INTRAUTERINE DEVICES INCLUDING LNG-IUD.PPT

Contraception
Need of Contraceptives
Anatomy of uterus
Types of contraception
Intra Uterine Devices-
Types of IUDs
Advantages of IUDs
Disadvantages of IUDs
Design of IUDs
Development of medicated IUDs
Copper bearing IUDs
Hormone releasing IUDs

1. DR.DEEPEKA.T.S.M.S(OBG).,
MRCOG(U.K).,FELLOW IN REPRODUCTIVE
MEDICINE
SENIOR RESIDENT, DEPARTMENT OF
OBSTETRICS AND GYNECOLOGY,
SNIMS.

2. CONTENTS
•Introduction
Contraception
Need of Contraceptives
Anatomy of uterus
Types of contraception
•Introduction of IUDs
•Intra Uterine Devices-
•Types of IUDs
•Advantages of IUDs
•Disadvantages of IUDs
•Design of IUDs
•Development of medicated IUDs
•Copper bearing IUDs
•Hormone releasing IUDs
•Comparative efficacy of medicated & non-medicated IUDs
•New development
•References

3. INTRODUCTIONINTRODUCTION
CONTRACEPTION:
•Contra-opposite/ prevent
•Ception- conception (union of male & female
gamates to reproduce new ones)
It is the method or technique or process
which results into temporary or permanent loss
of capability to reproduce or conceive a young
one.

4. NEED OF CONTRACEPTIVES
•1975- United state
•From approximately 27 million couples of child baring age 76.3% expressed
desire to prevent conception either temporarily or Permanently.
Method of
Contraception
% of those
served
Oral contraceptive pills26.3
Condom or Diaphragm 10.0
Intrauterine devices 6.4
Foam 2.6
Rhythm 2.2
Other 28.8

5. ANATOMY OF UTERUS
Pear shaped, thick-walled
muscular organ suspended in the
anterior wall of pelvic cavity.
Shape: triangular, flattened
antero-posteriorly.
Dimensions: (in normal state)
Length- 3 inches
Width- 2 inches
Parts-
 Fundus
Body (Uterine Cavity, Isthmus)
Cervix (Cervical canal, Internal
Os, External Os)
Openings-
Superior- fallopian tubes
Inferior- Vagina (mouth of
Uterus)

6. WALL OF UTERUS
•Endometrium – inner coat of uterine wall made up of
simple columnar epithelium, areolar connective tissue &
endometrial glands.
•Stratum Functionalis- innermost, sloughed off during
menstruation
•Stratum Basalis- permanent, gives new s. functionalis.
•Myometrium – Thick, muscular middle layer made up
of 3 layers of smooth muscles (Middle thick circular &
other two longitudinal)
•Peritoneum – External surface of uterus which
attaches uterus to pelvic cavity by ligaments

7. MENSTRUATION CYCLE
•During reproductive ages nonpregnant woman exihibit cyclic
changes in ovaries & uterus, called as Menstrual cycle.
•Typically of 28 days & divided into 4 phases-
Menstrual Phase (5 days)
Pre-ovulatory phase / Follicular phase (6-13 days)
Ovulatory phase (on 14
th
day)
Post-ovulatory phase / Leuteal phase (14-28 days)

9. KEY POINTS-
•Menstrual phase- (5 days)
•Decrease in levels of estrogen & progesterone
•Stimulates release of prostaglandins
•Produce arteriole constriction, decrease blood supply to s. functionalis
•Cells starts to die & s.functionalis sloughed off.
•Bleeding takes place for about 5 days.
•Follicular phase- ( up to 13
th
day)
•Estradiole is secreted from ovaries by secondary follicle
•Secondary follicle is converted in graffian follicle.
•Estrogen restores blood supply to endometrium & stimulates formation of
s. functionalis from s. basalis.
•S. functionalis starts to grow and become 3-4 mm thick.
•Endometrial glands increase in length & tortuosity.

