U.S. patent application number 15/094852 was filed with the patent office on 2016-08-04 for methods and systems for the treatment of polycystic ovary syndrome.
The applicant listed for this patent is Ziva Medical, Inc.. Invention is credited to Neil BARMAN, Roger OSBORNE, Garrett SCHWAB, Douglas SUTTON, Denise ZARINS.
Application Number | 20160220302 15/094852 |
Document ID | / |
Family ID | 52828744 |
Filed Date | 2016-08-04 |
United States Patent
Application |
20160220302 |
Kind Code |
A1 |
ZARINS; Denise ; et
al. |
August 4, 2016 |
METHODS AND SYSTEMS FOR THE TREATMENT OF POLYCYSTIC OVARY
SYNDROME
Abstract
Described here are methods and systems for the manipulation of
ovarian tissues. The methods and systems may be used in the
treatment of polycystic ovary syndrome (PCOS). The systems and
methods may be useful in the treatment of infertility associated
with PCOS.
Inventors: |
ZARINS; Denise; (Saratoga,
CA) ; BARMAN; Neil; (Menlo Park, CA) ; SCHWAB;
Garrett; (Oakland, CA) ; OSBORNE; Roger; (La
Honda, CA) ; SUTTON; Douglas; (Pacifica, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Ziva Medical, Inc. |
Oakland |
CA |
US |
|
|
Family ID: |
52828744 |
Appl. No.: |
15/094852 |
Filed: |
April 8, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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PCT/US2014/061159 |
Oct 17, 2014 |
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15094852 |
|
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61969042 |
Mar 21, 2014 |
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61892943 |
Oct 18, 2013 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 2018/00726
20130101; A61B 2090/378 20160201; A61B 2018/00559 20130101; A61B
18/1482 20130101; A61B 2017/00455 20130101; A61B 8/0841 20130101;
A61B 2018/00273 20130101; A61B 2018/00744 20130101; A61F 6/20
20130101; A61N 7/02 20130101; A61B 2017/00278 20130101; A61B
2017/3488 20130101; A61B 2018/00291 20130101; A61B 2018/00875
20130101; A61B 8/4433 20130101; A61B 2018/048 20130101; A61B
17/22004 20130101; A61B 2018/143 20130101; A61B 17/42 20130101;
A61B 2017/4233 20130101; A61B 2018/00577 20130101; A61B 2018/0293
20130101; A61B 2090/3966 20160201; A61B 18/1206 20130101; A61B
2018/00589 20130101; A61B 2018/00791 20130101; A61B 8/12 20130101;
A61B 18/06 20130101; A61B 2017/3405 20130101; A61B 2018/00732
20130101; A61B 18/22 20130101; A61B 2017/003 20130101; A61B
2017/3413 20130101; A61B 2018/00285 20130101; A61B 2018/00642
20130101; A61B 2090/3925 20160201; A61B 2018/00767 20130101; A61B
2018/00982 20130101; A61B 2018/00702 20130101; A61B 18/16 20130101;
A61B 2018/1432 20130101; A61B 8/4427 20130101; A61B 2017/306
20130101; A61B 2018/0072 20130101; A61B 2018/1475 20130101; A61B
2018/00196 20130101; A61B 8/085 20130101; A61N 7/022 20130101; A61B
18/1485 20130101; A61B 2018/00595 20130101; A61N 2007/0043
20130101 |
International
Class: |
A61B 18/14 20060101
A61B018/14; A61B 8/12 20060101 A61B008/12; A61B 18/12 20060101
A61B018/12 |
Claims
1. A system for performing an ovarian procedure comprising: a) a
docking device, the docking device comprising an elongate body and
having a proximal end, a distal end, and defining a lumen
therethrough; b) a radiofrequency energy element slidable within
and deployable from the lumen of the docking device; c) a
transvaginal probe comprising a handle and an ultrasound
transducer; d) a visual identifier or a mechanical lock for
coupling the docking device to the probe handle to maintain planar
orientation of the radiofrequency energy element relative to the
ultrasound transducer during the ovarian procedure; and e) a
generator configured to supply radiofrequency energy to the
radiofrequency energy element.
2. The system of claim 1, wherein the radiofrequency energy element
comprises an elongate body having a straightened length and a
radius of curvature, an active electrode, and a return
electrode.
3. The system of claim 2, wherein the straightened length ranges
between about 5.0 and about 40 mm.
4. The system of claim 2, wherein the radius of curvature ranges
between about 3.0 and about 10 mm.
5. The system of claim 1, wherein the lock comprises an adjustable
element having a locked position and an unlocked position.
6. The system of claim 1, wherein the generator is configured to
supply radiofrequency energy at a power of about 15 watts, and for
a duration of about 20 to 60 seconds.
7. The system of claim 1, wherein the radiofrequency energy element
comprises an echogenic material.
8. The system of claim 1, wherein a portion of the docking device
comprises an echogenic material.
9. The system of claim 1, wherein the radiofrequency energy element
and the docking device comprise an echogenic material having
different echogenicity.
10. The system of claim 1, wherein the radiofrequency energy
element comprises a plurality of areas of echogenic material having
different echogenicity.
11. The system of claim 1, wherein the mechanical lock is coupled
to the docking device.
12. A method for treating polycystic ovary syndrome comprising the
steps of: a) advancing a probe comprising a handle, an ultrasound
transducer, and a needle guide into the vaginal canal; b) advancing
an ovarian tissue apparatus into the needle guide, the ovarian
tissue apparatus comprising a docking device and a therapeutic
element; c) advancing the docking device through a vaginal wall; d)
penetrating an ovary at a single entry point with the docking
device or the therapeutic element; e) advancing the therapeutic
element from the docking device into the ovary; and f) delivering
energy to affect a volume of tissue within the ovary using the
therapeutic element to treat a symptom of polycystic ovary
syndrome.
13. The method of claim 12, wherein about 3 to 20% of the tissue
within the ovary is affected by the delivered energy.
14. The method of claim 12, wherein the step of delivering energy
is repeated through the single entry point in the ovary.
15. The method of claim 12, wherein advancement of the therapeutic
element occurs in the same plane as the imaging plane.
16. The method of claim 12, wherein the delivered energy is
radiofrequency energy.
17. The method of claim 16, wherein the radiofrequency energy is
delivered for about 20 to 60 seconds.
18. The method of claim 17, wherein the therapeutic element
comprises an elongate body having a straightened length and a
radius of curvature, an active electrode, and a return
electrode.
19. The method of claim 18, wherein the straightened length ranges
between about 5.0 and about 40 mm.
20. The method of claim 18, wherein the radius of curvature ranges
between about 3.0 and about 10 mm.
21. The method of claim 12, wherein a planar orientation of the
therapeutic element relative to the ultrasound transducer is
maintained during one or multiple ablation procedures on the
ovary.
22. The method of claim 21, wherein a mechanical lock or a visual
identifier is configured to maintain the planar orientation of the
therapeutic element relative to the ultrasound transducer and
during one or multiple ablation procedures on the ovary.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of International
Application No. PCT/US2014/061159 filed on Oct. 17, 2014, which
claims priority to U.S. Provisional Application Ser. No. 61/892,943
filed on Oct. 18, 2013 and U.S. Provisional Application Ser. No.
61/969,042 filed on Mar. 21, 2014. Each of the foregoing
disclosures is herein incorporated by reference in its
entirety.
FIELD
[0002] Described here are methods and systems for the manipulation
of ovarian tissues. The methods and systems may be used in the
treatment of polycystic ovary syndrome (PCOS). The systems and
methods may be useful in the treatment of infertility associated
with PCOS.
BACKGROUND
[0003] Polycystic Ovary Syndrome (PCOS) was initially characterized
in the 1930s by Stein & Leventhal. Features of the syndrome may
include: oligo/amenorrhea, oligo/anovulation, hirsutism, acne,
obesity, and characteristic polycystic appearance of the ovaries.
PCOS generally has significant effects on reproductive health
(e.g., oligo/amenorrhea and oligo/anovulation, bleeding,
endometrial hyperplasia, infertility, and increased risk of
endometrial cancers) as well as non-reproductive health (e.g.,
hyperandrogenism, carcinoma, insulin resistance,
hypercholesterolemia, hypertension, obesity, sleep apnea, and
cardiovascular disease). PCOS has historically been considered in
the context of hormonal dysregulation characterized by alterations
in gonadotropin secretion, increased androgen production, increased
insulin resistance, increased cortisol production, and obesity. It
has also been shown that PCOS is often accompanied by increased
activity of the sympathetic nervous system.
[0004] Treatment of PCOS can be costly to the health care system.
Key non-infertility treatments include: oral contraceptives (for
hormonal normalization), endometrial ablation (for anovulatory
bleeding), insulin sensitizing agents, anti-hypertensive agents,
statins, and treatments for severe acne and hirsutism.
[0005] Many women with PCOS may also require infertility treatment
during their lifetime. Treatment for PCOS infertility typically
follows a step-wise approach. For example, clomiphene citrate is
generally the first-line treatment with second-line treatment being
either gonadotropin administration or ovarian drilling (also
sometimes referred to as ovarian diathermy). If these treatments
are unsuccessful, in vitro fertilization (IVF) is attempted.
However, multiple pregnancies and live births (e.g., twins) are
common with clomiphene citrate, gonadotropin, and IVF treatments.
In infertility treatment, multiple pregnancies and live births is
often considered an undesirable result due to the associated
perinatal and neonatal morbidity and the associated elevated costs.
Furthermore, ovarian hyperstimulation syndrome (OHSS) may be more
common in women with PCOS undergoing gonadotropin or IVF treatment.
While OHSS is often mild and easily treated, more severe cases may
require aggressive treatment.
[0006] Alternatively, and as mentioned above, ovarian drilling may
be an option in treating PCOS, PCOS-associated symptoms/disorders,
and PCOS related infertility. Prior to the development of ovarian
drilling, many other types of surgery were performed on the ovaries
for the treatment of infertility. Ovarian wedge resection, a
well-established procedure first described in the late 1940s,
involves surgically removing wedge-shaped pieces of ovarian tissue
from polycystic ovaries. Despite the effectiveness of the
procedure, ovarian wedge resection has generally been abandoned in
favor of new techniques because of the frequent occurrence of
adhesions with the wedge resection technique. Other ovarian
surgeries for infertility in PCOS that have been performed are
ovarian electrocautery, ovarian laser vaporization, multiple
ovarian biopsies, and others.
[0007] Ovarian drilling/diathermy (OD) was developed in the 1970s
and 1980s by Gjonnaess. Recently, OD has been the most frequently
described ovarian surgery for infertility in women with PCOS. In
this laparoscopic procedure, radiofrequency energy, or other
techniques, is used to bore multiple holes in the ovary. The
physiologic mechanism is not well documented, but there are common
findings following the surgery including acute changes in ovarian
and pituitary hormones followed by a prolonged reduction of
circulating androgens. In randomized trials, rates of pregnancy and
live birth have been shown to be similar to those associated with
gonadotropin treatment, but with significantly reduced rates of
multiple pregnancies and live births.
[0008] Despite this evidence, ovarian drilling is not used as
frequently in clinical practice as other treatments for PCOS
infertility. This may be due to: (1) the lack of standardized,
consistent methods of targeting and performing surgeries on the
ovary; (2) the invasive nature of current OD technologies; (3) the
theoretical risk of adhesions from intervention on the ovaries; (4)
the surgical route of access is not a good fit for the clinical
practice patterns of fertility physicians; and (5) the uncertainty
of the mechanism of action. Accordingly, it would be useful to have
systems and methods that overcome the limitations of current
surgical procedures. Such systems may be designed to consistently
target ovarian tissues, reduce the level of invasiveness of the
procedure, reduce the risk of adhesions, and potentially target
specific tissue types to act more specifically tissues responsible
for the disease. Moreover, given that the ovaries or elements
therein may play an important role in governing other female health
issues such as timing of menopause, hot-flushes, fibroids, hormonal
dysregulation, endometriosis, adnexal pain, risk of endometrial
cancer, disturbances in glucose metabolism, or cardiovascular
health, it would be beneficial to have improved methods and systems
for treating these conditions as well as targeting of structures
within or nearby the ovaries that may enable treatment of these
conditions.
SUMMARY
[0009] Described here are methods and systems for manipulating
ovarian tissues within a patient. Exemplary ovarian tissues include
without limitation, the ovaries (e.g., medulla/stroma and/or
cortex), ovarian follicles/cysts, nerves associated with the
ovaries, suspensory ligaments, ovarian ligaments, broad ligaments,
the mesovarium, or a combination thereof. In this application, the
terms medulla and stroma are used interchangeably. Stromal tissue
generally comprises the middle or medullary region of the ovary.
The cortex (or outer region) of the ovary is generally where
follicles of different degrees of maturity tend to reside. These
follicles are sometimes called "cysts" in the setting of PCOS, and
in this application, follicle and cyst are used interchangeably.
The methods and systems may be used to treat one or more symptoms
of, or disorders associated with, polycystic ovary syndrome,
including infertility.
[0010] In general, the methods and systems are configured to access
ovarian tissue or a target region proximate the ovarian tissue
transvaginally, laparoscopically, percutaneously, via a natural
orifice route through the vagina-uterus-fallopian tubes, through an
open surgical approach or via an entirely non-invasive approach.
The methods and systems may treat ovarian tissues by mechanical
manipulation and/or removal, by delivery of chemical, biologic, or
pharmaceutical agents, by delivery of energy, or by applying
cooling/cold to the tissues. Exemplary treatment modalities may
include without limitation, delivery of one or more of the
following: a radiofrequency energy element; a direct heating
element; a cryoablation element; a cooling element; a mechanical
disruption and/or removal element; laser; a microwave antenna; an
unfocused ultrasound element; a partially-focused ultrasound
element; a focused (HIFU) ultrasound element; and/or an element for
delivering heated water/saline, steam, a chemical ablation agent, a
biologic or pharmaceutical agent, implantable pulse generator, a
passive or active (e.g., electronic drug delivery unit)
drug-eluting implant, a radioisotope seed, or a mechanical implant,
which may be either passive or active via application of remote
energy (e.g., ultrasound to induce vibration).
[0011] The systems described here generally comprise an ovarian
tissue apparatus capable of being advanced proximate to or within
an ovary, and in the case of PCOS, an ovarian follicle/cyst or
other target tissue (e.g., stroma). The ovarian tissue apparatus
may also include an engagement device, e.g., a docking device,
configured to engage ovarian tissue. The engagement device may be
configured to engage the outside surface of the ovary (e.g., the
capsule), the outer regions of tissue within the ovary (e.g., the
cortex), or the tissue inside the ovary (e.g., medulla, one or more
cysts). One or more therapeutic elements can be deployed via the
devices to apply one treatment or multiple treatments to the
ovarian cyst and/or ovarian tissue. The therapeutic elements may
deliver energy, e.g., radiofrequency energy, to effect treatment.
The devices and therapeutic elements may be advanced, deployed, or
otherwise positioned under image guidance, (e.g., transvaginal
ultrasound, transabdominal ultrasound, endoscopic visualization,
direct visualization, computed tomography (CT), or magnetic
resonance imaging (MRI), optical coherence tomography (OCT), an
ultrasound element on the device, or virtual histology).
Pre-treatment planning may also be completed prior to performance
of the procedure on the target tissue. For example, one or more of
the following may be obtained: the size, volume, and/or location of
the ovary; the size, volume and/or location of one or more ovarian
cysts; and the size, volume, and/or location of the medulla,
hormone levels, etc.
[0012] According to some embodiments described herein, which may
partially or as a whole combine with other embodiments, systems for
performing an ovarian procedure may include an ovarian tissue
apparatus, the ovarian tissue apparatus comprising a docking device
and a therapeutic element, the docking device comprising an
elongate body and having a proximal end, a distal end, and defining
a lumen therethrough, and the therapeutic element being slidable
within and deployable from the lumen of the docking device; a
transvaginal probe comprising a handle and an ultrasound
transducer; a mechanical lock or a visual identifier on a part of
the system; and a generator configured to supply energy to the
therapeutic element, where the mechanical lock or visual identifier
is configured to maintain planar orientation of the therapeutic
element relative to the ultrasound transducer and during a
procedure on an ovary. In some instances a non-linear (e.g.,
curved) therapeutic element may be employed, which allows the
therapeutic element to be fully visualized under 2-dimensional
ultrasound during therapy delivery, thereby ensuring that
non-target tissues are not treated. The curved structure may
further aid in anchoring the device in the target tissue, limiting
the risk of the device moving during treatment due to patient
movement or user error. The curved structure may also be configured
to match the contour of the ovary, allowing for improved
positioning within a variety of sized or shaped ovaries.
Additionally or alternatively, the curved structure may allow for
longer or additional electrodes to be delivered and used
simultaneously, allowing for larger ablation volumes per energy
application. This feature may limit pain experienced by the patient
and reduce procedure time. Anchoring either the docking device
and/or the therapeutic element in the target tissue may help the
user to move the ovary relative to surrounding non-ovary tissues to
improve and/or confirm visualization. Moving the ovary may also
allow the user to more easily reposition the device for subsequent
treatments. Additionally or alternatively, the docking device may
be configured to aid in anchoring the device in the target
tissue.
[0013] According to embodiments described herein, which may
partially or as a whole combine with other embodiments, systems for
performing an ovarian procedure may include a docking device, the
docking device comprising an elongate body and having a proximal
end, a distal end, and defining a lumen therethrough; a
radiofrequency energy element slidable within and deployable from
the lumen of the docking device; a transvaginal probe comprising a
handle and an ultrasound transducer; a mechanical lock for
releasably coupling the docking device to the probe handle to
maintain planar orientation of the radiofrequency energy element
relative to the ultrasound transducer during the ovarian procedure;
and a generator configured to supply radiofrequency energy to the
radiofrequency energy element. In some instances a non-linear
(e.g., curved) therapeutic element may be employed, which allows
the therapeutic element to be fully visualized under 2-dimensional
ultrasound during therapy delivery, thereby ensuring that
non-target tissues are not treated. As previously stated, the
curved structure may further aid in anchoring the device in the
target tissue, limiting the risk of the device moving during
treatment due to patient movement or user error. The curved
structure may also be configured to match the contour of the ovary,
allowing for improved positioning within a variety of sized or
shaped ovaries. Additionally or alternatively, the curved structure
may allow for longer or additional electrodes to be delivered and
used simultaneously, allowing for larger ablation volumes per
energy application. This feature may limit pain experienced by the
patient and reduce procedure time.
