Patent Application
20120071905
Menstrual bleeding is a part of normal life for women. The onset of menstruation, termed menarche, usually occurs at the age of 12 or 13. The length of a woman's monthly cycle may be irregular during her first one to two years. Once the menstrual cycle stabilizes, a normal cycle may range from 20 to 40 days and on average lasts 28 days. Age, weight, athletic activity and alcohol consumption are several factors that can affect menstrual cycles. For example, younger women (under the age of 21) and older women (over the age of 49) tend to have longer cycle times, generally averaging 31 days and over. Similarly, women who are very thin or athletic may have longer cycles. In contrast, women who consume alcohol on a regular basis tend to have shorter cycle times.
Nearly all women, at some time during their reproductive life, experience some form of menstrual irregularity or abnormality. These disorders range from mild to severe, often resulting in numerous lost work hours and the disruption of personal/family life each month. In general, physical symptoms such as bloating, breast tenderness, severe cramping (dysmenorrhea) and slight temporary weight gain frequently occur during most menstrual cycles. In addition, emotional hypersensitivity is also common, including depression, anxiety, anger, tension and irritability. These symptoms are generally worse a week or so before a woman's menstrual period and resolve afterward.
Many women also suffer from a condition called menorrhagia (heavy bleeding). Menorrhagia is a clinical problem characterized by substantial discomfort and heavy flow/bleeding, characterized by blood loss exceeding 80 cc/month. It is estimated that 1 in 5 women between the ages of 35 and 50, or approximately 6.4 million women in the United States alone, are affected by menorrhagia. Fibroids, hormonal imbalance and certain drugs, such as anticoagulants and anti-inflammatory medications, are common causes of heavy bleeding.
Women diagnosed with menorrhagia or dysmenorrhea have limited treatment options available to them. Currently, other than hormone therapy and a few experimental pain management techniques, hysterectomy (removal of the uterus) and endometrial ablation/resection (destruction of the uterine lining) are the clinically accepted treatment modalities for menorrhagia. These surgical procedures either eliminate or substantially reduce the possibility of childbearing. Further, hysterectomy requires up to a six-week recovery time following surgery and commonly a lifetime of hormone therapy when the ovaries are also removed. Endometrial ablation has a low success rate at achieving amenorrhea (cessation of menstrual bleeding). As a result, many of the women affected by menorrhagia are driven to make lifestyle-altering decisions.
Since the 1800's, attempts using various treatments have been made to control uterine bleeding by means other than hysterectomy. Alternative methods include chemicals, steam, ionizing radiation, lasers, electrocautery, cryosurgery and others. The long-term risk for some of these methods can be quite high and may lead to other more serious complications such as mesodermal tumors or uterine cancer.
Clinically, a condition known as Asherman's syndrome has been observed where adhesions within the uterine cavity disrupt the normal menstrual cycle. This leads to a reduction in bleeding from the normal menstrual cycle and often produces amenorrhea.
In 1894, Heinrich Fritsch was the first to describe amenorrhea resulting from traumatic obliteration of the uterine cavity following puerperal curettage. However, it was not until the late 1940's that knowledge about its association with uterine adhesions (synechiae) was first disseminated in medical journals by Joseph G. Asherman, for whom the condition is named. In 1957, the 17th Congress of the Federation of French Speaking Societies of Gynecology and Obstetrics proposed the following classification of uterine synechiae:
Traumatic Synechiae connected with surgical or obstetrical evacuation of the uterus;
Spontaneous synechiae of tuberculosis origin;
Synechiae occurring after myomectomy; and
Synechiae secondary to chemical or physical agents and likewise those resulting from atrophic changes.
In general, two types of traumatic synechiae are currently recognized. The first type is stenosis or obliteration of the endocervical canal. The second type of traumatic synechiae is partial or complete obliteration of the uterine cavity by conglutination of the opposing walls.
Other terms, such as endometrial sclerosis, traumatic uterine atrophy, uterine artesia, uterine synechiae and adhesive endometriosis, have also been used to describe the phenomena of Asherman's Syndrome. The severity of adhesion is generally classified into one of the following three groups or classes: Class I represents adhesions occurring in less than one-third of the uterine cavity with both ostia (i.e. openings of the fallopian tubes) visible; Class II represents adhesions occurring in one-third to one-half of the uterine cavity with one ostium visible; and Class III represents adhesions occurring in greater than one-half of the uterine cavity with no ostia visible.
Although Asherman's Syndrome has been studied extensively and numerous articles and papers have been written on the topic, uncertainty still exists as to the predominant causative factor(s) and biological mechanism(s). It is believed that if the endometrium is severely damaged, it may be replaced by granulation tissue. When this happens, the opposing uterine walls adhere to one another and form scar tissue. In particular, adhesions form and transluminally bridge the anterior and posterior surfaces of the uterus. The adhesions or tissue that is formed between the walls comprises connective tissue that is, typically, avascular. Soon after, the tissue may be infiltrated by myometrial cells and, later, covered by endometrium.
