Abstract:
An assembly for penetrating the uterus of an animal during a non-surgical procedure comprising a probe having an elongated body with a longitudinal axis and a probing member extending at least laterally outwardly at the forward end of the probe body, a channel extending between an inlet opening at a distance from the probing member and an outlet opening near the probing member, wherein the channel comprises at least one bend or curve, such that the axis of the channel near the outlet opening encloses an angle different from 180° with the longitudinal axis of the probe body, the probe being adapted to be inserted, forward end first, inside the cervix of the animal, and manipulatable to gently maneuver the probing member in a forward direction through the cervix to a position in which the probing member and the outlet opening are within or adjacent the body of the uterus.

Description:
RELATED APPLICATIONS 
     This application is a continuation under 35-U.S.C. §§120 and 365(c) of pending International Patent Application PCT/NL98/00689 filed on Dec. 4, 1998, and designating the United States of America. International Patent Application PCT/NL98/00689 claims priority from European Patent Application EP 97203804.6 filed on Dec. 4, 1997, and was published Jun. 10, 1999, as International Publication WO 99/27868, the contents of which are incorporated herein by this reference. 
    
    
     TECHNICAL FIELD 
     Invention relates to an assembly for penetrating the uterus of an animal during a non-surgical procedure, especially for the introduction of material such as embryos into the uterus of an animal. Such an assembly is known from international publication WO 96/35384. 
     BACKGROUND 
     The known assembly comprises a rigid metal probe, having a long tubular body with a central longitudinal axis and a probing member curving forwardly and laterally outwardly, substantially beyond the forward end of the probe body, the probe body having open forward and rearward ends. The probe is adapted to be inserted, forward and first, inside the cervix of the animal, the probe body then being manipulatable to gently maneuver the probing member in a forward direction through the cervix to a position in which the probing member and the forward open end of the probe body are adjacent the body of the uterus. For introduction of the probe into the cervix, a long tubular gripping instrument is provided, having an open forward end and an external formation configured for gripping the walls of the cervix when the instrument is inserted. The gripping instrument has to be pulled in a rearward direction to straighten the cervix to be able to introduce the probe. The probe body is sized for a coaxial insertion inside the gripping instrument from the forward end thereof, such that the rearward end of the probe body extends outside the rearward end of the gripping instrument. When the probing member is brought into the position adjacent the body of the uterus, as tested with a stainless steel detecting bar, a fluid carrier can be inserted through the probe body, into a position wherein the front end of the elongated fluid carrier extends in a longitudinal direction from the forward, open end of the probe body into the uterus body. Fluid containing the embryos or semen can then be expelled from the fluid carrier into the uterus body. 
     This known assembly has the disadvantage that it is complex, both in composition as well as in use. The assembly comprises a large number of separate parts to be positioned inside and maneuvered relative to each other, which can be difficult, time consuming and irritating for the animal, which will be detrimental to the result. Therefore, the animals have to be anaesthetized especially for enabling positioning of the animal on its back before introduction of the instrument. Furthermore, due to the rigidity of the probe and probe member and the fact that the probe member has to be introduced into the forward end of the gripping instrument, such that the probing member is enclosed within the soft, cork-screw-like forward part of the gripping member, whereby the rearward end of the probe body extends far outside the rearward end of the gripping member, this known assembly is difficult to maneuver. Furthermore, since the probe body is tubular, having open forward and rearward ends, the channel extending through the probe body can easily be contaminated with material from the vagina, cervix and/or uterus, prior to introduction of the fluid carrier into the channel. This can easily result in contamination of the fluid within the fluid carrier, thus influencing the result of the procedure negatively. Moreover, since the channel extends longitudinal through the probe body, the fluid carrier will depart from the probe body in the longitudinal direction of the probe body, and will thus be driven directly into the wall thereof, perpendicular to the longitudinal direction of the cervix. This can be irritating and hazardous for the animal and can furthermore result in further contamination of the fluid. Upon further introduction of the fluid carrier, the forward end, extending outside the probe body, will bend and will be pushed into one of the horns of the uterus, which could result in a fold in the fluid carrier, resulting in a blockage of the through bore of the fluid carrier, thus preventing or at least hindering the delivery of the fluid into the uterus body and cause lethal damage to the fragile embryos due to squeezing. 