[0014] Instead of being releasably coupled to the docking device,
in some embodiments the mechanical lock is fixedly attached to the
docking device. This system embodiment may have a variety of
effects therapy. This system embodiment, e.g., may allow for a
minimally-invasive, transvaginal approach, wherein the ovary would
be accessed using the docking device. By having the docking device
resemble a sharp needle, the docking device may be used to puncture
through the vaginal wall and into the ovary under transvaginal
image guidance. In some cases, this may allow for a single entry
point or fewer entry points into the ovary, reducing the risk of
adhesions as compared to surgical and laparoscopic approaches with
tissue dissection and entry points for each ablation in the ovary.
Once in position, the radiofrequency energy element may be deployed
into the tissue. In the case where a mechanical lock is used to
maintain planar orientation of the radiofrequency element, the
radiofrequency element may be non-linear (e.g., curved in a single
plane). Here the releasably securable mechanical lock allows the
therapeutic element to be flipped 180 degrees so in the case of an
asymmetrically shaped therapeutic element, additional regions of
the ovary could be accessed and treated without moving the delivery
catheter. The non-releasable version of the lock simplifies the
user experience when a therapeutic element does not need to be
flipped 180 degrees. Since transvaginal ultrasound imaging provides
a 2-dimensional image, it is important to maintain the orientation
of the radiofrequency element to ensure that the user can see the
entire structure. This allows the user to visually observe
deployment and confirm position within the ovary or target tissue,
adding to the safety and/or effectiveness of the procedure. The
advantages of a transvaginal approach over surgical or laparoscopic
approaches generally include one or more of the following: (a)
conscious sedation vs. general anesthesia which reduces cost and
patient risk, (b) no external scars, (c) less tissue manipulation
resulting in lower risk of adhesions, (d) fewer access points into
the ovary resulting in lower risk of adhesions, (e) faster recovery
time, and (f) it is a familiar access route for OB/GYN and
fertility physicians, and fits within existing care pathways.
[0015] According to some embodiments described herein, which may
partially or as a whole combine with other embodiments, systems
described herein may comprise additionally or alternatively an
ultrasound imaging and/or therapeutic element configured to be
placed in contact with the abdomen of a patient; an element(s) for
operatively connecting the ultrasound imaging and/or therapeutic
element to a console, comprised of a user interface, an element(s)
for delivering ultrasound for imaging, an element(s) for targeting
desired tissue, an element(s) for delivering energy (e.g.,
partially-focused ultrasound, HIFU), and an element(s) for a
feedback control system.
[0016] Methods for manipulating ovarian tissue of a patient may
include delivering pain management medications systemically and/or
locally (e.g., the vaginal wall, the ovary, the mesovarium),
accessing a target region proximate an ovarian tissue within the
patient; advancing an ovarian tissue apparatus to the target
region, the ovarian tissue apparatus comprising a docking device
and one or more therapeutic elements, the docking device comprising
a proximal end, a distal end, and a distal tip; moving the docking
device proximate to or within the ovarian tissue; deploying the one
or more therapeutic elements on or within the ovarian tissue;
assessing intra-procedural success; and minimizing the occurrence
of adhesions as seen with surgical approaches used in the past. The
docking device may or may not require physical contact with ovarian
tissues.
[0017] In some instances, it may be useful to employ methods that
minimize the occurrence of adhesion such as performing the
procedure via a single entry point or fewer entry points in the
ovary (the severity of adhesions may correlate with the number and
size of damage to the ovary surface); avoiding injury to the cortex
or regions of the cortex closest to the surface (e.g., several
millimeters) of the ovary; and leaving behind material
anti-adhesive barriers to improve healing at the ovary surface and
further reduce adhesion formation. It may also be beneficial to
include features for visualizing various portions of the system
using imaging as a guide. Depending upon the approach taken (e.g.,
transvaginal, percutaneous, laparoscopic), the apparatus may
include various mechanisms for improving visualization of the
portions of the system, e.g., the therapeutic elements.
[0018] Methods described herein for delivering energy to an ovary
and for treating polycystic ovary syndrome may include advancing a
probe comprising a handle, an ultrasound transducer, and a needle
guide into the vaginal canal; advancing an ovarian tissue apparatus
into the needle guide, the ovarian tissue apparatus comprising a
docking device and a therapeutic element; advancing the docking
device through a vaginal wall; penetrating an ovary at a single
entry point with the docking device or the therapeutic element;
advancing the therapeutic element from the docking device into the
ovary; and delivering energy to affect a volume of tissue within
the ovary using the therapeutic element to treat a symptom of
polycystic ovary syndrome; retracting the therapeutic element into
the docking device; and removing the ovarian tissue apparatus.
[0019] Alternative methods for treating polycystic ovary syndrome
as described herein may include advancing an ovarian ablation
system into the vaginal canal, the ovarian ablation system
comprising a docking device, a radiofrequency energy element, and a
transvaginal probe comprising a handle and an ultrasound
transducer; advancing the docking device through a vaginal wall
under image guidance using the ultrasound transducer; entering an
ovary through a single entry point using the docking device or the
radiofrequency energy element; advancing the radiofrequency energy
element within the ovary; and delivering radiofrequency energy to
ablate a volume of tissue within the ovary using the radiofrequency
energy element to treat a symptom of polycystic ovary syndrome.
[0020] Methods that may be useful in treating polycystic ovary
syndrome are also described herein. Such methods generally include
advancing an ovarian tissue apparatus proximate a polycystic ovary
within a patient, the ovarian tissue apparatus comprising a docking
device and one or more therapeutic elements, the docking device
comprising a proximal end, a distal end, and a distal tip;
deploying the one or more therapeutic elements from the docking
device proximate to or within a target tissue, e.g., an ovarian
cyst; and manipulating the polycystic ovary to effect a change in
the target tissue, one or more symptoms or physiological parameters
indicative of polycystic ovary syndrome or its related symptoms,
diseases, disorders, or a combination thereof.
[0021] Methods that may be useful in controlling pain associated
with non-surgical procedures are also described herein. Such
methods generally include delivering systemic pharmacologic
sedation (e.g., monitored anesthesia care (MAC) or conscious
sedation); delivering local anesthesia to the vaginal wall to
reduce discomfort in a transvaginal procedure; delivering local
anesthesia to the ovary, target tissue, mesovarium, or nerve tissue
proximate to the ovary to minimize discomfort associated with
application of the therapy; and delivering an epidural to minimize
discomfort and patient movement during the procedure.
[0022] Methods that may be useful in determining the
intra-procedural or post-procedural effect of the procedure are
also described herein. Such methods generally include comparing
pre-treatment planning parameters (e.g., the size, volume, and/or
location of the ovary; the size, volume and/or location of one or
more ovarian cysts; the size, volume, and/or location of the
medulla; hormone levels) with intra-procedurally-measured
parameters or post-procedurally-measured parameters. Examples
include: a visible reduction in ovary size or volume, a reduction
in the number of cysts, or a reduction in hormone levels, such as
anti-mullerian hormone.
[0023] According to some embodiments described herein, and which
may partially or as a whole combine with other embodiments, systems
for manipulating ovarian tissues generally include an ovarian
tissue apparatus configured for advancement through the vaginal
wall and proximate an ovarian tissue; and an energy generator
electrically coupled to the ovarian tissue apparatus, where the
ovarian tissue apparatus comprises a docking device and one or more
therapeutic elements, the docking device comprising an elongate
body having a proximal end, a distal end, a lumen extending from
the proximal end through the distal end, and a distal tip. In some
instances a non-linear (e.g., curved) therapeutic element may be
employed, which allows the therapeutic element to be fully
visualized under 2-dimensional ultrasound during therapy delivery,
thereby ensuring that non-target tissues are not treated. As
previously stated, the curved structure may further aid in
anchoring the device in the target tissue, limiting the risk of the
device moving during treatment due to patient movement or user
error. The curved structure may also be configured to match the
contour of the ovary, allowing for improved positioning within a
variety of sized or shaped ovaries. Additionally or alternatively,
the curved structure may allow for longer or additional electrodes
to be delivered and used simultaneously, allowing for larger
ablation volumes per energy application. This feature may limit
pain experienced by the patient and reduce procedure time.
Anchoring either the docking device and/or the therapeutic element
in the target tissue may help the user to move the ovary relative
to surrounding non-ovary tissues to improve and/or confirm
visualization. Moving the ovary may also allow the user to more
easily reposition the device for subsequent treatments.
Additionally or alternatively, the docking device may be configured
to aid in anchoring the device in the target tissue. In some
embodiments, a cooling or cryogenic console may be operatively
coupled to the ovarian tissue apparatus instead of or in addition
to an energy generator. Use of cooling or cryotherapy may limit the
amount of pain the patient experiences and may be used in
combination with energy to aid in controlling lesion size (e.g.,
limit conductive heating). Further, combining cooling or
cryotherapy with energy may allow for thermally cycling target
tissue from cold to hot, resulting in additional cellular
injury.
[0024] According to some embodiments described herein, and which
may partially or as a whole combine with other embodiments, the
system may generally include an ovarian tissue apparatus configured
for advancement through the vaginal wall and proximate an ovarian
tissue; one or more mechanical disruption and/or removal elements;
and means for removing target tissue from the body. Mechanical
disruption elements may be manipulated manually or automatically
(e.g., via a motor and/or drive system). Mechanical manipulations
may include rotation, translation and/or vibration. Removal
elements may include mechanical instruments for grasping or
capturing tissue or a lumen of the apparatus coupled with
aspiration or suction. The removed tissue may be used for
diagnosis, or components of removed tissue (e.g. oocytes or
cellular factors) may be useful in further care. In some
embodiment, means for removing target tissue from the body may also
include allowing the body's natural healing process to resorb
destroyed tissue and/or produce a stable scar.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] FIG. 1A depicts a stylized, anatomic view of the ovaries,
adnexa, uterus, and other nearby structures. FIG. 1B depicts a
stylized anatomic view of the structural elements within the
ovary.
[0026] FIGS. 2-5 depict embodiments of devices for creating space
in the area adjacent to the ovary for facilitating a procedure on
the ovaries.
[0027] FIGS. 6-10 and 11A-11B depict embodiments of guide/docking
device and associated methods for facilitating access to the
ovaries.
[0028] FIGS. 12A-12F, 13A-13D, 14A-14E, 15A-15B, 16A-16D, 17,
18A-18D, 19, 20A-20C, 21A-21B, and 22 depict embodiments of
therapeutic elements and methods for deploying the therapeutic
elements for treatment of the ovaries.
[0029] FIG. 23 depicts an embodiment of a system for energy
delivery via a transvaginal, laparoscopic, percutaneous, or
surgical procedure.
[0030] FIG. 24 depicts an embodiment of a device for providing
planar orientation of therapeutic element(s) during transvaginal
ultrasound-guided procedures.
[0031] FIG. 25 shows various views of an embodiment of a magnetic
needle guide.
[0032] FIG. 26 illustrates an exemplary method for providing planar
orientation of a curvilinear therapeutic element.
[0033] FIGS. 27A-27F depict another exemplary method and device for
providing planar orientation of therapeutic element(s) during
transvaginal ultrasound-guided procedures.
[0034] FIG. 28 depicts a further embodiment of a device for
providing planar orientation of therapeutic element(s) during
transvaginal ultrasound-guided procedures.
[0035] FIG. 29 illustrates an exemplary method of accessing ovarian
tissue transvaginally.
[0036] FIG. 30 illustrates an exemplary method of accessing ovarian
tissue laparoscopically.
[0037] FIG. 31 depicts another embodiment of a system and method
for ablating ovarian tissue.
[0038] FIG. 32 depicts an exemplary Power/Temperature Curve.
[0039] FIG. 33 depicts another exemplary Power/Temperature
Curve.
[0040] FIG. 34 depicts an embodiment of a system including a
neutral electrode for measurement of impedance.
[0041] FIGS. 35A-35C depict the system of FIG. 34 in varying
portions of the ovary.
[0042] FIGS. 36A-36C illustrates an exemplary method of limiting
travel of a therapeutic element into the ovary.
[0043] FIG. 37 depicts an embodiment of a non-invasive treatment
system.
DETAILED DESCRIPTION
[0044] Described here are methods and systems for manipulating
ovarian tissues within a patient. The methods and systems may be
used in the treatment of polycystic ovary syndrome (PCOS), and may
be particularly useful in the treatment of infertility associated
with PCOS. As previously stated, exemplary ovarian tissues include
without limitation, the ovaries, ovarian cysts, nerves associated
with the ovaries, suspensory ligaments, ovarian ligaments, broad
ligaments, the mesovarium, or a combination thereof.
[0045] In general, the methods and systems are configured to access
ovarian tissue or a target region proximate the ovarian tissue
transvaginally, laparoscopically, percutaneously, via a natural
orifice route through the vagina-uterus-fallopian tubes, through an
open surgical approach, or via an entirely non-invasive approach.
It may be beneficial to access the ovarian tissue or a target
region proximate the ovarian tissue transvaginally. The advantages
of a transvaginal approach over surgical or laparoscopic approaches
may include one or more of the following: (a) conscious sedation
vs. general anesthesia which reduces cost and patient risk, (b) no
external scars, (c) less tissue manipulation resulting in lower
risk of adhesions, (d) fewer access points into the ovary resulting
in lower risk of adhesions, (e) faster recovery time, and (f) it is
a familiar access route for OB/GYN and fertility physicians, and
fits within existing care pathways. As used herein, the term
"transvaginal" or "transvaginally" refers to access through the
vagina and into the peritoneal space, through the vaginal wall. The
methods and systems may treat ovarian tissues by delivery of one or
more of the following: a radiofrequency energy element; a direct
heating element; a cryoablation element; a cooling element; a
mechanical disruption element; laser; a microwave antenna; an
unfocused ultrasound element; a partially-focused ultrasound
element; a focused (HIFU) ultrasound element; and/or an element for
delivering heated water/saline, steam, a chemical ablation agent, a
biologic or pharmaceutical agent, implantable pulse generator, a
passive or active (e.g., electronic drug delivery unit)
drug-eluting implant, or a mechanical implant, which may be either
passive or active via application of remote energy (e.g.,
ultrasound to induce vibration).
[0046] When the methods and systems employ an image guided energy
delivery element (therapeutic element), it may be useful to
maintain planar orientation of the energy delivery element with an
imaging plane of view, as further described below. In the case of a
non-linear (e.g., curved) therapeutic element, this allows for the
therapeutic element to be fully visualized under 2-dimensional
imaging during therapy delivery, thereby ensuring that non-target
tissues are not treated. Furthermore, when performing an ovarian
procedure with the systems described herein, it may be beneficial
to minimize the number of entry points into the ovary (the severity
of adhesions may correlate with the number and size of damage to
the ovary surface). After accessing the ovary through the single
entry point, energy may be delivered from inside the ovary (instead
of from outside the ovary) to affect a volume of tissue and/or
treat polycystic ovary syndrome. For example, the number of
ablations needed to affect the desired volume of tissue may vary,
but could range from 1-10 ablations.
[0047] To further understand the methods and systems described
herein, a brief overview of female reproductive anatomy is
provided. Referring to FIG. 1A, the paired ovaries (2) lie within
the pelvic cavity, on either side of the uterus (3), to which they
are attached via a fibrous cord called the ovarian ligament (4).
The ovaries (2) are uncovered in the peritoneal cavity but are
tethered laterally to the body wall via the suspensory ligament (5)
of the ovary. The part of the broad ligament (6) of the uterus that
suspends the ovary is known as the mesovarium (7). FIG. 1B is an
expanded, cross-sectional view of the ovary (2) and surrounding
structures shown in FIG. 1A. Referring to FIG. 1B, the stroma or
medulla (8) comprises the middle or medullary region of the ovary;
the cortex (9) (or outer region) of the ovary tends to be where
follicles (10) of different degrees of maturity reside; primordial
follicles (12), which are very small and immature follicles,
comprise a reserve of future follicles for ovulation; a capsule
(14) encases the ovary (2), which is tethered to the broad ligament
(6) by the mesovarium (7); small blood vessels (16) and nerves (18)
enter the ovary (2) through the mesovarium (7), the ovarian
ligament (4), and the suspensory ligament (5) of the ovary.
[0048] A brief overview of several approaches to accessing ovarian
tissue is also provided, as depicted in FIG. 29. Referring to the
figure, a system for performing transvaginal ultrasound is shown.
An ultrasound probe (101) is placed inside the vagina (103) of the
patient (105). A cable (107) connects the handle (109) of the probe
to a monitor (111), allowing the user to visualize the ultrasound
images. A typical laparoscopic procedure is illustrated in FIG. 30.
The laparoscopic approach typically employs 2 or 3 small incisions
(201), through which various imaging and surgical tools (203) can
be introduced. Imaging is performed with a laparoscope (205), which
allows for direct visualization of tissues. The abdominal cavity is
filled with gas (207) to expand the field of view and allow for
manipulation of tissues.
I. METHODS
[0049] Disclosed herein are various methods for manipulating the
ovarian tissues of a patient. Manipulation of the ovarian tissues
may occur by mechanical manipulation of the tissues, by delivery of
chemical, biologic or pharmaceutical agents, cooling/cryotherapy,
or by delivery of energy to the tissues. Although the ovarian
tissues may be accessed using any suitable approach, the methods
described here generally use a transvaginal approach. The type of
approach utilized may depend on factors such as a patient's age,
comorbidities, need for other concomitant procedures, and prior
surgical history. Furthermore, in some instances it may be
desirable to provide protective elements and/or spacing devices
configured to spare or separate non-target tissues, or to prevent
excessive damage to the tissues. In some cases, for example thermal
treatment, the protective element can be the use of a temperature
sensor (e.g. a thermocouple or thermistor), and/or an active
cooling member (e.g., internally cooled electrode, irrigated
electrode, irrigated guide/docking device, etc., if heat is
generated). Embodiments of spacing devices may include mechanical
features incorporated into an apparatus and/or fluid infusion into
the region proximate to the ovary (e.g., the peritoneal space). In
some embodiments, the aspiration and irrigation functions are
performed via the same lumen within the apparatus.
