Antifertility effects of the intrauterine foreign body

CONTRACEPTION

ANTIFERTILITY

EFFECTS

OF

THE

Samir

El

Sahwi,

M.D.t

Dean

L.

Moyer,

M.D.

Section Department

of

Experimental

of

Obstetrics

University

of

of

Los Angeles, address:

FOREIGN

BODY*

Pathology and Gynecology

Southern

School

t Current

INTRAUTERINE

California

Medicine

California

Department

of

Alexandria

University,

90033

Obstetrics

and Gynecology Alexandria,

Egypt

ABSTRACT The

biological

effects

of the

a variety

of experimental

chemical

changes

marily

the

in

described in

the in

genital

of

the

IUFB,

is the presence in

of

by the

foreign

and/or

are the

underlying

cause

reaction

appears

to be the

Other

biological

phenomena

*

This

work

Accepted

changes

resulting

for

from

was supported

publication

July 1970 Vol. 2 No. 1

of

in

the

associated

15,

this

body

by a grant

June

in

from

1970

in

the

paper

It This

Ford

reactions

in all

vario-

species

polymorphonuclear that

changes

nonspecific

mechanism are most

Foundation.

of likely

pri-

been

and chemical

is probable

reaction.

the

have

and the

noted

in

and bio-

localized

effects

and quantitative

biochemical

effect.

principle

tissue

configuration

principally fluid.

been studied

body are

systemic

observation

cells,

the antifertility

foreign

foreign

used experimentally,

the uterine

as described

have

Significant

minor

the size,

species

and the

the

(IUFB)

qualitative

of

A persistent

unifying the

of

although

inflammatory

body

humans.

result

animal

design.

the endometrium

produced

tract

are the the

body

as in

the presence

D’ff I erences

tract

the experimental

studied cytes,

from

foreign

as well

reproductive

in a few species.

female

composition tions

resulting

female

intrauterine

animals

in

leukothe

cells

the uterus

foreign

IUFB

action.

secondary

body

CONTRACEPTION

INTRODUCTION During

the past decade,

in many species

as the cause of side humans spite

this

and the species the

the

effeck.

research,

literature

resulk

simultaneously

is seemingly

body

contradictory

of

has been performed

antifertility

together

an effort

action

is still

account

restrict

for

the

not

the application

clearly

the of

in

device.

In

defined,

Differences

much of

OS well

experience

to improve

IUFB’s

action

with

in some respects.

designs

and to some degree

research

the effective

in

of

the experimental

obtained,

for

experimentation

the mechanism

used and in

foreign

reasons

Animal

has been proceeding

of

intrauterine

to determine

in

the

variation

in

this

information

to humans. SPECIES

I.

DIFFERENCES:

In certain a large

oreas

scale

of

consequently,

extensive

the hope

the

that

such as mice, and pigs, The

the

foreign

have

ferrets,

as subhuman

differences

hamsters,

among these

out

applied

primates,

in

a variety

to humans.

guinea should

experimentation

impossible

of animals

chickens,

in

IUFB

on

in humans,

Experimental

pigs,

hove been used

animols

direct

is virtually

been carried

may be directly

rabbits,

body research,

mode of action

studies

results

rak,

as well

species

intmuterine

to determine

and

with onimals

cattle,

sheep

investigations.

be considered

under

the

following

items: A.

Differences The

cycle

in

physiology

ikelf.

monthly

For

Physiologic

of

reproduction

example,

shedding

cycle.

the

of

interval

is

between

fore

of animals

for

group

example the

physiologic of entry

uterus,

implantation,

the uterine

ore

these

group

(2-4). there

is a voriation

is five

longer

by an

the

in

Another

initiated

enters

(2-4)

even

ferret

the

of events

time

animals

in

mommals

the

lower

(1) and ferrets however,

changes

10 hours

to other

tion,

as rabbits

the

days

life

makes

the

rok

compared

span of

the

corpus

more

likely

in

in

have “reflex the are of

in

to be affected

with

an estrous ovulators,” the

time

rabbit

(1)

“spontaneous the estrous

to 20 days

luteum

the sexual

cycle

animals

duration

in

it

in guinea

the guinea

pig

by the sequence

IUFB.

differences

include

and stage

the duration as well

in

System:

a menstrual

e.g.,

compared Other

whereas

have

differs,

and in this

In addition,

in fundamentol

and primates

by coitus;

Reproductive

and ovulotion

ovulators” pigs.

of the

coitus

hours

which,

such

induced

and 24-36 cycle,

differs

humans

the endornetrium,

Some onimals, ovulation

i.e.,

Features

variations

of development

that

the

as the site

ovum

in

lies

and depth

the site

of the free of

in

of semen deposi-

fertilized the

implantation

ovum when

uterine of

it

cavity

be-

the ovum

in

cavity.

July 1970 Vol. 2 No. 1

CONTRACEPTION

B.

Differences

in the Anatomic

Features

In the human and monkey, an IUFB other

is medioted

hand,

usually ferrets short

have

occur

two

in the

(8),

however,

uterine

body

uterine

lumino

a bilateral effect

(13-16),

the mouse Bartke

while

found

the

that

same degree

the

extent

of

this action

by

Marston

lumina

of bilateral logical C.

closure

Differences Tissue

to the

foreign

IUFB of

in the and

body

ipsilateml

the

greater,

size

of the

may

explain

the

horn

(17,20).

why

also differs

to a lesser degree

contributes

to observed

D.

Differences Reaction

in the

more

the

susceptible

complete marked

are

rats,

that

effect

1970

is used

antifertility

as rabbits, found

in rabbits

of the

varies

In rats,

that

two

the

lack

a physio-

Bodies:

greatly

of tissue partly

the

explains

reaction IUFB

why effect

of tissues

is much

is usually

reaction

of the

among reaction

antifertility

to an

effect

generalized

to a foreign

same

species,

body

which

same experiment.