10. KEY POINTS-
•Ovulation-( on 14
th
day)
•Release of oocyte outside of ovaries into fallopian tube.
•Takes place at the day of 14 of M.C. under the influence of
Leutinizing hormone (LH) & Gonadotropin releasing hormone
(GnRH)
•Released oocyte remain viable for 2 days.
•Leutial phase-(15-28 day)
•In ovary graffian follicle collapse to form corpus luteum. It
release progesterone & estrogen.
•In uterus, these hormones promote growth, thickning & coiling
of endometrium. Glycogen is secreted by glands.
•Fertilization- changes remain constant
•No fertilization- corpus luteum disappear, decrease in level of
estrogen & progesterone. Menstruation occurs.

11. INTRA-UTERINE DEVICES
DEFINITIONDEFINITION
IUD’s are medicated devices intended to release a small quantity of drug
into uterus in a sustained manner over prolonged period of time.
3 most popular methods of contraception:
Oral contraceptive pills
Condoms or diaphragms
Intrauterine device
Methods of
contraception
Pregnancies Births Deaths MBR (Mortality
Benefit Ratio)
P M Total
None 60,000 50,000 12 0.0 12.0 -
Condom or
diaphragm
13,000 10,833 2.5 00 2.5 0.664
Oral pills 100 83 0.0 3.0 3.0 0.060
IUDs 2190 1825 0.44 0.3 0.74 0.015
MBR-Deaths per 1000 births averted as related to pregnancy (P) Or Method (M)
1,00,000 fertile women data with each method

12. TYPES OF IUD’S
•NON MEDICATED:
Ring shaped iud’s made of stainless steel which haven used by 50
millions women in china .
Plastic IUDS :
Fabricated from polyethylene or polypropylene which are sold in Asia,
south Africa ,south America.
Lippes loop iud & Saf -T-coil is still available commercially in US.
•MEDICATED:
Copper bearing IUD E.g. cu 7, CuT-380
Progesterone releasing IUDS e.g., Progestasert

13. DEVELOPMENT OF IUD’S
•1920- First generation IUD’s
•Constructed from silkworm gut & flexible metal wire
Eg. Grafenberg star & Ota ring
•Decline in popularity-
 Difficulty in insertion
Need for frequent removal- pain & bleeding
Other serious complications

14. DEVELOPMENT OF IUD’S
•Then-
•Several Plastic based IUD’s of varying sizes & shapes were prepared using
inert biocompatible polymers like-
Polyethylene
Polypropylene
Ethylene-vinyl acetate copolymers
Silicon Elastomer

15. DEVELOPMENT OF IUD’S
•Modern Era- development of
•Margulies- Plastic spirals
•Lippes- Loop
•Dalkon shield IUD
•Efficacy of these IUD’s was proportional to their surface area that
is in direct contact with endometrium.
•Larger IUD’s were more effective but expulsion rate is high as
these produce-
•Endometrial Compression
•Myocardial Distention
•Uterine cramps
•Bleeding

16. DEVELOPMENT OF MEDICATED IUD’S
•Tatum & Zipper (1967) develop T- Shaped polyethylene device.
•This significantly reduce side effects
•Pregnancy rate become to 18%
•Good Uterine tolerance
•Non-medicated IUD’s-
•Act through mechanical contact with endometrium
•Size is important factor
•Large size produce irritation & other side effects
•High expulsion rate
•No improvement in contraception efficacy.
•Starting of new era-
•As this devices acts as carrier of choice for intrauterine delivery of contraceptive
agents.

17. DEVELOPMENT OF COPPER BEARING IUD’S
•1969
•Zipper et. al. reported- copper attached to an
IUD markedly enhanced the effectiveness.
•T-shaped polyethylene device wound with 30
mm
2
copper wire (Cu-T-30)
•The pregnancy rate was reduced to 5% from
18%.
•Additional clinical evaluations with larger
surface area of copper wire
•200 mm
2
– found maximum contraceptive
efficiency.

18. 18
The device is made of T
shaped polyethylene plastic.
This device uses copper wire
wound to the stem of T.
Grades as per the surface
area of wire
•Cu-T-30,
•Cu-T-200,
•Cu-T-380.