[0050] In one variation, the method includes accessing a target
region proximate an ovarian tissue within the patient; advancing an
ovarian tissue apparatus to the target region, the ovarian tissue
apparatus comprising a docking device and one or more therapeutic
elements, the docking device comprising a proximal end, a distal
end, and a distal tip; contacting the ovarian tissue with the
docking device; and deploying the one or more therapeutic elements
on or within the ovarian tissue.
[0051] The docking device of the ovarian tissue apparatus may be
advanced using image guidance. Image guidance may be accomplished
using techniques such as but not limited to, transvaginal
ultrasound, transabdominal ultrasound, endoscopic visualization,
direct visualization, computed tomography (CT), or magnetic
resonance imaging (MRI), optical coherence tomography (OCT), an
ultrasound element on the device, virtual histology, or a
combination thereof. In some embodiments, for example alternatively
or in conjunction with image guidance, advancement and navigation
of the docking device may be accomplished using a steering
mechanism at least partially disposed within the distal end of the
docking device. For example, one or more steerable wires may be
disposed within the docking device running from the proximal end to
the distal tip of the device. Actuation of the steerable wires may
occur by manipulation of a mechanism on a handle at the proximal
end of the docking device. In some embodiments, the docking device
comprises a flexible distal end, or one or more flexible segments
to aid with navigation to the target ovarian tissue. In other
embodiments, the docking device comprises a rigid member, which may
have a sharpened tip. Proximal portions of the docking device may
be reinforced, e.g., with a braided shaft, material of increased
durometer, to provide improved pushability and torque control.
[0052] The ovarian tissue may be engaged in various different ways.
In some variations, the step of contacting comprises applying
vacuum to the ovarian tissue using the distal tip of the docking
device. In other variations, the step of contacting comprises
releasably securing one or more attachment elements to the ovarian
tissue. The attachment elements may comprise any suitable element
capable of releasably securing ovarian tissue. Embodiments of such
attachment elements include a hook, needle, barb, or combination
thereof. When vacuum is used to help engage the docking device to a
polycystic ovary, the vacuum may also be used to aspirate fluid
from one or more cysts. Aspiration of cyst fluid may reduce the
size of the cyst or reduce the total number of cysts on the ovary.
By reducing the size of the cyst, the tissue may be drawn closer to
or into contact with the therapeutic element(s), which may allow
for improved targeting of tissue (e.g., thecal cells) and/or
shorter treatments times. Aspiration of fluid may also aid in the
assessment that bleeding has been controlled after delivery of the
therapy.
[0053] According to some embodiments described herein, which may
partially or as a whole combine with other embodiments, the distal
end of the docking device comprises a tissue engagement element,
and the ovarian tissue is contacted using the tissue engagement
element. In some embodiments, the tissue engagement element
comprises a preformed shape, e.g., a predetermined curvature. The
preformed shape may conform to the shape of the ovarian tissue, and
aid in the deployment of the treatment elements from the docking
device. One or more therapeutic elements may be deployed from the
docking device on, into, or proximate to the ovarian or mesovarian
tissue. When the ovarian tissue is an ovary, the size of the ovary
may range from about 3 to 7 cm in length, about 1 to 4 cm in width,
and about 0.5 to 4 cm in thickness. Ovaries stimulated by
pharmaceutical agents such as gonadotropins may often be
larger.
[0054] According to embodiments described herein, which may
partially or as a whole combine with other embodiments, the
therapeutic element may comprise one or more of the following: a
radiofrequency energy element; a direct heating element; a
cryoablation element; a cooling element; a mechanical disruption
element; laser; a microwave antenna; an unfocused ultrasound
element; a partially-focused ultrasound element; a focused (HIFU)
ultrasound element; and/or means for delivering heated
water/saline, steam, a chemical ablation agent, a biologic, or
pharmaceutical agent, implantable pulse generator, a passive or
active (e.g., electronic drug delivery unit) drug-eluting implant,
a radioisotope seed, or a mechanical implant, which may be either
passive or active via application of remote energy (e.g.,
ultrasound to induce vibration). In some embodiments, the
therapeutic element comprises a radiofrequency energy element,
e.g., a radiofrequency electrode. In some embodiments, the
therapeutic element may comprise one or more curved needle
electrodes. Additionally or alternatively, the therapeutic element
may comprise one or more straight or curved wire electrodes.
According to embodiments described herein, which may partially or
as a whole combine with other embodiments, the therapeutic element
may comprise one or more active electrodes on an elongate body.
Here a return electrode may be provided on the distal end of the
docking device, or be deployable from the docking device.
Alternatively, a return electrode may be placed on the outside of
the patient. For example, in one variation, a return electrode may
be affixed to the ultrasound probe proximate the transducer. In
another variation, a return electrode may be incorporated into a
needle guide. In the case of a plurality of electrodes, any pair
may be activated in a bipolar manner or individually via a return
electrode. With regards to the use of the various types of
ultrasound, it could include variations that use ultrasound to
create thermal heating or non-thermal ultrasound to induce acoustic
cavitation.
[0055] Mechanical disruption elements could include mechanical
disruption of one or more target tissues (e.g., medulla, cortex,
nerves, cysts, etc.). The mechanical disruption may include
morcellating, tearing, compressing, stretching or otherwise
destroying tissue or causing it to alter its function (e.g., induce
apoptosis, trigger increased blood flow, trigger a healing
response, trigger maturation of oocytes, or trigger ovulation).
Injured/destroyed tissue may be removed mechanically or left within
the body, allowing the body's natural healing process to resorb the
destroyed tissue. The morcellated tissue may also be retrieved in
some instances if it can be used for diagnosis, or if components of
the removed tissue (e.g., oocytes or cellular factors) may be
useful in further care. Pharmacologic or biologic agents could be
delivered either as a one-time delivery, part of a slow-release
preparation, or implanted as a part of a biodegradable or
non-biodegradable device. These agents could also be implanted
within a casing (e.g., an electronic drug delivery unit) configured
to remotely control delivery of the casing's contents using a
controller external to the body. Exemplary biologic or
pharmacologic agents that could be employed include without
limitation: beta-blockers, anti-androgens (e.g., finasteride,
flutamide, nilutamide, bicalutamide, spironolactone, cyproterone),
follicular stimulating hormone, luteinizing hormone, other
hormones, neurotoxins or tissue toxins (e.g., botox, guanethidine,
ethanol), 5-alpha-reductase inhibitors (e.g., finasteride,
dutasteride, izonsteride, turosteride, and epristeride), insulin
modulating agents, aromatase inhibitors (e.g., letrozole,
exemestane, anastrozole), VEGF modulating agents, agents modulating
inhibin, agents modulating interleukins, pluripotent or multipotent
stem cell preparations, or cellular components. Furthermore, an
agent (e.g., radiopaque material, echogenic material, etc.) may be
left behind to tag the location(s) in which the therapeutic
agent(s) are delivered.
[0056] In one variation, one or more therapeutic elements are
advanced on or into an ovary. In another variation, the one or more
therapeutic elements are advanced on or into an ovarian cyst. The
one or more therapeutic elements may also be advanced from the
mesovarium on or into an ovary or an ovarian cyst. In one
variation, the one or more therapeutic elements are delivered to
multiple, predetermined areas on or within the ovarian tissue. In
other instances, a pattern of treatment is delivered on or into the
ovarian tissue. These patterns of treatment within the tissue could
be linear, curvilinear, helical, interrupted, continuous,
arbor-like (e.g., with a trunk and multiple offshoots), or may
comprise other suitable patterns. The therapeutic elements may be
utilized such that multiple treatments may be delivered through a
single outer entry point in the ovary. The therapeutic elements may
be delivered to treat any suitable medical condition of the female
reproductive anatomy, and may be particularly beneficial in the
treatment of polycystic ovary syndrome.
[0057] Some variations of the method deliver thermal energy to the
ovarian tissues. The thermal energy may increase the temperature of
the ovarian tissue (e.g., by heating) and/or ablate/coagulate
and/or desiccate/char the tissue. The thermal energy may also be
delivered to reduce the temperature of the ovarian tissue (e.g. by
cooling) or may cryoablate the tissue. Mechanically disrupting the
ovarian tissues with the one or more therapeutic elements is also
contemplated. For example, a steerable device could be used under
image guidance to maximize the number of ovarian cysts that are
ruptured as it was advanced in a path through the ovarian tissue,
this could be done alone or in combination with some form of
thermal energy. The mechanically disrupting portion of the device
could rupture a cyst, then imaging could identify rupturing a
subsequent cyst, and the process could be repeated.
[0058] Methods useful in treating PCOS may include advancing an
ovarian tissue apparatus proximate a polycystic ovary within a
patient, the ovarian tissue apparatus comprising a docking device
and one or more therapeutic elements, the docking device comprising
a proximal end, a distal end, and a distal tip; deploying the one
or more therapeutic elements from the docking device proximate to
or within an ovarian cyst; and manipulating the polycystic ovary or
ovarian cyst to effect a change in the ovarian cyst, one or more
symptoms or physiological parameters indicative of polycystic ovary
syndrome, or a combination thereof. An implantable pulse generator
could be used to apply periodic electric energy to modulate the
neurohormonal environment of the ovary. The implantable pulse
generator could be used to deliver energy proximate to various
ovarian structures (e.g. cortex, stroma, nerves, mesovarium). In
some variations of the method, the one or more therapeutic elements
are deployed from the docking device proximate to or within an
additional ovarian cyst. When the polycystic ovary or ovarian cyst
is manipulated, symptoms such as infertility, anovulation, acne,
obesity, abdominal pain, hirsutism, or psychological symptoms may
be treated or improved. Physiological parameters of the patient
that can be affected by manipulation of the polycystic ovary or
ovarian cyst may include androgen levels, number or size of ovarian
cysts, size of the ovary, levels of anti-mullerian hormone (AMH),
sex hormone binding globulin, level of luteinizing hormone (LH),
ratio of luteinizing hormone (LH) to follicular stimulating hormone
(FSH), lipid levels, fasting blood glucose, fasting blood insulin
levels, response to oral glucose tolerance testing, blood glucose
level, or measures of sympathetic nervous system activity (e.g.,
microneurography, norepinephrine spillover testing, or heart rate
variability). In one aspect of the PCOS treatment described herein,
a test of physiologic parameters can be performed pre-procedurally,
peri-procedurally or post-procedurally to guide therapy and/or
confirm clinical success of the treatment.
[0059] The ovarian tissue apparatus, including the docking device,
may be advanced transvaginally, laparoscopically, percutaneously,
via a natural orifice route through the vagina-uterus-fallopian
tubes, through an open surgical approach, or via an entirely
non-invasive approach. The steps of advancing, deploying, and
manipulating may be accomplished using image guidance, including
but not limited to transvaginal ultrasound, transabdominal
ultrasound, endoscopic visualization, direct visualization,
computed tomography (CT), or magnetic resonance imaging (MRI),
optical coherence tomography (OCT), an ultrasound element on the
device, virtual histology, or a combination thereof. In the case of
an entirely non-invasive approach, the steps may include
positioning an imaging and/or therapeutic element on the abdomen of
a patient, identifying target tissue, targeting said tissue, and
applying energy (e.g., partially-focused or focused ultrasound).
Hybrid approaches may also be utilized. For example, transvaginal
ultrasound may be used for imaging and/or targeting, while an
external therapeutic element could deliver energy. Further, having
ultrasound visualization in both the vagina and on the abdomen may
enhance targeting.
[0060] Alternatively, or in conjunction with image guidance, and as
previously described, advancement and navigation of the docking
device may be accomplished using a steering mechanism at least
partially disposed within the distal end of the docking device. For
example, one or more steerable wires may be disposed within the
docking device running from the proximal end to the distal tip of
the device. Actuation of the steerable wires may occur by
manipulation of a mechanism on a handle at the proximal end of the
docking device. In some embodiments, the docking device comprises a
flexible distal end, or one or more flexible segments to aid with
navigation to the target ovarian tissue. Proximal portions of the
docking device may be reinforced, e.g., with a braided shaft,
material of increased durometer, to provide improved pushability
and torque control.
[0061] The docking device may use a docking mechanism such that a
portion of the device arrives proximate to or to engages the
polycystic ovary, an ovarian cyst, or the mesovarium. In some
embodiments, the docking mechanism includes the application of
vacuum to the ovarian tissue using the distal tip of the docking
device. Alternatively or additionally, the docking mechanism
comprises releasably securing one or more attachment elements to
the polycystic ovary. The attachment elements may comprise any
suitable element capable of releasably securing the polycystic
ovary. Exemplary attachment elements include a hook, needle, barb,
or combination thereof. When vacuum is used to help engage the
docking device to a polycystic ovary, the vacuum may also be used
to aspirate fluid from one or more cysts. Aspiration of cyst fluid
may reduce the size of the cyst or reduce the total number of cysts
on the ovary. Aspiration may be used prior to, during, or after
delivery of the therapeutic element so that the therapeutic element
is more proximate to target tissue. Aspiration of fluid may also
aid in the assessment that bleeding has been controlled after
delivery of the therapy. The aspirated fluid could also be
collected and analyzed for another purpose.
[0062] In some embodiments, the distal end of the docking device
comprises a tissue engagement element, and the polycystic ovary is
contacted using the tissue engagement element. In some instances,
the tissue engagement element comprises a preformed shape, e.g., a
predetermined curvature. The preformed shape may conform to the
shape of the ovary, and aid in the deployment of the treatment
elements from the docking device.
[0063] In some embodiments, the guiding/docking device and the
therapeutic element are combined into a single entity. In other
embodiments, the guiding/docking device and the therapeutic element
are different but the two are used in tandem to deliver therapy
(e.g., the guiding/docking device has a therapeutic element such as
an electrode that may be used in combination or separate from other
deployed therapeutic elements. Alternatively, the electrode located
on the guiding/docking device may be used as a neutral electrode
with little/no therapeutic effect (e.g., heat).
[0064] In some aspects, the methods employed herein include using a
docking/guiding device to penetrate the ovary and permit delivery
of one or multiple therapeutic elements out of one or more
apertures in the guiding/docking device. In some embodiments, the
docking/guiding device may comprise, for example, a needle, and the
therapeutic element may comprise, for example, a shaft one
electrode or a plurality of electrodes. In some embodiments, the
shaft may be straight, but in other embodiments, the distal portion
of the shaft may be processed to have a pre-set shape. The
therapeutic element may be insulated along the majority of its
length or a discrete portion(s) of its length to electrically
isolate it from the docking device. In some embodiments, the
electrodes may wrap around the entire circumference of the shaft or
may only cover a portion of the shaft circumference in other
embodiments. In each of the embodiments described in the present
disclosure, the electrodes could be electrically isolated from each
other and deliver energy in a monopolar or bipolar fashion.
Monopolar configurations may allow for simpler device
configuration, but they require a neutral electrode. Bipolar
configurations may allow for energy to be contained within a more
limited field of tissues. When a bipolar method is used, one
electrode would serve as the active electrode and another electrode
would serve as the return electrode. In further embodiments,
multiple electrodes could deliver energy and the energy would
return to a neutral electrode located elsewhere, such as on the
skin of the patient, on the docking/guiding device, or on the
ultrasound probe. In some embodiments, the electrodes could also be
electrically connected to each other and deliver energy where the
return or neutral electrode is located elsewhere, such as on the
skin of the patient, on the docking/guiding device, or on the
ultrasound probe. Placing the neutral electrode on the outside of
the patient (e.g., skin) may allow for a simpler device
configuration. Placing the neutral electrode on the docking/guiding
device or the ultrasound transducer may help confine the energy
delivery to a smaller field and also change the diagnostic
information collected by impedance measurements. As shown in FIG.
31, a docking/guiding device (301) can be used to penetrate into
the ovary (303) and deliver a single therapeutic element (305) out
of the distal end (307) of the docking/guiding device (301). Here
the therapeutic element is delivered from the docking device at an
angle away from the trajectory of the docking/guiding device but
within the two-dimensional plane of an ultrasound field.
Docking/guiding device (301) may comprise a needle and the
therapeutic element (305) may include a curved shaft with two
electrodes (309) disposed thereon. The electrodes (309) may be
comprised of metallic bands, coils, wires (e.g., wound or braided),
laser cut tubing, or slotted tubular structures. They may wrap
entirely around the circumference of the therapeutic element shaft
(305) and may be separated by discreet insulated areas (311).
Additional detail relating to these devices and similar embodiments
is provided below.
[0065] One or more therapeutic elements may be deployed from the
docking device on or into the polycystic ovary, proximate to or
into an ovarian cyst, proximate to or into the mesovarium, or other
target structure. The one or more therapeutic elements may also be
advanced from a single docking location or multiple docking
locations on or within the polycystic ovary or an ovarian cyst; or
advanced from a single docking location or multiple docking
locations proximate to an ovarian cyst, or proximate to the
mesovarium. The docking location(s) could be on the medial and/or
inferior aspect of the ovary. The guiding/docking device could also
penetrate into the ovary. In one aspect of the methods, there may
be a single entry point on the outside of the ovary (by either the
guiding/docking device or the treatment element or the combination
thereof) through which multiple treatments could be delivered
thereby causing less damage to the outside of the ovary and
reducing the risk for adhesion formation. In another variation, the
energy is delivered to multiple, areas on or within the polycystic
ovary, an ovarian cyst, proximate to an ovarian cyst, proximate to
the junction of the ovarian stroma and cortex, or proximate to the
mesovarium allowing improved targeting or avoidance of certain
tissues (e.g., nerves or vasculature). In other instances, a
pattern of treatments is delivered on or within the polycystic
ovary, an ovarian cyst, proximate to an ovarian cyst, proximate to
the junction of the ovarian stroma and cortex, or proximate to the
mesovarium.