     FR-A-2477008 and FR-A-2432866 both disclose further assemblies for penetrating the uterus of an animal. These known assemblies both comprise a rigid tubular probe member, made of metal, which during use extends straight through the uterus and cervix, forcing apart any curved wall parts. Therefore, these probe members cannot be used with unsedated animals. 
     SUMMARY OF THE INVENTION 
     A main object of the present invention is to provide for an assembly for penetrating the uterus of an animal during a non-surgical procedure, wherein the drawbacks of the known method are overcome, maintaining the advantages thereof 
     An assembly according to the present invention comprises only a limited number of components, which are easy to manufacture and use, wherein the probe body can be introduced into the cervix of the animal directly, via the vagina, and can then be manipulated such that the probing member passes the cervix to a position within or adjacent the uterus body. Since the axis of the outlet opening encloses an angle with the longitudinal axis of the probe body, accumulation of contamination within the channel can be easily prevented, whereas blockage of the outlet opening by the wall of the uterus body, when the probe body is fully inserted, is easily prevented. An assembly according to the present invention provides for easy and safe penetration of the uterus of an animal during a non-surgical procedure, whereby the outlet opening of the channel and thus the place of introduction of, for example, embryos or semen is accurately reproducible. Thus, the chances of success of a non-surgical procedure performed with an assembly according to the present invention are very high. Thereby, the animals do not have to be anaesthetized or restrained to perform the procedure, but can be housed similar as when performing usual artificial inseminations. 
     At least part of the inside walls of the cervical channel is convoluted and lined with rounded prominences, some of which dovetail, occluding the canal. With an assembly according to the present invention, the probe being sufficiently flexible, the probe can be introduced into the cervix and manipulated such that the probing member can be maneuvered in between the prominences, partly pushing these apart, whereby the probe body can follow the curves of the cervical canal and at least partly follow the convolution of the inner walls by flexing, thereby passing the occlusions of the canal. The outlet opening of the channel can thus be brought easily, conveniently and accurately within or adjacent the uterus body. 
     In a further advantageous embodiment, an assembly according to the present invention is characterized by a second tubular member, being slidably insertable through the channel. This second tubular member can be easily used as a fluid carrier. Since the length of the second tubular member is greater than the length of the channel, the forward end of the second tubular member, provided with an outlet opening, can be pushed through the outlet opening of the channel by manipulating a rearward part of the second tubular member still extending outside the channel from the inlet opening thereof. In combination with the axis of the outlet opening of the channel enclosing an angle with the longitudinal axis of the probe body, the direction of extension of the forward end of the second tubular member through the outlet opening of the channel will be advantageous since the forward end of the second tubular member will not be driven directly into the inside wall of the uterus body but into one of the horn-like protrusions of the uterus body. Thus, blockage of the outlet openings is easily prevented. Furthermore, the tubular member can be introduced from the rearward end of the channel, after the probe body has been fully introduced. 
     By providing a tubular member extending along at least part of the probe body and the probing member, the channel can be easily provided. The tubular member can be attached to the probe body, at least near the probing member, for example, by adhesive or a mutual relatively soft and flexible coating, whereas the rearward end of the probe body and the tubular member can be separated. The rearward end of the tubular member can then be easily manipulated for introduction of, for example, a fluid carrier, a cannula or the needle of a syringe, without having to grip the rearward end of the probe body and vice versa. 
     In an alternative embodiment, an assembly according to the present invention features a channel which extends through the probe body and the probing member, the assembly thus being very easy to manufacture, for example, by bending from an elongated tubular piping. 
     In further elaboration, an assembly according to the present invention may be characterized by providing the outlet opening in the wall of the second tubular member, the forward end of the tubular member, being closed, provides for an advantageous direction for expelling fluid from the outlet opening, approximately perpendicular to the longitudinal direction of the tubular member, thereby even better preventing blockage of the outlet opening of the second tubular member should the forward end thereof be driven into the inner wall of the uterus body. Since the forward end of the second tubular member, extending from the channel within the uterus body, will be approximately straight, that is not bent over 180° or more, as the fluid carrier used with the known assembly, folding thereof is easily prevented, thus preventing occlusion of the channel within the second tubular member. 