Conventionally, intrauterine adhesions have been regarded as undesirable conditions (for example U.S. Pat. No. 6,211,217, issued to Spinale et al, U.S. Pat. No. 6,136,333, issued to Cohn et al. and U.S. Pat. No. 6,090,997, issued to Goldbert et al.). Indeed, in several known treatment methods for menorrhagia, it has been encouraged to avoid the creation of adhesions. Even in those circumstances where clinicians have experimented with adhesion formation, the results have not proved promising. For example, in the March 1977 edition of the Israel Journal of Medicine, an article by J. G. Schenker, entitled Induction of Intrauterine Adhesions in Experimental Animals and Women, described an experiment in which surgical sponges were implanted into the subcutaneous wall of the patient. The sponges remained in the subcutaneous wall until fibroblasts, or connective-tissue cells, populated the sponges. Next, the sponges were removed and implanted into the uterus of the same patient.
Schenker observed that, after a period of time, adhesions were formed in the areas adjacent to the location of the implanted fibroblast bearing sponge. No adhesions were observed in areas that did not have contact with the fibroblast bearing sponge. These experiments were carried out in several animal models (for example, rabbit, rat and primates) and humans. Schenker concluded that it was possible to artificially create adhesions within the uterus, but that such a procedure was not practical.
In U.S. Pat. No. 6,708,056 issued to Duchon et al., the contents of which are hereby incorporated by reference, a method for creating intrauterine adhesions resulting in amenorrhea was presented, including devices for creating such intrauterine adhesions. Specifically, Duchon et al. contemplated an implantable device comprised of biocompatible material which promotes tissue growth, resulting in adhesion formation.
Although adhesion formation remains one method of inducing amenorrhea, the inventors have discovered other methods for potentially obtaining a reduction in bleeding that preferably produces amenorrhea. For example, these methods may cause the complete replacement of the uterine functionalis/basalis endometrium, creating blockage of the uterine endocervical canal, creating a discrete architectural change of the uterine cavity and/or others are also believed to result in amenorrhea or at least a reduction in menstrual bleeding.
What are needed are improved methods and devices to take advantage of these newly understood mechanisms of action, as well as improved methods and devices for the previously discovered mechanisms. All of these items are to provide better treatment for abnormal uterine bleeding.
Therefore, it is an object of the present invention to overcome the limitations of prior treatments of excessive bleeding within a body cavity.
It is an object of the present invention to provide an implantable device for treating excessive bleeding in a body cavity.
It is another object of the present invention to provide a method of pretreating a uterus to better treat excessive bleeding.
In general, the present invention contemplates an implantable device for treating excessive bleeding in a body cavity. The device comprises a biocompatible material, for example, polyethylene teraphathalate (PET), which is deliverable into the body cavity. The biocompatible material contains an attribute that promotes tissue growth that results in adhesion formation within the body cavity.
The present invention also contemplates a method of creating adhesions in a body cavity. In general, the method comprises inserting an implantable device within the body cavity. The method also includes locating the implantable device at an optimal site within the body cavity, wherein the optimal site promotes effective adhesion formation for controlling bleeding.
The present invention also contemplates a method and devices for treating excessive bleeding within a body cavity without creating adhesions.
The present invention further contemplates a pretreatment method for creating trauma to a tissue within a body cavity.
Excessive menstrual flow or bleeding, termed menorrhagia, is indicative of abnormal sloughing of the endometrial tissue layer. Unlike conventional therapies such as hysterectomy or ablation/resection procedures, the embodiments of the present invention achieve reduced bleeding with the intended outcome of reduced bleeding or amenorrhea (cessation of bleeding) by way of an implant, which decreases or deactivates the endometrial tissue. There may be several contributing mechanisms or steps of action to create amenorrhea or reduced bleeding in a patient. Many of these mechanisms may or may not relate to the creation of adhesions, as non-adhesion based mechanisms of action may also achieve clinical amenorrhea to eliminate abnormal uterine bleeding.
One such mechanism, previously discussed in U.S. Pat. 6,708,056, involves the complete obliteration of the uterine cavity. Specifically, this involves replacement of the uterine endometrium and the adjacent virtual intrauterine cavity space with another tissue or substance such as would form an adhesion or other contact of the cavity wall(s). This adhesion may consist of fibrous-granulation tissue, extracellular matrix (e.g. collagen) or any other durable tissue (e.g. endometrial stromal tissue). Such tissue growths may be induced by an implanted material or device that creates a tissue response, an induced tissue trauma or a combination of both (trauma with response). Since all of the endometrial tissue with regenerative cycling potential has been replaced by a non-shedding or noncycling material or tissue, amenorrhea or at least reduced bleeding is thus induced. Additionally, the uterine cavity is completely obliterated, and the concept should result in infertility or an effective contraceptive. Further, the potential for endometrial cancer should be reduced since the endometrial tissue is either reduced, inactivated or eliminated.