[0066] Another aspect of the methods disclosed herein comprises
orienting the therapeutic element(s) with the transvaginal
ultrasonic probe, which is generally limited to 2-dimensional (or
planar) imaging. When the therapeutic element has a non-linear
geometry, e.g., if it is curved, it is desirable to maintain
visualization of the therapeutic element via the transvaginal
ultrasound probe. Here the method may include setting the
orientation of the therapeutic element in plane with the ultrasonic
probe such that as the therapeutic element is maneuvered or
deployed, the operator can visualize it. This may be employed via
the method of attaching the therapeutic device to the handle of the
ultrasound probe and/or by employing a needle guide configured to
attach to the ultrasound probe and provide a unique guiding
interface with the guiding/docking device. The method may also
involve a means to quickly decouple the orientation between the
therapeutic element and the visualization plane of the probe. For
example, the operator may choose to deploy the therapeutic element
in one plane but then rotate the ultrasound probe into another
plane (without changing plane of the therapeutic element) to verify
placement or view other surrounding tissues. According to some
embodiments, the coupling mechanism between the therapeutic element
and probe could provide a means of sliding or rotating the probe
into a new orientation but then quickly realigning the therapeutic
element and probe (such that the deployed element is back in the
visualization plane of the probe). In some instances, it may be
desirable to reorient the therapeutic element by exactly 180
degrees to allow for it to reach different regions of tissue in the
same imaging plane.
[0067] Another aspect of the methods disclosed herein comprises
enhancing the visualization (i.e., echogenicity) of the
guiding/docking device and/or therapeutic elements while using
ultrasound for visualization. The method may include providing a
region of increased echogenicity on the guiding/docking device
and/or therapeutic elements. In some embodiments, the region of
increased echogenicity is a region that traps gas. In some
embodiments, the region of increased echogenicity includes a
roughened surface covered by a polymer sheath, which traps gas
between the grooves of the roughened surface and the polymer
sheath. The trapped gas enhances the echogenicity beyond using
merely a roughened surface. In other embodiments, gas may also be
trapped by incorporating one or more lumens, pockets, or cavities
within the therapeutic element and/or the docking device. It may be
useful to have enhanced echogenicity only at the distal tip of the
therapeutic element and/or docking device, which could aid in
ensuring that it is within the desired target tissue. For example,
enhanced echogenicity at the distal tip may help with visualization
of the tip within the ovary, and indicate that a region proximal to
the tip is contained within the ovary. It may also be useful to
have differential echogenicity of different parts of therapeutic
element and/or docking device to provide better assessment of
device placement. In some instances it may be useful for the
therapeutic element or a portion thereof to comprise an echogenic
material having greater echogenicity than the echogenic material of
the docking device or other portions of the therapeutic
element.
[0068] Alternatively, the methods provided herein may include
limited rotation and/or translation of the guiding/docking device
and/or therapeutic elements while using ultrasound to enhance
visualization. For example, rotation of plus or minus up to 20
degrees of rotation could significantly improve visualization. The
limited rotation may be useful in maintaining the therapeutic
elements within the ultrasound visualization plane (if so desired)
while allowing the operator to quickly rotate the device back and
forth to enhance visualization. In other variations of the method,
translation plus or minus up to 0.25 mm may also significantly
improve visualization. This subtle translation could be achieved,
for example, by allowing the operator to easily shift the
therapeutic elements a small distance distally and proximally, such
as plus or minus up to 0.25 mm.
[0069] In another variation, the method may include enhancing the
visualization of the treatment zone. The method may be to use
energy delivery settings to ablate the tissue in a way that makes
the ablated tissue appear differently on ultrasound. For example,
it may be desirable to first ablate the tissue for approximately
5-15 seconds, followed by a short burst of higher power to then
desiccate/char the tissue. The desiccated/charred tissue may be
more echogenic, thus enhancing the visualization of the treatment
zone. Additionally or alternatively, the method may also involve
infusing air or other echogenic gas/material into a target zone to
mark that area. This may be done after performing a treatment to
mark the zone treated so that an overlapping treatment is not
subsequently performed.
[0070] In another variation, the method may include affecting the
target tissue in a fully non-invasive way. Here the method may
include placement of an ultrasound imaging and/or therapeutic
element onto the abdomen of a patient; operatively connecting the
ultrasound imaging and/or therapeutic element to a console
comprising a user interface, delivering ultrasound for imaging,
targeting desired ovarian tissue, and delivering energy (e.g.,
partially-focused ultrasound, HIFU).
[0071] One aspect of the methods disclosed herein provides for
pre-treatment planning prior to the manipulation of ovarian
tissues. For example, pre-treatment planning could be provided for
the treatment of PCOS, including PCOS infertility. Here the method
may include the step of performing non-invasive imaging to map the
size, morphology and location of the ovary, the quantity and
location of ovarian cysts, the location of ovarian cysts relative
to other anatomical landmarks, and/or the volume of target tissue
(e.g., stroma). Non-invasive imaging modalities may include
magnetic resonance imaging (MRI), computed tomography (CT),
transvaginal ultrasound, transabdominal ultrasound, or a
combination thereof. The images and mapping performed may aid the
care-giver in planning the therapeutic procedure and/or guide the
care-giver while performing therapy. The mapping procedure may
yield images, annotated images, and/or information related to the
relationship between cysts or other target tissue and other
anatomical landmarks.
[0072] Another aspect of the methods disclosed herein provides for
harvesting available oocytes in conjunction with delivering
therapy. In one variation, currently available tools and procedures
may be used to first harvest available oocytes or tissue containing
immature oocytes, which may then be stored for later use. For
example, oocytes may be harvested using a transvaginal approach
using transvaginal ultrasound and a needle. Alternatively, the
therapy may be applied first. In yet another variation, the same
tools utilized for providing the therapy may also be configured to
also allow for oocyte harvesting. The therapy-providing tools may
have improved features to aid in targeting, thus allowing for more
oocytes to be harvested. These features may include methods for
improved targeting, such as methods for steering, engaging the
ovary and/or imaging.
II. SYSTEMS
[0073] Further described herein are embodiments of systems for
manipulating ovarian tissues and/or treating PCOS, wherein one or
more features from any of these embodiments may be combined with
one or more features from one or more other embodiments to form a
new embodiment within the scope of this disclosure. The systems may
include an ovarian tissue apparatus configured for advancement
through the vaginal wall (transvaginally), laparoscopically,
percutaneously, via a natural orifice route through the
vagina-uterus-fallopian tubes, or through an open surgical
approach, and proximate an ovarian tissue; and an energy generator
electrically coupled to the ovarian tissue apparatus, where the
ovarian tissue apparatus typically comprises a docking device and
one or more therapeutic elements, the docking device typically
comprising an elongate body having a proximal end, a distal end, a
lumen extending from the proximal end through the distal end, and a
distal tip.
[0074] The ovarian tissue apparatus, docking device, therapeutic
element, etc., may be made from polymeric materials (e.g., PEEK,
polyester, ABS, nylon), metals (e.g., stainless steel), metal
alloys (e.g., platinum-iridium), and shape memory materials (e.g.,
nitinol, elgiloy) all of which are known in the art, and thus are
not described in detail here. In some variations, the diameter of
the elongate body of the docking device may range from about 3 Fr
(1 mm) to about 15 Fr (5 mm) In other variations, the length of the
elongate body of the docking device may range from about 15 cm to
about 60 cm.
[0075] The docking device may be a relatively rigid member (e.g.,
needle, trocar) or flexible member (e.g., catheter, steerable
catheter) with features configured to help with engagement of
ovarian tissues. For example, the distal tip of the docking device
may include one or more releasably securable attachment elements to
aid in engaging the docking device to ovarian tissues. The
releasably securable attachment elements may comprise one or more
hooks, needles, or barbs. Alternatively or additionally, the
docking device may be coupled to a vacuum source to enable
vacuum-assisted engagement of the tip of the device to ovarian
tissue. In some embodiments, the distal end of the docking device
comprises a tissue engagement element. The tissue engagement
element may have a preformed shape, e.g., a predetermined
curvature.
[0076] In further variations, one or more therapeutic elements are
delivered via the docking device. According to some embodiments,
the therapeutic elements may be slidably disposed within the
docking device. Here one or more ports may be disposed on the
elongate body of the docking device through which the slidable
therapeutic elements can be deployed into an ovarian tissue.
Additionally or alternatively, the therapeutic element may comprise
a lumen for delivering a thermal fluid, such as heated water or
saline, or a biologic or pharmacological agent such as
beta-blockers, anti-androgens (e.g., finasteride, flutamide,
nilutamide, bicalutamide, spironolactone, cyproterone), follicular
stimulating hormone, luteinizing hormone, other hormones,
neurotoxins or tissue toxins (e.g., botox, guanethidine, ethanol),
5-alpha-reductase inhibitors (e.g., finasteride, dutasteride,
izonsteride, turosteride, and epristeride), insulin modulating
agents, or aromatase inhibitors (e.g., letrozole, exemestane,
anastrozole), VEGF modulating agents, agents modulating inhibin,
agents modulating interleukins, pluripotent or multipotent stem
cell preparations, or cellular components. Furthermore, an agent
(e.g., radiopaque material, echogenic material, etc.) may be left
behind to tag the location(s) in which the therapeutic agent(s) are
delivered. The one or more ports may also be disposed on the tissue
engagement element. Additionally or alternatively, the one or more
therapeutic elements may include an electrode, a cryoablation
element, an ultrasound transducer, a laser, or a combination
thereof. The therapeutic element, docking device, or separate
device may also contain a lumen (or lumens) with suitable size to
deliver a sufficient volume of fluid, such as saline or lactated
ringers solution, to fill the abdominal cavity. This fluid could be
used to help separate tissues (move non-ovarian tissues away from
the ovary to reduce risk of injury when treating the ovary),
improve ultrasonic visualization by surrounding tissues with fluid,
shift tissues into new locations for improved visualization,
provide cooling or other protection to the ovary or neighboring
tissues while treating the ovary, or promote healing of the ovary
after the procedure is completed. In some embodiments, the inner
diameter of the docking device may range from 0.25 to 3.0 mm, from
0.25 to 2.5 mm, from 0.25 to 2.0 mm, from 0.25 to 1.5 mm, or from
0.25 to 1.0 mm to allow suitable flow rate while infusing or
withdrawing fluid from the abdominal cavity. In other embodiments,
the inner diameter of the docking device may range from 1.0 to 1.9
mm to allow suitable flow rate while infusing or withdrawing fluid
from the abdominal cavity. In other variations, the docking device
or therapeutic element could be used to aspirate fluid from within
the ovary or retrieve sample fluid from the abdominal cavity to
detect the presence of substances, such as blood, intestinal (e.g.,
fecal matter), or biomarkers, that provide information regarding
the safety or success of the procedure.
[0077] According to some embodiments, the system may also comprise
an energy generator so that energy can be delivered to ovarian
tissue via the therapeutic elements. The energy generator may be
configured to deliver one or more of the following: radiofrequency
energy, direct heating, cryoablation, cooling, laser, microwave,
unfocused ultrasound, partially-focused ultrasound, focused (HIFU)
ultrasound, heated water/saline, or steam. In addition, the energy
generator may be powered using a disposable battery, a
re-chargeable battery, or via mains power.
[0078] Additionally or alternatively, the system may also comprise
a mechanical drive system so that the therapeutic element rotates
and/or translates in order to disrupt and/or remove target tissue.
The mechanical drive system may incorporate a motor, a drive train,
and means for operatively connecting to the therapeutic element. In
some embodiments, only mechanical tissue manipulation may occur,
but in others, mechanical manipulation may occur in series or in
parallel with thermal energy as a means to cut and/or cauterize the
tissue to minimize the risk of bleeding.
[0079] The system may further include a processor that has an
algorithm operable to run a feedback control loop based on one or
more measured system parameters, one or more measured tissue
parameters, or a combination thereof. In any of the embodiments
described herein, one or more sensors may be included in the system
and may be used to measure the one or more system or tissue
parameters. The sensors may be temperature sensors, impedance
sensors, pressure sensors, or a combination thereof. The
temperature sensor may be used to measure electrode temperature.
The impedance sensor may be used to measure tissue impedance. When
implemented, the feedback control loop may be configured to modify
a parameter of energy delivery based on the measured one or more
system or tissue parameters. For example, the parameter of energy
delivery (or energy removal in the case of cooling/cryotherapy)
that may be modified is duration of energy delivery, power,
voltage, current, intensity, frequency, pulse, pulse width (e.g.,
duty cycle), temperature, type of energy delivery, flow rate,
pressure, or a combination thereof.
[0080] Any of the systems disclosed herein may further comprise a
user interface configured to allow user defined inputs. The
user-defined inputs may include duration of energy delivery, power,
target temperature, mode of operation, or a combination thereof.
The mode of operation may be a coagulation mode, a heating mode, a
cooling mode, a cryoablation mode, an ablation mode, a
desiccate/char mode, an irrigation mode, an aspiration mode,
mechanical disruption mode, tissue removal mode, or a combination
thereof. Any of the systems disclosed herein may further comprise
an automated treatment delivery algorithm that could dynamically
respond and adjust and/or terminate treatment in response to inputs
such as temperature, impedance, treatment duration, treatment power
and/or system status.
[0081] According to embodiments described herein, which may
partially or as a whole combine with other embodiments, the system
and method may include a transvaginal ultrasound probe for
placement in the vagina to aid with visualization of tissue and/or
navigation of system components. A docking/guiding device (e.g., a
docking catheter) may be coupled to the ultrasound probe and
advanced through the wall of the vagina directly into the
peritoneal space to engage the surface of the ovary (e.g., the
medial aspect of the ovary), or be advanced into the ovary, under
ultrasound guidance. Via this docking catheter, a treatment device
could be deployed such that one or more radiofrequency energy
treatment elements, e.g. electrodes, are delivered within the ovary
through a single entry point on the surface of the ovary. Following
delivery of the treatments, aspiration could be applied at the
aperture created in the ovary. Aspiration could also be achieved
via holes or slots in or near an electrode that are connected to a
lumen in the docking catheter. In an alternative embodiment,
aspiration may be applied prior to and/or during delivery the
treatments.
[0082] In some embodiments, e.g., prior to or after docking
on/engaging the ovary, the system may include a spacing device that
includes an expandable structure, or that is configured to infuse
fluid for creating space around the ovarian tissues or for
separating ovarian tissues. For example, the spacing device may
contain scaffolding, one or more balloons, or at least one port for
delivering fluid or gas into the space adjacent to the ovary, the
purpose of which would be to aid in the separation of tissues such
that the desired portion of the ovary could more optimally be
accessed and such that therapeutic elements could be delivered in a
way to minimize disruption of non-ovarian tissues. Referring to
FIG. 2, in one embodiment the spacing device (20) may include
scaffolding having an expanded configuration (22) and a collapsed
configuration (not shown). Here the expanded configuration (22) is
effected by movement of an outer shaft (24) relative to an inner
shaft (26). Upon motion of the outer shaft (24) relative to the
inner shaft (26), the scaffolding is able to transition from its
collapsed configuration to its expanded configuration (22). Other
expandable scaffolds may be constructed from self-expanding
materials that are constrained for delivery then expanded via
removing the constraint. The scaffold may be made from a polymer,
metal, metal alloy, or combinations thereof. The scaffold may also
comprise one or more wires, braid, a laser cut tube, or a slotted
tube.
[0083] In the embodiment shown in FIG. 3, the spacing device (30)
comprises a balloon (32) that is concentrically disposed about a
shaft (34). The balloon (32) is inflated via fluid (e.g., a liquid
or a gas) flowing through an infusion port (36) in the shaft
(34).
[0084] In another embodiment, as shown in FIG. 4, the spacing
device (40) includes a plurality of infusion ports (42) that may be
located at the distal end/or in one or more locations along the
length of the shaft (44) for the delivery of infusate (I) to create
space around target ovarian tissues or to separate ovarian tissues.
In some variations, the spacing devices may be used to displace
non-target tissues (e.g., bowel) during advancement of system
components, e.g., docking devices, from the vagina to the
ovary.
[0085] Furthermore, FIG. 5 shows an embodiment of an atraumatic or
flexible sheath-like device (50) that may be delivered and
potentially guided via a blunt dissection element (52) and
guidewire (54) or steering mechanism (not shown) through the
vaginal wall and proximate to the ovary. Once positioned, the
optional blunt dissection element (52) and/or guidewire (54) may be
removed and the guiding/docking device and or therapeutic
element(s) may be delivered through the lumen of the outer sheath
(56). The outer sheath (56) may serve as the guiding/docking device
with optional aspiration used to engage the ovary or infusion to
create additional space as described in association with FIG. 4. In
some instances, the guidewire (54) may be sharpened and used to
penetrate the ovary once the dissection element (52) is positioned
proximate the ovary. In this configuration, the guidewire (54) may
be positioned at a target location within the ovary. Once
positioned, the dissection element (52) may be removed and replaced
with therapeutic element(s) in an over-the-wire approach. The
guidewire (54) may optionally be removed prior to applying
therapy.
[0086] As previously stated, the guiding/docking device may be one
component of the systems described herein, and could be utilized to
facilitate access to the ovaries from the selected approach. The
guiding/docking device may have a preset shape that facilitates
navigation to the ovary and it could be torqueable. Additionally or
alternatively, it could have a steerable tip that could be actuated
by the handle. The guiding/docking device and the therapeutic
device could also be combined into a single device, e.g., an
ovarian tissue apparatus. The docking device generally comprises an
elongate body (e.g., a needle, trocar or catheter) having a
proximal end, a distal end, a lumen extending from the proximal end
through the distal end, and a distal tip. This lumen may be used to
deliver fluid and/or to aspirate.
[0087] Docking to the ovary can be accomplished using various
techniques. Referring to FIG. 6, docking to the ovary (60) can be
accomplished by a docking device (62) that applies vacuum (64)
through a lumen of the docking device (62). Alternatively, as shown
in FIG. 7, docking to the outside of the ovary (70) may be
accomplished by a docking device (72) via a concave surface or
surface that was mildly abrasive on the docking device (not shown),
or via one or more hooks (74) at the distal end (76) of the docking
device (72) that are configured to secure to a desired section of
the ovary (70). Instead of docking to the outside surface of the
ovary, docking within the tissue of the ovary (80) can also be
performed, as shown in FIG. 8. Here docking may be accomplished
using a docking device (82) having one or more needles or wires
(84) that are deployable through the distal end (86) of the docking
device (82), and which are configured to anchor within the tissue
of the ovary (80). The needles, wires, or hooks may also be
configured to deliver therapy (e.g., they may be wire electrodes or
may further incorporate electrodes for delivering energy and/or may
have mechanical motion applied to mechanically disrupt tissue). In
some instances, it may be useful to secure the ovary in a manner
that allows for repositioning for further treatments. Anchoring
either the docking device and/or the therapeutic element in the
target tissue may help the user to move the ovary relative to
surrounding non-ovary tissues to improve and/or confirm
visualization. Moving the ovary may also allow the user to more
easily reposition the device for subsequent treatments.
