Contraception Updates

Amr Nadim, MDProfessor of Obstetrics & Gynecology

Ain Shams Faculty of MedicineMaternity & Women’s Hospital

Definition

• Contraception (birth control) prevents pregnancy by interfering with the normal process of ovulation, fertilization, and implantation.

• There are different kinds of birth control that act at different points in the process.

• Unfortunately, there is no perfect form of birth control. – Only abstinence can protect against unwanted

pregnancy with 100% reliability.

Contraceptive OptionsHormonal Methods

•Progestin Only Injectables / Oral Contraceptives

•Combined Injectable / Oral Contraceptives

•Intrauterine Systems

•Implants

•Patches

•Vaginal rings

Contraceptive OptionsNon-Hormonal Methods

IUD

Barriers

NFP methods

Contraceptive OptionsSterilization Methods

Tubal Occlusion

Tubal ligation

Vas Ligation

What are the concerns of any couple What are the concerns of any couple about the method of family planning about the method of family planning they need?they need?

• When correctly used, all methods

are more effective than no method.

• Safe methods are those without

serious complications.

• Clients should be given their

preferred (or desired) method if it is

not medically contraindicated.

Risk Misperception & Patients

“…incorrect perceptions of excess risk of contraceptive products may lead women to use them less than effectively or not at all.”

Gardner J, Miller L. J Womens Health. 2005

Misperceptions Affect Health Decisions• 1995 – Warning: possible increased risk of

VTE among users of 3rd generation OCs

• Many women discontinued OC use

• Prescribing patterns changed

• Pregnancy and abortion numbers increased

• Deemed a “non-epidemic”

Chasen-Taber L. N Engl J Med. 2001. Drife L. Drug Saf. 2002. Furedi A. Lancet. 1998. Spitzer WO. Hum Reprod. 1997.

Definition of Risk

“The possibility of suffering

harm or loss.”The American Heritage Dictionary

of the English Language

Risk Calculations

Hennekens CH. Epidemiology in Medicine. 1987.

CausalityWeigh

pros and cons

Degree towhich

attributable

Associations vs. Causality• An association does not always mean exposure

caused outcome• It could be due to random chance or bias• Making a decision about causality requires that a

number of criteria be met, including (among others):– Strength of the association (as measured by relative risk,

for example)– Consistency of the association over multiple studies– Temporal sequence (exposure precedes outcome)

• The point is that a weak association found in a single study should not be taken as concrete evidence of a cause-and-effect relationship.

Grimes DA. Lancet. 2002.

Commonly Used Risk Calculations

Absoluterisk

Absoluterisk

reduction

Relativerisk

Absolute Risk

NY Academy of Medicine. 2005. Misselbrook D. Fam Practice. 2002.

• The percentage of people in a group who experience a discrete event

Number of People With Event

Total # of People At Risk

Example of Absolute Risk

• Of 100,000 women on 3rd generation OCs, 30 will develop venous thromboembolism (VTE) per year

Absolute risk

30 per 100,000 woman-years

Mills A. Hum Reprod. 1997.

Absolute Risk Reduction

NY Academy of Medicine. 2005.

• The difference in risk of the outcome between those exposed and those not exposed

• Risk in exposed – risk in unexposed

• Reflects the reduction in risk associated with an intervention

Example of Absolute Risk Reduction• Of 100,000 women on 2nd generation OCs,

15 will develop VTE per year

Absolute risk

15 per 100,000 woman-years

Absolute riskreduction

30 - 15 =15 per 100,000 woman-years

Mills A. Hum Reprod. 1997.

Attributable Risk

• Similar to absolute risk reduction

• Attributable risk is:– The difference in risk of the outcome

between those exposed and those not exposed

– Risk in exposed – rate in unexposed

• Reflects degree of risk associated with exposure

BMJ Collections. 2006.

Relative Risk

• Used to identify an association between exposure and outcome

Grimes DA. Lancet. 2002. Hennekens CH. Epidemiology in Medicine. 1987.

Exposure Outcome

Odds Ratio

• Used to identify an association between exposure and outcome in a case-control study

• Similar to relative risk

Hennekens CH. Epidemiology in Medicine. 1987.