19. ANTI-FERTILITY ACTION OF COPPER
•Cytotoxic, Spermatocidal & spermato-depressive action
•Competitive inhibitor of steroid-receptor interaction.
Eg. Cupric ions –Potent inhibitor
•17 estradiol & Progesterone binding to their receptors.
•Progesterone receptors were more susceptible.
•Progestational proliferation severely inhibited.
•Cu taken up by endometrial epithelium & stromata.
•Cu conc. in uterine cytoplasm –1.4 x 10
-6
M
•Little effect on sperm mobility.

20. KINETICS OF RELEASE OF COPPER
•Continuous release by ionization & chelation process.
•Diameter of wire was reduce with time by corrosion & flacking of
metal
•Cu-7 284 deliver Cu at a rate of following expression-
Dosage (mg)=0.3 * month + 3.79
•Release 9.87 µg/day
•Linear relationship between cumulative copper release with the
duration
•Reduction in copper release due to formation of-
•Corrosion layer- of protein
•Encrustation layer- of calcium (impermeable)

21. CLINICAL EFFECTIVENESS OF CU-BEARING
IUD
Clinical effectiveness for 3- years use of Cu-T-200
Event Year 1Year 2 Year 3
Pregnancies 2.6 2.5 3.6
Expulsions 7.3 2.3 2.5
Removals
Bleeding/ pain
other medical reasons
Planning pregnancy
Other medical reasons
8.7
2.7
1.9
2.3
7.3
2.4
4.4
3.4
5.2
2.0
7.0
7.9
Termination rates 25.5 22.3 28.3
Continuation rates 74.5 77.7 71.7
*Events per 100 women

22. CU-7
•Mfg by G.D. Searle & Co.
•First device approved by US- FDA for 3 yrs of use.
•Polypropylene plastic device shaped like 7
•89 mg copper wire around vertical limb with surface area of
200 sq. mm
•Release 9.87µg/day for 40 months
•Smaller volume (0.09 cm
3
) than Cu-T (0.16 cm
3
)

- easily
inserted in nulliparous women.
•No need of cervical dilation
•Removal is painless.

23. CLINICAL EFFECTIVENESS OF CU-T AND
CU-7

24. NEW DEVELOPMENTS
•Efficacy improved when copper wire is located on
the transverse arm as in close contact with upper
portion of uterine cavity.
•Cu-T-380A (US approval -1980)
•Two collars of Cu on transverse arm
•Each collar provides additional surface are of 30 sq. mm.
•Cu-T-200C
•Seven copper sleeves of Copper on both arms
•Efficious same as Cu-T-380A
•Retain physical integrity for 15-20 yrs.
•Long acting- beneficial to population in which medical care not readily
available.

25. NEW DEVELOPMENTS
•Multiload Cu IUD: MLCu-250
•Combination of Cu-T & Dalkon Shield without central plastic
membrane.
•Blunt apex of device fits in to vault of uterine cavity without
penetrating endometrial walls
•Two teeth-studded side arms adapt to the contours of the uterine
cavity
•During uterine contraction Fundus presses against upper edge of IUD,
results in bending of arms.
•Pregnancy rate- 0.3% only
•Expulsion- 1% only
•Other Devices-
•MLCu-250,
•MLCu-325
•MLCu-250 mini

26. HORMONE RELEASING IUD’S
•Use of hormone in IUD- initiated by Doyle & Clewe
•Then Croxatto et al showed that a progestin released at a
controlled rate from a silicone capsule inserted in rabbit
uterine cavity, prevent implantation.
•1970- Scommegna & coworkers affix progesterone containing
silicone capsules to modified Lippes loop. Granted US-patent.
•Early models had high expulsion rates or side effects.
•T-shaped progesterone releasing IUD were developed,
improvement in efficacy.
•Release rate of 65 µg/day was found to produce contraception
& selected as final design of IUD.