[0088] Docking could further be accomplished using a docking device
having a preset shape that is configured to fit the shape of the
ovary at a specific location. In this variation, the docking device
could be configured to engage ovaries having a size ranging from
about 3 to 7 cm in length, about 1 to 4 cm in width, and about 0.5
to 4 cm in thickness. For example, as shown in FIG. 10, docking
device (102) has a shaped portion (104) at its distal end that is
shaped to fit the junction of the ovary (106) and the broad
ligament (108) (e.g., near the mesovarium), and which could allow
therapeutic elements (110) disposed therein to be
advanced/delivered into the ovary adjacent to the mesovarium (112).
The multiple therapeutic elements (110) may be curved, but their
structure is not so limited, and any suitable configuration may be
employed. In one exemplary embodiment, the docking device may
comprise a cup configured to engage at least a portion of the outer
surface of an ovary. Here the cup may comprise a proximal end
configured for communication with a vacuum source and a distal end
for securing the ovary. The distal end of the cup can have an
arcuate or annular surface configured to match the contours of the
outer surface of the ovary. The distal end can also be sized to
match the dimensions of a human ovary, wherein the distal end has a
diameter of about 0.5 to 7.0 cm, about 0.5 to 6.0 cm, about 0.5 to
5.0 cm, about 0.5 to 4.0 cm, about 0.5 to 3.0 cm, about 0.5 to 2.0
cm, or about 0.5 to 1.0 cm. Additionally, the cup may comprise a
conical geometry for accommodating a variety of ovary sizes.
[0089] Further embodiments of the docking mechanism may include
securing the ovary at more than one point with a docking device.
With such a device (90) as shown in FIG. 9, docking could occur at
opposite sides of the ovary (92), which could facilitate delivery
of therapy across the entire ovary or between multiple points on
and/or within the ovary in a way that either mechanically
penetrates or does not mechanically penetrate the outer surface of
the ovary. A docking/guiding device (90) that grasps at two or more
places on the ovary (92) may have the ability to be actuated or
adjusted to widen or narrow the amount of ovarian tissue captured
between its contact points. Alternatively, therapeutic elements may
be delivered through the docking devices (90) and into the ovary
(92), facilitating independent control of positioning the
therapeutic elements.
[0090] FIGS. 11A and 11B depict yet further variations where the
docking/guiding device (200) could be used to target and/or capture
the mesovarium (202) (e.g., by looping around the mesovarium as
shown in FIG. 11B) to deliver therapy to the mesovarium (202)
and/or the suspensory ligament (206) or ovarian ligaments. In this
configuration, therapy may be delivered via electrodes incorporated
into the docking/guiding device (200), or via a separate
element.
[0091] The therapeutic elements may have any suitable
configuration, e.g., they may have any suitable length, diameter,
flexibility, geometry, shape memory, etc. suitable for the ovarian
tissue procedures described herein. In some variations, the
therapeutic elements include one or more curved structures that
comprise one more electrodes. A therapeutic element such as those
depicted in FIG. 12A-12F comprising one or more curved structures
with electrodes may be useful for a variety of reasons. The curved
structure may aid in anchoring the device in the target tissue,
limiting the risk of the device moving during treatment due to
patient movement or user error. The curved structure may also be
configured to match the contour of the ovary, allowing for improved
positioning within a variety of sized or shaped ovaries.
Additionally or alternatively, the curved structure may allow for
longer or additional electrodes to be delivered and used
simultaneously, allowing for larger ablation volumes per energy
application. This feature may limit pain experienced by the patient
and reduce procedure time. The curved structures may have a
straightened length and an unconstrained radius of curvature. The
straightened length may range from about 5.0 to about 40 mm, from
about 5.0 to about 35 mm, from about 5.0 to about 30 mm, from about
5.0 to about 25 mm, from about 5.0 to about 20 mm, from about 5.0
to about 15 mm, or from about 5.0 to about 10 mm. The unconstrained
radius of curvature may range from about 3.0 to about 10 mm, from
about 3.0 to about 9.0 mm, from about 3.0 mm to about 8.0 mm, from
about 3.0 mm to about 7.0 mm, from about 3.0 mm to about 6.0 mm,
from about 3.0 mm to about 5.0 mm, or from about 3.0 mm to about
4.0 mm. In some embodiments, the unconstrained radius of curvature
ranges from about 4.0 mm to about 6.0 mm.
[0092] The therapeutic elements may be advanced into the ovary in
various ways. For example, and as shown in FIGS. 12A-12E, upon
advancement of the docking device (300) through the capsule (316)
of the ovary (304), the therapeutic element(s) (306) are advanced
from inside the ovary (304) to a target location(s) within the
ovary (304). The therapeutic elements may be curved (FIG. 12A, 306)
or straight (FIG. 12B, 308), or they may take a spiral or helical
configuration (FIG. 12C, 310) or a random configuration (not shown)
when deployed, e.g., within an ovarian cyst (312). Alternatively,
and as shown in FIG. 12D, the therapeutic element (314) may be
configured to track about at least a portion of the perimeter of
the ovary (304) such that therapy targets tissue proximate the
cortex or follicles of the ovary (304). Alternatively, the
therapeutic element may be configured to track about at least a
portion of the ovary at or near the junction of the stoma and
cortex such that therapy may target tissue proximate to this
junction. The therapeutic elements may be provided as a feature of
the guiding/docking device. They may also be provided as elements
that can be deployed from a lumen within the guiding/docking device
or sheath-like device, as shown in FIG. 5. The therapeutic elements
(306) may be shaped such that they releasably secure the device
within the tissue when deployed, as shown in FIG. 12A.
[0093] The one or more therapeutic elements (306, 308, 310, 314)
may be advanced from the docking device (300) into the ovary (304)
one or multiple times and deployed within the ovary proximate to or
within ovarian cysts or other target tissue. One benefit of this
method may be that multiple therapies (e.g., multiple sequential
therapies where a single therapeutic element is repositioned, or
sequential/simultaneous deployment of multiple therapeutic
elements) could be delivered through a single entry/access point
(302) on the surface of the ovary, which may minimize the risk of
adhesions.
[0094] FIG. 12E depicts a variation where the docking/guiding
device (300) is used to penetrate into the ovary (304) and permit
delivery of one or multiple therapeutic elements (318) out of the
distal tip (320) or through one or more side ports (322). The
docking/guiding device (300) may comprise, for example, a 14 to 18
gauge needle approximately 20 to 45 cm long, and the therapeutic
element (318) may comprise, for example, one or more 0.020 cm to
0.076 cm diameter metal wire(s) that exit the side port (322), as
shown, or the distal tip (320). However, the diameter of the metal
wire may be as large as 0.140 cm. In some cases, the wire may
simply be a straight wire, but in other variations, the distal
portion of the therapeutic element (318) may be processed to have a
pre-set shape (e.g., a curve), as shown in FIG. 12E. The
therapeutic element may be insulated along the majority of its
length to electrically isolate it from the docking device (e.g.,
via a polyimide sleeve, PET heat shrink), if it is constructed of
metal. As such, only the distal portion of the wire(s) that extend
beyond the distal end or side port would be electrically connected
to the energy generator. When two wires are employed, they may be
deployed in a geometry similar to that shown in FIG. 12A with a
distance between the tips of the wires ranging from approximately 3
to 20 mm apart. However, in other instances the distance between
the tips of the wires may range from about 7.0 to 10 mm apart, or
up to about 15 mm apart.
[0095] The docking/guiding device may also be configured to rest on
the outer surface of the ovary (i.e., the distal tip of the docking
device is not inserted into the ovary). For example, as illustrated
in FIG. 12F, the docking device (300) may include a wider element
or shelf (324) proximal to the therapeutic element (326) to act as
a backstop and prevent it from penetrating deeper into the ovary
than a preset distance. For example, the shelf may have a diameter
greater than or equal to about 20% larger than the diameter of the
element to be inserted into the ovary.
[0096] Referring back to FIG. 10, the side holes (114) of the
guiding/docking device (102) could alternatively be used to
facilitate delivery of the therapeutic elements (110) in a
pre-specified consistent pattern of multiple entry points of the
ovary. This could be done to allow consistent targeting of a
preferential portion of the ovarian tissue or to deliver a
preferential pattern of therapies.
[0097] The system may also provide features that are configured to
rotate the one or more therapeutic elements during application of
energy to facilitate driving the therapeutic elements through the
tissue (e.g., cutting, removing, or ablating a volume of tissue),
resulting in a larger treatment zone.
[0098] The total affected volume of tissue within a given ovary may
range from about 240 mm.sup.3 to about 3000 mm.sup.3, with a single
ablation volume ranging from about 30 mm.sup.3 to about 3000
mm.sup.3 In some instances, about 3% to about 20% of the ovarian
volume is affected, e.g., by ablation. The system may be configured
such that ablations do not extend beyond a certain distance from
any edge of the electrode(s), e.g., 5 mm. The system may be further
configured such that the ablations are non-spherical in shape,
e.g., the in-plane longest dimension is greater than 2 times the
perpendicular depth. The system may be further configured such that
ablations can be delivered within the ovary in a way that spares
tissue within 2 mm of the outer surface (capsule) of the ovary.
[0099] Referring to the exemplary stepwise illustration in FIGS.
13A to 13D, a guiding/docking device (400) is advanced into the
ovary (402) and curvilinear therapeutic elements (404) deployed
from a location inside the ovary to a target area(s) (FIGS. 13A and
13B). The curvilinear therapeutic elements (404) are then rotated
in the direction of the arrow shown in FIG. 13C to affect, e.g.,
ablate, a volume of tissue (FIG. 13D, 406). A variety of the
therapeutic elements described herein may be rotated and/or
translated during the application of energy to reduce force
required to traverse through tissue, cut, coagulate,
desiccate/char, reduce treatment time and/or create a larger
treatment zone. These techniques may be employed with other
therapeutic elements as described herein and are not limited to
those shown in FIGS. 13A to 13C.
[0100] The system may also provide features that are configured to
move the therapeutic elements within a single 2-dimensional plane
through the tissue during application of energy to facilitate
driving the therapeutic elements through the tissue (e.g.,
cutting), resulting in a larger treatment zone, which is depicted
in the stepwise illustration of FIGS. 14A to 14E. Referring to
FIGS. 14A to 14E, a guiding/docking device (500) is advanced into
the ovary (502) and curvilinear therapeutic elements (504) deployed
from a location inside the ovary to a target area(s) (FIGS. 14A and
14B). The curvilinear therapeutic elements (504) are then actuated
in the direction of the arrows to change from an open configuration
(FIG. 14C) to a closed configuration (FIG. 14D) to affect, e.g.,
ablate, a volume of tissue (FIG. 14E, 506). Although curved
therapeutic elements are depicted, therapeutic elements comprising
any suitable geometry, e.g., straight therapeutic elements, may be
employed. Further, it is understood that any suitable therapeutic
element described herein may be translated in a 2-dimensional plane
of tissue during the application of energy to reduce force required
to traverse through tissue, cut, coagulate, desiccate/char, reduce
treatment time and/or create a larger treatment zone.
[0101] According to embodiments described herein, which may
partially or as a whole combine with other embodiments, the
therapeutic element may also comprise an expandable balloon that
may be used to anchor the device within the tissue, mechanically
disrupt tissue and/or deliver thermal energy (e.g., RF, microwave,
ultrasound, direct heat) or cooling (e.g., cold saline, cryo). In
one variation, as shown in FIG. 15A, a balloon (600) is mounted on
the guiding/docking device (602). In another variation, as provided
in FIG. 15B, the balloon (600) is delivered through the
guiding/docking device (600) by pushing it out. In a further
variation, the guiding/docking device may be advanced through the
ovarian tissue to create a channel into which the balloon is
delivered as the guiding/docking device is subsequently retracted.
One or more electrodes, antennae, or ultrasound transducers may be
positioned within the balloon or on the balloon surface to induce
heating of tissue directly and/or indirectly. Alternatively, a cold
or cryogenic material may be delivered and removed/outgassed via
lumen(s) within the guiding/docking device to induce cooling or
freezing of tissue.
[0102] FIG. 31 depicts another embodiment of a docking/guiding
device having a single therapeutic element. Here the
docking/guiding device (301) may comprise, for example, a 14 to 18
gauge needle approximately 20 to 45 cm long, and the therapeutic
element (305) may comprise, for example, a curved shaft having a
diameter of about 0.05 cm to about 0.13 cm and two electrodes
disposed thereon, as shown. The shaft may have a pre-set shape
(e.g., a curve with radius 0.38 cm to 1.6 cm). The therapeutic
element may be insulated along the majority of its length to
electrically isolate it from the docking device (e.g., via a
polyimide sleeve, PET heat shrink, Parylene, nylon, Pebax), if it
is constructed of metal. As such, the uninsulated portions would be
electrically connected to the energy generator. In another
variation, therapeutic element may be comprised of a
non-electrically conductive shaft with one or more electrically
conductive elements, e.g., electrodes. As previously described, the
electrodes may wrap around the entire circumference of the shaft or
may only cover a portion of the shaft circumference, in which case
the electrodes may or may not be angularly offset from one another.
The electrodes could be electrically isolated from each other and
deliver energy in a monopolar or bipolar fashion. In a bipolar
configuration, one electrode would serve as the active electrode
and the other electrode would serve as the return electrode. In
another variation, both electrodes could delivery energy and the
energy would return to a neutral electrode located elsewhere, such
as on the skin of the patient, on the docking/guiding device, or on
the ultrasound probe. The electrodes could also be electrically
connected to each other and deliver energy where the return or
neutral electrode (not shown) is located elsewhere, such as on the
skin of the patient, on the docking/guiding device, or on the
ultrasound probe. The electrodes may have a length of about 0.10 cm
to about 2.5 cm; a diameter of about 0.05 to about 0.4 cm, about
0.05 to about 0.3 cm, about 0.05 to about 0.2 cm, about 0.05 to
about 0.1 cm, about 0.2 to 0.4 cm, or about 0.076 cm to 0.14 cm;
and spacing of 0.050 cm to 0.64 cm.
[0103] Other systems and methods may be employed for treating
polycystic ovary syndrome, as illustrated in FIGS. 16A to 16D. For
example, the guide/docking device (700) may be advanced thorough
the ovary (702) in either a straight path (FIG. 16B) or in a
meandering/directed path (FIG. 16A). This could be done under
imaging to ensure that the guiding/docking device (700) was placed
in a desirable location throughout the delivery. The therapeutic
element (706) could then be delivered through a lumen on the
guiding/docking device (700) and into a cyst (708) and/or channel
(710) created by the guiding/docking device as it was retracted.
Aspiration could be performed by the guiding/docking device (700)
as it is being delivered or retracted. Alternatively, aspiration
could also be performed through the therapeutic element (706).
Alternatively, no aspiration could be performed. Once fully
deployed, the position of the entire therapeutic element (706) can
be confirmed in real-time using 2D or 3D imaging (e.g.,
transvaginal ultrasound), allowing for all planned treated areas to
be assessed/confirmed prior to application of energy. If desired,
the therapeutic element may be recaptured and re-deployed to
optimize position. Then, energy may be applied via the therapeutic
element, which is electrically coupled to an energy generator.
Optionally, the guide/docking device (700) and therapeutic element
(706) can be retracted to the next desired treatment location, and
energy applied. This optional step may be repeated until all
desired treatments are performed, resulting in a treated section.
Alternatively, and as shown in FIG. 16D, a longer portion of the
therapeutic element (706) can be exposed to multiple regions of the
ovary by an extended retraction of the guiding/docking device
(700). The treated section may be created by a single application
of energy over the length of the therapeutic element, multiple
applications of energy over portions of the therapeutic element, or
by continuously applying energy while simultaneously retracting the
guide/docking device (700) and/or therapeutic element (706). The
exemplary therapeutic element (706) used in this instance could be
an expandable mesh. FIG. 17 depicts an alternative therapeutic
element comprised of a flexible wire, cable, or coil (800). The
expandable mesh material may enhance or maximize contact with
tissue, especially within a cyst. Another example of a therapeutic
element that could be used in this setting is a balloon (e.g., as
shown in FIGS. 15A and 15B). Any of the other therapeutic elements
disclosed herein may also be utilized to administer treatment via
this method. The therapeutic element may also have an atraumatic
tip.
[0104] In the case of mechanical disruption, the therapeutic
element may comprise a rotating or translating element capable of
mechanically manipulating (e.g., destroying, stimulating) target
tissue, as illustrated in FIG. 18A to 18D. Here the tip (900) of a
guiding/docking device (902) may be used to facilitate access into
the ovary (904). Once positioned in a desired location within the
ovary (904), a mechanical disruption element (906, 908) may be
advanced in the direction of arrow (910) into the tissue. Once
deployed, the mechanical disruption elements (906, 908) may be
rotated in the direction of arrows (912) and/or translated in the
direction of arrows (914) to disrupt tissue. Motion of the
therapeutic element may be performed manually via a handle at the
proximal end of the device or via a motor and/or drive train
(battery or mains powered). Mechanical disruption elements may take
the form of a solid screw-like component (906), an expandable
wireform component (908), or other geometry that facilitates
desired tissue disruption. The expandable wireform component (908)
may be comprised of a self-expanding material (e.g., spring steel,
nitinol, elgiloy) that expands as tissue is morcellated. The
therapeutic element may also incorporate one or more electrodes
used to delivery energy to heat target tissue, ablate target
tissue, cauterize blood vessels, and/or cut tissue. The morcellated
tissue may be retrieved in some instances if it can be used for
diagnosis, or if it contains either oocytes or cellular components
that may be useful in further care. Electrodes may be either
separate elements mounted on the therapeutic element or the
therapeutic element itself.
