housing and includes at least one holding arm in the uterine cavity capable of taking at least two positions: —one free position in which at least one holding arm is separated from the axis; and —a retracted position in which at least one holding arm is substantially parallel to the axis. Use in medically assisted reproduction techniques.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is the U.S. National Phase Application of International Application No. PCT/IB2007/002913, filed Jun. 26, 2007, which claims the benefit of French Application No. FR 0653069, filed Jul. 21, 2006, the disclosures of each of which is hereby incorporated by reference. 
     FIELD OF THE INVENTION 
     The present invention concerns a recoverable intra-uterine system. 
     It is generally concerned with stabilizing and retaining in position a recoverable intra-uterine system used in the process of medically assisted procreation. 
     BACKGROUND 
     Intra-uterine systems that can be implanted and recovered non-invasively have been known for a number of years. 
     Generally speaking, these systems can be classified into three major families according to their indication or their mode of action. Of these, devices having an anti-conception indication, such as contraceptive IUDs, represent the great majority of cases and constitute the first category. 
     The second category consists of capsules loaded with a therapeutic substance and placed in the uterine cavity for diffusion and action in the organism. 
     Finally, the third category consists of intra-uterine devices indicated for in vivo assistance in medically assisted procreation processes. Thus there is known an intra-uterine device as notably described in the document WO 03/011200, intended to be placed in the uterine cavity for a period between a few hours and a few days, and enabling pre-implantation development of an embryo in vivo. 
     For each of these categories of devices, it is of primordial importance that the object placed in the uterine cavity non-invasively can remain positioned at the determined location for the indicated period and then recovered non-invasively. 
     To meet these specifications, the devices concerned must address two constraints, a priori contradictory. On the one hand, these devices must be both thin and compact to be placed in the uterine cavity and then removed, non-invasively, which imposes the passing through the cervical channel of the cervix. Moreover, they must be sufficiently bulky to be stabilized in the uterine cavity and not to be expelled by the natural contractions of the uterus. 
     In the prior art numerous variants and shapes have been proposed to address this two-fold constraint, but oriented exclusively to applications belonging to the first and second categories of devices described above. 
     Now, for the third category of devices used in the process of medically assisted procreation in vivo, an additional constraint becomes apparent when it is of primordial importance to preserve the integrity of the endometrium. This is because implantation of the embryo must take place in the same menstrual cycle of the patient and the endometrium must not be damaged in any way prior to implanting the embryo. 
     In particular, existing stabilization systems in the field of contraception, and in particular for retaining a contraceptive IUD in position in the uterus, are not satisfactory. This is because they can damage the endometrium, not only when retaining the device in position in the uterine cavity, by exerting a constant pressure against the endometrium (causing phenomena of contractions, possibly with hormonal activation), but also during removal of the device, the retaining elements rubbing on the endometrium over a great distance, thereby causing microlesions or inflammatory inductions, or bleeding. 
     Also, the document WO 03/011200 describes an intra-uterine device carrying stabilizing fins at a distal end of the housing. These stabilizing fins are liable to damage the endometrium, notably during removal of the device, and thereby to reduce the chances of successful subsequent implantation of the embryo. 
     SUMMARY OF THE INVENTION 
     An object of the present invention is to propose a recoverable intra-uterine system that removes the drawbacks cited above and in particular guarantees that the system is held in position in the uterine cavity and preserves the integrity of the endometrium, notably during removal of the system. 
     To this end, the present invention concerns a recoverable intra-uterine system comprising a housing adapted to contain one or a plurality of elements selected from among the group comprising an embryo, male and/or female gametes, a fertilized ovocyte, an unfertilized ovum and a combination of these elements, the housing having along an axis a distal end and a proximal end, and a device for retaining the recoverable intra-uterine device in the uterus. 
     According to the invention, the retaining device is arranged at the proximal end of the housing and includes at least one retaining arm in the uterine cavity adapted to assume at least two positions:
         a free position in which said at least one retaining arm is away from said axis; and   a removal position in which said at least one retaining arm is substantially parallel to said axis.       