     The invention further relates to a method for non-surgical introduction of material such as embryos into the uterus of an animal. Such method necessitates only the use of a probe with an elongated channel and a tubular member slidably insertable into the channel. A method according to the present invention can easily and very accurately be performed with a very high rate success. Such method is very animal friendly, quick and relatively inexpensive. 
     Further advantageous embodiments of an assembly and a method according to the present invention are described in the subclaims and the description. 
     To further clarify the invention, exemplary embodiments of a method and assembly according to the present invention will be described hereafter with reference to the drawings. 
    
    
     DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS 
     FIG. 1 is a schematic illustration of the uterus of a pig; 
     FIG. 2 is a side view of a probe according to the present invention, partly broken away, in a first embodiment; 
     FIG. 3 is a side view of a probe according to the present invention, partly broken away, in a second embodiment; 
     FIG. 4 is a side view of an assembly according to the present invention, introduced into the uterus of a pig; 
     FIG. 5 is an enlarged side view of an assembly according to the present invention, in cross-section, on an enlarged scale; 
     FIG. 6 is a further embodiment of an assembly according to the present invention; and 
     FIG. 7 is a still further embodiment of an assembly according to the invention. 
    
    
     Corresponding parts are designated by corresponding reference numbers throughout the description. 
     DETAILED DESCRIPTION 
     FIG. 1 shows schematically the anatomical configuration of the uterus of a pig. The uterus  1  comprises a uterus body  2 , a pair of horn-like extensions  3 A,  3 B, extending from the uterus body  2 , and a cervix  4  connecting the vagina  5  of the pig to the uterus body  2 . The inside walls defining the cervical canal  6  of the cervix are convoluted and lined with rounded prominences  7 , some of which interconnect to occlude the canal  6 . 
     An assembly and method according to the present invention are illustrated with respect to the non-surgical transplant of fluid comprising, for example, semen or especially embryos into the uterus of a pig. However, it will be understood that the same assembly and method can be used to carry out artificial insemination, non-surgical transfers and similar non-surgical methods of transfer of other fluids and material in porcine, bovine and other species. 
     FIG. 2 shows a first embodiment of a probe  8  according to the present invention, the probe  8  comprising a probe body  9  and a channel  10 . The probe body  9  is relatively long and has a longitudinal axis A, a probing member  11  extending at least laterally outward at the forward end  12  of the probe body and a gripping means  13  extending from the opposite rearward end  14  of the probe body  9 . In the shown embodiment, the probe body  9 , the probing member  11  and the gripping means  13  are made by bending a plastic rod into the desired shape, for example, a PVC rod. The longitudinal axis B of the probing member  11  encloses an angle α with the longitudinal axis A of the probe body, which angle α in the shown embodiment is approximately 90° . However, the angle α can also be a sharp or blunt angle, for example, between 45° and 135° , preferably between 60° and 120°. The length of the probing member  11  and the enclosed angle α can be chosen such that by manipulating the probe body, the probing member  11  can be introduced in between and manuevered past the prominences  7  of the canal  6  of the cervix  4 , as will be explained hereafter. The gripping means  13  comprises the bent rearward end  14  of the probe body  9 . The probing member  11  and the gripping means  13  are preferably positioned in the same plane when the probe  8  is in its initial position. This has the advantage that the position of the gripping means  13  provides for a direct indication of the position of the probing member  11  when introduced into the uterus  1 . The length of the probe body  9  is at least such that when the probing member  11  is positioned in or adjacent to the uterus body  2  or one of the horn-like extensions  3 A,  3 B, the rearward end  14  of the probe  8  extends well outside the vagina  5 , as is shown in FIG.  4 . Thus, the probe  8 , especially the probing member  11 , can be manipulated within the uterus body  2  by manipulation of the gripping means  13 , which extends well outside the uterus. 