[0105] The therapeutic element(s) may be constructed from a variety
of materials and in a variety of geometries. In its simplest form,
the therapeutic element may be comprised of round wire.
Alternatively, as shown in FIG. 19, the therapeutic element (1000)
may be disposed at the distal end (1002) of a guiding/docking
device in a manner such that it is capable of expanding upon
deployment. In some embodiments, the therapeutic element (1000) may
be constructed of a metal tube or wire (e.g., nitinol, elgiloy,
spring steel) with characteristics that allow for it to be shaped
into an expanded configuration (1006) and a collapsed configuration
(1008), and to form a sharp end (1010). The metal tube or wire may
be laser cut or otherwise processed to split the tube or wire in
half along a defined length (1012), which may, for example, range
from about 1-3 cm. The metal tube or wire may further be cut,
ground or otherwise processed to form a sharp end (1010). Once cut,
the two (as shown) or more therapeutic elements may be shape set or
formed into an expanded configuration (1006). When constrained by a
sheath (1004), the distal end is collapsed, and an exposed portion
of the sharp end (1010) used to penetrate the tissue and position
the device. Once in position, the therapeutic element (1000) may be
advanced out of the sheath and expanded into the tissue.
Alternatively, the outer sheath (1004) may be retracted to allow
the therapeutic element (1000) to become exposed. In some
instances, additional manipulation and/or application of energy may
be required to facilitate expansion of the therapeutic element.
Energy may simultaneously or sequentially be applied to affect the
target tissue. These techniques may also be employed with the
variety of therapeutic elements described elsewhere herein.
[0106] FIGS. 20A to 20C depict embodiments of exemplary light-based
therapeutic elements that may be used to heat or ablate target
tissue. FIG. 20A shows a fiber optic approach where a light fiber
(2000) is deployed from the distal end of a guiding/docking device
(2002), shown here as a needle. Once the light fiber (2000) is
positioned proximate the distal end (2004) of the guiding/docking
device (2002), it may be activated to generate heat within the
target tissue. The light fiber (2000) may be repositioned and
activated in multiple locations to complete the therapy. In some
cases, it may be desirable to extend the light fiber (2000) beyond
the distal end (2004) of the guiding/docking device (2002) up to
about 1 cm. In other cases, it may be desirable to recess the light
fiber (2000) proximal to the distal end (2004) up to about 5
mm.
[0107] FIG. 20B shows another variation where light (2006) from one
or more light fibers (not shown) exits the side of the
guiding/docking device (2002) via holes (2008). Once positioned,
the individual light fibers may be activated one at a time, in
pairs, in groups, or all simultaneously. Further, all fibers may
activate at the same or different power levels. Depending on the
configuration, the energy distribution around the circumference of
the guiding/docking device (2002) may be symmetric/concentric or
asymmetric/eccentric.
[0108] In some variations, the same light fiber(s) used to deliver
energy may also be configured to measure temperature via
operatively connecting the fiber to an IR temperature sensor. The
light fiber may then switch back and forth or multiplex in order to
intermittently monitor temperature during the treatment.
[0109] FIG. 20C shows an alternative light-based device where a
laser diode (not shown) and prism (2010) are used to deliver energy
to the target tissue. In this case, the laser diode may be located
anywhere proximal to the prism (2010), which is located near the
distal end of the guiding/docking device (2002), depicted as a
needle in this example. Once activated, the prism (2010) may direct
the energy out one or more side holes (2012) to generate the
desired heat within the target tissue. If the laser wave length
were extended into the infra-red range (e.g., >800 nm), then
light absorbing dyes could be used to increase the range or size of
affected tissue. Such dyes may be injected at the site through a
lumen in the guiding/docking device (2002) just prior to activating
the laser.
[0110] The therapeutic elements may also include multi-polar
embodiments, as shown in FIGS. 21A to 21B. Multi-polar electrode
approaches would have the effect of increased flexibility and/or
control over lesion formation. Since each electrode can be
controlled independently, each may also be capable of monitoring
tissue characteristics (e.g., impedance or temperature). These
characteristics may be used by the controller and/or user to adjust
the application of energy to optimize therapy and/or provide safety
shut-offs. For example, if the temperature of two electrodes is
lower than a pre-specified target and the other two electrodes are
at or above said pre-specified target, the controller may increase
the power level to those two electrodes to increase the tissue
temperature at those two electrodes. FIG. 21A depicts a multi-filar
configuration where multiple (e.g., four) electrodes (3000) are
spaced around the circumference of a guiding/docking device (3002)
with a layer of insulation or insulative jacket (3004) (e.g., PET
heat shrink) between the electrodes (3000) and the guiding/docking
device (3002). Herein the guiding/docking device (3002) is
constructed from metal (e.g., a 14 to 18 gauge needle). The
electrodes (3000) consist of individual conductive wires that are
adhered to the insulative jacket (3004) and extend along the length
of the guiding/docking device (3002) and are electrically isolated
from one-another via an insulative jacket (3006) (e.g., PET heat
shrink) along the proximal shaft. In this configuration, the active
length of each electrode may range from about 3 mm-15 mm, and the
diameter of each electrode may range from about 0.012 cm-0.026 cm.
In an alternative embodiment each conductive wire may be
individually insulated along the proximal length with insulation
removed along the distal portion to form the electrodes. These
electrodes may be energized, for example, in a monopolar or bipolar
(e.g., 90.degree. or 180.degree. apart in a four electrode
configuration) fashion.
[0111] In yet a further variation, as shown in FIG. 21B, multiple
(e.g., four) circumferential electrodes (3008) are positioned
around the guiding/docking device (3002) with insulative layers
similar to those described in FIG. 21A. In this configuration, the
electrodes may be comprised of metallic bands, coils, or wires and
may be spaced apart by about 3 mm-5 mm. These electrodes may be
energized, for example, in a monopolar or bipolar (e.g., adjacent
or alternating pairs) fashion.
[0112] The energy delivery element may also comprise a bipolar
coaxial needle device, as depicted in FIG. 22, where the outermost
element is the return electrode (4000), which in this variation
consists of a 16 to 18 Gauge hypodermic tube insulated on the
outside with a layer of polyester shrink tubing or other
non-conducting material (e.g., parylene)(4002). The insulating
layer begins at a specified distance, L1, from the distal end
(4010) and extends fully proximal. Inside the outermost element is
the active electrode (4006), consisting of either a solid shaft or
hollow tube, with an insulating layer (4008) beginning a specified
distance, L2, from the distal tip (4004) and extending fully
proximal. L1 and L2 may range from approximately 2 to 8 mm. In some
instances, the distance between the two electrodes is fixed, but in
others, it may be adjustable. If adjustable, the generator may be
configured to detect changes in the distance and display
recommended power settings or automatically adjust power settings
based on detected distance. By way of example, should the distance
increase, the power and/or time may be increased. Alternatively,
there may be a mechanical indicator at or near the proximal end of
the device (e.g., incorporated into the handle) that shows the
distance along with the recommended power level. In this case, the
operator would then manually set the power via the user interface
on the generator. If the return electrode (4000) is significantly
larger than the active electrode (4006), bipolar application of
energy may result in substantial heating of the active electrode
with minimal or no heating of the return electrode. This would
allow for a single lesion to be generated proximate the active
electrode without the need for a separate neutral electrode placed
on the patient's skin. It would also allow for the neutral
electrode to monitor tissue characteristics in contact with it,
which may be used as an indicator of when to cease treatment. For
example, the active electrode may heat tissue via resistive and/or
conductive heating until the neutral electrode detects an increase
in temperature or impedance. The system may then cease application
of energy should a pre-set or user-controlled threshold be reached.
If the distance between the electrodes is adjustable, it provides
the advantage of user adjustability. For example, if the patient
has a very large ovary, the user may choose to position the
electrodes further away from each other to generate a larger
lesion, thus reducing procedure time. In this instance, both
electrodes may be approximately the same size, such that they both
heat the tissue and potentially create a continuous lesion between
them via resistive and/or conductive heating.
[0113] As previously stated, the therapeutic elements may consist
of one or more of the following: a radiofrequency energy element; a
direct heating element; a cryoablation element; a cooling element;
a mechanical disruption element; a laser/light; a microwave
antenna; an unfocused ultrasound element; a partially-focused
ultrasound element; a focused (HIFU) ultrasound element; and/or
means for delivering heated water/saline, steam, a chemical
ablation agent, a biologic or pharmaceutical agent, a drug-eluting
implant, a radioisotope seed, or a mechanical implant, which may be
either passive or active via application of remote energy (e.g.,
ultrasound to induce vibration). There may be mechanical methods
built into the device design to prevent the therapeutic element
from being advanced more deeply than a predetermined depth.
[0114] If energy is being applied via one or more electrodes or
elements, it may be applied in a monopolar, bipolar, or combined
fashion; each element may fire simultaneously or sequentially;
energy may be applied in a continuous or pulsed fashion, and the
system may have a user interface (FIG. 23, 5010) that allows the
user to choose which electrodes or elements are active to customize
the therapy for each patient. Different combinations of electrodes
could be used to deliver energy such that patterns of treatment are
achieved. For example, one embodiment could contain three
electrodes (A, B, C). Any or all three could deliver energy in a
monopolar fashion and/or any combination of electrodes could also
deliver energy in a bipolar fashion (e.g., A to B, B to C, A to C).
Energy delivery could alternate in pulses (mono A, followed by mono
B, followed by mono C, followed by bipolar A to B, bipolar B to C,
etc.). Or, different frequencies of energy could be delivered
simultaneously or sequentially (e.g., mono at 465 kHz and bipolar
at >1 MHz). These combinations may also be used for tissue
mapping prior to or during the delivery of therapy. A monopolar
application of energy would have the effect of generating a
treatment area adjacent to the electrode and may be used to
generate larger lesions at higher power in shorter time, relative
to a bipolar application. A bipolar application of energy would
have the effect of generating a treatment area adjacent to each
electrode with the potential to create a continuous lesion spanning
the volume between the electrodes via either resistive or
conductive heating. A bipolar application of energy may also allow
for lower power and smaller lesions. In addition, a bipolar
application of energy may also allow for tissue characteristics
(e.g., impedance, temperature) to be monitored at each electrode
and adjustments made either before (e.g., user or system selected
based on tissue characteristics, such as impedance, or based on
electrode position) or during treatment (e.g., switching which
electrode is active versus the return). A combined application of
both monopolar and bipolar energy would also have the effect of
generating a treatment area based upon tissue characteristics
monitored at each electrode or between pairs of electrodes (e.g.,
impedance, temperature) with the added ability to use a single
electrode, if appropriate. In this instance, the return electrode
may be outside the ovary or on the skin of the patient. A
continuous application of energy may have the effect of generating
a lesion via a combination of both resistive and conductive
heating. Application of energy in a pulsed fashion would limit the
amount of conductive heating and may allow for additional
measurements to be made between pulses, when energy is turned off
or reduced to a lower power. These additional measurements may then
be used to alter or cease the application of energy and/or to
provide additional feedback to the user. The use of different
frequencies may allow for reduced or increased electrical coupling
between multiple conductors (e.g., wiring) or electrodes. In the
case of tissue mapping, the use of different frequencies may elicit
different responses from different types of tissues and/or
different states of tissues (e.g., ablated tissue or unablated
tissue). Furthermore, in the case of ablation creation, the use of
different frequencies may create different lesion
characteristics.
[0115] A generator is generally included in the systems described
herein to create energy to be delivered through the therapeutic
element(s). The systems may include sensing elements on either the
therapeutic element and/or on the guiding/docking device to detect
parameters such as temperature, impedance, or other parameters that
could guide therapy delivery. A feedback control system may use
detected parameters within software algorithms such that treatment
is delivered automatically and could be automatically stopped when
certain temperature, time, power and/or impedance thresholds have
been crossed. The system could also deliver two or more different
sets of energy parameters. For example, to the system could be
configured to deliver lower energy or temperature for a longer time
(e.g., to ablate and/or otherwise affect a larger volume of tissue)
and higher energy or temperature for a short time (e.g., to control
bleeding and/or desiccate/char tissue to enhance visualization).
The parameters of the therapeutic element or the pattern of the
targeting within the ovary could be configured to preferentially
target certain regions and/or tissues and spare others. The sensing
elements could also be used before treatment is applied to
characterize or map the target tissue; for instance, impedance
measures could be used to sense if the docking/guiding device
and/or therapeutic element is adjacent or within cysts, to sense if
portions the docking/guiding device and/or therapeutic element are
within the ovary or outside the ovary, or to sense where portions
of the docking/guiding device and/or therapeutic element are
relative to the vasculature or other important structures. The
sensing elements could also be used during treatment to dynamically
adjust treatment parameters. The sensing elements could be used to
measure temperature and/or impedance. For example, a
temperature-sensing element could be located on each of a plurality
of electrodes. In some variations, two temperature-sensing elements
could be located on a single electrode. Power could be adjusted
based on the hottest temperature-sensing element or could be
adjusted based on some combination of the multiple sensing
elements, such as an average or weighted average. In another
example comprised of bipolar electrodes and temperature sensing
elements on each electrode, the active electrode (the electrode
delivering the energy) could be interchanged with the return
electrode before or during energy delivery based on the measured
temperatures and/or impedances.
[0116] Furthermore, the sensing elements could also be used to
detect if the device moves inappropriately during the treatment
delivery. For example, device movement could be inferred by sensing
sudden changes in temperature, impedance, and/or power. In one
variation, the sudden changes could be based on an instantaneous
measurement exceeding some predetermined threshold away from an
averaged measurement. In another variation, the variance of a
signal, such as power, could be tracked during treatment and
movement could be inferred when the variance deviates by a
predetermined threshold, such as a percentage difference. If
movement is inferred, then the generator could automatically
terminate energy delivery and/or inform the user that the device
has moved.
[0117] When radiofrequency energy is employed, the generator may
deliver the energy at a power of 30 watts or less, and for a
duration of 60 seconds or less. In some variations, the generator
may deliver the energy at a power ranging from 4 to 15 watts, and
for a duration of 10 to 45 seconds. The radiofrequency energy may
be supplied in a pulsed or continuous fashion. In other variations,
the generator may deliver the energy at a first power range (e.g.,
0 to 30 watts or 4 to 15 watts) for a first duration (e.g., 10 to
45 seconds) followed by a second, higher power range for a second,
shorter duration (e.g., less than 10 seconds). The specific power
settings may be pre-determined or may be determined based on
current or previously acquired system feedback, such as
temperature, impedance, power, and/or time. One example of using
previously acquired system feedback is to adjust the second, higher
power range based on the maximum power utilized during the first
duration. Applying higher power ranges or temperatures towards the
end of the energy delivery can create different lesion
characteristics including, but not limited to, increased volume of
tissue necrosis, cauterization of blood vessels, and enhanced
echogenicity via increased tissue desiccation, tissue contraction,
and/or formation of steam or microbubbles. To prevent or minimize
the amount of tissue deposition on the therapeutic element due to
the ablations (which could lead to sticking when retracting or
deploying the therapeutic element), coatings or surface treatments
may be optionally applied to the any of the therapeutic elements
described herein. Examples of coatings include Parylene, PTFE,
hydrogels, silicone oil, and oxidation. If the coating is not
electrically conductive, then additional surface treatments such as
acid etching or laser etching, could be selectively applied to the
coating to allow electrical energy to pass through.
[0118] FIG. 32 depicts an exemplary Power/Temperature Curve wherein
energy is delivered in a two-phased approach such that the first
stage (S1) is designed to heat the tissue and a second stage (S2)
is designed to char/desiccate the tissue and/or cause steam and/or
microbubble formation. At the start of the energy delivery (t1)
power is linearly ramped to a pre-set power (P1) over time, t2.
Shortly after t2, temperature (A) is compared to a pre-determined
target range (Tmin-Tmax) (e.g., 65 to 85 degrees C.). If
temperature (A) is less than Tmin, power may step or ramp up until
the temperature is greater than Tmin. This is depicted by power
(P2) and temperature (B). As a safety feature, a maximum power may
be set. As the tissue heats and changes its characteristics,
temperature may also increase. Should the temperature (C) reach or
exceed a pre-set maximum temperature (Tmax), either the treatment
could be terminated (not shown) or power could be reduced over time
(P3) until the temperature (D) once again falls below Tmax at time
(t3). At the end of first stage (S1), the algorithm then enters the
second stage (S2), where power ramps in a linear or step-wise
fashion to a maximum power, Pmax and hold until time (t5), upon
which energy delivery is terminated. The period defined by (t5-t4)
may, for example, be between 3 to 10 seconds in order to
char/desiccate/coagulate the tissue or cause steam and/or
microbubble formation.
[0119] Alternatively, the generator may deliver power in a manner
to achieve a desired target temperature but limit the power to some
maximum power (e.g., 30 watts or less) in the event the target
temperature cannot be achieved. FIG. 33 depicts an exemplary
Power/Temperature Curve wherein energy is delivered in a two-phased
approach such that the first stage (S1) is designed to heat the
tissue and a second stage (S2) is designed to char/desiccate the
tissue or cause steam and/or microbubble formation. At the start of
the energy delivery (t1), power is linearly ramped until a minimum
target temperature (Tmin) (e.g., 65 to 85 degrees C.) is reached.
This event is denoted by power (P1) and temperature (A) at time
(t2). As a safety feature, a maximum power may be set. The
generator then continually adjusts power in an effort to maintain
the minimum temperature (Tmin) without exceeding a pre-set maximum
temperature (Tmax). As the tissue heats and changes
characteristics, a sudden increase in temperature may occur (not
shown). Should the temperature reach or exceed the maximum
temperature (Tmax), the generator will adjust power down or
terminate the treatment. At the end of the first stage (S1) which
occurs at time (t3), the algorithm then enters the second stage
(S2), where power is ramped in a linear or step-wise fashion to a
second power, P2, and holds until time (t4), upon which energy
delivery is terminated. The period defined by (t4-t3) may, for
example, be between 3 to 10 seconds in order to
char/desiccate/coagulate the tissue or cause steam and/or
microbubble formation.