Exposure Outcome

Relative Risk: Example 1

Absolute risk

3rd Generation OCs

30 per 100,000 woman-years

Absolute risk

2nd Generation OCs

15 per 100,000 woman-years

Relative risk = 30 / 15 = 2

Mills A. Hum Reprod. 1997.

Interpreting Relative Risk

Relative risk = 1

No increase in risk in exposed group

compared with unexposed group

Relative risk > 1

Increased risk in exposed group

Relative risk < 1

Decreased risk in exposed group

Hennekens CH. Epidemiology in Medicine. 1987.

Risk & Health Decisions

“Decisions about risk are not technical,but value decisions.”

Baker B. In: Risk Communication and Public Health. 1999.

Relative Risk: Example 2

Relative risk = 20 / 10 = 2

Risk of cesarean delivery with elective induction of labor

20%

Risk of cesarean delivery with spontaneous onset of labor

10%

Relative risk with induction:20% 10%

Grimes DA. Lancet. 2002.

more…

Relative Risk: Example 2 (continued)

• Interpretation:

Grimes DA. Lancet. 2002.

more…

“The risk of cesarean delivery with elective induction of labor is 2 times that associated with spontaneous labor.”

“The risk is twice as high.”

Or, alternatively stated:

Relative Risk: Example 2 (continued)

Graph of relative risk of 2

0.1

1

10

Re

lativ

e r

isk

(log

sca

le) Increased risk

Decreased risk

Grimes DA. Lancet. 2002.

Relative Risk: Example 3

= 0.5

Rate with prophylactic antibiotics

6%

Rate without prophylactic antibiotics:

12%

Relative risk: 6% 12%

Relative risk = 6 / 12 = 0.5

Grimes DA. Lancet. 2002.

more…

Relative Risk: Example 3 (continued)

Graph of relative risk of 0.5

0.1

1

10

Re

lativ

e r

isk

(log

sca

le) Increased risk

Decreased risk

Grimes DA. Lancet. 2002.

Comparing Relative Risks of 2 and 0.5

Zone of increased risk

Zone of reduced risk

2

0.5

0.1

1

10

Re

lativ

e R

isk

(lo

g s

cale

)

Grimes DA. Lancet. 2002.

Comparative Risks of VTE

Shulman LP. J Reprod Med. 2003. Chang J. In: Surveillance Summaries. 2003.

Inci

den

ce o

f VT

E p

er

100

,000

wo

ma

n-ye

ars

0

20

40

60

Pregnancy High-dose OC

Low-dose OC

General Population

Causes of Risk Misperception about Hormonal Contraceptives

Weighing the Risks & Benefits

Burkman R. Am J Obstet Gynecol. 2004.

Decision Aid for Risk Communication

O’Connor A, Legare F, Stacey D. BMJ. 2003.

Clarify situation

Provide information

Clarify patient’s values

Screen for implementation problems

A Final Thought

“Two times a very rare event is still a very rare event.”

David Grimes, MD2006

WHO Eligibility Criteria for Contraceptive UseWHO Eligibility Criteria for Contraceptive UseWHO Eligibility Criteria for Contraceptive UseWHO Eligibility Criteria for Contraceptive Use

CategoryCategoryDescriptionDescriptionWhen clinical When clinical judgment is judgment is

availableavailable

When clinical When clinical judgment is judgment is

limitedlimited

11No restriction for No restriction for

use use Use the method under Use the method under

any circumstances any circumstances Use the methodUse the method

22Benefits generally Benefits generally

outweigh risks outweigh risks Generally use the Generally use the

method method

33Risks generally Risks generally

outweigh benefitsoutweigh benefits

Use of method not Use of method not usually recommended, usually recommended, unless other methods unless other methods

are not are not available/acceptable available/acceptable

Do not use the Do not use the methodmethod

44Unacceptable Unacceptable

health riskhealth riskMethod not to be used Method not to be used

Source: WHO, 2004.Source: WHO, 2004.

New Methods

Single-rod Implant

LNG IUS

PatchVaginal Ring

Monthly Injectable

Pill Generations• High court ruling 2002 –failed to show increase of VTE

odds ratio between 3rd and 2nd generation• Medicines Committee Advice 1999

– The absolute risk of VTE taking third generation pills is very small & is much less than the risk in pregnancy.