Superimposed

Secondary

for

insertion.

of the

not prone

lo such

in these

infection

Some species,

infection

effect IUFB’s

effect the

in mice,

suggests

rat which

animals

of o secondary

IUFB.

to a uterine

asepsis

that

Infection

as a

Body:

or absence

action

of

is not pres-

although

end

degree

of tissue

in the

Occurrence

to a Foreign

The presence modifies

differences

that

body

the

antifertility

between

horns in

(11).

IUFB

to Foreign

in response

The extent

two

he concluded

strains

React

(17-19).

the

the

has on incomplete

produced

two

had occurred.

as in the

rabbit

If the

two

has a bilateral

effect

cervical

of a foreign

usually

induces

The same bilateral

four

for example,

leukocytes

which

throughout

presence

small

of

of

Tissues to

is not as marked

horn

quantity

of

In rabbits,

relatively

at the

out

the

of the

concluded

communication

Capacity

to the

species.

in one

uterine

in the

reaction

confluent

effect

of the

They

and

to form a

usually

IUFB

and

determined.

(11).

anatomically

antifertility

mammalian the

are

effect

IUFB (5-7)

horn

between

of mice,

of the In mice

(12).

the

on the

cervix

a unilaterol

antifertility

is genetically Kelly

ferrets

of

rots,

As o result,

in one

and

have

strains

the

canal.

anastomosed,

only

in different and

above

communication

will

this bilateral

to the

uterine

naturol

IUFB

the effects

inserted

(9-11)

surgically

and the effect

inserted.

cervical

IUFB

in mice

are

if the

ent

was shown

July

effect rat

and

IUFB was

the

an

System:

Rrrbbits and

horns unite

into

and

cavity

cavity.

horns,

the

uterine

opens

confluent

is severed,

(10)

uterine

two

which

horns of the

entire

in which

the

are

is one uterine

the

separate horn

antifertility

separate

there

throughout

of the Reproductive

IUFB

IUFB

0s mice

and

in association

with

an

This infection

may

partially

in these

infections. animals

following

such

had a

animals. Parr,

et

localized

though

explain

species,

using

effect

are

IUFB even

Other al.,

insertion

rats,

the such

germ-free

similar

to the

(17).

Vol. 2 No. 1

3

CONTRACEPTION

I I.

EXPERIMENTAL A.

VARIATIONS:

Composition Different

materials

of

IUFB’s:

substances

have

ranged

been

stones

sutures

used primarily

in small

humans

are generally

composed

although

some

domestic

animals

steel,

IUFB’s

copper,

been used with

four

nickel,

new

tional

Lippes

silicone

loop

rate

of Shell

removal

placed

IUFB’s

with

in

Variations ments

the

IUFB

the

device

torting

its

shape.

of

IUFB

the

general,

pregnancies

the

larger

pain

which

C.

Differences

required in

the

been shown IUFB’s IUFB

in

to alter

or the spiral. the bow than

higher

the

various

coils,

1959-1966, number of

of

the of

after

the

area of

(26)

the

In loop was re-

the

IUFB

was

rates.

uterine

cavity,

and humans

the smaller

use for

one year.

of patients

in

experienced

In

(27).

the number However,

of

bleeding

and

(28).

shapes the

IUFB

effect. bows and

of

IUFB’s

sutures

number

loops

when

been used which

different

(28).

The

shapes.

In a summary

was associated

compared

of expulsions

devices

have

of

inside the uterine cavity have The most common shapes of

bow configuration

two

reasons.

Lippes of

adding in the

IUFB:

pregnancies

the other

loop tradi-

been used in animals OF the while in some experiThUS,

bow),

and even

contraceptive

In contrast, either

of

the

showed that in reduction

pregnancy

animals

spiral,

the device

of motility ik

surface

number

triangles

are rings,

use between

significantly

Shape

animals,

degree

humans

of

of

and may even be distending or disdemonstrated that the size differences

in both

occur

a greater

rings,

cylinders, and the

expulsions

have

species.

(loop,

silicone

results

stiffness

and the

have

spring,

the

in

on experience

medical

of

increased

IUFB’s

small

role

removal

In experimental include

of

whole uterus reports have

device

device,

and other

used

animals,

or catgut

data

in sulfate

IUFB’s:

different

an important

and fewer

the

of

of

a relatively

fills the Several

larger

with

Size size

in animals

play

the

the

Those

The report loop” resulted

polyethylene

the expulsion

Relative

covers

pain

density

the relative

and

others

bleeding,

in

ring.

the

used

in small

nylon

steel

surgical

and barium

(22-25).

data with

and these

to silk

presently

presented

band,

IUFB’s,

(21)

while

of silk,

“silicone

(Shell-526),

the

in

same species

the

low

a reduction

Differences

steel

as the steel

for

the

IUFB’s

steel

Tietze

these

of

womb

polyethylene

threads

report, e.g.,

in

by polyprophylene

associated

shape

IUFB’s,

where

composition

The of

of stainless

He compared

D as well

of

loop,

(20).

of mixtures

plastic,

to the polyethylene

the

8.

of

the

the camel

made of polyethylene,

lead,

(25).

in

in

animals

In a recent

types

used

used

are composed

are usually

(18,20).

and Shel I loop

4

have

from

a

the

loop

to either

was much

of

with

lower

with

(28).

July 1970 Vol. 2 No. 1

CON’I’RACEP’I’ION

D.

Time

of

Insertion

of an IUFB:

It has been shown to the estrous that

while

serted

IUFB’s

on days

on day of

cycle

animals

IUFB

is inserted date

immediately

Both

systemic IUFB,

and

General Several

reports

cally

through

the

A.

local

or Systemic

EFFECTS

effects

in

later

than

when

on days

is much

higher

when

it

show

when

in-

placed

8 and when

17

the

is inserted

at a

the

OF

IlJFB’s

reproductive

organs

have been attrib-

as follows:

Effect:

suggest

that

the effects

pituitary-ovarian

Inhibition (33)

of

of

the

IUFB

may be mediated

Those systemic

axis.

