U.S. patent application number 16/005649 was filed with the patent office on 2018-10-11 for devices, systems, and methods for treating obstetric and gynecological disorders.
The applicant listed for this patent is Ohio State Innovation Foundation. Invention is credited to Edmund Funai, Charles Lockwood, Ali R. Rezai.
Application Number | 20180289959 16/005649 |
Document ID | / |
Family ID | 50489387 |
Filed Date | 2018-10-11 |
United States Patent
Application |
20180289959 |
Kind Code |
A1 |
Lockwood; Charles ; et
al. |
October 11, 2018 |
DEVICES, SYSTEMS, AND METHODS FOR TREATING OBSTETRIC AND
GYNECOLOGICAL DISORDERS
Abstract
One aspect of the present disclosure relates to a therapy
delivery device for treating an obstetric or gynecological disorder
other than urinary incontinence in a subject. The therapy delivery
device can include a housing, at least one electrode, and a power
source. The housing can be configured for implantation in a
reproductive system of the subject. The at least one electrode can
be connected to the housing and be configured to deliver an
electrical signal to an autonomic nervous system nerve target. The
power source can be in electrical communication with the at least
one electrode.
Inventors: |
Lockwood; Charles; (Bexley,
OH) ; Funai; Edmund; (New Albany, OH) ; Rezai;
Ali R.; (Columbus, OH) |
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Applicant: |
Name |
City |
State |
Country |
Type |
Ohio State Innovation Foundation |
Columbus |
OH |
US |
|
|
Family ID: |
50489387 |
Appl. No.: |
16/005649 |
Filed: |
June 11, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15440705 |
Feb 23, 2017 |
10016599 |
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16005649 |
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14850089 |
Sep 10, 2015 |
9616226 |
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15440705 |
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PCT/US2014/022423 |
Mar 10, 2014 |
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14850089 |
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61776046 |
Mar 11, 2013 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61N 1/36107 20130101;
A61N 1/36007 20130101; A61N 1/36139 20130101; A61N 1/0521 20130101;
A61N 1/36171 20130101; A61N 1/36071 20130101; A61N 1/0551
20130101 |
International
Class: |
A61N 1/36 20060101
A61N001/36; A61N 1/05 20060101 A61N001/05 |
Claims
1.-25. (canceled)
26. A therapy delivery system for treating an obstetric or
gynecological disorder other than urinary incontinence in a
subject, the therapy delivery system comprising: a housing
configured for implantation in a reproductive system of the
subject; at least one electrode connected to the housing and
configured to deliver a magnetic signal to an autonomic nervous
system (ANS) nerve target; and a controller programmed to direct
delivery of the magnetic signal to the at least one electrode to
modulate activity at the ANS nerve target site to treat the
obstetric or gynecological disorder.
27. The therapy delivery system of claim 26, wherein the housing is
configured for implantation in a uterus, a vagina, an ovary, a
fallopian tube, or a cervix of the subject.
28. The therapy delivery system of claim 26, wherein the controller
is programmed to deliver a magnetic signal comprising magnetic
pulses.
29. The therapy delivery system of claim 26, wherein the ANS nerve
target is a parasympathetic nerve.
30. The therapy delivery system of claim 29, wherein the
parasympathetic nerve is a pelvic splanchnic nerve.
31. The therapy delivery system of claim 26, wherein the ANS nerve
target is a sympathetic nerve.
32. The therapy delivery system of claim 31, wherein the
sympathetic nerve is a hypogastric nerve, a hypogastric plexus, an
inferior hypogastric plexus, a uterovaginal plexus, a T10-L1
sympathetic ganglion, a pudendal nerve, an efferent sympathetic
fiber thereof, or an afferent sympathetic fiber thereof.
33. The therapy delivery system of claim 26, wherein the obstetric
or gynecological disorder is preterm labor.
34. A therapy delivery system for treating an obstetric or
gynecological disorder other than urinary incontinence in a
subject, the therapy delivery system comprising: a housing
configured for implantation in a uterus, a vagina, an ovary, a
fallopian tube, or a cervix of the subject; at least one electrode
connected to the housing and configured to deliver a magnetic
signal to a sympathetic nerve target; and a controller programmed
to direct delivery of the magnetic signal to the at least one
electrode to modulate activity at the sympathetic nerve target to
treat the obstetric or gynecological disorder.
35. A method for treating an obstetric or gynecological disorder
other than urinary incontinence in a subject, the method comprising
the steps of: providing a therapy delivery device, the therapy
delivery device including a housing, at least one electrode
connected to the housing wherein the electrode comprises a coil
configured to deliver magnetic stimulation, and a pulse generator;
placing the therapy delivery device into a reproductive system of
the subject so that the at least one electrode is in magnetic
communication with an ANS nerve target; and activating the therapy
delivery device to deliver a magnetic signal to the ANS nerve
target to modulate activity at the ANS nerve target to treat the
obstetric or gynecological disorder.
36. The method of claim 35, wherein said providing step further
includes providing a closed-loop therapy delivery system, the
system including a sensing component and a controller that are in
communication with the housing, the sensing component being
configured to detect at least one physiological parameter
associated with the obstetric or gynecological disorder, the
controller being configured to automatically coordinate operation
of the pulse generator and the sensing component.
37. The method of claim 36, further comprising the steps of:
sensing at least one physiological parameter associated with the
obstetric or gynecological disorder: generating a sensor signal
based on the at least one physiological parameter; and activating
the therapy delivery device to adjust application of the magnetic
signal to the ANS nerve target in response to the sensor signal to
treat the obstetric or gynecological disorder.
38. The method of claim 35, wherein the obstetric or gynecological
disorder is selected from the group consisting of preterm labor,
fecal incontinence, infertility, irregular menstrual cycle,
polycystic ovary syndrome, dysmenorrhea, amenorrhea, sexual
dysfunction, visceral pain syndromes, uterine pain syndromes,
vulvodynia, vaginismus, pre-menstrual stress, and pre-menstrual
dysphoric disorder.
39. The method of claim 35, wherein said placing step further
includes implanting the housing in a uterus, a vagina, an ovary, a
fallopian tube, or a cervix of the subject.
40. The method of claim 35, wherein the ANS nerve target is a
parasympathetic nerve.
41. The method of claim 40, wherein the parasympathetic nerve is a
pelvic splanchnic nerve.
42. The method of claim 35, wherein the ANS nerve target is a
sympathetic nerve.
43. The method of claim 42, wherein the sympathetic nerve is a
hypogastric nerve, a hypogastric plexus, an inferior hypogastric
plexus, a uterovaginal plexus, a T10-L1 sympathetic ganglion, a
pudendal nerve, an efferent sympathetic fiber thereof, or an
afferent sympathetic fiber thereof.
Description
RELATED APPLICATION
[0001] This application claims the benefit of U.S. Provisional
Patent Application Ser. No. 61/776,046, filed Mar. 11, 2013, the
entirety of which is hereby incorporated by reference for all
purposes.
TECHNICAL FIELD
[0002] The present disclosure relates generally to neuromodulatory
devices, systems and methods, and more particularly to devices,
systems, and methods for treating obstetric and gynecological
disorders other than urinary incontinence.
BACKGROUND
[0003] Although women are half of the U.S. population, women's
health disorders have historically received far less attention than
men's. The Agency for Health Care Policy and Research (AHCPR) cites
studies indicating that one in four women ages 30-59 has
experienced urinary incontinence alone. AHCPR estimates that the
annual costs for caring for women with urinary incontinence are
$11.2 billion. As many as 40% of women may experience mental health
disturbances related to reproductive function, and nearly 40
million American women experience some form of sexual
dysfunction.