Another mechanism, similar to the previously described mechanism, involves obliteration of all or a portion of the endometrium, followed by replacement of the endometrium by another cellular tissue substance or extracellular matrix (e.g. collagen). However, unlike what may occur in the previously described mechanism, the opposing walls of the uterine cavity are not completely adhered together. Similarly, the tissue response may be induced by an implanted material or device, induced trauma, or both. However, if an implant device is utilized, it would be composed of material(s) that creates a barrier to limit tissue in-growth to prevent the opposing uterine walls from adhering together. Therefore, an intrauterine cavity is maintained within the barrier protected portion of the implant, allowing for continued access to the intrauterine cavity for diagnostic purposes and to prevent fluid collections, such as hematometra (retention of blood within the uterus).
Yet another mechanism of amenorrhea involves creating a complete blockage, closure or obstruction of the intrauterine cavity anywhere in the lower uterine segment to the internal endocervical os, preventing menstrual blood or other fluid from escaping or draining from the uterine cavity. Although the endometrium still exists in the remaining cavity above the obstruction, menstruation stops, generally without resulting in hematometra. The inability of the shedding endometrium to pass or drain from the cavity may inactivate the endometrium so that it no longer cycles, thus creating amenorrhea without hematometra. The complete blockage of uterine outflow may be produced by tissue adhesion(s) or growth that is induced by an implanted material or device that creates a tissue response, an induced trauma or a combination of both. Such an obstruction or closure may consist of fibrous granulation tissue, extracellular matrix (i.e. collagen) or any other durable tissue such as endometrial stromal tissue. Additionally, the cervical blockage may include and/or result from mechanical devices that cause endocervical blockage.
Another mechanism of amenorrhea involves creating discrete architectural changes of the uterine tissues and/or its cavity, such as creating connections between opposing uterine walls. These connections may be produced by creating adhesion(s) in a small uterine cavity region instead of involving the complete cavity and may consist of fibrous granulation tissue, extracellular matrix (i.e. collagen) or any other durable tissue such as endometrial stromal tissue. The adhesion(s) may result from an implanted material or device that creates a tissue response, an induced trauma or a combination of both. Alternatively, the architectural change may also be effectively produced with a mechanical connection that does not rely on adhesion formation.
Amenorrhea may result in these contexts by several possible mechanisms, either singularly or in concert with other signaling or mechanical pathways. For example, the adhesions or mechanical connections may alter signaling or disrupt the peripheral nerve system associated with the uterus with the net effect of variable endometrial inactivation. For example, a neural change could produce an involuntary reflex of the lower uterine segment or internal endocervical os muscles, resulting in out flow occlusion of the cavity. In another example, midline adhesion(s) or mechanical connection(s) between the uterine walls may alter the mechanics of the uterine muscle or cavity preventing normal menstrual cycling. In yet another example mechanism, the endometrium surrounding the adhesion does not develop to full functionalis thickness, possibly due to a maturation arrest that prevents the endometrium from completing its cycle and halting the menstrual cycle.
Another mechanism of amenorrhea involves insertion of a device within the uterine cavity that creates contact with the endometrial tissue(s) without creating adhesions. Such changes may be the result of direct contact pressure from the device on the endometrium or may be the result of cellular signaling changes when contact between the endometrial surfaces lack direct contact secondary to the device.
In regard to the previously described mechanisms of amenorrhea, multiple implant device embodiments are herein described according to the present invention to take advantage of these possible mechanisms. Others have been described in copending U.S. application Ser. No. 10/850,761 filed May 21, 2004 entitled Intrauterine Implant and Methods of Use, the entire contents of which are incorporated herein by reference. Generally, many of the embodiments described in this application utilize various forms of polyethylene teraphathalate (PET), also commonly referred to as polyester. Dacron is the trade name for one commonly produced PET material. The invention (including the embodiments described) may be composed of other biocompatible materials alone or in combination with PET or other similar materials.
PET is a preferred uterine implant material due to its ability to elicit a tissue response, which is bioreactive in nature, followed by a fibrotic tissue incorporation or reaction. This response is discussed in detail in co-pending U.S. application Ser. No. 10/851,364 filed May 21, 2004, entitled Bioreactive Methods and Devices for Treating Abnormal Bleeding, the entire contents of which are hereby incorporated by reference. In addition to eliciting a tissue response, PET may be used as a scaffolding to support, enhance and/or control the primary tissue in-growth and potentially combine with another biocompatible material that creates tissue trauma or specific tissue access. Coatings such as collagen, TGF-beta, hormones (such as progesterone) or other stimulants that may enhance or accelerate a tissue response are also contemplated by this invention. For the purposes of this application, a bioreactive material is intended to refer to all types of materials that are not only biocompatible but also a material that causes a biological response in the body. In a preferred embodiment, a bioreactive material is one where the biological response is a fibrotic or other durable tissue response.