In humans,

IUFB

This

(44‘45)

hibition

with

concept

and goats

In humans,

several

lowering

the

urinary

cycles

with

of women

with

excretion

were

IUFB’s

Prolongation

of

ence of an IUFB longation found

of

the

of life

effects

which

systemi-

have been

of

similar

effect

Vol.

time,

gland

2 No.

1

IUFB

the

release

interval

when

The the

of

were

of

leads

on both

the in

to insides. effect,

by the IUFB

noted

differences

of

In

in

(47).

a group

LH

and

FSH

(103). interval: of

as well

LH

were

In rabbits, resulting

in

as an increase

interference

IUFB’s

one horn

insertion

techniques

(36).

is indicated

patterns

ovulation

in

report

may have a systemic

luteo

ofter

in

presence

in suppression

implantation

some quantitative

(37).

reflecting

was described

the

levels

bioassoy

coitus-ovulation

thus

and

in both

the

may result

of an IUFB

gonadotrophic

that

by a recent

lutea

that

the post-mating

pituitary

which

In the domestic

ovulation

to suggest

the corpora

pregnandiol

a delay

inhibits

first

presence

indicate

using

development:

IUFB

supported

corpora

span of

to be less pronounced

periods

the the

normal

causes

of the

content

was again

although

noted

the

hyperestrogenism

reports the

Ovulatory

B.

of

of

luteum

(34),

(35) was the

(46),

of development

and shortening

and corpus

buffalo

Pincus

is associated

ovulation. pigs

ovulation

and the water

ovaries.

1970

fitted

relation

rats

pregnancy

less effective

rate

rather

in in

are as follows:

fowl

July

insertion

Experiments

are

when

post-partum

and are summarized

1.

an

IUFB

(32).

to the

described

they

the expulsion

BIOLOGICAL

uted

of

in preventing

ineffective

In humans,

time (29,30).

mating,

are almost

(31).

the

results

effective

2 or 3 following

later

that

the

are completely

1 and they

pregnancy

in

may alter

of

LH

in place

the presa proin

release for

the

IH

was

longer

some adaptation to their presence (38). in sheep, and this effect could be inhibited

A by

5

CONTRACEPTiON

In heifers, the lag in ovulation time was not an injection of HCG (39). as significant with an increase occurring only in the weight of the pituitary but without an increase in pituitary LH (40). In rob with IUFB’s, no detectable effeck on pituitary function could be observed (41) which is consistent with the fact that the IUFB does not disturb the regularity of the estrous cycle in rats (42). C. Other systemic effick: The IUFB causes a prolonged or elevated oxytocin secretion (48) and some investigators have found elevated blood levels of oxytocin ;‘, IUFB users (49). Most investigators have concluded that the menstrual cycle is normal in humans which is confirmed by endometrial biopsies @O-52), urinary pregnandiol levels, visualization of corporn lutea at lapamtomy as well as histochemical studies of the ovaries (42). A recent report on vaginal smears in humans showed that the IUFB has no effect on the menstrual cycle and does not alter the cytologic examinations from the normal pattern (53). In agreement with this, in monkeys, the IUFB does not change the length of the menstrual cycle (54).

2.

Local Effects or Effects on the Genital

Tmct:

A. Effeck of the IUFB on the ovaries: In cattle (55,56), sheep (57,58) and guinea pigs (59), the presence of an IUFB in one uterine horn leads to Since this inhibition of the corpus luteum in the ovary of the same side. effect.is unilateml, it is believed that the IUFB results in increased production of a uterine luteolytic factor which is mediated locally through the utem-ovarian axis reaching the ipsilateral ovary. Several factors are and their role in association with IUFB’s known to have a luteolytic effect, should be explained, e.g., distension of the uterus (60), endometrial luteolysins (61,62), accumulation of mucopolysaccharides (63) and inflammatory reactions in the uterus (64). Pmstaglandins are normally present in the human endometrium and menstrual blood (65). Recent reports demonstrated that they have antifertility (66) and luteolytic effeck (67). This calls for the assumption that they might be potentially involved in the luteolytic effect of IUFB’s. B. Effect of IUFB’s on the oviducts: Several been described in awciation with IUFB’s.

changes in the oviducts have

(1) Inhibition of egg pick-up by the oviduct: This effect was observed In these birds, inin domestic fowls by several investigators 68,69). sertion of a loop of silk suture resulted in almost entire cessation of oviposition in spite of the fact that owlation continued at nearly the same mte as before operation (68).

6

July

1970

Vol. 2 No. 1

CONTRACEPTION

(2)

Altemtions

side

tend

calcium that

into

the

while

in oviductal

to have

the shell

IUFB

others

may

shorten

suggest

that

cells

to provide

ovum

(71).

(3)

Delay

of transport

with

been

ova

described

(I 1).

Doyle

remained

and

control

tube

side were

the

result

cal

obstruction

(4)

and

(72)

between

of ova the

inseminated the

oviduck (75),

monkeys could

IUFB side,

has

the ova

those of the was rarely as

and possibly

the

even

tubes:

mechani-

if fertilized,

implanted

tubes uterus

of syn-

ovum.

in super-ovulated

However,

menstruating

the

of a lack

the fertilized

and

of the

reaches

because

and (73)

In humans,

peristalsis

Such and

ovum acceleration

not be demonstmted

in normally

IUFB’s

investigators

(11).

through

(74).

of the

to be an artifact

IUFB stimulates

in mbbik

(‘70),

“tube-locking” with

by other

procedure

the endometrium

A

while

of

of the tubal

This effect it

junction

the ovum,

was also shown

artificially

(9).

in the mating

that

denied

on the

uterus

and does not become

chronization

in mbbik

that

IUFB

speculate

matumtion

in association

who considered

of tmnsport

for the

4 of pregnancy,

in the

Kelly

assumed that

to such an extent

through

reported

the

span of the ovum

the oviducts:

but has been

of the uterotubal

Acceleration

prematurely

through

up to day

of differences

Margulies

an effect

(9),

already

seen by Manton

secretion

in the oviduct

Margolis

in the

life

IUFB suppresses the capacity

of ova

in mice

eggs from

of the deposition

some investigators

the fertilizable sufficient

retention

impairment

In rabbits,

the

fertilized

In chickens,

indicating

(68,69).

epithelial

effect

function:

soft shells,

by other

monkeys

after

investigators natural

mating

On the other hand, there are reports (43,76), or in humans (77). which show that the rate of ectopic pregnancy is lower in women having

an IUFB

having

an

rapid

transport

in China, has been IUFB usen

the

and of ova

however, fairly

through

showed

constant

among

usually

that

the

population

:

In humans,

Tubal

tent

&

does not cause

incidence

tubes the

(72,28).

incidence

the

rapidly

involved tubal

of ectopic increasing

of study

gestation number

of

(78).

tests have

obstruction

not

evidence

A statistical

in this study

patency

mechanical

in women

as indirect

established

or spasm of the

(79).