SUMMARY
[0004] The present disclosure relates generally to neuromodulatory
devices, systems and methods, and more particularly to devices,
systems, and methods for treating obstetric and gynecological
disorders other than urinary incontinence.
[0005] One aspect of the present disclosure relates to a therapy
delivery device for treating an obstetric or gynecological disorder
other than urinary incontinence in a subject. The therapy delivery
device can comprise a housing, at least one electrode, and a power
source. The housing can be configured for implantation in a
reproductive system of the subject. The at least one electrode can
be connected to the housing and be configured to deliver an
electrical signal to an autonomic nervous system (ANS) nerve
target. The power source can be in electrical communication with
the at least one electrode.
[0006] Another aspect of the present disclosure relates to a
therapy delivery device for treating an obstetric or gynecological
disorder other than urinary incontinence in a subject. The therapy
delivery can comprise a housing, at least one electrode, and a
power source. The housing can be configured for implantation in a
uterus, a vagina, an ovary, a fallopian tube, or a cervix of the
subject. The at least one electrode can be connected to the housing
and be configured to deliver an electrical signal to a sympathetic
nerve target. The power source can be in electrical communication
with the at least one electrode.
[0007] Another aspect of the present disclosure relates to a
closed-loop therapy delivery system for treating an obstetric or
gynecological disorder other than urinary incontinence in a
subject. The therapy delivery system can comprise a housing, at
least one electrode, a power source, a sensing component, and a
controller. The housing can be configured for implantation in a
reproductive system of the subject. The at least one electrode can
be connected to the housing and be configured to deliver an
electrical signal to an ANS nerve target. The power source can be
in electrical communication with the at least one electrode. The
sensing component can be configured to detect at least one
physiological parameter associated with the obstetric or
gynecological disorder. The controller can be configured to
automatically coordinate operation of the power source and the
sensing component. The controller can also be configured to direct
delivery of the electrical signal to the at least one electrode to
modulate activity of the ANS nerve target.
[0008] Another aspect of the present disclosure relates to a method
for treating an obstetric or gynecological disorder other than
urinary incontinence in a subject. One step of the method can
include providing a therapy delivery device. The therapy delivery
device can include a housing, at least one electrode connected to
the housing, and a power source in electrical communication with
the at least one electrode. Next, the therapy delivery device can
be placed into a reproductive system of the subject so that the at
least one electrode is in electrical communication with an ANS
nerve target. The therapy delivery device can then be activated to
deliver an electrical signal to the ANS nerve target to modulate
activity at the ANS nerve target and thereby treat the obstetric or
gynecological disorder.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] The foregoing and other features of the present disclosure
will become apparent to those skilled in the art to which the
present disclosure relates upon reading the following description
with reference to the accompanying drawings, in which:
[0010] FIG. 1 is schematic illustration of the female reproductive
system;
[0011] FIG. 2 is a schematic illustration showing the autonomic
innervations of the female reproductive system;
[0012] FIGS. 3A-D are a series of schematic illustrations showing
alternative perspectives of the female reproductive system and its
autonomic innervations;
[0013] FIG. 4 is a schematic illustration showing another
alternative perspective of the female reproductive system and its
autonomic innervations;
[0014] FIG. 5 is a block diagram illustrating a therapy delivery
device according to one aspect of the present disclosure;
[0015] FIG. 6 is a block diagram illustrating a closed-loop therapy
delivery system according to another aspect of the present
disclosure;
[0016] FIG. 7 is a process flow diagram illustrating a method for
treating an obstetric or gynecological condition other than urinary
incontinence according to another aspect of the present disclosure;
and
[0017] FIG. 8 is a schematic illustration showing a therapy
delivery device implanted in a uterus of a subject suffering from
an obstetric or gynecological disorder other than urinary
incontinence.
DETAILED DESCRIPTION
Definitions
[0018] Unless defined otherwise, all technical and scientific terms
used herein have the same meaning as is commonly understood by one
of skill in the art to which the present disclosure pertains.
[0019] In the context of the present disclosure, the terms
"autonomic nervous system nerve target" or "ANS nerve target" can
refer to any tissues of the sympathetic nervous system (SNS) or
parasympathetic nervous system (PNS) including, but not limited to,
neurons, axons, fibers, tracts, nerves, plexus, afferent plexus
fibers, efferent plexus fibers, ganglia, chain, pre-ganglionic
fibers, post-ganglionic fibers, afferents, efferents, and
combinations thereof, whose activity can be modulated by the
present disclosure. This also includes the spinal cord, DRG, and
the plexus and nerve fibers associated with blood vessels.
[0020] As used herein, the term "subject" can be used
interchangeably with the term "patient" and refer to any
warm-blooded organism including, but not limited to, human beings,
pigs, rats, mice, dogs, goats, sheep, horses, monkeys, apes,
rabbits, cattle, farm animals, livestock, etc.
[0021] As used herein, the terms "modulate" or "modulating" with
reference to an ANS nerve target can refer to causing a change in
neuronal activity, chemistry and/or metabolism. The change can
refer to an increase, decrease, or even a change in a pattern of
neuronal activity. The terms may refer to either excitatory or
inhibitory stimulation, or a combination thereof, and may be at
least electrical, magnetic, optical or chemical, ultrasound,
infrared, or a combination of two or more of these. The terms
"modulate" or "modulating" can also be used to refer to a masking,
altering, overriding, regulating, synchronizing, controlling,
changing, optimizing, or restoring of neuronal activity.
[0022] As used herein, the terms "substantially blocked" or
"substantially block" when used with reference to activity at or
associated with an ANS nerve target can refer to a complete (e.g.,
100%) or partial inhibition (e.g., less than 100%, such as about
90%, about 80%, about 70%, about 60%, or less than about 50%) of
nerve conduction through the ANS nerve target.
[0023] As used herein, the term "activity" when used with reference
to an ANS nerve target can, in some instances, refer to the ability
of a sympathetic or parasympathetic nerve, neuron, or fiber to
conduct, propagate, and/or generate an action potential. In other
instances, the term can refer to the frequency at which a nerve or
neuron is conducting, propagating, and/or generating one or more
action potentials at a given moment in time. In further instances,
the term can refer to the frequency at which a nerve or neuron is
conducting, propagating, and/or generating one or more action
potentials over a given period of time (e.g., seconds, minutes,
hours, days, etc.).
[0024] As used herein, the term "electrical communication" can
refer to the ability of an electric field generated by an electrode
or electrode array to be transferred, or to have a neuromodulatory
effect, within and/or on an ANS nerve target.
[0025] As used herein, the term "obstetric disorder" can refer to
any disease or condition caused by, related to, or associated with
pregnancy. Non-limiting examples of obstetric disorders can include
abortion, abruption, breech birth, cephalo-pelvic disproportion,
dermatoses of pregnancy, diabetes, eclampsia, ectopic pregnancy,
gestational diabetes, HELLP syndrome, hypertension, intrauterine
growth restriction, macrosomia, obstetric fistula, obstetric
hemorrhage, pelvic girdle pain, placenta praevia, pre-eclampsia,
premature birth, prolonged gestation, labor disorders, ovulation,
infertility, preterm labor or prematurity, uterine rupture, fecal
incontinence, and uterine incarceration.