PET filaments or fibers are the individual elements that make up a yarn bundle. The filaments can be in different shapes such as round, oval, tri-lobal or others. The size of the filaments is measured in Denier, a textile term. One denier is approximately equal to 10 micrometers or 0.0004 inches in diameter. For example, a preferred fiber size is between about 1 and 20 denier. For a specific amount of material, a fine filament denier with more filaments in the yarn bundle may be preferred over a higher denier filament with fewer filaments, due to the increased surface area the former option provides (in which case it is preferred that the filaments are loosely arranged in the yarn bundle). The increased surface area has the potential to increase tissue exposure and thus may provide a better tissue response. Additionally, multifilament yarn configurations are generally more compliant and conforming than monofilament configurations of similar Denier and material type.
Yarns can have a flat surface, as seen in
The fabric construction determines the macro porous configuration of PET or other fabrics potentially used with the implant. Such a fabric may be knit, woven, or non-woven. A knit mesh construction or a non-woven needle felt are two example fabric constructions preferred to provide an open scaffold to encourage tissue in-growth after being evaluated in animal testing. Fibrous tissue in-growth is enhanced by pore sizes of at least about 50-250 micrometers and preferably a pore size in the range of 100 to 200 micrometers. Fabric constructions that provide open channels between layers also may promote tissue proliferation.
Referring to
Generally, the T-shaped structure has two arms 102a and a single elongated body 102b. Further, the T-shaped structure 102 provides a semi-rigid deploying structure for the PET fabric 101, which impedes the T-shaped uterine implant from being ejected by uterine contractile forces. Once implanted within the uterus 104, the PET fabric 101 promotes the formation of intrauterine adhesions, thus reducing and/or deactivating the endometrial tissue and reducing or eliminating the bleeding.
In one specific example of the T-shaped uterine implant 100, a Mirena Intra Uterine Device (IUD) stent may be used as the T-shaped structure 102 (once the hormone cylinder is removed) and a thin layer of Bard DeBakey Double Velour PET (Style #6110) cardiovascular fabric may be used as the PET fabric, fastened by polypropylene sutures 103 to the T-shaped structure 102. The T-shaped uterine implant 100 may then be positioned within the uterus 104 of a patient using a simple delivery tube cannula (e.g. 6 mmID) and a stylet (e.g. pusher rod). The delivery tube allows the uterine implant 100 to be packed within the tube and pushed out within the intrauterine cavity 104 in the desired treatment location, preferably positioned similarly to a typical Mirena IUD. Preferably, the T-shaped implant 100 is implanted within a patient, causing a fibroproliferative, stromal or other tissue response within the uterus 104 that leads to adhesion(s), resulting in reduced bleeding or preferably amenorrhea, similar to what is observed clinically with Asherman's syndrome. The device described has been implanted in patients and followed for a period of 30 to 90 days to observe fibroproliferative and stromal tissue responses.
In practice, the narrow end 100b of the T-shaped uterine implant 100 is first loaded into a cannula sheath (not shown), while the arms 100a are folded up away from the narrow end 100b and towards each other. The T-shaped uterine implant 100 is then completely loaded into the distal end of the cannula sheath (patient end) while a stylet (not shown) is introduced into the proximal portion of the cannula sheath until it abuts with the implant tip. Next, minimum cervical dilation of approximately 6.5 mm is achieved and, if desired, uterine cavity pretreatment can be performed. Pre-treatment procedures such as resection, endometrial ablation, dilation and curettage or others may be used prior to implantation of the T-shaped uterine implant 100. Further details of example pre-treatment procedures are described elsewhere in this application. Next, the cannula is introduced into the endocervical canal through the exocervical os with gentle forward advancement until it reaches the superior fundic wall 113 of the intrauterine cavity. The cannula is then retracted 2 cm so that the proximal tip of the cannula is 2 cm from the superior fundic wall 113. Next, the stylet is advanced approximately 1.5 cm while holding the cannula sheath in place, allowing deployment of the arms 100a while leaving the body 100b within the cannula. The stylet and cannula sheath are then readvanced to the superior fundic wall to position the arms 100a in the desired extended position with the arm tips extended towards the cornu. The stylet is then held in place as the cannula sheath is retracted, deploying the implant body 100b. Finally, the stylet may be withdrawn from the patient, leaving the T-shaped uterine implant 100 within the intrauterine cavity approximately as shown in
In an embodiment related to the implant of
As shown in
At the same time the deployment stent 405 is being urged toward the fundic wall, a suture 409 that is attached at one end to the lower portion of the implant 401 is held in tension by the user so as to ensure that the fabric of the implant 401 is fully expanded and to ensure that it lays flat with within the uterine cavity. Once this has been achieved, the suture 409 is then cut and removed from the fabric of the implant 401.