[0120] An exemplary system (5000) is illustrated in FIG. 23. In
this embodiment, the system is configured for monopolar energy
delivery using a neutral electrode (5002), which would be affixed
to the skin of the patient. Bipolar configurations would eliminate
the need for an externally-placed neutral electrode. For example,
the therapeutic element (5004) may be configured to have two or
more electrodes of approximately the same size and spaced apart to
deliver energy in a bipolar or multi-polar fashion (not shown).
Alternatively, the neutral electrode (5002) may be incorporated
into the docking/guiding device (5006). In a further variation, the
neutral electrode may be incorporated into a cover placed over the
transducer of the ultrasound probe or incorporated into the needle
guide. In these cases, the neutral electrode may be larger than the
electrode located on the therapeutic element such that only the
electrode located on the therapeutic element heats significantly.
Furthermore, the sensing elements (5008) may be used to measure
parameters either intra-procedurally or post-procedurally to assess
for technical success of the procedure. For instance, impedance
changes could accompany desirable changes in tissue characteristics
in successful treatment delivery.
[0121] Some variations of the system could be configured with
bipolar electrodes to deliver therapeutic doses of energy. Here a
neutral electrode (affixed to the skin of the patient, incorporated
into the docking/guiding device, or incorporated elsewhere away
from the distal end of the device) could be utilized to measure
impedance values from one or each of the therapeutic electrodes
before or during energy delivery. The impedance values between the
therapeutic bipolar electrodes and/or between a therapeutic
electrode and the neutral electrode could be used to determine the
relative location of the therapeutic elements within the ovary. An
example is shown in FIGS. 34 and 35A-35C. Therapeutic elements,
such as electrodes, A and B could be configured in a bipolar manner
such that energy is delivered from A and returned to B (or vice
versa) to generate a therapeutic effect Impedance could also be
measured between A and B. A neutral electrode, N, could be used to
measure impedance from A to N and from B to N by applying low,
non-therapeutic levels of energy. Optionally or additionally, a
sensing element, C, could be located at the tip of the device to
measure the impedance between C and N, A and C, and/or B and C.
Comparing these different impedance measurements could provide
feedback for the relative locations of A, B, and C.
[0122] FIGS. 35A-35C provide examples where electrode A and
electrode B are both inside the ovary. In FIG. 35B, electrode A is
inside the ovary and electrode B is partially outside the ovary. In
FIG. 35A, the impedances of A-to-N and B-to-N are similar since the
electrical paths are similar. However, in FIG. 35B, the impedances
of A-to-N and B-to-N could be measurably different depending on the
composition of the non-ovarian tissue-contacting electrode B. In
one variation, the non-ovarian tissue could be bowel filled with
gas and result in higher impedance. Other tissues adjacent to the
ovary that could result in higher impedance are fat deposits. In
another variation, the non-ovarian tissue could be bowel, muscle,
or a blood supply such that the impedance of B-to-N is lower than
the impedance of A-to-N. Based on these impedance measurements, the
generator could provide the operator with different feedback
regarding the relative location of the device. Similarly, FIG. 35C
depicts electrodes A and B within stromal tissue of the ovary and
sensing element C within a follicle or cyst Impedance measurements
A-to-B, A-to-C, and/or B-to-C (or optionally A-to-N, B-to-N,
C-to-N), could be used to impute that the sensing element at the
tip of the device is within a follicle and thus closer to the outer
surface of the ovary. Therefore, the generator could provide
feedback to the operator to stop advancing the device in order to
prevent the tip from unintentionally exiting the ovary.
Additionally, if sensing element C did exit the ovary, the
impedance measurements from A-to-B, A-to-C, and/or B-to-C (or
optionally A-to-N, B-to-N, C-to-N) could be used to detect this
condition.
[0123] According to embodiments described herein, which may
partially or as a whole combine with other embodiments, it may be
useful for the systems to include features configured to maintain
the orientation of the energy delivery elements, e.g.,
radiofrequency energy elements, in a single plane, which may be
desirable for visualization optimization. The features for
maintaining planar orientation may include the use of ribbon and/or
use of side ports on the guide/docking device to better guide
deployment. In other variations, orienting a planar therapeutic
element such that it is in plane with a 2-dimensional ultrasound
field may be accomplished by placing visual cues or identifiers
(e.g., markers comprised of an echogenic material; markers
comprising echogenic bands, rings, arcs, or other geometric
structures, etc.) or tactile cues or identifiers (e.g., a wing-like
structure) on a portion of the device, e.g., the proximal end of
the device that deploys the therapeutic element into the ovary. For
transvaginal procedures, providing features for maintaining the
rotational orientation between the ultrasound probe/transducer, the
guiding/docking device and/or the therapeutic element may also be
employed. FIG. 24 shows an exemplary system (6001) for maintaining
therapeutic elements (6000) in the two-dimensional plane with the
ultrasound visualization field/plane. For needle-guided
transvaginal procedures, a needle guide (6002) is affixed to the
shaft of the probe to ensure that the tip of the needle is always
within the field of view of the probe (6004). The needle guide
(6002) may also ensure that the needle enters the field of view
from the same location and travels along the same angle with
respect to the head of the ultrasound probe/transducer (6004).
However, when therapeutic elements with a curvilinear shape (6000)
need to be deployed, planar orientation must be maintained in order
to see them as the probe (6004) or other system elements are
manipulated. In one instance, the needle guide may incorporate a
unique geometry that mates with a guide on the docking device. In
this instance, an offset coupler (6006) may be affixed to the
needle guide (6002). The offset coupler (6006) may include a guide
rod (6008), which can slide through an advancing handle (6010) by
sliding an advancing mechanism (6012) forward to force the
therapeutic elements (6000) into the tissue. The advancing
mechanism (6012) may then be pulled back to recapture the
therapeutic elements (6000) when finished.
[0124] Referring to the embodiment shown in FIG. 26, a curvilinear
therapeutic element (7000) is shown within the ultrasound field of
view (7002). If the docking/guiding device (7004) and/or
curvilinear element (7000) are rotated a few degrees with respect
to the ultrasound transducer (7006), then the curvilinear element
(7000) would no longer exist within the same plane as the
ultrasound visualization plane and the curvilinear element would no
longer appear on the ultrasound display. Therefore, the operator
would need to rotate the docking/guiding device (7004) and/or
curvilinear element (7000) until the curvilinear element reappeared
on the ultrasound display. This could increase procedure time and
increase the risk of patient injury by requiring additional
manipulation of the device. It may also be beneficial to have an
alignment feature that orients or aligns the curvilinear element to
the ultrasound visualization plane in a manner that ensures the
curvilinear element is visible as it deploys. Visualizing the
entire element as it deploys may allow the operator to more
precisely position the element in the desired location. In other
embodiments, it may only be necessary to see the distal tip of the
curvilinear element (7000), to ensure that it is still within the
target tissue. Visualization of the distal tip of the curvilinear
element (7000), optionally combined with visualization of the
distal tip of the docking/guiding device (7004), may provide
adequate visualization for precise positioning.
[0125] In some cases, it may be desirable to have the ability to
decouple and re-couple the docking/guiding device from the needle
guide in situ. FIG. 25 depicts an exemplary magnetic detachable
needle guide (8000), which may be combined with other embodiments
described herein. For example, the needle guide (8000) may
incorporate a trough (8002) with embedded neodymium magnets (8004)
underneath it that may be used to position and hold a metallic
docking/guiding device in place, while also making it
removable.
[0126] Alternative mechanisms for maintaining planar alignment are
provided in FIGS. 27A to 27F. For example, an alignment adapter
(9000) may be attached to a handle (9002) of a transvaginal
ultrasound probe (9004). Alignment adapter (9000) may be removably
attached to the ultrasound probe handle (9002) by snapping on,
strapping, clamping circumferentially via a two-piece or hinged
clamshell, or other suitable ways. In order to be adaptable to a
variety of ultrasound probes, the mating surface (9006, shown in
the cross-sectional view of FIG. 27B) may include features such as
a low durometer or other suitably conformable polymer (e.g.,
neoprene, polyurethane, silicone, etc.). These features may be
molded into alignment adapter (9000) or provided as separate insert
pieces. The alignment adapter (9000) may further comprise a
receiving lumen or cavity (9008) between the main body of the
alignment adapter and a guide (9010) of the guiding/docking device
(9012). The alignment adapter (9000) may also include an adjustable
element (e.g., a mechanical lock) (9014) that may be used to fix or
hold steady the guiding/docking device (9012) or allow it to be
moved. For example, when the adjustable element (9014) is in a
locked (down) position (FIG. 27C), it aids in aligning the
guiding/docking device (9012) and/or therapeutic elements (9016)
within the ultrasound visualization plane. In the unlocked (up)
position (FIG. 27D), the guiding/docking device (9012) may be
freely rotated (or rotation may be limited to, for example, about
90 degrees in a clockwise or counter-clockwise direction).
Additionally, the alignment adapter could allow some limited
rotation, such as plus or minus up to 20 degrees of rotation, even
in the locked position. For example, the opening in the mechanical
lock (9014) could be enlarged such that the guide (9010) could
rotate about 10 degrees in the locked position. The limited
rotation can be useful in maintaining the therapeutic elements
within the ultrasound visualization plane while allowing the
operator to quickly rotate the device back and forth to enhance
visualization due to the motion. Similarly, subtle motion (for the
purpose of enhanced visibility) could be achieved by allowing the
operator to easily shift the therapeutic elements a small distance
distally and proximally, such as plus or minus up to 0.25 mm. The
adjustable element may comprise a notch configured to mate with the
docking device to help effect locking. The docking/guiding device
(9012) may be introduced while the adjustable element (9014) is in
the unlocked position (FIG. 27D) or in a partially-locked position
(FIG. 27E) where the guide (9010) need not be perfectly straight
and will aid in aligning the docking/guiding device (9012) as it is
lowered. The geometry of the adjustable element (9014) may also be
tapered such that the docking/guiding device (9012) may rest in
proper alignment but still be free to rotate easily, if desired. If
rotation or translation of the docking/guiding device (9012) is
desired, it may further incorporate a hub (9020) to make
manipulation easier. Furthermore, the alignment adapter (9014) may
further comprise sliders, knobs, and/or levers, which can be used
to advance/withdraw the docking/guiding device, deploy/retract
therapeutic elements, engage/disengage the alignment mechanism,
etc. Due to the alignment feature, the therapeutic elements can be
maintained within the visualization plane of the ultrasound probe
during an ovarian procedure.
[0127] For example, as illustrated in FIG. 27F, mechanical lock
(not shown) may be used to orient a curvilinear element in a first
planar orientation (9022) followed by retraction and redeployment
in a second planar orientation (9024), allowing for two treatments
to be applied within the same visualization plane (9026) of the
ultrasound probe.
[0128] In the embodiment shown in FIG. 28, the alignment adapter
(9028) can be a lock that is removably affixed to the handle of the
ultrasound probe (9030) via a temporary adhesive located at the
interface between the alignment adapter (9020) and ultrasound probe
(9030). The adapter could also be attached with a conformable strap
or clamp. Here alignment adapter (9028) includes a receiving
alignment channel (9032) with a geometry that prevents or limits
rotation once engaged (e.g., square or rectangular). The proximal
end of a guiding/docking device (9036) incorporates an alignment
element (9034), which mates with the receiving alignment channel
(9032) to maintain the planar orientation of the therapeutic
elements (9042) and the visualization plane of the ultrasound
probe. As described previously, the alignment mechanism could allow
some limited rotational or translational motion to enhance
visualization. For example, the alignment channel (9032) could be
larger than the alignment element (9034) by 0.025 cm which would
allow some rotation but still maintain the therapeutic element
within the ultrasound visualization plane. The guiding/docking
device (9036) further comprises a handle (9040), which may be used
to manipulate the device and/or may further incorporate features
for deploying the therapeutic elements (9042). Such deploying
features may include a slider, knob, wheel, crank, and/or levers,
which can be used to deploy/retract therapeutic elements
(9042).
[0129] According to embodiments described herein, which may
partially or as a whole combine with other embodiments, the
guiding/docking device may comprise a handle, which may be used to
manipulate the device and/or may further incorporate features for
deploying the therapeutic elements as well as incorporating
features to limit the travel of the guiding/docking device. Since
the distal tip of the guiding/docking device may contain a needle
(or otherwise sharp) point to pierce through the vaginal wall and
capsule of the ovary, it may be desirable to prevent the needle tip
from traveling too far distally and causing unintentional injury.
In one embodiment, as shown in FIG. 36A, the handle (not shown)
could provide tactile and/or visual feedback to inform the operator
that the needle tip (411) of the guiding/docking device (409) is
located at the distal end of the needle guide (401). This point can
be referred as the zero point. Maintaining the needle tip at the
zero point can prevent the needle tip from contacting the vaginal
wall (403) while the operator manipulates the ultrasound probe
(405) for visualization and/or device placement. Furthermore, the
handle could contain a limiting mechanism that limits the distal
travel of the guiding/docking device to prevent the needle tip from
exiting most ovaries during the initial needle puncture, e.g., a
travel distance of about 3 cm (or e.g., about 1.5 to about 4 cm)
from the zero point where the guiding/docking device can freely
travel back and forth as long as the tip does not exceed the
maximum travel distance. Once the operator inserts the
docking/guiding device (409) into the ovary (407) (as shown in FIG.
36B), then the operator may release the limiting mechanism on the
handle. Additionally or optionally, the handle may comprise a
mechanism to allow the operator to adjust the maximum travel
distance. This would allow the operator to insert the needle tip
(411) more distally towards the capsule of the ovary (407) (as
shown in FIG. 36C) and define a new maximum travel distance for the
needle tip (411). This could prevent the operator from
inadvertently advancing the needle tip beyond the ovary and could
also prevent the needle tip from exiting the ovary in the event the
ovary were to move due to patient respiration or other patient
movement.
[0130] In other variations, the travel of the guiding/docking
device may be controlled by increasing friction as it is advanced
but can be retracted with less friction. Another variation could
include a limiting mechanism such that the guiding/docking device
and handle can only be advanced about 3 cm (or e.g., about 1.5 to
about 4 cm) from the zero point. Then another mechanism in the
handle, such as a wheel, lever, or slider, could be used to advance
the guiding/docking device further into the ovary. This would
prevent gross motions of the handle from advancing the needle tip
beyond the ovary.
[0131] As previously stated, non-invasive treatment systems may be
employed. FIG. 37 depicts an exemplary non-invasive treatment
system. Referring to the figure, system (501) is comprised of an
imaging and/or therapeutic element (503), configured for contact
with the abdomen (505) of a patient (507); a connection (509)
(e.g., cable) for connecting the imaging and/or therapeutic element
(503); and a console (511), comprising a user interface (513), a
feedback control system (515), one or more ultrasound sources (517)
configured for imaging or application of energy to affect target
tissue, and a mechanism for interpreting imaging data to enable
targeting of desired target tissue.
[0132] Target tissues of an ovarian procedure may include the
following: follicles, follicles of a particular size range (e.g.,
pre-antral follicles), stroma, thecal cells, stromal cells,
granulosal cells, mesovarium, or nerves. In one instance,
follicles, stroma, or thecal cells could be preferentially targeted
and the vasculature could be relatively avoided. In another
instance, the settings of the therapeutic element could be selected
such that nerves are targeted and the vasculature could be
relatively spared. In another instance, the cortex of the ovary
could be targeted, and the stroma of the ovary could be relatively
spared. In another instance, the stroma of the ovary could be
targeted, and the ovarian cortex could be relatively spared. In
another instance, the interface of the stroma and cortex could be
preferentially targeted. In another instance, the mesovarium could
be preferentially targeted. In another instance, the granulosal
cells in antral and pre-antral cells may be preferentially
targeted. In a further instance, the nerves in the pedicle of
tissue connecting the ovary to surrounding tissues (i.e.,
mesovarium) could be targeted using treatment methods that spare
the nearby vasculature (e.g., cryotherapy, selective
heating/ablation, electroporation). Certain tissues (e.g., nerves)
may be more susceptible to destruction at lower ablation
thresholds, such that those tissues could be preferentially
targeted. Some tissues may have particular acoustic or material
properties (e.g., fluid-filled follicles) such that some forms of
energy (e.g., ultrasound) could be used to specifically target
those tissues. For example, in the case of HIFU, ultrasound imaging
could be used to map the location of the follicles in the cortex of
the ovary, and then energy could be directed to regions proximate
to follicles clearly visible on ultrasound.
[0133] After or while delivering the therapeutic element,
aspiration could be performed either through the guiding/docking
device, through the therapeutic element, or through a device that
contains both a docking and therapeutic element. The aspiration
could be used to assist in reduction of cyst size, to assess if
bleeding is controlled, to collect fluid for analysis, to remove
any space created between tissues using fluid or gas, or for
another purpose. The aspiration port could also be used to inject
gas or other material, which might be used to change imaging
characteristics of that region of the ovary; this could be used to
label/mark portions of the ovary that had already been treated.
[0134] At the conclusion of the procedure, the docking element, the
therapeutic element, or a combination thereof could be used to
deliver materials, active agents, etc. to assist in the healing
process and prevent the formation of adhesions. Some examples of
these are the commercially available agents Interceed.RTM.
Absorbable Adhesion Barrier (Ethicon, Somerville, N.J.),
Seprafilm.RTM. Adhesion Barrier (Genzyme, Bridgewater, N.J.), and
Adept.RTM. Adhesion Reduction Solution (Baxter, Deerfield, Ill.).
These and other agents made of modified sugars, cellulose, fabrics,
and colloids have been used in other surgical cases to minimize the
frequency of surgical adhesions.
[0135] It is contemplated that in certain cases where the desired
clinical effect was not achieved or where it was achieved but then
subsequently the condition re-occurred, repeat procedures could be
needed. In these cases, it might be necessary to target a different
portion of the ovary, different cysts, or a different portion of
the mesovarium. The inventors contemplate the need for using the
system to specifically re-treat the same portion of tissue as the
original treatment or a distinctly different portion of tissue from
the first intervention.
III. EXEMPLARY COMBINATIONS OF FEATURES
[0136] The following tables disclose various features of the
methods and systems provided herein that can be combined to
manipulate ovarian tissues and/or treat PCOS.