[0026] As used herein, the term "gynecological disorder" can refer
to any disease or condition that affects the female genital tract
and/or reproductive organs. Non-limiting examples of gynecological
disorders can include abnormal menstrual periods, abnormal pap
smears, endometriosis, fibroids, menopause, ovarian masses, pelvic
inflammatory disease, pelvic pain (e.g., visceral and uterine pain
syndromes), polycystic ovarian syndrome, sexually transmitted
diseases, urinary tract infections, uterine bleeding, vaginitis,
sexual dysfunction (e.g., anorgasmia, dyspareunia, hypoactive
desire and arousal disorders), amenorrhea, dysmenorrhea,
vulvodynia, vaginismus, pre-menstrual stress, abnormal vaginal
discharge, vaginal itching, cervical polyps, cervicitis, and
pre-menstrual dysphoric disorder.
[0027] As used herein, the terms "treat" or "treating" can refer to
therapeutically regulating, preventing, improving, alleviating the
symptoms of, and/or reducing the effects of an obstetric and/or
gynecological disorder. As such, treatment also includes situations
where an obstetric and/or gynecological disorder, or at least
symptoms associated therewith, is completely inhibited, e.g.,
prevented from happening or stopped (e.g., terminated) such that
the subject no longer suffers from the obstetric and/or
gynecological disorder, or at least the symptoms that characterize
the obstetric and/or gynecological disorder.
[0028] As used herein, the singular forms "a," "an" and "the" can
include the plural forms as well, unless the context clearly
indicates otherwise. It will be further understood that the terms
"comprises" and/or "comprising," as used herein, can specify the
presence of stated features, steps, operations, elements, and/or
components, but do not preclude the presence or addition of one or
more other features, steps, operations, elements, components,
and/or groups thereof.
[0029] As used herein, the term "and/or" can include any and all
combinations of one or more of the associated listed items.
[0030] As used herein, phrases such as "between X and Y" and
"between about X and Y" can be interpreted to include X and Y.
[0031] As used herein, phrases such as "between about X and Y" can
mean "between about X and about Y."
[0032] As used herein, phrases such as "from about X to Y" can mean
"from about X to about Y."
[0033] It will be understood that when an element is referred to as
being "on," "attached" to, "connected" to, "coupled" with,
"contacting," etc., another element, it can be directly on,
attached to, connected to, coupled with or contacting the other
element or intervening elements may also be present. In contrast,
when an element is referred to as being, for example, "directly
on," "directly attached" to, "directly connected" to, "directly
coupled" with or "directly contacting" another element, there are
no intervening elements present. It will also be appreciated by
those of skill in the art that references to a structure or feature
that is disposed "directly adjacent" another feature may have
portions that overlap or underlie the adjacent feature, whereas a
structure or feature that is disposed "adjacent" another feature
may not have portions that overlap or underlie the adjacent
feature.
[0034] Spatially relative terms, such as "under," "below," "lower,"
"over," "upper" and the like, may be used herein for ease of
description to describe one element or feature's relationship to
another element(s) or feature(s) as illustrated in the figures. It
will be understood that the spatially relative terms can encompass
different orientations of a device in use or operation, in addition
to the orientation depicted in the figures. For example, if a
device in the figures is inverted, elements described as "under" or
"beneath" other elements or features would then be oriented "over"
the other elements or features.
[0035] It will be understood that, although the terms "first,"
"second," etc. may be used herein to describe various elements,
these elements should not be limited by these terms. These terms
are only used to distinguish one element from another. Thus, a
"first" element discussed below could also be termed a "second"
element without departing from the teachings of the present
disclosure. The sequence of operations (or steps) is not limited to
the order presented in the claims or figures unless specifically
indicated otherwise.
[0036] Overview
[0037] A brief discussion of the pertinent neurophysiology is
provided to assist the reader with understanding certain aspects of
the present disclosure. The nervous system is divided into the
somatic nervous system and the ANS. In general, the somatic nervous
system controls organs under voluntary control (e.g., skeletal
muscles) and the ANS controls individual organ function and
homeostasis. For the most part, the ANS is not subject to voluntary
control. The ANS is also commonly referred to as the visceral or
automatic system.
[0038] The ANS can be viewed as a "real-time" regulator of
physiological functions which extracts features from the
environment and, based on that information, allocates an organism's
internal resources to perform physiological functions for the
benefit of the organism, e.g., responds to environment conditions
in a manner that is advantageous to the organism. The ANS acts
through a balance of its two components: the SNS and the PNS, which
are two anatomically and functionally distinct systems. Both of
these systems include myelinated preganglionic fibers which make
synaptic connections with unmyelinated postganglionic fibers, and
it is these fibers that then innervate the effector structure.
These synapses usually occur in clusters called ganglia. Most
organs are innervated by fibers from both divisions of the ANS, and
the influence is usually opposing (e.g., the vagus nerve slows the
heart, while the sympathetic nerves increase its rate and
contractility), although it may be parallel (e.g., as in the case
of the salivary glands). Each of these is briefly reviewed
below.
[0039] The SNS is the part of the ANS comprising nerve fibers that
leave the spinal cord in the thoracic and lumbar regions and supply
viscera and blood vessels by way of a chain of sympathetic ganglia
(also referred to as the sympathetic chain, sympathetic trunk or
the gangliated cord) running on each side of the spinal column,
which communicate with the central nervous system via a branch to a
corresponding spinal nerve. The sympathetic trunks extend from the
base of the skull to the coccyx. The cephalic end of each is
continued upward through the carotid canal into the skull, and
forms a plexus on the internal carotid artery; the caudal ends of
the trunks converge and end in a single ganglion, the ganglion
impar, placed in front of the coccyx.
[0040] The SNS controls a variety of autonomic functions including,
but not limited to, control of movement and secretions from viscera
and monitoring their physiological state, stimulation of the
sympathetic system inducing, e.g., the contraction of gut
sphincters, heart muscle and the muscle of artery walls, and the
relaxation of gut smooth muscle and the circular muscles of the
iris. The chief neurotransmitter in the SNS is adrenaline, which is
liberated in the heart, visceral muscle, glands and internal
vessels, with acetylcholine acting as a neurotransmitter at
ganglionic synapses and at sympathetic terminals in skin and
skeletal muscles. The actions of the SNS tend to be antagonistic to
those of the PNS.
[0041] The neurotransmitter released by the post-ganglionic neurons
is nonadrenaline (also called norepinephrine). The action of
noradrenaline on a particular structure, such as a gland or muscle,
is excitatory in some cases and inhibitory in others. At excitatory
terminals, ATP may be released along with noradrenaline. Activation
of the SNS may be characterized as general because a single
pre-ganglionic neuron usually synapses with many post-ganglionic
neurons, and the release of adrenaline from the adrenal medulla
into the blood ensures that all the cells of the body will be
exposed to sympathetic stimulation even if no post-ganglionic
neurons reach them directly.
[0042] The PNS is the part of the ANS controlling a variety of
autonomic functions including, but not limited to, involuntary
muscular movement of blood vessels and gut and glandular secretions
from eye, salivary glands, bladder, rectum and genital organs. The
vagus nerve is part of the PNS. Parasympathetic nerve fibers are
contained within the last five cranial nerves and the last three
spinal nerves and terminate at parasympathetic ganglia near or in
the organ they supply. The actions of the PNS are broadly
antagonistic to those of the SNS--lowering blood pressure, slowing
heartbeat, stimulating the process of digestion etc. The chief
neurotransmitter in the PNS is acetylcholine. Neurons of the
parasympathetic nervous system emerge from the brainstem as part of
the Cranial nerves III, VII, IX and X (vagus nerve) and also from
the sacral region of the spinal cord via Sacral nerves. Because of
these origins, the PNS is often referred to as the "craniosacral
outflow".