     The channel  10  is provided for by a tube  15 , preferably made of a flexible material such as plastic, silicone, rubber or the like, positioned alongside at least a substantial part of the probe body  9  and the probing member  11 . The channel  10  comprises an inlet opening  16  near the rearward end  14  of the probe  8  and an outlet opening  17  near the free end of the probing member  11 , that is, near the forward end  12  of the probe  8 . Since the part  18  of the tube  15  near the outlet opening  17  extends alongside the probing member  11 , the central axis C of the part  18  extends at least approximately parallel to the longitudinal axis B of the probing member  11 , enclosing approximately the angle α with the longitudinal axis A of the probe body  9 . The forward end of the tube  15  and the forward end  12  of the probe body  9  are embedded in a casing  19  made preferably of a relatively soft, flexible material, such as elastomer, silicone, rubber or the like, to connect the forward end of the tube  15  to the probe body  9  and probing member  11  and may also protect the inside walls of the uterus  1  and cervix  4 . The outlet opening  17  is positioned approximately adjacent the free end of the probing member  11 , and is closed by a membrane  20 , which is pierceable or which can be pushed away, as will be explained later. The membrane  20  prevents contamination of the inside of the channel  10  during manipulation of the probe through the vagina into the cervix and uterus body  2 . 
     The tube  15 , and thus the channel  10 , preferably has a length which is substantially greater than the length of the probe body  9 , whereby the flexible rearward part  21  is free from the probe body  9 . Thus, the inlet opening  16  of the channel  10  is easily accessible, for example, from an angle different from the longitudinal axis A of the probe body  9  when introduced into the uterus  1 . 
     In FIG. 5, an assembly according to the present invention is shown, in an enlarged scale, comprising a probe  8  according to FIG. 2, through which a tubular element  21  is introduced, as will be explained hereafter. 
     The probe  8  is covered, with at least its forward part to be introduced into the uterus, by a thin, flexible sheet, for example, a plastic foil, which can be tubular (not shown). Then, the forward end  12  of the probe  8  is introduced through the vagina into the cervix, until the probing member  11  abuts one of the prominences  7  at the entrance of the canal  6 . Then, if necessary, the probe  8  is rotated, preferably in a reciprocal manner, mainly around its longitudinal axis A, by manipulation of the gripping means  13 , such that the probing member  11  is gently urged in between the prominences  7 , thereby partly moving the prominences  7  apart and partly flexing the probe body  9 . The protective sheet can be pulled away over the probe body  9 . Thus, the forward end  12  of the probe can be gently urged forward past the prominences  7 , at least partly following the bends and curves of the cervix  4 , as is shown in FIG.  4 . Once the forward end  12 , that is, the probing member  11 , has been pushed past the prominences  7  of the cervix  4 , the forward end  12  of the probe  8  can be introduced into the uterus body  2 , until the probing member  11  is positioned near one of the horn-like extensions  3 A,  3 B. An indication  23  has been provided on the probe body  9 , for example, a coloring, at a distance from the probing member  11  corresponding to the average length of the uterus body, cervix and vagina of the relevant animal taken together. Furthermore, the resistance of the inside wall of the uterus body in comparison to the resistance of the cervical canal will provide an indication of the position of the probing member  11  within the uterus body  2 . 
     When the probe  8  is brought into the position as shown in FIG. 4, the tip  24  of the tubular member  22  is slidably introduced into the inlet opening  16  of the channel  10  within the tube  15 . The forward end of the tip  24  is closed, whereby an outlet opening  25  is provided in the wall  26  of the tubular member  22 , at a relatively short distance from the tip  24 . The tubular member  22  further comprises an inlet opening  27  at the tail  28 , that is, the opposite rearward end of the tubular member  22 , in which, for example, the needle  29  of, for example, a syringe  30  has been introduced. The tip  24  of the tubular member  22  is pushed forward through the channel  10  until the tip  24  abuts the membrane  20 . By forcing the tip  24  forward, the membrane  20  will be pierced or pushed aside, after which the outlet opening  25  will be pushed past the outlet opening  17  of the channel  10 , the tip  24  extending freely within the uterus body  2  or one of the horn-like extensions  3 A,  3 B thereof. Then a fluid, containing, for example, semen or embryos, to be introduced into the uterus  1  is introduced from the syringe  30 , through the channel  32  of the tubular member  22  and out the outlet opening  25  into the uterus body  2  or horn-like extension  3 B. Since the tubular member  22  is fully guided by the channel  10 , that is, the tube  15 , folding of the tubular member  22  or any other occlusion thereof is prevented. Therefore, a proper introduction of the fluid into the uterus body  2  or horn-like extension  3 B is guaranteed. 