     Accordingly, thanks to the arrangement of the retaining device at the proximal end of the housing, the system introduced into the uterus is held in position in the region of the cervical channel and the area of contact between the retaining arm or arms of the retaining device and the endometrium is small. The beneficial effects of these features reduce the pressure induced by the intra-uterine system on the uterine cavity. 
     Moreover, during removal of the device, the retaining arm lying substantially on the axis of the housing, there is very limited or even no rubbing on the wall of the endometrium beyond the cervical channel. 
     Furthermore, thanks to the arrangement of the retaining device in the uterine cavity at the proximal end of the housing, the active part of the system, consisting of the housing, is positioned above the retaining arm or arms in the uterine cavity, and thus entirely enclosed within the uterine cavity. 
     Moreover, when the system is placed in the uterine cavity with its associated retaining device, the retaining arm(s) is or are inside the uterine cavity, beyond the cervix, and are not liable to obstruct the cervix and to impede the existing flow of fluid between the uterus and the vagina. 
     According to one particular feature of the invention, said at least one retaining arm is further adapted to assume an introduction position in which said at least one retaining arm is substantially parallel to said axis and is an extension of housing. 
     Thanks to this particular arrangement of the retaining device, the retaining arm being aligned with the housing, the whole of the system can be introduced into a standard transfer catheter used to introduce the recoverable intra-uterine system into the uterine cavity beyond the cervix. 
     When the arm is aligned with the housing, the retaining device does not form any increased thickness around the housing and can be introduced into a transfer catheter with a small inside diameter, and thus a small outside diameter, adapted to pass through the cervix. 
     According to an advantageous feature of the invention, said at least one retaining arm is arranged on elastic means exerting a return force adapted to retain said at least one retaining arm in the free retaining position. 
     Thanks to the presence of these elastic means, the arm(s) of the retaining device is or are automatically placed in their free retaining position when the recoverable intra-uterine system is introduced into the uterine cavity, after removal of the transfer catheter used to introduce it. 
     The recoverable intra-uterine system is therefore held in position in a reliable and natural manner without requiring additional manipulation by the practitioner. 
     Another aspect of the invention is directed to a combination of a transfer catheter and an intra-uterine system wherein said system is housed in the catheter. 
     The housing and the associated retaining device can therefore be placed in the uterus using the transfer catheter. 
     Other features and advantages of the invention will become more apparent in the following description. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       In the appended drawings, provided by way of nonlimiting example: 
         FIG. 1  is a diagrammatic view of a recoverable intra-uterine system conforming to one embodiment of the invention; 
         FIG. 2  is a perspective view diagrammatically illustrating the fitting of a recoverable intra-uterine system from  FIG. 1  into a transfer catheter; 
         FIG. 3  is a view in section illustrating diagrammatically the recoverable intra-uterine system from  FIG. 1  during its introduction into the uterine cavity; 
         FIG. 4  is a figure analogous to  FIG. 3  illustrating the recoverable intra-uterine system in the uterine cavity; and 
         FIG. 5  is a view analogous to  FIGS. 3 and 4  illustrating the recoverable intra-uterine system during its removal from the uterine cavity. 
     
    
    
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
     As shown in  FIG. 1 , the recoverable intra-uterine system comprises firstly a housing  10  intended to be placed in the uterus. 
     This housing  10  is intended to be placed in the uterine cavity for a period between a few hours and a few days with a view to pre-implantation development of an embryo in vivo. 
     To this end, the housing  10  is adapted to contain an embryo, male and/or female gametes, a fertilized ovocyte, an unfertilized ovum or a combination of these various elements. 
     This housing  10  can be produced in silicone and provided with a series of perforations  11  in its wall enabling interaction between the interior of the housing and the exterior medium in which the housing  10  is placed, that is to say the uterine medium. 