Effects (1)

the

despite

(5)

were

observed

this may be considered

that tubes

C.

than

IUFB,

on the uterus:

Effeck

on the myometrium:

described

in association

July 1970 Vol. 2 No. 1

Several with

changes

in the myometrium

IUFB’s.

7

CONTRACEPTION

(a)

Myometrial

of an

IUFB

rats (80) occur

hypertrophy

in the

and

after

rabbits

ovariectomy

Othen

believe

tend

indicate

uterus

(b)

indicate

that

In humans,

There

with

reported

(87). cavity

opposed that

or be rapidly

inner

This may

motilit

to premature motility.

:

IUFB

btit did

not affect that

the cervix

ik

an

in vivo --

In wdmen,

the

of

contractions

IUFB’s that

mechanism

of action

animal

revealed

reported

experi’ments

the myometrium

of which

of

IUFB’s. showed

plays

in sheep fundus to

entering

the

the oviduct of a silk

IUFB’s

(89,

thread

activity

(9l),

(92).

on uterine

found

that

the

of increased

uterine

of the uterus.

They in the

a minimal

This concept that

the

groups where

(93)

adaptation

activity

without

from the

a short period

by rapid

myometrial

to increased

that

experiments

muscle

et al.

of

this might

to show this effect

effects

owm

of contractions

towards

greater

failed

produced

that

found

on the effect

Behrman,

followed

concluded

in control

studies

are variable.

insertion

Other propagated

upwards

experiments

(88)

the amplitude

IUFB than

In mk, in vitro 90). -7 on uterine contractlons

fertilized

in the presence

to bdlieve

frequency.

was more often

the

destruction

of the ova secondary

more contractions with

contact

premature

that

increased

disten-

of the

It has been

cavity

Brinsfield

the

impair

physical

The observation

expulsion

(85),

(86).

to increased

(87).

uterine

it may

separation

from thd uterus

In sheep,

showed

propagation

lead

partial

the

tone

tone

IUFB distends

that

and may undergo

mpld y from the

of an

the

result

with

muscle

do not make

be due

8

that

regarding

the muscle

of the cavity.

uterine

into

reports

iGFB has ‘led ‘some investigators

motility

of the

in myometrial

Some investigators

walls

expelled

Uterine

+ disappears

while

(80).

the sensitivity

tone.

the blastocysk

the endometrium,

presence

cause

several

it increases

the probable

tonicity

an

are

shown that

it has been

the uterine

with

it is (80).

by hydracortisone,

as the

results

IUFB does not change

sion of the uterine normal,ly

that

is due to inflammation,

inflammation which

in

can

effect

not be prevented

estrogens,

have

cavity

suggested

indicates

IUFB may increase

tone: the

others

uterine

hypertrophy

to a local

this effect

of t e IUFB on myometrial

while

(c)

that

The presence hypertrophy

(84).

Myom;trial

effect

that

rather

could

the

to circulating

hypertrophy

but

to exclude

that

effect:

myometrial

and adrenalectomy

this hypertrophy

would

caused The fact

changes

Some investigators others

cavity

(81,82).

not due to systemic but since

or uterotrophic

uterine

when

role

is supported a device

the uterine

by

was inserted

cavity,

no

July 1970 Vol. 2 No. 1

CONTRACEPTION

antifertility

effeck

were

(96).

In another

transducers

simultaneously

attached

found

that

are increased

propagation

there

the fundus

to the cervix

contractions marked found

with

vaginal that

muscular

amplitude with

activity

evolved

leading

were

found

transfer

of

days

later

monkeys

that

the principal Effects

may be listed

Histological (a)

mechanism

No

change:

to assume that

studies

cavity

at-

with

IUFB’s.

recovery

This

confirms

action

the is not

of the

changes

two

between

of the ovum in monkeys

endometrial

and

based on

in ova recoveries

of the antifertility

along

in the rat

IUFB.

associated

this

Tissue

endometrial

contamination

after infection

with

mucus following

low

with

changes

staphylococci,

horns

such

bacterial

fibrosis

infection

(99,100).

bacteria

and

inflammatory A tran-

in humans as the

virulence

in mice

have been observed

stromal

actual

occurs

The

pregnancy

of the endometrium,

insertion

the introduction

canal.

mechanical.

may prevent

In humans,

IUFB

on the

theory.

infiltration,

(83,98).

are not associated immediately

was purely

device

IUFB

led some investigators

(20) and in both

with

plasma cell

of the

This

IUFB

small

conflicts

vascularity

endocervical

(42).

edema and thickening

lymphocytosis, changes

on the effect

of the

endometritis:

include

except

horn

(9-12)

Chronic

increased

studies

no change

a relatively

the entire

which

Early

the effect

that

and ferrek

monly

were

of the uterine

as follows:

disclosed

observation

sient

im-

by body movements

Indirect

The

(95)

of

changes:

endometrium

(b)

with

transducers

recordings

no difference

on the endometrium:

IUFB’s

the

distorted

expulsion

pattern

coincides

in which

and those with

premature

showing

process.

ova to the uterine

showed

from

coordinated

and Moawad

a prelabor

which

(97),

significantly

“marker”

the control concept

surface

to be unsatisfactory.

to four

with

in monkeys

starting

seen in patients

of this

using

Behrman

Similar

Bengtsson

at a time

study

IUFB,

waves

of a loop,

to disturbance

to the uterine

contractions were

were

IUFB’s.

insertion

to the

menses (94).

high

In an experiment tached

during

bleeding

following

plantation

(2)

produced

three

result

of

from the cervical

of an IUFB

through

The bacterial

invaders

streptococci,

and diphtheroids

the

are most com(101).

