Abstract:
A catheter including a shaft including a body with a proximal portion and a distal portion, the body defining an opening from the proximal portion to the distal portion, the distal portion having an exterior dimension suitable for insertion into a body of a subject as a procedural instrument, the distal portion having an end that is beveled in a first direction across an end opening, such that a length of the shaft to a first point is a first length and a length of the shaft to a second point on the end is a second length longer than the first length, a portion of the shaft extending from the second point defining a tip, wherein the tip comprises a material that has sufficient rigidity to penetrate an endometrial lining of a subject and sufficient flexibility to resist penetration of a uterine muscle of a subject.

Description:
CROSS-REFERENCE TO RELATED APPLICATION  
       [0001]     This application is a continuation-in-part of co-pending U.S. patent application Ser. No. 10/725,623, filed Dec. 1, 2003 which is a continuation-in-part of co-pending U.S. patent application Ser. No. 10/080,177, filed Feb. 19, 2002, and which is a continuation-in-part of U.S. patent application Ser. No. 09/759,415, issued as U.S. Pat. No. 6,623,422 on Sep. 23, 2003. 
     
    
     BACKGROUND  
       [0002]     1. Field  
         [0003]     The embodiments disclosed herein relate generally to endoscopic devices, including hysteroscopes and related devices for microsurgical use.  
         [0004]     2. Description of Related Art  
         [0005]     Improving the success of in vitro fertilization (IVF) depends on many factors, one of which is the delivery or transfer of the embryo to the endometrial lining of the uterus and the successful implantation of the embryo therein. It is well known in the art that assisting an embryo to adhere to, or implant within, a predetermined area of the endometrial lining of the uterine wall, as opposed to simply releasing the embryo into the uterus, will enhance the success of IVF.  
         [0006]     One method of assisted embryo transfer is found in U.S. Pat. No. 6,010,448 to Thompson in which an embryo is transferred with the aid of an endoscopic device, via a flexible catheter, to the endometrial lining and affixed thereto with an adhesive.  
         [0007]     Another method of embryo transfer is taught in U.S. Pat. No. 5,360,389 to Chenette in which, after using pressurized CO 2  gas to distend the uterine walls, an endoscope is used to select an implantation site. A catheter is then used to forcibly inject the embryos into the endometrial lining.  
         [0008]     While the embryo transfer methods of these prior art types may be generally satisfactory for their intended purposes, implantation problems can arise in which the trauma to the delicate embryos by either an injection or “adhesion” may yield less than optimal solutions and fail to achieve high IVF success rates. Accordingly, improved devices that may be useful, in one aspect, in intrauterine procedures such as IVF are desired. An improved embryo transfer method is also desired.  
       SUMMARY  
       [0009]     A catheter, an endoscope (hysteroscope), and a method of introducing at least one embryo into a uterus of a subject is described. One object of the device(s) and/or method is to provide a simple gentle method for intrauterine procedures such as embryo transfer and implantation. To accomplish this gentle transfer, an improved catheter (referred alternatively and interchangeably herein as “microcatheter”) with a beveled opening and tip is described. The catheter is able to work as both a microsurgical instrument, used in a method described herein to form an embryo-receiving pocket within the endometrial lining of a subject&#39;s uterus, and as the vehicle for transferring an embryo into the pocket. It has been observed that by gently securing an embryo within a pocket of endometrial lining, many of the risks of IVF, such as a tubal pregnancy, misplacement of the embryo, and loss of the embryo can be minimized. Tubal pregnancies, for example, are virtually eliminated according to this method. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0010]      FIG. 1  is a side view of an embodiment of a catheter or microcatheter.  
         [0011]      FIG. 2  is a side view of the distal end of the microcatheter of  FIG. 1 .  
         [0012]      FIG. 3  is a perspective top side view of the distal end of the microcatheter of  FIG. 1 .  
         [0013]      FIG. 4  is a schematic, cross-sectional side view of an embodiment of a hysteroscope.  
         [0014]      FIG. 5  is a cross-section side view of a distal end of the microcatheter of  FIG. 1  containing an embryo for implantation.  
         [0015]      FIG. 6  is a first sequential view of an embodiment of a method of assisted embryo implantation, which shows the survey of the endometrial lining for an implantation site.  
         [0016]      FIG. 7  is a second sequential view of the method of assisted embryo implantation, which shows the formation of an embryo-receiving pocket at the selected implantation site.  
         [0017]      FIG. 8  is a third sequential view of the method of assisted embryo implantation, which shows the implantation of the embryo within the pocket of  FIG. 7 .  
         [0018]      FIG. 9  is a fourth sequential view of the method of assisted embryo implantation, which shows the closure of the embryo-receiving pocket over the embryo. 