– There is a small excess risk of 10 cases of VTE per 100,000 women compared with those taking second generation pill.

• Provided women are fully informed of the small risks & do not have medical contraindications, it should be a matter of clinical judgement and personal choice which COC is prescribed.

1st, 2nd and 3rd Generation Progestins

• The terms "new', "newer, "second generation" and "third generation" do not accurately describe OC progestins.

• Progestins are best classified into – Gonanes (Levonorgestrel, desogestrel, gestodene and

norgestimate)– Estranes (Norethindrone, Lynestrenol)

• Estranes and gonanes differ in :– Bioavailability

• The greater the posthepatic bioavailability , the lower is the dose needed to be used.

– Only norethindrone, gestodene and levonorgetrel are active as such. Other progestins are prodrugs and so need to be given in higher dosages to compensate for hepatic biotransformation.

1st, 2nd and 3rd Generation Progestins– Serum half-lives

• Long serum half life is associated with more consistent cycle control

and greater contraceptive protection in the event of missed pills.

• The shortest half life is that of norethindrone (7 hours) and the

longest is that of levonorgestrel (15 hours).

– Relative binding affinity to the progesterone receptors.• Greater relative binding affinity means that a smaller dose is needed

for a consistent clinical effect to be achieved. Among OC progestin,

levonorgestrel has the highest relative binding affinity followed by the

active metabolite of the desogestrel.

• Strong Evidence suggests that all progestins effectively reduce free

testosterone levels by 40-50% in average women.

1st, 2nd and 3rd Generation Progestins

– All OCs inhibit the 5 -reductase in the skin

resulting in lower levels of active

dihydrotestosterone with subsequent better

control of acne and hirsutism.

There is no evidence to support that one class

of progestin is superior to another with

regard to androgen related conditions.

Anti-androgenic ProgestogensCyproterone Acetate-(in Diane/ Brenda)

• Anti-androgen with progestogenic qualities

• Binds strongly to androgen receptors and prevents action of testosterone

• Major indication is in those with significant hirsutism or acne

• Takes 3 months for effect on acne and 6 months for effect on hirsuitism

• Can accelerate effect by adding in extra Androcur initially

Anti-androgenic Progestogens Drosperinone-(in Yasmin)

• Yasmin-Ethinyloestradiol 30 µg and drospirenone 3mg

• Drosperinone related to Spironolactone– Has mild diuretic effects-

less fluid retention– Antiandrogenic effects

• Weight Loss ?- mainly due to fluid loss-0.5 kg over 12 months

New Oral Contraceptives

• Yasmin – 30mcg ethinylestradiol +3mg drosperinone

• Cerazette – 75 mcg desogestrel

• ovulation inhibition • efficacy same as for COCs• ?12 hours leeway but current licence 3 hours as other POPs• safe if migraine with aura or risk of VTE• trend towards more amenorrhoea and less bleeding with

time• no effect on lactation

Cerazette

• A 75 mg POP containing desogestrel• Assumed to inhibit ovulation

Emergency Contraception• WHO Study in 1996-7

compared the older Yuzpe method using high dose Combined Pills (Nordiol 2 X 2) with high dose progestogen-only regime(0.75 mgs LNG X2)

• The POP regime was found to be more effective with less side effects.

• Yuzpe and the WHO trial both used divided doses (12 hours), up to 72 hours after USI

Emergency Contraception - Effectiveness

LNG YUZPEPregnancy rate 1.1% 3.2%

Efficacy rate(pregs.prevent-ed vrs pregs.expected)

85% 76%

Emergency Contraception

• Both methods are more effective the earlier they are commenced after USI

• Less nausea on progestogen only method- 2% vrs 22%

• No need for routine anti-emetics

Emergency Contraception

• Microlut +25 pills where cost or confidentiality an issue

• 2 pill progestogen-only ECP: Postinor 2

Hot off the Presses!