27. HORMONE RELEASING IUD’S
ANTI-FERTILITY ACTION OF PROGESTERONE
•Secretion of secretary phase is hormonally
controlled
•Optimum amt. of estrogen &
progesterone required for proper
development.
•Implantation of blastocyst takes place on
secretary endometrium.
•Decidual reaction- after implantation
•Stromal cells enlarge & grow as
polyhedral cells rich in glycogen &
lipids. These changes takes place in
presence of implanted blastocysts.
•Once decidual reaction occurred,
implantation of blastocyst cannot take place
again.
•Endometrial hyper-maturation is
unfavorable for implantation.
•Maturation of endometrium is associated
with decidual formation which is induced by
Progesterone.

28. CLINICAL EFFICACY OF
PROGESTERONE RELEASING IUD’S
•Dependant upon daily dose of
progesterone released
Dose release per day
(µg)
Pregnancy
rate (%)
No Progesterone 22
10 5.2
25 2.7
65 1.1
120 0.6
Life table analysis of the clinical effectiveness of
Progestasert
Events Parous women Nulliparous
women
Pregnancy 1.9 2.5
Expulsions 3.1 7.5
Removals 12.3 16.4
Continuation rate 79.1 70.9

29. POTENTIAL DEVELOPMENT
•Membrane Controlled Reservoir type
D.D.Ds-
Polymeric membrane encapsulates the drug & also
controls the release.
•Two types
•Single Component System
•Multiple Component System
Cont.

30. MEMBRANE CONTROLLED RESERVOIR TYPE D.D.D
•Single Component System
•Drug in solid form encapsulated in capsule of
biocompatible polymeric material
•Polymer- Silicone elastomer / Polyethylene
•E.g. Scommegna’s silicone-based IUD
•Drug release- zero order kinetics
•Silicone elastomer widely used previously as
polymer- do not posses required tensile
strength or elastic modulus.
•To overcome drawbacks- copolymers of
Poly(dimethylsiloxone) with polycarbonate or
polyurethane were prepared.
Cont.

31. •Multi component System-
•Encapsulation of liquid medium saturated with
excess of drug in rate controlling polymeric
membrane.
•E. g. Progestasert (Alza Corp.)
•Membrane- Ethylene vinyl acetate
copolymer
•38 mg of Progesterone suspended in
silicone oil
•Release at constant rate of 65 µg/day
•Zero order release rate till drug solution
become unsaturated
•60% of loading dose in reservoir
compartment depleted during first year.
•Useful life is 1 yr.

32. POTENTIAL DEVELOPMENT
•Polymer-matrix Diffusion-Controlled
D.D.Ds-
Homogenously dispersing drug particles in a cross
linked polymeric matrix
•Two types
•Retrievable Matrix Device
•Biodegradable Matrix Device

33. POLYMER-MATRIX DIFFUSION-CONTROLLED D.D.D
•Retrievable Matrix Device-
•Retrieved or removed after termination of
treatment
•Preparation-
1)Mix drug powder with a semisolid silicone
elastomer  vulcanization at room / low temp.
2)Mix drug powder with low density polyethylene
particles  Melt & extrude
•Drug release is linearly proportional to square root
of time
Cont.

34. •Biodegradable matrix device:
•No need of retrieving at the termination of
treatment.
•Preparation –
Dissolve drug + Biodegradable polymer e.g.
Poly(lactic acid)  in common organic solvent 
Melt pressing at elevated temp. after flashing off
solvent
•Drug release is combination of polymer hydrolysis &
drug diffusion

35. POTENTIAL DEVELOPMENTS
•Sandwich-type D.D.D.
•Hybrid of polymer membrane permeation
with polymer matrix diffusion
•Thin rate controlling membrane
encapsulates a high permeable drug
dispersing matrix.
•Release rate can be improved by coating
porous support with silicone elastomer.
•E.g. Nova-T (Leiras Pharmaceuticals, Finland)
•Drug Levonorgesterel (more potent
progesterone analog)
•T shaped polyethylene support by a sandwich
type silicone based drug reservoir
•Daily release – 20 µg
•Lifetime- more than 5 yrs.