[0043] In the PNS, both pre- and post-ganglionic neurons are
cholinergic (i.e., they utilize the neurotransmitter
acetylcholine). Unlike adrenaline and noradrenaline, which the body
takes around 90 minutes to metabolize, acetylcholine is rapidly
broken down after release by the enzyme cholinesterase. As a result
the effects are relatively brief in comparison to the SNS. Each
pre-ganglionic parasympathetic neuron synapses with just a few
post-ganglionic neurons, which are located near, or in, the
effector organ, a muscle or gland. As noted above, the primary
neurotransmitter in the PNS is acetylcholine such that
acetylcholine is the neurotransmitter at all the pre- and many of
the post-ganglionic neurons of the PNS. Some of the post-ganglionic
neurons, however, release nitric oxide as their
neurotransmitter.
[0044] As shown in FIGS. 1-4, the female reproductive system is
innervated by the PNS and the SNS. The female reproductive organs
can be subdivided into the internal and external genitalia. The
internal genitalia are those organs that are within the true
pelvis. These include the vagina, uterus, cervix, uterine tubes
(oviducts or fallopian tubes), and ovaries. The external genitalia
lie outside the true pelvis. These include the perineum, mons
pubis, clitoris, urethral (urinary) meatus, labia majora and
minora, vestibule, greater vestibular (Bartholin) glands, Skene
glands, and periurethral area.
[0045] The vagina extends from the vulva externally to the uterine
cervix internally. It is located within the pelvis, anterior to the
rectum and posterior to the urinary bladder. The vagina lies at a
90.degree. angle in relation to the uterus. The vagina is held in
place by endopelvic fascia and ligaments. The vagina is lined by
rugae, which are situated in folds throughout. These allow easy
distention, especially during child bearing. The structure of the
vagina is a network of connective, membranous, and erectile
tissues. The pelvic diaphragm, the sphincter urethrae and
transverse peroneus muscles, and the perineal membrane support the
vagina. The sphincter urethrae and the transverse peroneus are
innervated by perineal branches of the pudendal nerve. The pelvic
diaphragm primarily refers to the levator ani and the coccygeus and
is innervated by branches of sacral nerves S2-S4. The nerve supply
to the vagina is primarily from the ANS. Sensory fibers to the
lower vagina arise from the pudendal nerve, and pain fibers are
from sacral nerve roots.
[0046] The uterus is the inverted pear-shaped female reproductive
organ that lies in the midline of the body, within the pelvis
between the bladder and the rectum. It is thick-walled and
muscular, with a lining that, during reproductive years, changes in
response to hormone stimulation throughout a woman's monthly cycle.
The uterus can be divided into 2 parts: the most inferior aspect is
the cervix; and the bulk of the organ is called the body of the
uterus (corpus uteri). Between these two is the isthmus, a short
area of constriction. The body of the uterus is globe-shaped and is
typically situated in an anteverted position, at a 90.degree. angle
to the vagina. The upper aspect of the body is dome-shaped and is
called the fundus; it is typically the most muscular part of the
uterus. The body of the uterus is responsible for holding a
pregnancy, and strong uterine wall contractions help to expel the
fetus during labor and delivery.
[0047] The vasculature of the uterus is derived from the uterine
arteries and veins. The uterine vessels arise from the anterior
division of the internal iliac, and branches of the uterine artery
anastomose with the ovarian artery along the uterine tube. The
nerve supply and lymphatic drainage of the uterus are complex.
Lymphatic drainage is primarily to the lateral aortic, pelvic, and
iliac nodes that surround the iliac vessels. The nerve supply is
attained through the SNS (by way of the hypogastric and ovarian
plexuses) and the PNS (by way of the pelvic splanchnic nerves from
the second through fourth sacral nerves).
[0048] The cervix is the inferior portion of the uterus, separating
the body of the uterus from the vagina. The cervix is cylindrical
in shape, with an endocervical canal located in the midline,
allowing passage of semen into the uterus. The external opening
into the vagina is termed the external os, and the internal opening
into the endometrial cavity is termed the internal os. The internal
os is the portion of a female cervix that dilates to allow delivery
of the fetus during labor. The vasculature is supplied by
descending branches of the uterine artery, which run bilaterally at
the 3 o'clock and 9 o'clock position of the cervix. The nerve
supply to the cervix is via the PNS by way of the second through
fourth sacral segments. Many pain nerve fibers run alongside these
parasympathetics. Lymphatic drainage of the cervix is complex. The
obturator, common iliac, internal iliac, external iliac, and
visceral parametrial nodes are the main drainage points.
[0049] The present disclosure relates generally to neuromodulatory
devices, systems and methods, and more particularly to devices,
systems, and methods for treating obstetric and gynecological
disorders other than urinary incontinence. The ANS regulates the
intrinsic function and balance of each body organ, including the
female reproductive system (e.g., the uterus, cervix, vagina,
external genitalia and ovaries) and the components of the
genitourinary (GU) system. As described in detail below, the
present disclosure advantageously provides devices, systems, and
methods for modulating the portion of the ANS that innervates the
female reproductive and GU systems to effectively normalize,
regulate, optimize, change, or modulate the ANS and thereby treat,
prevent, retard, or reverse obstetric and/or gynecological
disorders. By employing such devices, systems and methods, the
present disclosure can treat obstetric and/or gynecological
disorders by selectively modulating parasympathetic and/or
sympathetic input and output of the female reproductive and GU
systems.
[0050] Therapy Delivery Devices and Systems
[0051] In one aspect, the present disclosure includes various
therapy delivery devices and related systems configured to treat an
obstetric and/or gynecological disorder other than urinary
incontinence in a subject. In some instances, therapy delivery
devices that may be used to practice the present disclosure may be
positioned directly on or in an ANS nerve target associated with an
obstetric and/or gynecological disorder other than urinary
incontinence. In other instances, therapy delivery devices that may
be used to practice the present disclosure can be positioned below
the skin of a subject but not directly on or in an ANS nerve target
associated with an obstetric and/or gynecological disorder other
than urinary incontinence. In further instances, therapy delivery
devices that may be used to practice the present disclosure can
comprise external devices, e.g., positioned in a lumen of the
female reproductive tract (e.g., in the uterus, cervix or vagina)
adjacent an ANS nerve target associated with an obstetric and/or
gynecological disorder other than urinary incontinence. In still
further instances, therapy delivery devices used to practice the
present disclosure can comprise an external device, e.g.,
positioned on the skin of a subject adjacent an ANS nerve target
associated with an obstetric and/or gynecological disorder other
than urinary incontinence. Therapy delivery devices can be
temporarily or permanently implanted within, on, or otherwise
associated with a subject suffering from, afflicted by, or
suspected of having an obstetric and/or gynecological disorder
other than urinary incontinence.