• Lancet article published December 2002 showed– POP emergency contraception retained some

effectiveness up to 120 hours (5 days) after unprotected sex

– A single stat dose of 1.5 mgs seemed to be slightly more effective than the divided dose

Von Hertzen H et al. Lancet 2002; 360:1803-10

• FPA Health has now changed its Clinical Protocols on ECP to reflect this study

• TGA recently approved ECP as a pharmacist-supplied item

Absorption of oral preparations• hormones are absorbed from the upper small intestine.

• peak plasma levels reached within 2 hours

• vomiting within 2 hours of ingestion reduces the amount of hormones absorbed, & missed pill instructions should be followed during the attack and for the next 7 days.

• in the case of combined oral contraception, the pill free interval should be omitted if less than 7 pills remain in the packet.

• diarrhoea (unless severe) is unlikely to affect drug levels; there are no studies showing any pharmacological basis for failure.

Metabolism in the liver• Drugs which increase metabolism of EE and

progestogens, during and up to one month after stopping treatment.

– anticonvulsants (with the exception of sodium valproate, clobazam, vigabactrin, gabapentin and lamotrigine),

– griseofulvin,

– barbiturates,

– ritonovir (and possibly other protease inhibitors amprenavir, indinavir, lopinavir, nelfinavir, and saquinavir)

Use of COC and liver enzyme inducing drugs

• COC users need at least 50mcg of EE to ensure contraceptive action

• efficacy may be further increased by tricycling, and/or decreasing the pill free interval

• common practice (for which there is no evidence) to consider the absence of break through bleeding as a marker of sufficient contraceptive cover in this situation.

Use of progestogens and liver enzyme inducing drugs• POP users should switch to injectables or another form

of contraception• IUS no evidence of interaction

– most of its progestogenic effect is directly on the endometrium with little absorption

• EHC experts suggest that the dose is increased by 50% – levonorgestrel 0.75 mg 2 + 1 tablets or 3 tablets stat

• injectable progestogen methods are often given 2 weeks early– data sheet for Depo-Provera states that no

adjustment is needed

Powerful enzyme inducing drugs• Rifampicin and rifabutin are such powerful enzyme

inducers that even short courses of 2 days of the former – (used as prophylaxis in close contacts of cases of

Neisseria meningitis) reduce contraceptive efficacy for a month.

• Longer courses may have an interactive effect for up to 2 months after stopping.

• Oral contraceptive methods should not be relied on during this time.

• The same principles should apply to injectables, implants and IUS

Broad spectrum antibiotics • EE is excreted into the bile; and reabsorbed into the

circulation from the colon • broad-spectrum antibiotics (mainly ampicillin and

tetracycline)affect these bacteria • accepted UK practice that COC used alone is unreliable

while taking short courses of penicillins and tetracyclines and for 7 days after stopping; the pill free interval should be omitted if less than 7 pills remain in the pack– when the drug is continued beyond 2 weeks, the gut flora appear

to become resistant, allowing a return to reabsorption of EE.

• effectiveness of the POP, progestogen-only emergency contraception, injectables, implants and IUS are not affected by broad spectrum antibiotics.

The only drugs known to have a clinicallysignificant impact on contraceptive efficacy

• rifampicin and rifamycin,

• griseofulvin,

• some anticonvulsants

– topiramate,

– barbiturates,

– carbamazepine,

– primidone

• ritonovir,

• and in some women short courses of tetracyclines and ampicillin.

Why Another Contraceptive Method?

CHOICE CHOICE

Varney SJ. Pharmacoeconomics. 2004

Why Implantable Contraception?

• Long duration of action• Not patient dependent• Continuous steady state steroid levels• Avoidance of first-pass effect from GI

absorption and hepatic metabolism• High bioavailability

Why is it among the most effective?

“Implants constitute one of the safest and most effective forms of contraception that exist.”

World Health Organization. 2003

WHO, 2003

Unmet Need for Contraceptive Method

Highly effective

SafeNo daily

motivationRapidly

reversible

Implant Systems6-Rod

Norplant2-Rod Jadelle

1-Rod Implanon

Contraceptive Implant Track Record

1966Implant R&D 

Population Council. www.popcouncil.orgOrganon Data on File

1968Ongoing clinical trails

1985 WHO acceptance

1990Norplant launch US

1993Norplant launch UK

more…

Contraceptive Implant Track Record (continued)

Population Council. www.popcouncil.orgOrganon Data on File

1998 Implanon enters international market

2002 Jadelle approved but not marketed in US

2002 Norplant removed from US

2006 FDA approves Implanon

Subdermal Implant

• Single-rod system with disposable inserter

• Releases etonogestrel(3-ketodesogestrel) for three years

• As of July 2002 not approved by the

FDA

Features of Contraceptive Implants

Reinprayoon D, et al. Contraception. 2000.Diaz S. Contraception. 2000.