During the first week, polymorphonuclear leukocytes and mononuclear cells (lymphocytes and macrophages) are present in the endometrium

-July

1970

Vol. 2 No. 1

(102).

Subsequently,

larger

quantities

of

9

CONTRACEPTION

mononuclear

cells

metrium.

months although for years

term

represent

the

of the

endometrium gral

part

affect

secondary

of the

superficial

metrial

areas

in hysterectomy (d)

thread

thread

pressing the

with

the

effect

the ability

(42).

surface, of endobeen

seen

the time

portion

of the

of insertion formation

antifertility

decidual

uterus

blocked (105).

without

findings

is not the

is not

effect.

reaction

as a contraceptive These

the

of the endometrium

&cidua

lower

formation

would

luteum

It wos shown in rats that

of IUFB’s.

of decidual

some of their

and humans.

ik

(106).

of the

function

IUFB have

retains

of decidualization

the ontifertility

cells at the

function

indentations

animals

so that

not inhibit

decidualization

on

to be an inte-

the corpus

still

IUFB may act

inhibition

inhibition

in the

but did an

and

However,

the

placed

that

occurring

of the epitheliol

inhibits

be altered

A suture hamsters,

threads

(104,105).

but

implantation

even

(102)

in both

can

prevented

infection

in vascular

of decidualization:

to decidualize of the

Flattening in contact

of uterine

cells

the plasma

IUFB’s exert

changes

and perhaps

specimens

Inhibition

insertion

use

plasma

shown

that

of the vascular

ulcerations

(98)

but

by which

these itself,

many

remain

investigators

to IUFB was suspected

(c) ,Pressure effects: erosion,

cells

(102).

mechanism

the uterus

the endo-

after

when

it has been present

stimulation

on fertility.

many

of a previous

insertion

(157),

into

disappear

endometritis”

is not usually

IUFB

emigrate

of inflammatory

Although

“chronic

tombstone

In ewes

effects

types

in the endometrium,

infection

cells

eventually

in most potients.

ore present

time

cells

the other

the diagnostic active

and also plasma

These plasma

indicate

main

In monkeys, in association

In

supthat

cause there

with

of

was no the

IUFB

(107). (e)

Endometrial

of I&B’s animals pyometra, humans, uterine in their

10

metaplasia:

in rats produced (85),

and

in one +her report,

metoplasia lshihama carcinoma

In one study,

or!

(109)

* epidennoid and

the

squamous metaplasia the

IUFB’s

carcinoma

Oppenheimer

was not detected

in any

(110)

chronic in 20%

presence of the

produced (108). stated

of the

In that

IUFB users

studies.

July

1970 Vol. 2 No. 1

CONTRACEPTION

Increased

number

of mast ceils:

that histamine

(f)

release

from the mast cells

function that

in implantation

the presence

release

results

endometrium

(115).

when

a silk

known in the

number

effect

of mast cells other

since

did

with

a reduction

an

in the

that is

was no increase (116).

compound

not prevent

when

in the

fact

There

who do not consider

that

48/80,

which

the antifertility

this compound

was given

effect

(117).

In con-

in the

normal

number

show no alteration

in association

humans showed

by the

layers,which

there

it had an antifertility

cattle

of mast cells

supported

for nidation In fact,

to rats,

this histamine

in the endometrium

of the suture.

an essential

of mast cells

in the muscle

investigators releaser,

doses,

with

effect,

histamine

in higher trast

was placed

indicate

is some indication

number

This is further

is important

is a potent

interferes

no antifertility

however,

are, histamine

IUFB

reports

may perform

There

in an increased

suture

to have

(113,114).

of an

and

In rats,

IUFB

(42),

number

and

a study

of mast cells

in

in

IUFB users (118). (9)

Polymorphonuclear

consistent mental

conditions

infiltration

may play

a role

to being Several

illary

(121)

walls

leukocyte

have

luteolytic

lysis of these

showed

that

present

inside

tion

in the

et al. along

found

the entire

the antifertility attributed

been

lumen

in the

for an

wall that length

effect

this difference

in association

effect

it

and

lysis of capthat may

lumen.

leukocytic

a silk

suture

has a generalized

to the

while around

leukocytic

was generalized along the whole and localized around the device

(96)

it must be

ln conventional

localized

from

Greenwald

lumen.

of the horn,

ovotoxic, result

and

was

in

from the actions

factors

induce

IUFB

increased

of the

IUFB to be effective,

cavity

these

(11,14,17,96,

is conceivable

uterine

with

that

of the

such as the

oxytocic

experi-

leukocytic

side effects

increase

of the most

different

to believe

shown to result

and

the uterine

uterine

(17)

or the

and/or

cells

in order

for ik

activities,

(120)

components,

spermicidal, the

tissues and

in the antifertility

biologic

action

under

a polymorphonuclear

responsible

bactericidal of

species

This has led some investigators

addition 119).

uterine

One

infiltration:

seen in all

has been

in the

IUFB’s. cells

leukocytic

phenomena

infiltmmk,

in germ-free the device. infiltration

Parr,

effect rats, They which

horn in the conventional in the germ-free rok.

rats More

recently, Parr (122) showed that leukocytic extracts have a toxic effect on rat embryos in vitro. In the ewe, a recent study showed

July

1970

Vol.

2 No.

1

that

the

IUFB %teaes

the acute

inflammatory

11

CONTRACEPTION

response of the uterus

to the presence A recent

as semen or bacteria showed

that

the

on the surface phages

of foreign cytologic

(158).

IUFB stimulates of the

may actively

substances study on humans

the accumulation

IUFB and endometrium phogocytize

of macrophages

(123).