     As clearly shown in  FIG. 1 , this housing  10  is of elongate shape along an axis X. 
     In this embodiment, the housing  10  consists of an elongate cylindrical tube. 
     By way of nonlimiting example, the length of the housing in the direction X can be substantially equal to 10 mm, the inside diameter of the housing  10  being between 0.4 and 0.5 mm and the outside diameter of the cylindrical housing  10  being between 0.7 and 0.8 mm. 
     This elongate housing  10  therefore has, in the direction of its introduction into a uterine cavity along the axis X, a distal end  12  and a proximal end  13 . 
     The housing  10  has at its distal end  12  a stopper  14 , for example of titanium, which is a tight fit in the end of the housing  10  and closes it. This stopper  14  can be removed after use of the intra-uterine system to extract the embryos and/or elements that have been placed temporarily in the uterine cavity, in particular with a view to their selection and re-implantation in the uterine cavity. 
     The housing  10  also has a proximal stopper  15  at its proximal end  13 . 
     The housing  10  is associated with a device  20  for retaining the intrauterine system in the uterus. This retaining device  20  is disposed at the proximal end  13  of the housing  10 . 
     In this embodiment, the retaining device  20  comprises a cylindrical tube  21 , a bent wire  22  forming a spring and a retaining arm  23 . 
     The cylindrical tube  21  is fixed at one end  21   a  to the proximal end  13  of the housing  10 . 
     In practice, the proximal stopper  15  includes an extension  16  the diameter whereof is adapted to fit inside the cylindrical tube  21 , at one end  21   a.    
     For example, this extension  16  is glued to the cylindrical tube  21 . 
     The stopper  15  is assembled to the housing  10  at the proximal end  13  simply because the housing  10  is a tight fit over the stopper  15 . 
     In practice, this stopper  15  can have a frustoconical shape enabling a sealed fit of the stopper  15  in the end  13  of the housing  10 . 
     The cylindrical tube  21  is produced in a biocompatible material, like the housing  10 , for example silicone. 
     In practice, this cylindrical tube  21  can have a length of the same order as that of the housing  10 , substantially equal to 10 mm, and have a diameter slightly greater than that of the housing  10 . 
     By way of nonlimiting example, the inside diameter of the cylindrical tube  21  can be between 0.5 and 0.6 mm and the outside diameter of the cylindrical tube  21  can be between 0.9 and 1 mm. 
     The cylindrical tube  21  is therefore aligned with the housing  10  in the direction of the axis X. 
     The bent wire  22  forming a spring is mounted in the cylindrical tube  20  at its second end  21   b.    
     In practice, the bent wire  22  forming a spring is attached to the inside of the cylindrical tube  21 . 
     In practice, in this embodiment, the bent wire  22  forming a spring has a first end  22   a  disposed in the cylindrical tube  21 , at the proximal end  13  of the housing  10 , and a second end  22   b.    
     The first end  22   a  of the bent wire  22  forming the spring extends in the direction of the axis X in alignment with the housing  10  and the cylindrical tube  20 . 
     The terminal portion  22 ′ a  of the first end  22   a  is conformed as a coil spring. This coil spring portion is attached to the inside of the cylindrical tube  20 , for example by means of a silicone adhesive. 
     The second end  22   b  of the bent wire  22  forming a spring comprises a terminal portion covered by a protective sleeve  24 . This terminal portion of the second end  22   b  covered by the protective sleeve  24  constitutes the retaining arm  23  of the retaining device, this retaining arm being adapted to retain the device in the uterine cavity as described hereinafter. 
     In this particular embodiment, the bent wire  22  forming a spring includes two bends  22   c ,  22   d  so that an intermediate portion  22   e  extends between the first end  22   a  and the second end  22   b  of the bent wire  22  forming a spring. 
     In practice, this bent wire  22  forming a spring can be produced from a stainless steel spring of which a first part, corresponding to the terminal portion  22 ′ a  of the first end  22   a , is conformed as a coil spring and a second part is straightened and bent to produce a rectilinear portion of the first end  22   a , the intermediate portion  22   a  and the second end  22   b  of the bent wire. 