Once the suture 409 has been cut and removed from the fabric of the implant 401, the user begins to retract the deployment stent 405 back into the cannula 407 as shown in
Referring to
In addition to creating the previously described tissue response within the uterus 104 with fabric 146, the uterine implant 140 may illicit or draw on a more robust fibrosis healing response from fallopian tubes 108 and/or the endocervix 116. The implant would facilitate drawing the cells necessary for a fibroproliferative response into the main cavity. Fibrosis and adhesions within the uterus 104 are sometimes difficult to create without trauma and/or contact with the tissue lying below the endometrium. The normal cycling of the endometrium, which lines the cavity, may prevent or inhibit the pathways/mechanisms related to generating a fibroproliferative response similar to that observed in other parts of the body. However, the mucosal tissues are biologically different in the endocervix 116 and fallopian tubes 110 than the uterus 104, since they do not cycle and regularly regenerate their mucosal layer. Thus, the fallopian tubes and endocervical regions are potentially more receptive for inducing a fibroproliferative response. In this respect, the extension 142, 144 may enhance initiation and propagation of this tissue response by inducing a trauma or a foreign body response. The fibrosis caused by the extensions 142, 144 may effectively spread across the uterine implant 140, which acts as a scaffold for the tissue. The resulting mass of fibrosis tissue may result in additional pressure within the uterus 104 or possibly replacement of the endometrium, but in either case bleeding is reduced and amenorrhea is preferably obtained.
Referring to
The V-shaped member 122 is preferably composed of a semi-rigid material that can flex under strains and gently conform along the funneled lateral walls of the uterus, yet is rigid enough to prevent ejection by uterine contractile forces. Simple calculations of stiffness for the material may be used to determine a desired V-shaped member 122 diameter. The stiffness, S of the V-shaped member 122 is proportional to 3EI/L3, where E represents the elastic modulus of the material, I represents the second moment of area, and L represents the length. For example, the V-shaped member 122 may be composed of a nitinol wire 0.020 to 0.025 inches in diameter. Thus, the V-shaped member 122 may flex when positioned within a cannula for deployment within a uterus 104. Preferred example dimensions of the V-shaped member 122 include a maximum width of the V shape of about 3.2 cm and a height of about 4.2 cm to match the size and shape of a typical uterus.
The randomly oriented yarn fibers 124 are fixed to the V-shaped member 122, filling out the space directly between the V of the member 122. Thus, once implanted into the uterus 104, the randomly oriented yarn fibers 124 contact nearly the entire uterine cavity and stimulate a tissue response. PET textured multifilament yarn is preferred, having a preferable minimum pore size of about 50 to 250 micrometers between yarn fibers. The open structure created by the randomly oriented yarn fibers 124 provide a scaffold to promote tissue in-growth within the device that can result in adhesions between the uterine walls.
In operation, the V-shaped yarn implant 120 is preferably implanted within the uterus 104 of a patient with a cannula (not shown) or delivery tube, similar to above, which allows the V-shaped yarn implant 120 to be compressed and positioned within the uterus 104. The V-shaped yarn implant 120 deploys within the uterus 104 to match its overall funnel shape, providing maximum contact between the uterine walls and the yarn fibers 124.
Preferably, approximately 5 fabric implants 152 are deployed within a uterus 104 (one or two at a time) through transcervical approach involving a cannula as similarly described above. The number of rolls can be varied based on uterine size and other factors. Without a rigid or semi-rigid inner structure, the fabric implants 152 better conform to the shape of the uterus 104, creating a larger area of contact with the uterine walls. Additionally, there is no stent or other solid object that may inhibit tissue in-growth from penetrating through the device.
The fabric implant 156 may be implanted by a similar procedure as described in T-shaped implant device 100, using a cannula during a transcervical procedure. Once implanted, the fabric implant 156 creates adhesions that result in an architectural change along the centerline of the uterine cavity.
In another preferred embodiment, seen in
In a similar preferred embodiment, a small implant (not shown) comprised of PET may be implanted into the endocervix 116 or internal cervical os 116a, causing a fibroproliferative response that totally occludes the canal and blocks access to the uterus 104. Thus, the cervical PET or other fabric implant would induce amenorrhea by a mechanism similar to the previous embodiment.
In another preferred embodiment of the present invention, an implant device contains an antimicrobial agent to induce tissue trauma within the uterus, killing endometrial cells and eroding down to the junction of the endometrium with the myometrium (junction) or into the myometrium, where a fibroproliferative or other tissue response can be stimulated. Since adhesion creation often requires contact with the junction or myometrium, incorporation of an antimicrobial coating may alleviate the need for pre-treatment procedures.