These macro-

the spermatozoa,

and possibly

the ovo.

Biochemical (a)

chonaes:

Increased

of histamine with

histamine

IUFB’s

(124).

is considered

in the presence

This observation

the

Increased

IUFB-bearing time uterine traumo

(c)

uptake:

insertion,

oxygen

to the

uterine

horns

sulfate

-

taken

uptake

declined

from doubled

slowly

with

both

in the

The significance

by the insertion

of the

of the mild

and acute

pres-

and sheep amounts

(126, of

This effect may be it was shown in rats that the

(128).

in the

had a certain Utilizing

Bo, et al.

using an

other

found

at the site

investigators

of the endometrial IUFB

glycogen

IUFB-horn

degree

intraperitoneal

and progesterone-treated

stain,

Increased

In cattle of increased

not increased

which

35S,

of depolymerization

(d)

(42).

since

of the sulfomucopolysaccharides in ovariectomized

in patients

slices

oxygen

may be an expression

production

were

in those animals

blue

reactions

in the endometrium.

mucopolysaccharides

Alcian

and stated

and he attributed

was seen in monkeys

inflicted

to inflammation

of sodium

of decidualization

disagreed

inflammatory

but this increase

the oviducts

mucopolysaccharides

in both

that

mucopolysaccharides:

IUFB’s led

except

to the

histamine

IUFB.

Increased

secondary

lack

Endometrial

consumption

to the uterus

the

since

of decidualization

(125).

The same effect

of the

127),

oxygen

tissues and

increased ence

body

horns of rats showed

after (85).

is important

for implantation

foreign

in the amount

tissues in association

however,

of decidualization

by the

shortly

Parr,

is not needed

inhibition

(b)

an increase

inducer

and this explains of IUFB’s.

histamine

caused

In rats.,

to be the physiologic

in rats (113,114), that

levels:

was seen in the endometrial

that

there

of the

of infection injections is an increase

foreign

rats (130).

concluded ground

that

body Using

the

a failure

substance

occurred

(132,133).

accumulation:

In rots,

the presence

of an

IUFB results in glycogen accumulation at the basal layers of the endometrium early in pregnancy and is considered to indicate that the secretion effect

12

may be defective

was not seen

in either

in

IUFB-bearing

rabbits

(131)

horns (129).

or humans

This

(132,133).

July 1970 Vol. 2 No. 1

CON’I’RACEP’I‘IOK

(e)

Retardation

pholipid

ratio

in the

increase

at the time

there

occurs

mtio

in the endometrium.

in

IUFB

an increase

users

matumtion (f)

Increased the

enzymes) is located

in

to be related

(135).

A similar

(s)

Changes

that

an IUFB

estrogens.

increase

increased

some of the actions

of

in menstrual

blood

Several

of the endometrium: e .g .

the sensitivity

, estrogen

implantation

and progesterone,

in

acts

it

showed

tract

in a manner

is possible

This

rats which

of the genital

histamine

of the

(B4,130,137-139).

experiments

of estrogens,

was

of endometrium

(136)

affect

the sensitivity since

of rat in blood

fluid

infiltration

IUFB’s

stimuli,

by seveml

However,

(lysosomal

washings

in uterine

leukocytic

IUFB’s

incapable

is supported

phosphatase

in the uterine

sensitivity

that

to-hormonal it

to be delayed

It has been observed

and acid

in B-glucumnidase

in hormonal

rendering

concept

activity:

in women with

have suggested

endometrium thus

the

to the

increase

has been reported

was found

most of the B-glucuronidase

leukocytes,

thought

ovulation,

to phospholipid

(134).

increased

Since

to phoswith

as a lag in the biochemical

of B-glucuronidase

IlJFB’s.

Coincident

increase

beta glucuronidase

are markedly

with

studies

This

and was interpreted

levels

nonphospholipid

in the nonphospholipid

of the endometrium

that horns

of the

of ovulation:

that

to

similar

this

to

response

may be caused by histamine. Changes e.g.,

in the sensitivity

increased

by investigators, estrogen.

tion

whether tion (3) that

the

study

.but

further

the observation

that

injection

horn into an untreated horn itself (142). The following

July

as a major

that

of

as defined

cause of

at the time

are required

system

environment:

belief

than

of

implanta-

to determine

is pathognomonic

of ovula-

investigators.

causes the uterine This

these

studies

channel

(42,142,143).

for

to progesterone,

of the endometrium

was suggested

by these

on uterine

IUFB

tract

have also been described

to the blastocyst

the nucleolar

as suggested

Effects

matumtion

non-receptivity

(140,141),

sensitivity,

but appear to be more controversial

Asynchronous

in an ultrastructural uterine

of the genital

or decreased

A number

fluid

was substantiated of uterine

of

to be hostile fluid

investigators

believe

to the blastocvsts

in animal collected

I

experiments

by

from an IUFB-

produced the same effect as the device changes have been described to account

characteristics:

1970 Vol. 2 No.

1

13

CONTRACEPTION

(a)

increase

et al. of

have

lysing

percent

of fibrinolytic shown that

fibrin

(144). greater

monkeys

an

(b)

Increase fluid

resulting

undoubtedly

(145

147).

(c)

Increase

The urea blood, into

the

urea

in urea

is the urea

total are

of the preimplantation

(e)

Changes

uterine

fluid

growth might that

the

steel

intmuterine fluid

(150).

in the

Effect

of IWB’s

carbohydmte

this pH.

Studies

difference pH during

IUFB and non-IUFB

ewes

showed en elevated longed progestagen

karyopyknotic effect (151).

(63).

of

increases

in

of preimplan-

non-protein

nitrogen

and

The carbohy-

levels:

A reduction

fluid:

the various

who

in the

however,

in pH between

that

the

the

human

use stainless composition

did

animal

of

not reveal

IUFB and

the control

and animal

findings

phases of the menstrual

of comparing

IUFB

one study suggested

in women

between

an alkaline

and blastocyst

to suspect

In humans,

nutrition

(147).