[0052] Therapy delivery devices of the present disclosure can be
configured to deliver various types of therapy signals to target an
ANS nerve target associated with an obstetric and/or gynecological
disorder other than urinary incontinence. For example, therapy
delivery devices of the present disclosure can be configured to
deliver only electrical energy, only magnetic energy, only a
pharmacological or biological agent, or a combination thereof. In
one example, a therapy delivery device 10 (FIG. 5) of the present
disclosure can comprise a housing 12 configured for implantation in
a reproductive system of a subject, at least one electrode 14 that
is connected to the housing and configured to deliver an electrical
signal to an ANS nerve target, and an integral or remote power
source 16, which is in electrical communication with the one or
more electrodes and configured to produce one or more electrical
signals (or pulses). In another example, therapy delivery devices
can include a pharmacological or biological agent reservoir, a
pump, and a fluid dispensing mechanism. Non-limiting examples of
pharmacological and biological agents can include chemical
compounds, drugs (e.g., prazosin, clonidine), nucleic acids,
polypeptides, stem cells, toxins (e.g., botulinum), as well as
various energy forms, such as ultrasound, radiofrequency
(continuous or pulsed), magnetic waves, cryotherapy, and the like.
In yet another example, therapy delivery devices can be configured
to deliver magnetic nerve stimulation with desired field focality
and depth of penetration. One skilled in the art will appreciate
that combinations of the therapy delivery devices above
configurations are also included within the scope of the present
disclosure.
[0053] In some instances, therapy delivery devices can comprise a
stimulator (or inhibitor), such as an electrode, a controller or
programmer, and one or more connectors (e.g., leads) for connecting
the stimulating (or inhibiting) device to the controller. In one
example, which is described in further detail below, the present
disclosure can include a closed-loop therapy delivery system 20
(FIG. 6) for treating an obstetric and/or gynecological disorder
other than urinary incontinence. As shown in FIG. 6, the therapy
delivery system 20 can include a housing 12 configured for
implantation in a reproductive system, at least one electrode 14
that is connected to the housing and configured to deliver an
electrical signal to an ANS nerve target, a power source 16 in
electrical communication with the at least one electrode, a sensing
component 22 configured to detect at least one physiological
parameter associated with the obstetric and/or gynecological
disorder, and a controller 24 configured to automatically
coordinate operation of the power source and the sensing component.
Each of the sensing component 22, electrode 14, controller 24, and
power source 16 can be in electrical communication with one another
(e.g., via a physical connection, such as a lead, or a wireless
link). In some instances, the sensing component 22 can comprise an
electrode. In other instances, the electrode 14 can comprise a coil
configured to deliver magnetic stimulation. In further describing
representative electrodes, which are described in the singular, it
will be apparent that more than one electrode may be used as part
of a therapy delivery device. Accordingly, the description of a
representative electrode suitable for use in the therapy delivery
devices of the present disclosure is applicable to other electrodes
that may be employed.
[0054] An electrode 14 can be controllable to provide output
signals that may be varied in voltage, frequency, pulse-width,
current and intensity. The electrode 14 can also provide both
positive and negative current flow from the electrode and/or is
capable of stopping current flow from the electrode and/or changing
the direction of current flow from the electrode. In some
instances, therapy delivery devices can include an electrode 14
that is controllable, i.e., in regards to producing positive and
negative current flow from the electrode, stopping current flow
from the electrode, changing direction of current flow from the
electrode, and the like. In other instances, the electrode 14 has
the capacity for variable output, linear output and short
pulse-width, as well as paired pulses and various waveforms (e.g.,
sine wave, square wave, and the like).
[0055] The power source 16 can comprise a battery or generator,
such as a pulse generator that is operatively connected to an
electrode via the controller 24. The power source 16 can be
configured to generate an electrical signal or signals. In one
example, the power source 16 can include a battery that is
rechargeable by inductive coupling. The power source 16 may be
positioned in any suitable location, such as adjacent the electrode
14 (e.g., implanted adjacent the electrode), or a remote site in or
on the subject's body or away from the subject's body in a remote
location. An electrode 14 may be connected to the remotely
positioned power source 16 using wires, e.g., which may be
implanted at a site remote from the electrode(s) or positioned
outside the subject's body. In one example, an implantable power
source 16 analogous to a cardiac pacemaker may be used. In another
example, the power source 16 can be located in a handheld device,
such as a cell phone, or in an article of clothing, such as a belt
or waistband.
[0056] The controller 24 can be configured to control the pulse
waveform, the signal pulse width, the signal pulse frequency, the
signal pulse phase, the signal pulse polarity, the signal pulse
amplitude, the signal pulse intensity, the signal pulse duration,
and combinations thereof of an electrical signal. The controller 24
may be used to convey a variety of currents and voltages to one or
more electrodes 14 and thereby modulate the activity at an ANS
nerve target. The controller 24 may be used to control numerous
electrodes 14 independently or in various combinations as needed to
provide stimulation or inhibition of nerve activity. In some
instances, an electrode 14 may be employed that includes its own
power source, e.g., which is capable of obtaining sufficient power
for operation from surrounding tissues in the subject's body, or
which may be powered by bringing a power source 16 external to the
subject's body into contact with the subject's skin, or which may
include an integral power source.
[0057] The electrical signal (or signals) delivered by the
controller 24 to the electrode 14 may be constant, varying and/or
modulated with respect to the current, voltage, pulse-width, cycle,
frequency, amplitude, and so forth. For example, a current may
range from about 0.001 to about 1000 microampere (mA) and, more
specifically, from about 0.1 to about 100 mA. Similarly, the
voltage may range from about 0.1 millivolt to about 25 volts, or
about 0.5 to about 4000 Hz, with a pulse-width of about 10 to about
1000 microseconds. In one example, the electrical signal can be
oscillatory. The type of stimulation may vary and involve different
waveforms known to the skilled artisan. For example, the
stimulation may be based on the H waveform found in nerve signals
(i.e., Hoffman Reflex). In another example, different forms of
interferential stimulation may be used.
[0058] To increase nerve activity in a portion of an ANS nerve
target, for example, voltage or intensity may range from about 1
millivolt to about 1 volt or more, e.g., 0.1 to about 50 mA or
volts (e.g., from about 0.2 volts to about 20 volts), and the
frequency may range from about 1 Hz to about 10,000 Hz, e.g., about
1 Hz to about 1000 Hz (e.g., from about 2 Hz to about 100 Hz). In
some instances, pure DC and/or AC voltages may be employed. The
pulse-width may range from about 1 microsecond to about 10,000
microseconds or more, e.g., from about 10 microseconds to about
2000 microseconds (e.g., from about 15 microseconds to about 1000
microseconds). The electrical signal may be applied for at least
about 1 millisecond or more, e.g., about 1 second (e.g., about
several seconds). In some instances, stimulation may be applied for
as long as about 1 minute or more, e.g., about several minutes or
more (e.g., about 30 minutes or more).
[0059] To decrease activity in a portion of an ANS nerve target,
for example, voltage or intensity may range from about 1 millivolt
to about 1 volt or more, e.g., 0.1 to about 50 mA or volts (e.g.,
from about 0.2 volts to about 20 volts), and the frequency may
range from about 1 Hz to about 10,000 Hz, e.g., about 50 Hz to
about 2500 Hz. In one example, an electrical signal can have a
frequency range of about 1000 Hz or greater (e.g., high frequency
stimulation) to effectively block nerve conduction. In some
instances, pure DC and/or AC voltages may be employed. The
pulse-width may range from about 1 microseconds to about 10,000
microseconds or more, e.g., from about 10 microseconds to about
2000 microseconds (e.g., from about 15 microseconds to about 1000
microseconds). The electrical signal may be applied for at least
about 1 millisecond or more, e.g., about 1 second (e.g., about
several seconds). In some instances, the electrical energy may be
applied for as long as about 1 minute or more, e.g., about several
minutes or more (e.g., about 30 minutes or more may be used). In
some instances, the controller 24 can be configured to deliver an
electrical signal to the electrode 14 so that activity of an ANS
nerve target is continuously and substantially blocked.