For example, an antimicrobial silver ion coating may be added to an implant discussed in this application by using ion beam deposition on the implant's fibers or alternately by integrating the antimicrobial into the fibers during the polymerization and extrusion process. Needle felt fabrics constructed from the fibers with impregnated silver may then be used to create an implant device with a desired shape, including but not limited to, the shapes described elsewhere in this application, for example. In this manner, the antimicrobial silver wears away, develops a zone of inhibition, retards growth or otherwise injures the endometrial tissue, allowing the fibers to stimulate and create adhesions within the uterus.
In addition to antimicrobial agents, other trauma inducing agents may be administered or eluted from an implanted device. For example, silver nitrate, tetracycline, alcohols, and other agents.
As previously described, creating a fibroproliferative or other tissue response which bridges between the uterine walls and obliterates the entire cavity remains a compelling mechanism for creating amenorrhea. However, discrete architectural changes of the uterine cavity that involves adhesions or mechanical connections that bridge between the uterine walls, may also reduce menstrual bleeding or result in amenorrhea.
The uterus is a muscle that undergoes mechanical contractions due to a variety of biological and physical stimuli. These contractions are a normally occurring event during menstruation. During a typical normal contraction, the muscle experiences a contraction/stress pattern that is transmitted between the myometrial muscle fibers in the anterior and posterior walls in a circumferential fashion. This contraction forms a pulsatile wave across the cavity. When the body is subjected to or imparts an electrical or mechanical stimulus, there is generally a feedback loop that allows the body to make physiological adjustments when necessary or to continue to respond normally if the feedback is normal.
The previously described myometrial muscle contraction may be normally expected in an unaltered uterus. However, a uterus having both the anterior and posterior walls joined together may develop additional interactions from the contracting opposite wall near or in the middle of the uterine cavity. With this interaction, contracting stress patterns and stress magnitudes may be changed during a contraction, both local to the attachment site and more globally to the entire or a distant region of the uterus. These changes may result in abnormal tissue feedback that would result in biological changes, altering and possibly stopping menstrual bleeding.
In this respect, a preferred embodiment is illustrated in
In a similar preferred embodiment, the posterior and anterior walls of the uterus 104 may be joined with a biological adhesive, such as fibrin or a polymer adhesive such as cyanoacrylate. Thus, an architectural change is created within the uterus, inducing reduced bleeding and preferably amenorrhea.
When implanted, the tie member 180 creates tension between the fasteners 182, pulling the walls of the uterus 104 together, preferably near the lower or middle regions of the uterus 104. The large size of the fasteners 182 spread out the bearing load of the tie rod member 182 and inhibit tissue breakdown and pull through of the implant. The tie member 180 and fasteners 182 may be deployed through a laproscopic minimally invasive surgical approach, external to the uterine cavity. Additionally, transvaginal or open surgical procedures may also be used.
Although mechanical connectors have primarily been described as embodiments for architecture modifying devices, the architecture change can also be obtained by discreet adhesions between the walls. Thus, any of the embodiments within this disclosure that create a bridging adhesion between the uterine walls can result in an architecture change that can preferably result in amenorrhea or possibly reduced bleeding. This includes the T-shaped and V-shaped devices, as well as the tissue penetrating devices listed in the following paragraphs.
The shape memory tubes 186 may be deployed into the uterus 104 through a cannula 187. A distal end of the cannula 187 is placed at the target location in the uterus 104, where the change in architecture is desired from the tissue adhesion. As the shape memory tubes 186 are advanced out from the cannula 187, they bend to their pre-shaped form, curling and thus penetrating into the endometrium 172 and myometrium 170.
If the wire strut 191, seen in
The bioresorbable implant device 192 is delivered into the uterus 104 with a cannula 187. The implant device 192 is loaded within the cannula 187 so that the partially bioresorbable elements 193 are folded proximally, towards the user. As the central member 194 is moved out of the cannula 187 at a desired treatment location within the uterus 104, the partially bioresorbable elements 193 extend radially outward, penetrating the endometrium and myometrium layers. This penetration of partially bioresorbable elements 193 may be further enhanced by moving the implant device 192 in a proximal direction, forcing the partially bioresorbable elements 193 deeper into the tissue of the uterus 104. The central member 194 and partially bioresorbable elements 193 remain within the uterus 104, creating a fibrotic tissue response. As soon as about 2 to 4 weeks after deploying the implant device 192, the bioresorbable material begins to breakdown and resorb into the body, making the implant device 192 more compliant and likely less uncomfortable to the patient. The PET within the partially resorbable elements 193 and within the central member 194 provide the scaffold for the tissue growth and do not resorb. Additionally, since the partially bioresorbable elements 193 penetrate into the myometrium, treatment prior to the implantation procedure may not be required. In an alternative preferred embodiment, the elements 193 may be completely bioresorbable, allowing the elements 193 to penetrate into the myometrium, then completely degrade.
In operation, a cannula 187 is used to position the tissue penetrating implant 210 at a desired location within the uterus 104. The pointed end 218a of the delivery sheath 218 and the boring needle 212 are advanced together into the uterine tissue 104, puncturing and penetrating the endometrium and into the myometrium.