36. LNG-IUS
•What is LNG-IUS?A hormonal intrauterine device (IUD)
that releases levonorgestrel.
•Used for contraception and treatment of certain
gynecological conditions.

37. •Mechanism of Action
•How does it work?
•Thickens cervical mucus to prevent sperm passage.
•Thins the endometrial lining, reducing the likelihood of implantation.
•Suppresses ovulation in some users.
•Different Brands:Mirena
•Kyleena
•Liletta
•Skyla
•Emily

38. •Duration of Use:Ranges from 3 to 7 years, depending on the
brand.
•Benefits
•Contraceptive Effectiveness:
•Over 99% effective.
•Additional Health Benefits:
•Reduces menstrual bleeding and cramping.
•Can improve symptoms of endometriosis.
•May protect against certain gynecological cancers.

39. •Side Effects
•Common Side Effects:
•Irregular bleeding or spotting.
•Hormonal side effects: headaches, breast tenderness, mood changes.
•Serious Risks:
•Risk of pelvic inflammatory disease (PID).
•Perforation of the uterus during insertion.
•Eligibility Criteria:
•Suitable for many women, including those who have not had children.
•Not recommended for those with certain conditions (e.g., severe uterine
abnormalities).

40. POTENTIAL DEVELOPMENTS
•Estriole Releasing IUD’s
•Synthesis of estradiole dependant
uterine RNA is essential for
implantation
•Estriole binds with uterine receptors
& compete with estradiole. But
incapable of inducing uterine growth.
•It interfere with synthesis of
estradiole induced uterine RNA,
preventing implantation.
•Release rate of 1.25 µg/day
effectively inhibits development &
implantation of blastocyst.

41. COMPARATIVE EFFICACY OF
MEDICATED AND NON MEDICATED
IUDS
Use of Cu -7 group was declined due to the
problem of excessive bleeding .
Irregular bleeding was higher in Cu – 7 group
(13.4%) than in progestasert group (7.5%).
But progestasert has a limited life span of one
year which is disadvantageous as compared to
three year users life of Cu -7.
Cont.

42. Changes in enzymatic activity-
Copper bearing IUD produce significant variations in
secretary phase of the endometrium with two fold
increase in total enzyme activity.
Progesterone releasing IUD induced no (or only
small ) change in activity of lysosomal enzymes and
increased the stability of lysosomal membrane during
secretary phase.
The changes in activities and sub cellular distribution of
lysosomal enzymes induced by non medicated
placebo IUD were found to be quantitatively small
and of limited biological significance .
Cont.

43. Changes in endometrium-
The plain and copper bearing spring coil IUDs the
cyclic patterns of endometrium was preserved .
Progesterone releasing IUDs produce the
histological changes that made endometrium unsuitable
for implantation .
Mestranol releasing device produces proliferative
or hyperplastic changes in both glandular & stromal
cells with prevention of secreatory changes in
endometrium which become unreceptive to ova
Cont.

44. Changes in menstrual bleeding-
Insertion of copper bearing IUDs has resulted in
increased in menstrual blood loss and decreased in Hb
compared to pre insertion cycle
Insertion of progesterone releasing IUDs yielded
either no change or reduction in menstrual blood loss &
no significant variation in Hb conc.

45. The copper IUD prevents ectopic pregnancies.
This contraceptive is very cost effective
(inexpensive) over time.
Use of an IUD is convenient, safe & private.
The IUD may be inserted immediately following
the delivery of a baby or immediately after an
abortion.
Some studies of IUDs have shown a decreased
risk for uterine cancer. There is also some
evidence that IUDs protect against cervical
cancer.

46. DISADVANTAGES OF IUD’S
•There may be cramping, pain after insertion.
•The number of bleeding days is slightly higher than normal
•Somewhat increased menstrual cramping.
•If bleeding pattern is bothersome, patient should contact the
doctor.
•The IUD provides no protection against sexually transmitted
infections.
•There is a higher initial cost of insertion. However, after 2
years, it is the most cost-effective contraceptive method.
•The IUD must be inserted by a doctor, nurse or physician’s
assistant.