[0060] The electrode 14 may be mono-polar, bipolar or multi-polar.
To minimize the risk of an immune response triggered by the subject
against the therapy delivery device, and also to minimize damage
thereto (e.g., corrosion from other biological fluids, etc.), the
electrode 14 (and any wires and optional housing materials) can be
made of inert materials, such as silicon, metal, plastic and the
like. In one example, a therapy delivery device can include a
multi-polar electrode 14 having about four exposed contacts (e.g.,
cylindrical contacts).
[0061] As discussed above, the controller 24 (or a programmer) may
be associated with a therapy delivery device. The controller 24 can
include, for example, one or more microprocessors under the control
of a suitable software program. Other components of a controller
24, such as an analog-to-digital converter, etc., will be apparent
to those of skill in the art. In some instances, the controller 24
can be configured to record and store data indicative of the
intrinsic sympathetic or parasympathetic tone or activity in the
subject. Therefore, the controller 24 can be configured to apply
one or more electrical signals to the electrode 14 when the
intrinsic sympathetic or parasympathetic tone or activity of a
subject increases or decreases above a certain threshold value (or
range of values). The controller 24 can be attached or connected to
the housing 12 of a therapy delivery device 10 or, alternatively,
the controller can be included as part of an external monitoring
device (not shown), such as a handheld device (e.g., a cell phone).
Such monitoring devices can be used by the subject and/or a medical
practitioner to continuously monitor functioning of the therapy
delivery device and/or signs and symptoms of the obstetric and/or
gynecological disorder. In some instances, such monitoring devices
can be programmed to adjust treatment parameters on demand or as
part of a pre-programmed regimen.
[0062] Therapy delivery devices can be pre-programmed with desired
stimulation parameters. Stimulation parameters can be controllable
so that an electrical signal may be remotely modulated to desired
settings without removal of the electrode 14 from its target
position. Remote control may be performed, e.g., using conventional
telemetry with an implanted power source 16, an implanted
radiofrequency receiver coupled to an external transmitter, and the
like. In some instances, some or all parameters of the electrode 14
may be controllable by the subject, e.g., without supervision by a
physician. In other instances, some or all parameters of the
electrode 14 may be automatically controllable by a controller
24.
[0063] In one example, a therapy delivery device can be configured
for percutaneous placement or implantation. In this instance, the
therapy delivery device can comprise one or more implantable
electrodes shaped or configured, for example, as a wire, a rod, a
filament, a ribbon, a cord, a tube, a formed wire, a flat strip, or
a combination thereof. In one example, one or more of the
electrodes can comprise a laminotomy electrode array. Laminotomy
electrodes, for example, generally have a flat paddle configuration
and typically possess a plurality of electrodes (e.g., 2, 3, 4 or
more) arranged on the paddle. The arrangement of electrodes on the
paddle may be in rows and columns, staggered, spaced, circular, or
any other arrangement that will position the electrodes for optimal
delivery of electrical energy. The one or more implantable
electrodes may be controlled individually, in series, in parallel,
or any other manner desired. Once implanted, the implantable
electrode(s) may be held in position using any method known to the
skilled artisan, such as stitches, epoxy, tape, glue, sutures, or a
combination thereof.
[0064] In another example, a therapy delivery device can be
configured for intravascular or intraluminal placement or
implantation. In some instances, a therapy delivery device
configured for intravascular or intraluminal placement or
implantation can be configured in an identical or similar manner as
the expandable electrode disclosed in U.S. patent application Ser.
No. 11/641,331 to Greenberg et al. (hereinafter, "the '331
application"). In other instances, the therapy delivery device can
be configured for intravascular or intraluminal placement or
implantation at an implantation site that is adjacent, or directly
adjacent, an ANS nerve target associated with an obstetric and/or
gynecological disorder other than urinary incontinence. In one
example, a therapy delivery device 10 can comprise a housing 12
configured for placement in a reproductive system (e.g., a uterus,
a cervix, or a vagina of the subject) of a subject such that at
least one electrode 14 of the therapy delivery device is in
electrical communication with the ANS nerve target. In such
instances, the therapy delivery device 10 can be configured similar
or identical to a cervical cap, a cervical ring, a pessary, a
tampon, a diaphragm, an intrauterine device, tocodynamometer,
internal fetal scalp electrode, intrauterine pressure catheter, or
any type of percutaneous electrode and/or transvaginal system.
[0065] In yet another example, a therapy delivery device can be
configured for transcutaneous neuromodulation using magnetic
stimulation. A magnetic stimulation device or system can generally
include a pulse generator (e.g., a high current pulse generator)
and a stimulating coil capable of producing magnetic pulses with
desired field strengths. Other components of a magnetic stimulation
device can include transformers, capacitors, microprocessors,
safety interlocks, electronic switches, and the like. In operation,
the discharge current flowing through the stimulating coil can
generate the desired magnetic field or lines of force. As the lines
of force cut through tissue (e.g., neural tissue), a current is
generated in that tissue. If the induced current is of sufficient
amplitude and duration such that the cell membrane is depolarized,
nervous tissue will be stimulated in the same manner as
conventional electrical stimulation. It is therefore worth noting
that a magnetic field is simply the means by which an electrical
current is generated within the nervous tissue, and that it is the
electrical current, and not the magnetic field, which causes the
depolarization of the cell membrane and thus stimulation of the
target nervous tissue. Thus, in some instances, advantages of
magnetic over electrical stimulation can include: reduced or
sometimes no pain; access to nervous tissue covered by poorly
conductive structures; and stimulation of nervous tissues lying
deeper in the body without requiring invasive techniques or very
high energy pulses.
[0066] In another example, transcutaneous neuromodulation can
include positioning an electrode (or electrodes) on a skin surface
so that an electrical signal (or magnetic field) can be delivered
to an ANS nerve target associated with an obstetric and/or
gynecological disorder other than urinary incontinence.
Transcutaneous neuromodulation can additionally include partially
transcutaneous methods (e.g., using a fine, needle-like electrode
to pierce the epidermis). In other instances, a surface electrode
(or electrodes) or magnetic coil can be placed into electrical
communication with the ANS nerve target. In one example, a
transcutaneous neuromodulation device can be configured to deliver
an electrical signal to an ANS nerve target via transvaginal
stimulation, transcervical stimulation, transabdominal stimulation,
or transpelvic stimulation. Generally, an electrical signal used
for transcutaneous neuromodulation may be constant, varying and/or
modulated with respect to the current, voltage, pulse-width, cycle,
frequency, amplitude, and so forth (e.g., the current may be
between about 1 to 100 microampere), about 10 V (average), about 1
to about 1000 Hz or more, with a pulse-width of about 250 to about
500 microseconds.
[0067] Other examples of transcutaneous therapy delivery devices
and systems that may be used as part of the present disclosure are
described in U.S. Provisional Patent Application Ser. No.
61/693,946, filed Sep. 19, 2012, and 61/702,876, filed Aug. 28,
2012. It will be appreciated that transcutaneous therapy delivery
devices and systems can additionally or optionally include any
wearable item, accessory, article of clothing, or any object,
device, or apparatus that a subject can use and, during use, comes
into close or direct contact with a portion of the subject's body
(e.g., the subject's neck). Examples of such transcutaneous
neuromodulation devices can include vests, sleeves, shirts, socks,
shoes, underwear, belts, scarves, wrist bands, gloves, ear pieces,
band-aids, turtle neck, pendants, buttons, earrings, stickers,
patches, bio-films, skin tattoos (e.g., using neuro-paint), chairs,
computers, beds, head rests (e.g., of a chair or car seat), cell
phones, and the like.