Once the delivery sheath 218 has achieved a desired depth of penetration, a user manipulates the pushing member 216 to deploy the fiber implant 214 into the tissue. The delivery sheath 218, the needle 212, and the pushing member 216 are then retracted from the delivery site, leaving the fiber implant 214 partially within the uterine tissue 104 and partially within the uterine cavity. Thus, the PET fibers of the fiber implant 214 create a surrounding and/or ingrowth tissue response in the myometrium, as well as act as a tissue scaffold for ultimately creating a tissue bridge across the uterine cavity 104. As seen in
In a similar preferred embodiment (not shown), the fiber implant may have a solid, resorbable middle (e.g. hydrophobic) probe core 215, eliminating the use of the boring needle. Instead, the pointed end of the delivery catheter solely penetrates the tissue of the uterus. Following reabsorption, the implant will have a central canal through which to propagate the tissue response associated with the implant fabric.
As previously described in this application,
In another preferred embodiment (not shown), beads may be enclosed in a fabric bag, such as a PET fabric described elsewhere in this application. Fewer larger beads will create localized contact pressure that may help focally erode or traumatize the tissues, while many smaller beads will tend to provide a more uniform contact pressure. Although the more uniform pressure may not fully erode the tissue layers, it may provide additional trauma or help inactivate the endometrium. The beads easily move within the fabric bag, allowing the bead-bag implant to conform to the shape of the uterine cavity, yet maintain contact and pressure on the uterine tissue. Thus, the pressure and contact provided by the implant will induce fibrotic or other tissue growth, ultimately reducing bleeding and preferably inducing amenorrhea.
In yet another preferred embodiment, a pressurized balloon implant (not shown) includes a compliant material, preferably being covered in a PET fabric, such as the PET fabrics disclosed elsewhere in this specification. The pressurized balloon implant is preferably inflated with liquid after implantation within the uterus. As the implant inflates, it creates contact and pressure against the uterine cavity tissue with the PET fabric. In this manner, a fibrotic or other tissue response may be induced, reducing bleeding and preferably inducing amenorrhea.
In another preferred embodiment of the present invention (not shown), tissue response inducing fibers, such as PET, may be suspended within a fluid, and then injected/pumped into the uterine cavity. The fluid may then be slowly removed from the uterus, leaving the tissue response inducing fibers within the uterus. Alternately, these fibers may also be suspended in a fluid, which can harden or solidify once pumped into a uterus, allowing the tissue response inducing fibers such as PET to contact the uterine walls and cause a tissue response.
In another preferred embodiment seen in
As previously described in this application, amenorrhea may be induced through a variety of methods, mostly requiring the generation of a durable tissue response, such as fibrotic tissue within the uterus. Durable tissue is differentiated from non-durable tissue due to its capability in resisting some level of separation or shearing force from the uterine wall and/or breakdown, reabsorption or shedding. The endometrium has macroscopic jelly-like properties, lacking resistance to shearing forces that would be tolerated by a durable tissue. Hence, it is desired to expose the implant devices to tissue near the endomyometrial junction or myometrium (about 1 mm or more below the junction) in order to obtain a durable tissue response. When the myometrium is exposed to the implant, the tissue in-growth and adhesions are the result of a fibroproliferative response that generates granulation tissues with resulting collagen deposition, a response similar to wound healing or tissue repair. When the tissue near the endomyometrial junction is exposed to the implant, adhesions are created that consist of an aglandular histiocytic and/or stromal appearing tissue of mesenchymal origin. Some of the implants disclosed herein are designed to contact the aforementioned tissues by their very designs. However, other designs may require pre-treatment of the uterus prior to implantation to optimally generate the desired tissue response.
Endometrial resection is one pretreatment method according to the present invention, involving the complete or partial removal of both the functionalis and basalis endometrium with a variable thickness of inner myometrium. Common methods of achieving endometrial resection include the use of electrosurgical loops or roller ball devices. The endometrium is accessed trans-cervically with the patient potentially under general anesthesia. These methods cut away the endometrium with each pass of the surgical instrument with coagulation of the new surface created in the uterine cavity. If high temperatures or energy levels are used, the newly exposed tissues may be thermally fixed which would potentially block direct contact with viable myometrial tissue and prevent the desired tissue response.
Complete resection may be an effective standalone treatment for AUB, since generally previously reported amenorrhea rates as high as 50% can be obtained. The use of an implant, as described herein, would allow for increased amenorrhea rates, higher than for resection alone. Alternately, a partial resection could be used with an implant device, reducing the invasiveness and skill required to perform an effective procedure.