In rats,

function

on rats,

for the

in concentration

development

pH is lowered

Cervix

denaturation

to be essential

for spermatozoa

There is little information regarding presence of an IUFB. Sperm penetration

14

in the

by

infiltrating

to the viability

increase

blastocyst

the difficulty

on the

configuration,

believed

The discrepancy

uterine

emphasizes

to cause

rings due to a change

(149).

significant

horn

lysis of cells

has led some investigators

by altering

concentration:

is known

in the pH of uterine

contraceptive

uterine any

which act

of

of

concentra-

is not contributed

blastocysts.

impair

is vital

strength

(147).

fluid

may significantly

The

ionic

structural An

(148).

in the

in uterine

cavity

from those

-on the blastocysts

nitrogen

fluid

result

in the

effect

non-protein

their

noted

Reduction

dmtes

clots

in the protein

may be detrimental

blastocysts

(d)

and

Since

has also been

the mean

concentrations:

change

a dehydrating

by disrupting

concentration

tation

and the

in the uterine

fluid.

IUFB,

lysis in fibrin

from increases

but presumably

proteins

an

Shaw,

is capable

in the endometrial

and globulin

have

present

with

fluid:

fluid

IUFB.

in albumin

tions

endometrial

placed

than

in the viscosity

uterine

D.

clot

was significantly

increase

of endometrial

monkey

In monkeys

lysis of a fibrin without

activity

the

and human

cycle

studies.

Vagina: changes in the of the cervical

cervix and vagina in the mucus occurred in both

A study of the vaginal changes in IUFB users index curve with an early peak and a proThese changes

were

assumed to be the

July

1970

result

Vol. 2 No. 1

CONTRACEPTION

of a loco1 tissue

reaction

In the same study, in

the group

reported

of women

a high repork

in

incidence

the

in

the

Pincus

Jopan

report

study

incidence On

IUFB’s.

have

smears

might

have

been

from

oltered

of bacterial

the other

smears

demonstrated

has suggested

than

hand,

Pincus

in association that

there

between

the

that

high

the

due to the

ovarian

vaginitis

function.

was noted

and collaborators

with

IUFB’s

(111,152).

is no significant

IUFB

users

and a control

incidence

presence

difference group

of suspicious

of active

smears

histiocytes

from

(53).

Effect

of

IUFB’s

on Saerm:

pnsc.:

Studies

rt~ lzation

Quantitative sperm

decreased in the

non-IUFB IUFB

(10 days)

uterus

reaching

(154)

the site

tive

study

(2)

Sperm

their

own

believed (72).

has yet

fertilization

been

sperm

is inhibited

might

have

after

the

numbers

(63).

cells

were

compored

fallopian

more to the

alterations

done shortly

period

of

their but

in

after presence

spermatozoa

tubes,

of

In

found

may produce

do not prevent

In rabbik,

ligoting

(155).

both

This

the same effect

in some animal

a long

the

when

IUFB’s

sperm

from

no quantita-

performed.

capacitation: fluid

in

that

on humans

IUFB’s

that

(11,12,20).

cavities

sperm

that

and ofter

that

showed

of ewes

Studies

(153)

showed

of

horns

showed

device

and oviductal

decapacitoted

Morgulies

and ferrets by the

in ewes

uterine

containing

in humans

insertion

the

mice

aft&ted

performed the

that

IUFB

horns.

transport

sperm

in

it was noted

frequently

on rats,

are not

sperm studies

were

addition,

in

rather

the

of suspicious

of suspicious

One

the uterus E.

from

device in

using

incidence

Recent (53,112).

to the

on increase

uterine and the

led some workers

(70);

experiments

the ends,

however,

horns

are distended

ability

by

to capacitate

to assume

fertilization

thot

is not

the

IUFB

inhibited

(156).

CONCLUSIONS Tissue occurring

changes primarily

were

noted

IUFB

appear

from

the

the experimental

foreign

body,

foreign

during

the

the animal

last

which

appears of

secondarily,

to be universal

inflammatory mononuclear

July 1970 Vol. 2 No. 1

cells cells)

to all in

biological both these

not

species

the

have

although

in

in

tract

studied

to t.~.

is the and/or

composition

and the

variation

resulting

from

and in effeck

However,

polymorphonuclear endometrium

reactions

effects humans

as

effects

ond chemical

biological all.

been described systemic

used experimentally,

usually

(primarily

IUFB

reproductive

numerous Some of

but

the tract

configumtion

size,

been studied

decade.

in one or more species

of

female

species

The

hove

noted

numbers

The on the

designs.

action

reproductive

species.

body

the

female

to be dependent

in

animals

the

in several

of

intrauterine

resulting in

have

been

one observation

presence

of

leukocytes uterine

the

experimental

increased and,

fluid.

It is

15

CONTRACEPTION

likely directly

that

the unifying

related

degradation

products

the endometrium. this paper

16

result

principle

to the quality as well

It is likely as secondary

of the

antifertility

and quantity

of the

as the associated that

effect

biochemical

mony of the biological

phenomena

to the

of the

inflammatory

inflammatory

IUFB

cells

changes effects cell

is

and their

occurring summarized

in in

reaction.

July 1970 Vol. 2 No. 1

CONTRACEPTION

REFERENCES

1.

Walton, Exp.

2.

A.

A. :

polecat

Exp.

The formation, hybrids,

on ovulation

rupture

and closure

and some associated

Chang,

J.

and Walton,

A.:

Biol.

11:307,

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17

CONTRACEPTION

15.

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processes

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18

‘Report

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July 1970 Vol. 2 No. 1

.‘I

CONTRACEPTION

29.

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K.L.

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introcervical 30.

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33.

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N.C.,

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of the pituitary

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1953.

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52:149, K .P.

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1970.

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Amsterdam,

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R. and Bitman,

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19

CONTRACEPTION

43.

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Oxytocin

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55.

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56.

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20

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57.

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26:14,

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of ovarian

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B.B.

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37:103,

J.

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42:614,

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W.J.:

W.J.:

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Biol.

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21

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72.