     
    
     DETAILED DESCRIPTION  
       [0019]     Referring now to the drawings, illustrated in  FIGS. 1-3  is one embodiment of a microcatheter. Microcatheter  10  includes, in this embodiment, proximal portion  5  and distal  15 . Microcatheter  10  includes shaft or cannula  25  having a lumen therethrough. Shaft  25  terminates at distal shaped end  30 . Proximal portion  5  includes, at proximal end  22 , a hub to mate with operational syringe  20 , with plunger  21 . The hub is, for example, a luer lock fitting. In one embodiment, extending approximately 25-30 millimeters from the hub is stabilizer  27  of, for example, a polymer tube having an inner diameter slightly greater than an external diameter of shaft  25 .  
         [0020]     Shaft  25  defines a lumen therethrough for, representatively, introducing one or more embryos into a uterus of a subject. In one embodiment, shaft  25  is an extruded one piece polymer material having a length on the order of 70 centimeters (cm). Suitable polymers for shaft  25  are selected such that the shaft has sufficient rigidity to be advanced through an endoscope, specifically through an endoscopic cap inserted in an endoscope (see, e.g., endoscopic cap  221  in  FIG. 4 ) to penetrate the endometrial lining of a subject&#39;s uterus (see, e.g.,  FIGS. 5-9  and the accompanying text). The polymer material is also selected such that shaft  25  is flexible enough so the shaft does not penetrate the uterine muscle of the subject. One suitable polymer is polycarbonate (e.g., transparent polycarbonates). Tetrafluoroethylene (e.g., TEFLON™), polyurethane, polyethylene, and nylon materials may also be suitable. A suitable outside diameter for a proximal portion of shaft  25  is on the order of one millimeter (mm) or less. Shaft  25  includes a distal portion including shaped end  30 . An external marking (e.g., marking  38 ) may be included at a position, for example, one centimeter (cm) from the distal end of shaft  25  to provide a visual identification of either the volume of contents within microcatheter  10  or a location of microcatheter  10 , for example, in tissue. One way to form marking  38  is by placing a ring-shaped heat shrink on shaped end  30  and thermally bonding the ring to the shaft.  
         [0021]     Shaped end  30  of microcatheter  10  includes base region  31  of a similar diameter as the flexible hollow shaft  25  (e.g., 1 mm or less) and then tapers over 1 to 3 mm into narrow distal end  33  which is, for example, approximately one to two centimeters in length, with a representative outside diameter of 0.8 mm or less (e.g., an outside diameter less than the outside diameter of a non-tapered portion of the shaft). In one embodiment, distal end  33  has an interior diameter of approximately 10 micrometers (μm) or larger, preferably between 400 to 500 μm.  
         [0022]     Microcatheter  10  also includes angled or beveled opening  34  at its distal end. Beveled opening  34  extends between first point  40  that defines a length of shaft  25  and second point  45  at a distal end of the opening. Angle, γ, of beveled opening  34  between a projection including first point  40  and second point  45  and a perpendicular projection from point  45  of shaft  25  is 0° to 45°. A representative length, L 1 , of beveled opening  34  is 0.1 to 1.5 millimeters (mm).  
         [0023]     Opening  34  may be formed only between first point  40  and second point  45  or extend into portion  35  as shown in  FIG. 3 .  
         [0024]     Extending distally from second point  45  is tip  35 .  FIG. 2  illustrates a sharp transition between beveled opening  34  and tip  35 . It is appreciated that the transition may be gradual (e.g., curved).  
         [0025]     Surface  355  of tip  35  (on the side of beveled opening  34 ) may have an angle, β, relative to opposite surface  356  of 0° to 45° and a length, L 2 , on the order of 0.1 mm to 3 mm. In one embodiment, tip  35  is part of the polymer body of shaft  25 . To form tip  35 , a polymer tube may be cut to a length that includes tip  35 . Beveled opening  35  may then be formed by a second proximal cut that does not extend completely through the tube. The portion of tubing extending distally from beveled opening  34  (from second point  45 ) may then be trimmed into an arrow-like shape to form tip  35  (e.g., with a tip or point defining the distal end).  
         [0026]     Opening  34  is the vehicle through which an embryo is delivered into the implantation site and may also be the microsurgical instrument used to form an implantation pocket within the endometrial lining as described with reference to  FIGS. 5-9  and the accompanying text. A point at the distal end of shaft  25  representing the greatest length of shaft  25  defines tip  35 . A portion of the body of shaft  25  including tip  35  may be beveled in a direction opposite bevel angle γ to yield a more refined cutting tool.  