Endometrial ablation is another pretreatment method according to the present invention which is similar to resection. Endometrial ablation is intended to destroy all endometrial layers and a portion of the inner myometrium within the uterine cavity by a variety of ablation tools, such as high temperature circulating water, low temperature freezing probes, microwaves, RF resistance heating, and chemicals. It may be possible to use one or more of these techniques to achieve the desired myometrial tissue exposure prior to implant insertion, however any dead tissue created by these techniques should preferably be removed from the uterine cavity and endocervical canal before inserting an implant device.
Generally, endometrial ablation methods can be standalone treatments for AUB, often having effectiveness similar or slightly better than resection. Additionally, ablation is easier to perform on a patient and is potentially less invasive. These ablation techniques, in combination with a uterine implant, may significantly improve patient outcomes over ablation alone.
Dilation and curettage (D&C) is another pretreatment according to the present invention which includes dilation of the cervix and mechanical scraping of the endometrium to remove the functionalis layer of the endometrium, variable basalis endometrium and potentially some superficial myometrium. D&C is less penetrating into the uterine tissue than resection or ablation but is generally not as effective of a treatment for AUB alone; since the procedure does not remove as much endometrium and its junction with the myometrium. However, it may be possible to reach some areas of the endomyometrial junction with a more aggressive curettage, especially when the endometrium is thinnest after menstruation. D&C may be an effective pretreatment prior to inserting a uterine implant, especially if the device design takes advantage of the potentially variable and non-uniform exposure of the junction or myometrium, such as though an abrasive, pressure or other mechanism.
Cycle timing is another pretreatment according to the present invention where various drugs are administered to a patient to provide consistent menstrual cycle timing at the time of implant insertion. This timing allows an implant to be implanted within a patient when the endometrial tissue is at a desired thickness. For example, if the implant device is to be implanted when the endometrial tissue thickness is at a minimum, Zoladex, birth control or a similar cycle controlling drug could be utilized to synchronize the menstrual cycle and allow for implant insertion at a specific point in the menstrual cycle.
Hormones are another pretreatment method according to the present invention. Such hormonal pretreatment can be used alone or in combination with other pretreatment methods, including other pretreatments discussed herein. In such pretreatments, hormones are injected just prior to, at the time of, or after implanting a uterine device to enhance or direct a tissue response. In one example, estrogen may be used to produce a fibrinolysis effect within the uterus. In another example, progesterone may be injected into a patient, which may promote signaling that leads to a fibrous response within the uterus, especially when used with a uterine implant. Although progesterone is commonly used for hormone therapy to cause menstruation, it is always given during the secretory phase of the endometrial cycle when estrogen levels within a patient are high. However, progesterone is not commonly given earlier in the cycle (e.g. early proliferative phase), which could stimulate adhesions through the generation of tissues such as collagen. Thus, early progesterone pretreatment during the menstrual cycle, in combination with an uterine implant may increase the outcome of inducing amenorrhea.
Although the invention has been described in terms of particular embodiments and applications, one of ordinary skill in the art, in light of this teaching, can generate additional embodiments and modifications without departing from the spirit of or exceeding the scope of the claimed invention. Accordingly, it is to be understood that the drawings and descriptions herein are proffered by way of example to facilitate comprehension of the invention and should not be construed to limit the scope thereof.
This application is a continuation-in-part of U.S. application Ser. No. 10/726,433 filed Dec. 3, 2003 entitled Method And Apparatus For Creating Intrauterine Adhesions which is a continuation of U.S. application Ser. No. 09/840,951 filed Apr. 24, 2001 entitled Method And Apparatus For Creating Intrauterine Adhesions now U.S. Pat. No. 6,708,056 which is a non-provisional application claiming priority to U.S. Provisional Application Ser. No. 60/256,529 filed Dec. 18, 2000 and U.S. Provisional Application Ser. No. 60/199,736 filed Apr. 25, 2000, both of which are now abandoned. This application is also a continuation-in-part of U.S. application Ser. No. 10/851,364 entitled Bioreactive Methods and Device for Abnormal Bleeding filed May 21, 2004 which is a non-provisional application claiming priority to U.S. Provisional Application Ser. No. 60/472,643 filed May 21, 2003. This application is also a continuation-in-part of U.S. application Ser. No. 10/850,761 entitled Intrauterine Implant and Methods of Use filed May 21, 2004 which is a non-provisional application claiming priority to U.S. Provisional Application Ser. No. 60/472,644 filed May 21, 2003. All of the above applications are incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| 60256529 | Dec 2000 | US | |
| 60199736 | Apr 2000 | US | |
| 60472643 | May 2003 | US | |
| 60472644 | May 2003 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 10978176 | Oct 2004 | US |
| Child | 13251743 | US | |
| Parent | 09840951 | Apr 2001 | US |
| Child | 10726433 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 10726433 | Dec 2003 | US |
| Child | 10978176 | US | |
| Parent | 10851364 | May 2004 | US |
| Child | 10978176 | US | |
| Parent | 10850761 | May 2004 | US |
| Child | 10851364 | US |