     Depending on, for example, the form and position of the horn-like extensions  3 A,  3 B and the uterus body  2  and cervix  4  relative to each other, the length of the probe body  9 , the enclosed angle α between the longitudinal axes A and B, the angle enclosed between the longitudinal axis A and central axis C and the flexibility of at least the probe body  9  can be chosen appropriately. By way of example, which should by no means be understood as limiting the scope of the present invention, dimensions are given for an assembly according to the present invention, convenient to be used for introduction into the uterus of a pig. The probe body can have an overall length of approximately 950 mm, with a circular cross-section having a diameter of 3 mm. A first indicator is positioned at approximately 115 mm, and a second indicator at approximately 310 mm from the rearward end  14 . The enclosed angle α is approximately 110°, and the length of the probing member  11  approximately 10 mm. The tube  15  has an inside diameter of 1.5 mm, and the tubular member  22  an inside diameter of approximately 0.7 mm. The excess length of the tube  15  is, for example, 170 mm over the length of the probe body  9 , and the excess length of the tubular member  22  over the tube  15 , for example, is 350 mm. The distance between the tip  24  and the outlet opening  25  of the tubular member  22  will be approximately 5 mm. The modulus of elasticity of the probe body, which is made of PVC, is preferably just under 3000 N/mm 2 . An appropriate choice of dimensions and materials to be used will nevertheless be sufficiently clear to the person skilled in the art. 
     FIG. 3 shows an alternative embodiment of a probe  108  according to the present invention, made of a single, bent, tube-like probe body  109 . The probe body  109  is, for example, made of plastic, such as PVC, PE, PA, silicone or any other suitable material. The forward end  112  of the probe body  109  has been bent over an angle α, again for example 90°, for forming the probing member  111 . The forward end  112  might be embedded in a soft casing  119 , as discussed before. The rearward end  114  of the tube-like probe body  109  has been bent over an angle β for forming the gripping means  113 . The gripping means  113  and the probing member  111  are once again positioned in the same plane. Through the probing member  111  and the probe body  109  extends the channel  110 . In the rearward end  114  of the probe  108 , an inlet opening  116  has been provided, preferably such that the longitudinal axis A of the probe body  109  extends through the inlet opening  116 . Within the outlet opening  117  of the channel  110 , within the probing member  111 , a stop  120  has been provided for temporarily closing the outlet opening  117 , thus prohibiting contamination of the inside of the channel  110 . Once again, the probe body  109  is sufficiently flexible to at least partly follow bends, curves and prominences of the cervix and/or uterus body of a uterus  1  of an animal. 
     During use, the probe  108  can be brought into position as shown in FIG. 4 in a manner similar to the one as described with reference to the embodiments shown in FIG.  2 . Then, the tip of a tubular member  122  (not shown), similar to the tubular member  22  as shown in FIG. 5, can be introduced through the inlet opening  116  into the channel  110  and can then be pushed forward until the tip thereof is in abutment with the stop  120 . The stop  120  can then be pushed out of the outlet opening  117 , thus enabling the tip, especially the outlet opening  125  (not shown) of the tubular member  122  to be urged into the uterus body or horn-like extension of the relevant uterus. Then, an appropriate fluid can be introduced from a syringe into the uterus as described hereinbefore. Such stop  120  is preferably attached to the assembly to enable retraction thereof with the assembly. 