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L.C .:

24:515,

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Chang,

M.C.

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74.

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by

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Jr.

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the

W.A.

Kar,

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776,

393,

82.

84.

Siegler,

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action

1969.

of intm-uterine

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Conf.

Plan.

Planned

Parent.

Parenthood

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pregnancy

mechanism

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Erdos,

Ledger,

W.J.

Israel,

S.J.:

T.,

Fed.,

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101:

C.R.,

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H.J.:

J .A .M.A.

Brown-Grant,

K.

:

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C.:

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207:1378,

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body on the genital

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1966.

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Gramss,

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traceptive

22

force

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Tubal

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23

CONTRACEPTION

100.

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24

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Anat.

morphology

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of an intrauterine

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on endometrial

Congress

Effect

Int.

F.G., devices

October

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Dettmann,

Conf.,

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CONTRACEPTION

113.

Shelesnyok, plantation

114. 115.

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Some Rec.

Shelesnyak, Mothur, vice

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M.C.: in the rat. M.C

V.S.

A.J.,

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Banik,

U.,

Reprod. 118.

Jap. 119.

S.,

Craig,

J.M.:

Hirsch,

Ganoff, vitro

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123.

Parr,

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Histamine

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re-

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The effect

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and deciduomata

from polymorphonuclear

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a toxic l:l,

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in

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of leukocyte

extracts

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The cytology

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contmceptive

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antihistamines.

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Vascular

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July

1970

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2 No.

1

25

CONTRACEPTION

128.

129.

Sudha,

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Ind.

Med.

J.

Parr,

Chakravarti,

Glycogen

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contraceptive 130.

Bo, W.J.,

Moore,

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Kar,

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The effect

Chabon,

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Ind.

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Effect

and function.

body on

Steril.

contraceptive

uterus.

I. and Stone, structure

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of a foreign

of the uterus.

M.L.,

Sedlis,

A.

Fe&l.

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15:618,

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Response of human endometrial

lipid

56:X%,

Biol.

on his-

3:141,

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of intrauterine

Amer.

J.

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The intrauterine

to the intrauterine

ring for

device

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control.

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P.J.

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Fettil.

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tological

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the glycogen 351,

R.N.

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Collard,

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S.G.

Wynn, metrium.

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Wynn,

R.M.:

8:45,

26

156:1508,

and Sawaragi,

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Science R.M.

Metabolism

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H .S.:

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CONTRACEPTION

142.

Batta, fluid

S.K.

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in rats with

The anti-implantation

R.R.:

an intra-uterine

silk

thread

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property J.

l&prod.

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16:145,

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Marston, vice

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Shaw,

S.T.,

145.

Kar,

A.B.:

Kar,

A.B.,

S.R.:

1964,

No.

A.D.,

Effect

86,

Goel,

fluid.

Kar,

Engineer,

A.D.,

A.B.,

Sedlis,

contraceptive

Gynec. A.,

p.

steel

Marcus,

S.L.:

Fibrin

prateolysis

intrauterine

Pincus,

York,

Garcia,

device.

A.,

Proceedings

Excerpta

Medica

S.R.:

of

Foundation

Effect

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rats to estrogen.

Congress

Series

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P.K.

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in the presence

963,

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July 1970 Vol. 2 No. 1

Obstet.

Dasgupta,

P.R.

device

Gynec.

P.R. 1968.

A.K.:

of uterine

ond

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101:966,

and Srivastava,

on urea content

M.L.:

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24:878,

Stone,

D.

Effect

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New

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86,

p. 235. S.:

H.:

body on the pH of uterine

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E.:

Acta

Cytohormonol

Cytol.

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Proceedings

Medica

Sperm migration

of intrauterine

using

1967.

1964.

devices. Excerpta

pH of women

30:114,

and Connefl,

and Rocamora,

intra-uterine

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tract

V.P.,

contraceptive

forms of contraception.

C-R.

using plastic 2-3,

J.

Dasgupta,

Gynec.

Sedlis,

Kamboi,

of an intrauterine

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using various

October

Amer.

E. and Stone,

The effect

J.V.,

G.,

in the

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contraceptive

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Reyniak,

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Reprod.

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of an intra-uterine

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Engineer,

in patients 152.

D.L.:

and without

in intrauterine

2-3,

Series

composition

fluid 151.

with

studies

October

Congress

4:159,

Obstet.

150.

Effect

(In Press).

Conf.,

an intrauterine

149.

and Moyer,

Variations

Experimental

Chowdhury,

148.

P.:

in the rhesus monkey.

Kamboj, V.P. and Chowdhury, Kar, A.B., Goswami, A., foreign body on the response of the uterus of ovariectomized Steroids

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Nature

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transport

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monkey

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Intemationol

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Obstet.

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27

CONTRACEPTION

154.

Morgenstern, Noyes,

L.L.,

R.W.:

in the chronic

Orgebin-Crist,

Observations presence

M.C

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Clewe,

on spermatozoa

of intrauterine

T.H .,

Bonney,

W.A.

and

in the human uterus and oviducts

devices.

Amer.

J. Obstet.

Gynec.

96:

114, 1966. 155.

Soupart, layed

156.

P. and Orgebin-Crist,

in vivo by double

Eckstein,

: Mechanism

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Cooper,

B.S.,

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devices

J. 158.

Obstet.

Cooper, leukocytic J.

28

Obstet.

Hawk,

Gynec. B.S.

and

Brit.

106:93, Hawk,

function

106:98,

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of rabbit

J. Exp.

26:52,

spermatozoa

Zool.

163:3ll,

contraceptive

de1966.

devices

in

1970.

by ovarian

hormones

in the endometrium

and intra-

of the ewe.

Amer.

1970. H.W.:

responses and bactericidal Gynec.

horn.

of intro-uterine Med.

Stimulation

H.W.:

of vascular

Capacitation

of uterine

of action

women and other mammals. 157.

M.C.:

ligation

Stimulation activity

by intrauterine in the sheep

devices uterus.

of Amer.

1970.

July

1970

Vol. 2 No. 1