[0068] Therapy delivery devices can be part of an open- or
closed-loop system. In an open-loop system, for example, a
physician or subject may, at any time, manually or by the use of
pumps, motorized elements, etc., adjust treatment parameters, such
as pulse amplitude, pulse-width, pulse frequency, duty cycle,
dosage amount, type of pharmacological or biological agent, etc.
Alternatively, in a closed-loop system 20 (as discussed above),
treatment parameters (e.g., electrical signals) may be
automatically adjusted in response to a sensed physiological
parameter or a related symptom or sign indicative of the extent
and/or presence of an obstetric and/or gynecological disorder. In a
closed-loop feedback system 20, a sensing component 22 can comprise
a sensor (not shown in detail) that senses a physiological
parameter associated with an obstetric and/or gynecological
disorder can be utilized. More detailed descriptions of sensors
that may be employed in closed-loop systems, as well as other
examples of sensors and feedback control techniques that may be
employed as part of the present disclosure are disclosed in U.S.
Pat. No. 5,716,377. One or more sensing components 22 can be
implanted on or in any tissue or organ of a subject. For example, a
sensing component 22 can be implanted in or on a component of the
ANS, such as nerves, ganglia, afferents or efferents, or the spinal
cord. Alternatively or additionally, a sensing component 22 can be
implanted on or in a structure or component of the female
reproductive system or GU system.
[0069] It should be appreciated that implementing a therapy
delivery device as part of a closed-loop system can include placing
or implanting a therapy delivery device on or within a subject at
an ANS nerve target associated with an obstetric and/or
gynecological disorder other than urinary incontinence, sensing a
physiological parameter associated with the obstetric and/or
gynecological disorder, activating the therapy delivery device to
apply an electrical signal to the ANS nerve target, and adjusting
application of the electrical signal to the ANS nerve target in
response to the sensor signal. In some instances, such
physiological parameters can include any characteristic, sign,
symptom, or function associated with an obstetric and/or
gynecological disorder, such as a chemical moiety or nerve activity
(e.g., electrical activity). Examples of such chemical moieties and
nerve activities can include the activity of a sympathetic or
parasympathetic nerve or nerve structure (e.g., ganglia or a
ganglion), protein concentrations, electrochemical gradients,
hormones (e.g., prostaglandin levels), neuroendocrine markers,
inflammatory mediators, electrolytes, laboratory values, vital
signs (e.g., blood pressure), skin temperature, core temperature,
serum markers, blood vessel dilation, catecholamines, markers of
locomotor activity, optical or infrared indicia of cervical tissue,
uterine contractions, follicle size, or other signs and biomarkers
associated with the obstetric and/or gynecological disorder.
[0070] Methods
[0071] Another aspect of the present disclosure includes methods
for treating an obstetric and/or gynecological disorder other than
urinary incontinence in a subject. In general, methods of the
present disclosure can include the steps of: providing a therapy
delivery device; placing the therapy delivery device into a
reproductive system of the subject so that the at least one
electrode is in electrical communication with an ANS nerve target
associated with an obstetric and/or gynecological disorder other
than urinary incontinence; and activating the therapy delivery
device to deliver an electrical signal to the ANS nerve target to
modulate activity at the ANS nerve target and thereby treat the
obstetric and/or gynecological disorder. Subjects treatable by the
present disclosure can, in some instances, be diagnosed with (or
suspected of having) an obstetric and/or gynecological disorder as
well as, or optionally, one or more related or unrelated medical
conditions. For example, methods of the present disclosure can be
employed to treat fecal incontinence, improve fertility, normalize
ovulation, regulate the menstrual cycle (e.g., for birth control),
treat pain syndromes (e.g., visceral or uterine), and/or treat
sexual dysfunction (e.g., anorgasmia, dyspareunia, hypoactive
desire, arousal disorders, etc.).
[0072] In some instances, the step of placing a therapy delivery
device (e.g., at least one electrode thereof) into electrical
communication with an ANS nerve target can entail different
surgical and/or medical techniques, depending upon the target, for
example. In some instances, a therapy delivery device can be
surgically placed into electrical communication with an ANS nerve
target via a percutaneous or endoscopic route. In other instances,
a therapy delivery device can be placed into electrical
communication with an ANS nerve target via an intravascular or
intraluminal route. In further instances, a therapy delivery device
can be placed into electrical communication with an ANS nerve
target via a transcutaneous approach.
[0073] In some instances, a therapy delivery device can be placed
into a reproductive or GU system of a subject so that at least one
electrode thereof is in electrical communication with a
parasympathetic nerve, such as a pelvic splanchnic nerve, an
efferent parasympathetic fiber thereof, or an afferent
parasympathetic fiber thereof. In other instances, a therapy
delivery device can be placed into a reproductive or GU system of a
subject so that at least one electrode thereof is in electrical
communication with a sympathetic nerve, such as a hypogastric
nerve, a hypogastric plexus (e.g., an inferior hypogastric plexus),
a uterovaginal plexus, a T10-L1 sympathetic ganglion, a pelvic
sympathetic ganglion, a pudendal nerve, an efferent sympathetic
fiber thereof, or an afferent sympathetic fiber thereof.
[0074] After placing the therapy delivery device, the therapy
delivery device can be activated to deliver an electrical signal to
the ANS nerve target and thereby modulate the activity of the ANS
nerve target. In some instances, delivery of an electrical signal
to the ANS nerve target can completely or substantially block or
modulate the activity at the ANS nerve target. Therefore, in such
instances, delivery of an electrical signal to the ANS nerve target
can prevent a sign and/or symptom associated with an obstetric
and/or gynecological disorder from either increasing or decreasing
(as compared to a control or baseline). In other instances,
delivery of an electrical signal to the ANS nerve target can cause
a sign and/or symptom associated with an obstetric and/or
gynecological disorder to decrease (as compared to a control or
baseline). The therapy delivery device can be activated at the
onset of a sign and/or symptom associated with an obstetric and/or
gynecological disorder or, alternatively, the therapy delivery
device can be activated continuously or intermittently to reduce or
eliminate the frequency of such sign(s) and/or symptom(s).
[0075] Delivery of the electrical signal to the ANS nerve target
can affect central motor output, nerve conduction, neurotransmitter
release, synaptic transmission, and/or receptor activation. For
example, a sympathetic nerve may be electrically modulated to
alter, shift, or change sympathetic activity from a first state to
a second state, where the second state is characterized by a
decrease in sympathetic activity relative to the first state. As
discussed above, delivery of an electrical signal to the ANS nerve
target can substantially block activity of the ANS nerve target. In
some instances, delivery of the electrical signal to the ANS nerve
target can achieve a complete nerve conduction block of the ANS
nerve target for a desired period of time. In other instances,
delivery of the electrical signal to the ANS nerve target can
achieve a partial block of the ANS nerve target for a period of
time that is long enough to decrease activity therein. The degree
to which activity of the ANS nerve target is modulated can be
titrated by one skilled in the art depending, for example, upon the
nature and severity of the obstetric and/or gynecological disorder
in the subject.