     FIG. 6 shows a further alternative embodiment of an apparatus according to the invention, similar to the assembly according to FIG.  5 . In this assembly according to FIG. 6, the tubular member  22  is divided in a relatively short first part  22 A, comprising the tip  24  and the outlet opening  25 . This first, relatively short part is connected to a second part  22 B with a relatively great length through a hollow connecting element  31 , forming a fluidum connection between the first and second parts  22 A,  22 B. This assembly can be used as follows. The semen or embryos to be introduced through the outlet opening  25  into the cervix are enclosed within the first part  22 A, in which they can be transported and stored. To this end, the connecting member  31  can be replaced by a stopper element (not shown). Directly before use, the stopper element is removed and the first part  22 A is connected to the second part  22 B through the connecting element  31 , after which the tubular member  22  is brought into position for introduction of the embryos (or semen) through the outlet opening by the syringe  30 . In an embodiment as shown in FIG. 7, the stopper element  33  is connected to a rod or wire  34  sufficiently flexible to follow bends and curves in the tubular member  22  and sufficiently rigid to push the stopper element  33  through at least the first part  22 A of the tubular member  22 , which wire  34  extends through the second part  22 B of the tubular member  22 , such that the free end  35  thereof extends outside the tubular member  22 . By this wire  34 , the stopper element  33  can be pushed forward, such that the embryos or semen are forced out through the opening  25 . The wire  34  can be fixed to the stopper  33  or positioned free in the tubular member  22 . An assembly according to FIGS. 2 and 3 can be amended in a similar way. Such assembly has the advantage that storage and transport of the semen or embryos is easy, as is handling thereof. 
     As can be understood from the description and the drawings, the outlet opening  25 ,  125  of the tubular member  22 ,  122  can be brought into a position with minimal pressure of the inside wall of the uterus very easily, even though the forward end of the probe assembly cannot be seen by the person manipulating the probe assembly. Thus, a proper delivery of the fluid into the uterus body is guaranteed. It will be directly clear that the fluid could also be introduced into the uterus body directly through the channel  10 ,  110  without the use of the tubular member  22 ,  122 , as long as the outlet opening  25 ,  125  is open or opened before or upon introduction. 
     A flexible assembly according to the present invention has the advantage that it can be introduced into the vagina, cervix and uterus of an animal, even if it is not sedated. Therefore, a method according to the present invention can be performed without the necessity of assistance by a veterinarian or surgeon or the like. Especially with introduction of embryos, an assembly according to the present invention is advantageous since a very high rate of success can be obtained with a normal number of embryos necessary. For example, with an assembly according to the present invention, about thirty well-developed embryos were brought into the uterus of pigs, which resulted in pregnancy for approximately 60% of the pigs, or an average carrying about 9 to 10 embryos on the thirty-fifth day of their pregnancy. This is, for this moment, a high rate of success, especially for a non-surgical method. 
     Within the scope of the present invention a number of variations on the embodiments shown and described hereinbefore are possible. 
     For example, the probe body and tube, as shown in FIG. 2, could be produced as one single part, having, for example, an approximately oval or FIG. 8 like cross-section, the channel being positioned off center. Furthermore, the gripping means could be dispensed of or could be provided for in a different manner, for example, as a knob-like element attached to the probe body. If so desired, the outlet opening  25 ,  125  of the tubular member  22 ,  122  could be positioned in a different place, for example, in the end face of the tubular member, whereas also a number of spaced-apart outlet openings could be provided for, thus even better ensuring at least one free outlet opening during use. Furthermore, the probe body could, for example, be curved in an unstressed, initial position, the curve being comparable to the possible curvature of the cervix of the relevant animal. A probe or probe assembly according to the present invention can be of a reusable type but is preferably of a dispensable type. Instead of using a syringe for introduction of relevant material such as semen or embryos into the uterus, it is also possible to introduce such material into the tubular member  22 ,  122  through the outlet opening  25 ,  125  prior to introduction of the tip into the channel, whereby the material can be introduced into the uterus body or horn-like extensions thereafter by using a syringe, forcing a fluid through the tubular member, thus pushing the material, contained in the tip of the tubular member, out through the outlet opening. Thus, only a limited volume of fluid has to be introduced into the uterus. Furthermore, the material could be brought into the channel or tubular member by different means, for example, by using a pump or the like. The probe body can be partly relatively rigid and partly relatively flexible, due to a choice of material and/or construction. 
     Those and similar variations are considered to fall within the scope of the present invention.