         [0027]      FIG. 4  shows a schematic, cross-sectional view of an embodiment of a hysteroscope. In this embodiment, hysteroscope  200  includes operational section  211  at one end (a proximal end) and hybrid insertion arm  212  at a second end (a distal end). Hybrid insertion arm  212  is generally tubular (defining one or more lumens therethrough) and includes proximal portion  218  of a generally rigid material, such as stainless steel or a rigid polymer material, and distal portion  219  of a relatively flexible material (e.g., a polymer material such as polycarbonate or polyethylene). Representatively, proximal portion  218  has a length on the order of about 5 to 30 centimeters (cm) with about an outside diameter (OD) on the order of 3 to 4 mm. Distal portion  219  has a representative length of 3 to 15 cm and a representative OD of 2.5 to 4 mm, preferably 3.0 to 3.5 mm, and preferably a representative diameter slightly smaller (at least toward distal end  230 ) than proximal portion  218 .  
         [0028]     Referring to  FIG. 4 , operational section  211  includes handle portion  227  that is preferably knurled for better holding and feel. Coupled to a distal end of handle portion  227  is lever holder  228 . Disposed within lever holder  228  is articulating lever  229  that is coupled through, for example, wire members (e.g., braided wire members) to distal portion  229 . Representatively, deflection of articulating lever  229  about lever holder  228  deflects distal portion  219  of hybrid insertion arm  212  to the same degree. In one embodiment, articulating lever  229  rotates about a single axis 60° in two directions (e.g., clockwise and counterclockwise) for a total range of deflection of 120°. Protruding stops  213  on lever holder  228  may be included to limit articulation of articulating lever  229 .  
         [0029]     Referring to  FIG. 4 , at a proximal end of handle portion  227  of hysteroscope  200  is access port  216 . Access port  216  provides access to operational channel or lumen  220 . Operational channel  220  extends through the device from operational section  211  to hybrid insertion arm  212  terminating at distal tip  230 . In this embodiment, access port  216  is axially aligned with operational channel  220 . In one regard, the axial alignment aids the insertion of instruments such as a microcatheter into operational channel  220 .  
         [0030]     In some embodiments, a microcatheter or other instrument may be inserted in operational channel  220  through access port  216  at the same time as a gas or fluid is administered through the hysteroscope to a patient. To minimize leakage of gas or fluid around a microcatheter (e.g., microcatheter  10 ) or other instrument, endoscopic cap  221  is placed in access port  216 . Endoscopic cap  221  of an elastic material has an opening therethrough to allow access to operational channel  220 . In one procedure, endoscopic cap  221  is fitted into access port  216  and a blunt needle (e.g., an 18 gauge needle) having a lumen of a diameter suitable to allow the passing of a microcatheter or other instrument therethrough is inserted through endoscopic cap  226 . The microcatheter or other instrument is then inserted through the blunt needle and advanced into operational channel  220  as desired. Once the microcatheter or other instrument is positioned, the blunt needle may be removed.  
         [0031]     Also at a proximal end of handle portion  227  of hysteroscope  200  is a portion of illumination train  240  including illumination holder  244 . A plurality of illumination fibers (e.g., glass fibers) are disposed within illumination holder  244  and join operational channel  220  within handle  227 .  
         [0032]     At a proximal end of handle  227  is a portion of image train  255  including eyepiece  256 . Eyepiece  256  is coupled to lumen  236  (see  FIGS. 9 and 10 ) which joins operational channel  220  within handle  227  and is axially aligned within a primary lumen extending from operational section  211  to hybrid insertion arm  212 .  
         [0033]     Coupled at a proximal end of operational channel  220  is valve  226  to, in one position, seal or block operational channel  220  and, in another position, to allow insufflation gas or an instrument such as a microcatheter to be passed through operational channel  220 . In another embodiment, valve  226  may have three positions to, for example, provide individual access ports for an instrument and for gas or fluid (e.g., allowing introduction of a gas or fluid through operational channel  220  at the same time an instrument is inserted through operational channel  220 ). In one embodiment, valve  226  includes a positioning portion that may be handled by an operator to position valve  226  and that is sterilizable, removable and replaceable. A microcatheter and/or insufflation gas, in one embodiment, may alternatively be introduced to operational channel  220  at entry port  216 .  
         [0034]      FIGS. 5-9  show the sequential performance of an embryo implantation procedure representatively using microcatheter  10  and hysteroscope  200 . The biology, timing and biochemistry involved in embryo selection and in optimizing the subject for implantation is not the topic of this invention. It is well known by those skilled in the art of how best to harvest and fertilize eggs and how best to select viable embryos. Volumes of scientific literature also exists on the hormonal, pharmaceutical and other chemical factors which should be orchestrated, monitored and taken into account when selecting the timing for embryo implantation. Accordingly, such information is omitted.  