     Thus the retaining arm  23  produced at the second end  22   b  of the bent wire  22  forming a spring is arranged on elastic means consisting mainly of the intermediate part  22   e  and the bends  22   c  and  22   d  of the bent wire  22  forming a spring. 
     As shown clearly in  FIG. 1 , these elastic means exert a force returning. the retaining arm  23  to a stable position in which the retaining arm  23  is moved away from the axis X along which the housing  10 , the cylindrical tube  20  and the first end  22   a  of the bent wire forming a spring extend. 
     By way of nonlimiting example, the diameter of the steel wire used to form the bent wire forming a spring can be between 0.1 and 0.2 mm. 
     The length of the coil spring portion  22 ′ a  can be substantially equal to half the length of the cylindrical tube  20 , and for example equal to 5 mm. 
     Moreover, the protective sleeve  24  can be produced from a nylon tube mounted on the terminal portion  22 ′ b  of the second end  22   b  of the bent wire  22 . This nylon tube can be glued to the steel wire, for example using a silicone glue. 
     By way of nonlimiting example, the length of the protective sleeve can be substantially equal to 5 mm, the outside diameter being between 0.4 and 0.5 mm and the inside diameter being between 0.15 and 0.25 mm to enable introduction of the steel wire. 
     In addition to this retaining device  20  fixed to the housing  10 , the recoverable intra-uterine system also includes a removal thread  30  for pulling the device out of the uterus. 
     This removal thread  30  can be of nylon and have a total length of 150 mm and a diameter of 0.1 mm. 
     In this embodiment, this nylon thread  30  is fastened to the terminal portion  22 ′ a  in the form of a coil spring. 
     In practice, the nylon thread  20  can be fixed to the interior of the spiral of the coil spring, before the spiral is introduced into the cylindrical tube  21 . By heating this terminal portion  22 ′ a , the nylon thread is welded to the inside of the spiral and thus fastened to the bent wire  22 . 
     The terminal portion  22 ′ a  associated with the removal thread  30  is then introduced into the cylindrical tube  21  and glued as indicated above by means of a silicone glue. 
     The various positions that the retaining arm  23  can assume when using the recoverable intra-uterine system are described next with reference to  FIGS. 2 to 5 . 
     In practice, the housing  10  is assembled to the retaining device, and more particularly to the cylindrical tube  21 , after introducing into the housing elements such as male and female gametes. 
     During the introduction of these elements, the distal stopper  14  is in place at the distal end  12  of the housing  10 . 
     After introducing the gametes, the stopper  15  is fitted to the end  13  of the housing  10 , at the same time as fitting the retaining device  20  because the cylindrical tube  21  is fixed to the extension  16  of the proximal stopper  15 . 
     For the introduction of the intra-uterine system into the uterine cavity there is used, in the conventional way, as shown in  FIG. 2 , a catheter  40  that takes the overall form of an elongate cylindrical tube of appropriate length able to accommodate the whole of the intra-uterine system, that is to say, successively, the housing  10 , the cylindrical tube  20  and the wire  22  forming a spring associated with the retaining arm  23 . 
     Moreover, the removal thread  30  extends beyond the transfer catheter. 
     Furthermore, a semi-rigid rod  45  is also used, bearing on the retaining device, at the free end  21   b  of the cylindrical tube  21 . 
     As clearly shown in  FIG. 3 , this semi-rigid rod is sufficiently long to project from the free end of the catheter. 
     In this introduction position, as clearly shown in  FIG. 2 , the retaining arm  23  is substantially parallel to the axis X of the housing  10  and is an extension of the housing  10 . 
     In practice, in this introduction position, the bent wire forming a spring is compressed to close up the angles at the bends  22   c  and  22   d  against the return force exerted by the wire  22  forming a spring. 