[0076] In another aspect, the present disclosure can include a
method 30 (FIG. 7) for treating an obstetric and/or gynecological
disorder other than urinary incontinence in a subject. One step of
the method 30 can include providing a therapy delivery device 10
(Step 32). In one example, the therapy delivery device 10 can
comprise an electrode array configured for percutaneous
implantation in the subject. At Step 34, the therapy delivery
device 10 can be placed into direct electrical contact with an ANS
nerve target. In some instances, "direct electrical contact" can
mean that the therapy delivery device 10 is placed on or in the ANS
nerve target. In other instances, "direct electrical contact" can
mean that the therapy delivery device 10 is located adjacent or
directly adjacent (but not in physical contact with) the ANS nerve
target such that delivery of an electrical signal can modulate a
function, activity, and/or characteristic of the ANS nerve
target.
[0077] After placing the therapy delivery device 10 into direct
electrical contact with the ANS nerve target, an electrical signal
is delivered to the ANS nerve target (Step 36). The therapy signal
can be delivered in an amount and for a time sufficient to modulate
activity at the ANS nerve target and thereby treat the obstetric
and/or gynecological disorder. In one example, an electrical signal
can be delivered to a pelvic splanchnic nerve by an electrode or
electrode array that is placed directly on or in the nerve. In such
instances, an electrical signal can be delivered to the pelvic
splanchnic nerve continuously, periodically, or on an as needed
basis to increase parasympathetic activity and thereby increase
vaginal secretion production, improve orgasmic contraction of the
uterus and vagina, and/or improve sexual sensation in the
subject.
[0078] Another aspect of the method 30 includes sensing a
physiological parameter associated with the obstetric and/or
gynecological disorder (Step 38). To this end, the method 30 can
further include providing (and placing) a closed-loop therapy
delivery system 20 (as described above). In one example, the
closed-loop therapy system 20 can be configured for percutaneous
implantation in the subject. Once the system 20 is implanted, the
sensing component 22 can detect a physiological parameter of
interest, such as electrical activity of the ANS nerve target (or a
different nerve target), which may be indicative of intrinsic
sympathetic or parasympathetic tone in the subject. The detected
level(s) of electrical activity can then be relayed to the
controller 24, which determines if the detected level(s) is/are
within a normal or abnormal range or level. Where the detected
level(s) is/are within an abnormal range (e.g., at an elevated or
decreased level as compared to a control or baseline), the
controller 24 can cause the power source 16 to deliver an
electrical signal to the at least one electrode 14. The electrical
signal is then delivered to the ANS nerve target to modulate
activity thereof. While the electrical signal(s) is/are being
delivered to the ANS nerve target, the sensing component 22 can
continue to detect the level of electrical activity within the ANS
nerve target (or other nerve target). When the level of electrical
activity in the ANS nerve target is equal, or about equal to, a
normal or baseline level, the controller 24 can cease delivery of
the electrical signal(s) to the electrode 14. By continuously or
intermittently monitoring the intrinsic sympathetic or
parasympathetic tone or activity of the subject, the closed-loop
therapy delivery system 20 can automatically normalize autonomic
activity and thus effectively treat the obstetric and/or
gynecological disorder.
[0079] Another aspect of the present disclosure can include
transvascular or transluminal delivery of an electrical energy to
an ANS nerve target associated with an obstetric and/or
gynecological disorder other than urinary incontinence. Thus, in
some instances, the method 30 can include providing a therapy
delivery device configured for transvascular or transluminal
insertion and placement within the subject. For instance, a therapy
delivery device configured for intravascular placement in a subject
can include an expandable electrode as disclosed in the '331
application. In another example, a therapy delivery device can be
configured for placement in a reproductive or GU system of a
subject. In such instances, the therapy delivery device can be
configured similar or identical to a cervical cap, a cervical ring,
a pessary, a diaphragm, an intrauterine device, or any type of
percutaneous electrode and/or transvaginal system. Non-limiting
examples of vessel and lumens into which the therapy delivery
device can be inserted include vasculature supplying the female
reproductive and GU systems, such as arteries (e.g., an internal
iliac artery), veins, a vagina, a cervix, a uterus, a rectum, or
any other bodily orifice. The therapy delivery device can be
surgically inserted into the vessel or lumen via a percutaneous,
transvascular, laparoscopic, or open surgical procedure.
[0080] In one example of the present disclosure, a therapy delivery
system 20 can be inserted into the uterus of a subject (FIG.
8).
[0081] After inserting the therapy delivery device into the vessel
or lumen, the therapy delivery device can be advanced (if needed)
to an intraluminal target site so that the therapy delivery device
is in electrical communication with the ANS nerve target. In some
instances, advancement of the therapy delivery device can be done
under image guidance (e.g., fluoroscopy, CT, MRI, etc.).
Intraluminal target sites can include intravascular or intraluminal
locations at which the therapy delivery device is capable of being
positioned or implanted without damage or functional impairment to
the subject. For example, an intraluminal target site can include a
portion of a vessel or luminal wall that is innervated by (or in
electrical communication with) an ANS nerve target, such as
neurons, axons, fibers, tracts, nerves, plexus, afferent plexus
fibers, efferent plexus fibers, ganglion, pre-ganglionic fibers,
and post-ganglionic fibers of the ANS associated with an obstetric
and/or gynecological disorder.
[0082] In one example, the therapy delivery system 20 can be
positioned in a uterus of a subject (as shown in FIG. 8) so that at
least one electrode 14 of the system is in electrical communication
with an ANS nerve target, such as one or more fibers of the
inferior hypogastric plexus.
[0083] After placing the therapy delivery device, an electrical
signal can be delivered to the ANS nerve target. The therapy signal
can be delivered in an amount and for a time sufficient to modulate
activity in or at the ANS nerve target and thereby treat the
obstetric and/or gynecological disorder.
[0084] In another aspect, the method 30 can include providing a
therapy delivery device configured for placement on the skin of the
mammal. For example, a therapy delivery device can be configured
for transabdominal or transpelvic delivery of an electrical signal
to an ANS nerve target associated with an obstetric and/or
gynecological disorder. In some instances, the therapy delivery
device can be positioned about the subject, without penetrating the
skin of the subject, so that the therapy delivery device is in
electrical communication with the ANS nerve target. Non-limiting
examples of ANS nerve targets into which the therapy delivery
device can be placed into electrical communication with can include
a parasympathetic nerve, such as a pelvic splanchnic nerve, an
efferent parasympathetic fiber thereof, or an afferent
parasympathetic fiber thereof, a sympathetic nerve, such as a
hypogastric nerve, a hypogastric plexus (e.g., an inferior
hypogastric plexus), a uterovaginal plexus, a T10-L1 sympathetic
ganglion, a pelvic sympathetic ganglion, a pudendal nerve, an
efferent sympathetic fiber thereof, or an afferent sympathetic
fiber thereof.
[0085] After placing the therapy delivery device, an electrical
signal is delivered to the ANS nerve target. The therapy signal can
be delivered in an amount and for a time sufficient to modulate
activity in or at the ANS nerve target and thereby treat the
obstetric and/or gynecological disorder. It will be appreciated
that a system 20 (as described above) can be implanted via an
intravascular or intraluminal approach to enable closed-loop
treatment of an obstetric and/or gynecological disorder.
[0086] From the above description of the present disclosure, those
skilled in the art will perceive improvements, changes and
modifications. For example, nerve targets other than, or in
addition to, ANS nerve targets can include spinal tissue, such as
the spinal cord, spinal dorsal columns, ventral and dorsal spinal
cord nerves, and dorsal root ganglia. Such improvements, changes,
and modifications are within the skill of those in the art and are
intended to be covered by the appended claims. All patents, patent
applications, and publication cited herein are incorporated by
reference in their entirety.
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