         [0035]     Prior to any intrauterine activity, an embryo must be placed in microcatheter  10 . Microcatheter  10  will be used to both prepare the site for implantation and to transfer the embryo “E” into the site. Shown in  FIG. 5  is an embryo “E” immersed in a culture medium “CM” placed near distal end  33  of microcatheter  10 . The culture medium “CM” serves the important role of maintaining the health and viability of the embryo “E” during the procedure. In this embodiment, the culture medium “CM” used is a “modified Human Tubal Fluid” manufactured by Irvine Scientific of Irvine, Calif. Considering the rapid pace of advancements in IVF, new and varied culture media will undoubtedly be developed or become available. Accordingly, the method described should not be limited to that culture media described herein, but rather to any suitable culture media which serves the function of maintaining embryo viability during the implantation procedure.  
         [0036]     Prior to placing the embryo “E” into microcatheter  10 , a first quantity of culture medium “CM” is drawn into microcatheter  10  and followed by a back measure of atmospheric air “A2” (e.g., 10-20 microliters (μL)). Next, the embryo “E”, bathed in more culture medium “CM” (e.g., 5-10 μL), is drawn into distal end  33  of microcatheter  10  followed by a front measure of atmosphere air “A” (e.g., 5-10 μL), thereby sandwiching the embryo “E” between a first and second measure of atmospheric air “A” and “A2”. Once loaded with the embryo “E”, microcatheter  10  is ready for use in the implantation procedure. Each measure of atmospheric air may be, for example, about three to twenty microliters in volume.  
         [0037]     In one procedure, endoscopic cap  221  is inserted into access port  216  of hysteroscope  200  (see  FIG. 4 ). A blunt needle having a lumen of a diameter suitable to allow the passing of microcatheter  10  therethrough, is inserted through endoscopic cap  221 . Microcatheter  10  loaded as described above is threaded into operational channel  220  of hysteroscope  200 , so that tip  35  is approximately one to two centimeters (cm) from distal end  230 . The blunt needle may then be removed from the endoscopic cap so that the cap snugly surrounds microcatheter  10 .  
         [0038]     Distal portion  212  of representatively hysteroscope  200  is guided into the uterus “U” ( FIG. 6 ). During the insertion of the hysteroscope  200 , N 2  gas  101  is fed into the uterus “U” pressurizing or insufflating the uterus “U” and thereby distending the uterine walls “W”. Depending on the needs of the operator, and the uterus of the subject, the gas  101  may be automatically maintained at a constant pressure or the operator may vary the pressure. The distension of the uterine walls “W” enhances the visualization through hysteroscope  200  within the uterus “U”.  
         [0039]     Once an embryo implantation site “I” is selected, microcatheter  10  is inserted into the endometrial lining “L” ( FIG. 7 ) with tip  35  moved generally along the path of arrow  300  making a small incision two to five millimeters (mm) deep in the endometrial lining “L” to form a small flap “F”. The front measure of atmospheric air “A” is then released from microcatheter  30  and acts to lift up the small flap “F” of the endometrial lining “L”.  
         [0040]     Shown in  FIG. 8  is the embryo-receiving pocket “P” formed beneath the small flap “F”. The actual implantation of the embryo “E” into the embryo-receiving pocket “P” is performed with the same microcatheter  30  used to form the embryo-receiving pocket “P” and is accomplished by depressing plunger  21  of syringe  20  (see  FIG. 1 ) to gently urge the embryo “E” and the back measure of atmospheric air “A2” out of microcatheter  30  and into embryo-receiving pocket “P”.  
         [0041]     The back measure atmospheric air “A2” forms a cushion around the embryo “E” which helps to protect it when the microcatheter is removed ( FIG. 9 ) and the small flap “F” drops back into place over the embryo “E” along the line of arrow  201 . To complete the procedure, hysteroscope  200  is then gently removed from the subject and post-IVF precautions and protocols should be used. Another possible advantage of a successful implantation of the embryo “E” within the endometrial lining “L” is that the length of the post-IVF precautions may be reduced.  
         [0042]     Dependent on the subject, the number of viable embryos available and the aperture, up to two embryos may be implanted into a single pocket “P”. In the case of embryo implantations into multiple pockets, additional embryos, each bathed in culture medium, are sandwiched between a measure of atmospheric air within the microcatheters and implanted into separately formed pockets “P”.  
         [0043]     Certain presently preferred embodiments of apparatus and methods for practicing the invention have been described herein in some detail and some potential modifications and additions have been suggested. Other modifications, improvements and additions not described in this document may also be made without departing from the principles of the invention. For example, the microcatheter (e.g., microcatheter  10 ) and hysteroscope (e.g., hysteroscope  200 ) have been described with reference to an IVF procedure. It is appreciated that such devices need not be specified together and either may have other uses beyond IVF procedures. Representatively, the hysteroscope may be used in connection with other devices such as biopsy forceps or other procedures such as irrigation/aspiration. The microcatheter and hysteroscope (end) are also contemplated in other than intrauterine procedures. One non-limiting example would be gastroenterological procedures.