[0137] In Table 1, exemplary combinations of features for
transvaginal, laparoscopic, percutaneous, or via a natural orifice
route through the vagina-uterus-fallopian tubes approaches are
provided.
TABLE-US-00001 TABLE 1 Column 7 Column 3 Column 4 Column 6 Pattern
of Column 8 Column 1 Column 2 Tissue Ovary Column 5 Therapeutic
Therapeutic Aspiration/ Access Visualization Separation docking
Landmarks Mechanism Delivery Compression Transvaginal transvaginal
fluid suction/ ovarian Tissue Heat Superior aspiration at
ultrasound aspiration/ features Ablation [FRY ovary interface
vacuum cysts (monopolar, bipolar, multimodal), HIFU, Direct Heat,
microwave, unfocused/partially focused ultrasound, laser,
saline/water, steam] Laparoscopic transabdominal air concave bony
Tissue Warming Near aspiration ultrasound surface [RF (monopolar,
vasculature/ within ovary bipolar, mesovarium multimodal), HIFU,
Direct Heat, microwave, unfocused/partially focused ultrasound,
laser, saline/water, steam] Via a CT mechanical hook/ broad
non-thermal away from aspiration to natural scaffold needle
ligament/ acoustic cavitation vasculature/ area orifice ovary
mesovarium surrounding route junction ovary through the vagina-
uterus- fallopian tubes Percutaneons MR mechanical abrasive
Cryoablation Maximize ovary external balloon surface (cooled
element, interruption compression liquid nitrogen, of cysts CO2,
dry-ice) endoscopic none lasso Tissue Cooling preferential ovary
internal visualization (cooled element, for cortical compression
saline/water) ovary OCT Mechanical preferential none disruption for
medullary ovary virtual drug - implant delivery to histology
permanent or limit/minimize biodegradeable vs. disruption
no-implant, types of ovarian of drugs: beta- capsule blockers,
anti- androgens, neurotoxins or tissue toxins, 5- alpha-reductase
inhibitors, or aromatase inhibitors ultrasound on mechanical
implant delivery to guide or (permanent vs. maximize therapeutic
biodegradeable), disruption of element could be activated ovarian
externally capsule Notes: specific embodiment may include none of
features in a column or more than one feature in a column; oocyte
harvesting may be done pre-procedure; either the guiding element or
the treatment element or the combined guiding/treatment element may
be steerable; optional anti-adhesive materials may be delivered to
prevent adhesion formation, therapeutic element could be
irrigated
[0138] In Table 1 (transvaginal, laparoscopic, percutaneous, or via
a natural orifice route through the vagina-uterus-fallopian tubes
approaches), visualization of the procedure and/or tissues could be
performed using any of the visualization techniques described in
the 2nd column, tissue separation may be done via any of the
techniques described in the 3rd column, the ovary could be engaged
and the device could dock on the ovary via any of the techniques in
the 4th column, any of the tissue landmarks that could be used in
aiding the procedure are listed in the 5th column, any of the
therapeutic mechanisms that may employed by the device are
described in the 6th column, possible patterns of therapy delivery
are listed in column 7, and the various options for aspiration or
ovarian compression that may be used in any of the embodiments are
listed in column 8.
[0139] Table 2 provides exemplary combinations of features that
could be used for open surgical approaches.
TABLE-US-00002 TABLE 2 Column 6 Column 3 Column 5 Pattern of Column
7 Column 1 Column 2 Ovary Column 4 Therapeutic Therapeutic
Aspiration/ Access Visualization docking Landmarks Mechanism
Delivery Compression surgical transvaginal suction/ ovarian Tissue
Heat Superior aspiration at ultrasound aspiration/ features
Ablation [RF ovary interface vacuum cysts (monopolar, bipolar,
multimodal), HIFU, Direct Heat, microwave, unfocused/partially
focused ultrasound, laser, saline/water, steam] CT concave bony
Tissue Warming Near aspiration surface [RF (monopolar, vasculature/
within ovary bipolar, mesovarium multimodal), HIFU, Direct Heat,
microwave, unfocused/partially focused ultrasound, laser,
saline/water, steam] MR hook/ broad non-thermal away from
aspiration to needle ligament/ acoustic cavitation vasculature/
area ovary mesovarium surrounding junction ovary direct abrasive
Cryoablation Maximize ovary external visualization surface (cooled
element, interruption of compression liquid nitrogen, cysts CO2,
dry-ice) endoscopic lasso Tissue Cooling preferential for ovary
internal visualization (cooled element, cortical ovary compression
saline/water) OCT Mechanical preferential for none disruption
medullary ovary virtual drug - implant delivery to histology
permanent or limit/minimize biodegradeable vs. disruption of
no-implant, types ovarian of drugs: beta- capsule blockers, anti-
androgens, neurotoxins or tissue toxins, 5- alpha-reductase
inhibitors, or aromatase inhibitors ultrasound on mechanical
delivery to guide or implant maximize therapeutic (permanent vs.
disruption of element biodegradeable), ovarian could be activated
capsule externally Notes: specific embodiment may include none of
features in a column or more than one feature in a column; oocyte
harvesting may be done pre-procedure; either the guiding element or
the treatment element or the combined guiding/treatment element may
be steerable; optional anti-adhesive materials may be delivered to
prevent adhesion formation, therapeutic element could be
irrigated
[0140] In Table 2 (surgical approaches), visualization of the
procedure and/or tissues could be performed using any of the
visualization techniques described in the 2nd column, the ovary
could be engaged and the device could dock on the ovary via any of
the techniques in the 3rd column, any of the tissue landmarks that
could be used in aiding the procedure are listed in the 4th column,
any of the therapeutic mechanisms that may employed by the device
are described in the 5th column, possible patterns of therapy
delivery are listed in column 6, and the various options for
aspiration or ovarian compression which may be used in any of the
embodiments are listed in column 7.
[0141] Other methods may include the non-invasive targeted delivery
of energy to ovarian tissues. Table 3 provides exemplary
combinations of elements that could be used to construct a
system/device for such delivery of energy.
TABLE-US-00003 TABLE 3 Column 5 Pattern of Column 6 Column 1 Column
2 Column 3 Column 4 Therapeutic Aspiration/ Access Visualization
Landmarks Therapeutic Element Delivery Compression non-
transvaginal ovarian Tissue Heat Ablation Superior invasive
ultrasound features [RF (monopolar, (external) cysts bipolar,
multimodal), HIFU, Direct Heat, microwave, unfocused/partially
focused ultrasound, laser, saline/water, steam] transabdominal bony
Tissue Warming [RE Near ultrasound (monopolar, bipolar,
vasculature/ multimodal), HIFU, mesovarium Direct Heat, microwave,
unfocused/partially focused ultrasound, laser, saline/water, steam]
CT non-thermal acoustic cavitation MR broad Cryoablation (cooled
away from ovary external ligament/ element, liquid vasculature/
compression ovary nitrogen, CO2, dry-ice) mesovarium junction
fiducial Tissue Cooling (cooled Maximize element, saline/water)
interruption of cysts Mechanical disruption preferential for
cortical ovary drug - implant preferential for permanent or
medullary biodegradeable vs. no- ovary implant, types of drugs:
beta-blockers, anti- androgens, neurotoxins or tissue toxins, 5-
alpha-reductase inhibitors, or aromatase inhibitors mechanical
implant delivery to (permanent vs. limit/minimize biodegradeable),
could disruption of be activated externally ovarian capsule
delivery to maximize disruption of ovarian capsule Notes: specific
embodiment may include none of features in a column or more than
one feature in a column
[0142] In one variation, non-invasive imaging may also be employed
to percutaneously or via a natural orifice route through the
vagina-uterus-fallopian tubes place at least one fiducial within
the patient, e.g., in the proximity of the target ovarian tissue,
which may be used during the delivery of therapy to target
treatment locations. Fiducials may be constructed of any material
chosen for biocompatibility and compatibility with the desired
imaging modality used during the therapeutic procedure. The
fiducial may be placed either percutaneously or via a natural
orifice route through the vagina-uterus-fallopian tubes via a
needle, microcatheter, or other suitable delivery system through
the abdominal wall, transvaginally, laparoscopically, or
surgically.
[0143] In another variation, a device could be placed within the
vagina. The device may be used with integrated imaging or use of a
non-integrated imaging device (e.g., transvaginal ultrasound or
abdominal ultrasound) to deliver either mechanical manipulation
(e.g., sound, vibration, or other mechanical manipulation) or
energy (e.g., electrical current) preferentially to the ovaries or
portions of the ovaries. In the case of energy delivery, this could
be either an ablative or non-ablative (e.g., energy similar to that
used in transcutaneous electrical nerve stimulation) form of
energy. This could be done repeatedly in a single session or
temporally spaced as necessary.
IV. EXAMPLES
[0144] The following examples further illustrate embodiments of the
systems and methods disclosed herein, and should not be construed
in any way as limiting their scope.
Example 1
Ablation Volume with a Bipolar System Including a Straight
Therapeutic Element and Using Max Power of 4 Watts
[0145] An ovarian tissue apparatus having a bipolar electrode
configuration was created using two Platinum-Iridium (90%/10%)
bands mounted on a straight polymer shaft. The electrode outer
diameters were 1.27 mm and the lengths were 3.0 mm. The electrodes
were spaced 3.0 mm apart from each other and a temperature sensor
was mounted on the inner diameter of each electrode. To evaluate
lesion (ablated tissue) sizes, raw chicken breast was placed around
the electrodes and a RF generator delivered energy to one electrode
while the other electrode was used as part of the return path to
the generator. RF energy was delivered for 30 seconds in order to
achieve a target temperature of approximately 80.degree. C. The
maximum power observed was approximately 4 watts. A cross-section
of the resulting lesion (cut lengthwise) showed apparent tissue
necrosis measuring 3.8 mm wide and 10.4 mm long. Approximating the
lesion volume as a cylinder (with diameter of 3.8 mm and length of
10.4 mm and volume=1/4.times..pi..times.D2.times.L), the lesion was
calculated to have a volume of ablated tissue of 118 mm.sup.3 While
this experiment was conducted with a straight therapeutic element,
similar results would be expected using a curved therapeutic
element.
Example 2
Ablation Volume with a Bipolar System Including a Straight
Therapeutic Element and Using Max Power of 10 Watts
[0146] A similar experiment was conducted with the same electrode
configuration described in Example 1. In this example, however, RF
energy was delivered for a total of 15 seconds and targeted a
maximum temperature of approximately 100.degree. C. The maximum
power utilized in this case was approximately 10 watts. A
cross-section of the resulting lesion showed apparent tissue
necrosis approximating an ellipse with a major axis, D1, of 4.5 mm
and minor axis, D2, of 3.9 mm Assuming a lesion length of 10 mm,
the resulting lesion volume was calculated as 138 mm.sup.3 (where
volume=.times..pi..times.D1.times.D2.times.L).
Example 3
Ablation Volume with a Bipolar System Including a Curved
Therapeutic Element
[0147] Experiments were conducted utilizing a similar bipolar
electrode configuration as described in Example 1. However, the
electrodes were mounted on a curved polymer shaft with an
approximate radius of 7 mm Both Platinum-Iridium (90%/10%)
electrodes had outer diameters of 1.27 mm and lengths of 3.0 mm.
The electrodes were spaced 3.0 mm apart from each other and a
temperature sensor was mounted on the inner diameter of each
electrode. In one experiment, RF energy was delivered for 30
seconds in order to achieve a target temperature of approximately
90.degree. C. A cross-section of the resulting lesion (cut
lengthwise) showed apparent tissue necrosis measuring 6.7 mm wide.
In another experiment, RF energy was also delivered for 30 seconds
in order to achieve a target temperature of approximately
90.degree. C. A cross-section of the resulting lesion showed
apparent tissue necrosis approximating an ellipse with a major
axis, D1, of 6.0 mm and minor axis, D2, of 3.8 mm Assuming a lesion
length of 9 mm, the resulting lesion volume can be estimated as 161
mm.sup.3 (where
volume=1/4.times..pi..times.D1.times.D2.times.L).
V. FURTHER EXAMPLES
[0148] Furthermore, the following examples, including any of the
indicated combinations thereof, are disclosed herein and are
comprised within the scope of the present disclosure.
[0149] 1. A system for performing an ovarian procedure
comprising:
[0150] a) an ovarian tissue apparatus, the ovarian tissue apparatus
comprising a docking device and a therapeutic element, the docking
device comprising an elongate body and having a proximal end, a
distal end, and defining a lumen therethrough, and the therapeutic
element being slidable within and deployable from the lumen of the
docking device;
[0151] b) a transvaginal probe comprising a handle and an
ultrasound transducer;
[0152] c) a mechanical lock or a visual identifier on a part of the
system; and
[0153] d) a generator configured to supply energy to the
therapeutic element,
wherein the mechanical lock or visual identifier is configured to
maintain planar orientation of the therapeutic element relative to
the ultrasound transducer and during a procedure on an ovary.
[0154] 2. The system of example 1, wherein the therapeutic element
comprises one or more curved structures, the curved structures
comprising electrodes and having a straightened length and radius
of curvature.
[0155] 3. The system of example 1 or example 2, wherein the
therapeutic element comprises two curved structures.
[0156] 4. The system of example 2 or example 3, wherein the
straightened length ranges between about 5.0 and about 40 mm.
[0157] 5. The system of any of examples 2-4, wherein the radius of
curvature ranges between about 3.0 and about 10 mm.
[0158] 6. The system of example 1, wherein the therapeutic element
comprises a curved electrode.
[0159] 7. The system of any of the preceding examples, wherein the
therapeutic element comprises an elongate body having a
straightened length and a radius of curvature, an active electrode,
and a return electrode.
[0160] 8. The system of example 7, wherein the straightened length
ranges between about 5.0 and about 40 mm.
[0161] 9. The system of example 7 or example 8, wherein the radius
of curvature ranges between about 3.0 and about 10 mm.
[0162] 10. The system of any of examples 1-9, wherein the
mechanical lock comprises an adjustable element having a locked
position and an unlocked position.
[0163] 11. The system of example 10, wherein the adjustable element
comprises a notch configured to mate with the docking device when
the alignment adapter is in the locked position.
[0164] 12. The system of any of examples 1-11, wherein the
generator is configured to supply radiofrequency energy at a power
of 30 watts or less, and for a duration of 20 seconds or less.
[0165] 13. The system of any of examples 1-12, wherein the
generator is configured to supply continuous or pulsed
radiofrequency energy.
[0166] 14. The system of any of examples 1-13, wherein the distal
end of the docking device comprises one or more attachment elements
for releasably securing an ovary.
[0167] 15. The system of example 14, wherein the one or more
attachment elements comprise a hook, needle, or barb.
[0168] 16. The system of any of examples 1-15, wherein the
therapeutic element comprises an echogenic material.
[0169] 17. The system of any of examples 1-15, wherein a portion of
the therapeutic element comprises an echogenic material.
[0170] 18. The system of any of examples 1-17, wherein a portion of
the docking device comprises an echogenic material.
[0171] 19. The system of any of example 1, wherein the therapeutic
element comprises an electrode, a cryoablation element, a cooling
element, a laser, or a combination thereof.
[0172] 20. A method for treating polycystic ovary syndrome
comprising:
[0173] a) advancing a probe comprising a handle, an ultrasound
transducer, and a needle guide into the vaginal canal;
[0174] b) advancing an ovarian tissue apparatus into the needle
guide, the ovarian tissue apparatus comprising a docking device and
a therapeutic element;
[0175] c) advancing the docking device through a vaginal wall;
[0176] d) penetrating an ovary at a single entry point with the
docking device or the therapeutic element;
[0177] e) advancing the therapeutic element from the docking device
into the ovary;
[0178] f) delivering energy to affect a volume of tissue within the
ovary using the therapeutic element to treat a symptom of
polycystic ovary syndrome;
[0179] g) retracting the therapeutic element into the docking
device; and
[0180] h) removing the ovarian tissue apparatus.
[0181] 21. The method of example 20, further comprising
repositioning the therapeutic element and repeating the step of
energy delivery through the single entry point.
[0182] 22. The method of example 20 or example 21, wherein the step
of energy delivery comprises ablating a volume of tissue.
[0183] 23. The method of any of examples 20-22, wherein advancement
of the therapeutic element occurs in the same plane as the imaging
plane.
[0184] 24. The method of any of examples 20-23, wherein the
affected volume of tissue ranges from about 240 mm.sup.3 to about
3000 mm.sup.3.
[0185] 25. The method of any of examples 20-24, wherein the
affected volume of tissue ranges from about 30 mm.sup.3 to about
3000 mm.sup.3.
[0186] 26. The method of any of examples 20-23, wherein the
affected volume of tissue ranges from about 3 to 20% of the
ovary.
[0187] 26. The method of any of examples 20-26, wherein the
delivered energy is radiofrequency energy.
[0188] 27. The method of example 26, wherein the radiofrequency
energy is delivered for 15 to 45 seconds.
[0189] 28. The method of example 26 or example 27, wherein the
power of the radiofrequency energy is 30 watts or less.
[0190] 29. The method of any of examples 26-28, wherein delivery of
the radiofrequency energy is continuous or pulsed.
[0191] 30. The method of any of examples 20-29, wherein the
therapeutic element comprises one or more curved structures, the
curved structures comprising electrodes and having a straightened
length and radius of curvature.
[0192] 31. The method of example 30, wherein the therapeutic
element comprises two curved structures.
[0193] 32. The method of example 30 or example 31, wherein the
straightened length ranges between about 5.0 and about 40 mm.
[0194] 33. The method of any of examples 30-32, wherein the radius
of curvature ranges between about 3.0 and about 10 mm.
[0195] 34. The method of example 20, wherein the therapeutic
element comprises a curved electrode.
[0196] 35. The method of example 20, wherein the therapeutic
element comprises an elongate body having a straightened length and
a radius of curvature, an active electrode, and a return
electrode.
[0197] 36. The method of example 35, wherein the straightened
length ranges between about 5.0 and about 40 mm.
[0198] 37. The method of example 35 or example 36, wherein the
radius of curvature ranges between about 3.0 and about 10 mm.
[0199] 38. The method of any of examples 20-37, wherein the symptom
of polycystic ovary syndrome is infertility.
* * * * *