     In this position, the first and seconds ends  22   a ,  22   b  and the intermediate portion  22   e  are adjacent to each other and in a direction parallel to the axis X. 
     The retaining arm  23  is then aligned with the cylindrical tube  21  and the housing  10 , beyond the free end  21   b  of the cylindrical tube  21 , so as not to constitute an increased thickness and to enable introduction of the whole of the system into the transfer catheter  40 . 
     As clearly shown in  FIG. 3 , the system in its introduction position is introduced into the uterine cavity u until the whole of the system lies beyond the cervix. 
     To be more precise, the whole of the system inside the transfer catheter  40  passes successively through the vagina v, then the cervix c before entering the uterine cavity. 
     After removal of the catheter, as shown in  FIG. 4 , the elastic means of the wire  22  forming a spring are adapted to position the retaining arm  23  in a position away from the axis X of the housing, corresponding to a free position of retention in the uterine cavity. 
     To remove the catheter, the practitioner holds the housing  10  associated with the retaining device  20  in position using the semi-rigid rod  45 . 
     Whilst retaining the device in place using the semi-rigid rod, the practitioner withdraws the catheter  40  in translation along the semi-rigid rod  45 . 
     Once the catheter has been entirely withdrawn, the semi-rigid rod  45  is also withdrawn, the housing  10  being retained inside the uterine cavity in particular by the positioning of the retaining arm  23  in a position away from the axis X of the housing  10 . 
     As shown clearly in  FIG. 4 , the contact of the retaining arm  23  inside the uterine cavity is limited to the portion close to the cervix c, in the vicinity of the cervical channel i. 
     Then, on removal of the device after a period of pre-implant development, as shown in  FIG. 3 , the retaining arm  23  is adapted to assume a removal position in which it is substantially parallel to the axis X of the housing. 
     In practice, in this removal position, the retaining arm  23  pivots about a bend  22   d  connecting the second end  22   b  to the intermediate portion  22   e  of the bent wire  22  forming a spring. 
     This removal position of the retaining arm  23  substantially parallel to the axis X is thus the opposite of the introduction position. 
     As clearly shown in  FIG. 5 , on removal of the device, the retaining arm  23  comes into contact with only a very small portion of the endometrium, in the vicinity of the cervical channel i. 
     Thus thanks to mounting the retaining arm  23  on the bent wire  22  forming a spring, this retaining arm  23  can assume two distinct and opposed positions for introduction and removal of the system, providing optimum limitation of the contact between the retaining arm and the endometrium during movements of the system. 
     Thus the endometrial layer that covers the uterine cavity in its fundus portion f, the body portion p and the cervical channel portion i comes very little into contact with the device introduced into the uterine cavity u, and in particular the retaining device. 
     The latter comes mainly into contact with the cervix c, which has no endometrial layer, and to a lesser degree with the cervical channel i. 
     This feature is particularly important when, at the time of implanting the embryo, the latter is placed in contact with the endometrial layer of the uterus to enable nidation and development of the embryo in the uterus. 
     Of course, the present invention is not limited to the embodiment described above. 
     In particular, the retaining device could include a number of retaining arms, for example disposed symmetrically relative to the longitudinal axis X of the housing  10 . 
     Moreover, how the retaining arm is mounted at the proximal end  13  of the housing  10  is not limiting on the invention in any way. 
     Thus the cylindrical tube  21  could be dispensed with, the wire  22  forming a spring being fixed directly at its end  22   a  to the proximal end  13  of the housing  10 . 
     Moreover, the wire  22  forming a spring could include only one bend  22   c , with no intermediate portion  22   e , the bend  22   c  connecting the first portion  22   a  directly to the second portion  22   b.    
     The retaining arm  23  would then be adapted to occupy only two positions, a free retaining position in which the retaining arm is moved away from the axis X of the housing  10 , and an introduction and removal position in which the retaining arm is disposed substantially parallel to the axis X of the housing  10 , aligned with that housing  10  and the cylindrical tube  21 .