• Highly effective• Not motivation dependent• Can be used during

lactation • Discreet, virtually invisible• Rapidly reversible

more…

Features of Contraceptive Implants (continued)

Reinprayoon D, et al. Contraception. 2000.Diaz S. Contraception. 2000.

• Stable hormone levels • Extended protection• Contain no estrogen• Safe

Limitations of Contraceptive Implants

• Can cause irregular bleeding

• Requires clinician visits for insertion and removal

• Does not protect from STDs

Single-Rod Implant

One rod 4 cm x 2 mm

• Core • 40% ethylene vinyl acetate

(EVA)• 60% etonogestrel (68 mg)

• Rate-controlling membrane• 100% EVA

Pharmacology

ANON. Obstet Gynecol. 2007

ClassProgestin-only

RouteSubdermal

FormulationImplantable rod; 68 mg etonogestrel

Bioavailability~100%

MetabolismHepatic via CYP3A4

Half-life~ 25 h

ExcretionPrimary urine; some fecal

Mechanism of Action• Suppresses ovulation

• Increases cervical mucus viscosity

• Alters endometrium

IMPLANONTM Physician insert, 2006

Components of the Single-Rod Implant Insertion System

Funk S. Contraception. 2005

Preparation Tips

• Supine position• Nondominant arm, flexed

and externally rotated• Subdermal groove• Hold applicator up

(vertical) before insertion

Insertion Steps Overview

Mark site and sterilize

more…

Inject local anesthetic just under skin

Remove applicator, maintain sterility

Verify implant is within needle of applicator

Remove needle cover

Insertion Steps Overview (continued)

Stretch skin at insertion site (a)

Lift or tent skin with needle tip while inserting and insert needle to full length (b)

more…

Press the obturator support to break seal of applicator

Insertion Steps Overview (continued)

Palpate to verify correct insertion

Turn obturator 90 degrees and fix with one hand (c)

With other hand, pull needle out (d)

Removal Tips

• Inject local anesthetic under rod

• Incision over distal end• Use sharp or blunt

dissection if encapsulated• Insert new implant

through same incision or opposite arm

Removal Steps Overview

Locate rod and mark site (a)

Sterilize site

Press down on proximal end of rod

Inject local anesthetic under distal end of rod (b)

more…

Removal Steps Overview (continued)

Close with steri-strip closure

Use scalpel to make 2–3 mm incision over distal end (c)

Gently push rod toward incision, then grasp with mosquito forceps (d)

Trouble Shooting: Removals

• Unrecognized non-insertion• Deep placement• Significant weight gain• Migration

James P. Aust N Z J Obstet Gynecol. 2006. Piessens SG. Aust N Z J Obstet Gynecol. 2005.

Vaginal Ring

• Steroid release

– Progestin: Etonogestrel: 120 mcg/day (~1500 pg/ml)

– Estrogen: Ethinyl estradiol: 15 mcg/day (~20 pg/ml)

• Worn for three weeks out of four

• Approved by the FDA in October 2001

Vaginal Ring: Characteristics

• Self administered

• Insertion every four weeks

• Foreign body in vagina

• Expulsions

• Limited published data on efficacy

Vaginal Ring: Efficacy

Number of women16

Woman-cycles of use16 cycles

Cumulative pregnancy rate

Limited published data

Timmer and Mulders. Clin Pharmacokinet 2000;39:233

Contraceptive Patch

• Steroid release

– Progestin: norelgestromin 150 mcg/day

– Estrogen: ethinyl estradiol 20 mcg/day

• Worn for three weeks out of four

• Approved by the FDA in November 2001

Contraceptive Patch: Characteristics

• Self administered

• Once-a-week administration

• Hormonal side effects

• Efficacy similar to combined oral contraceptives

Audet et al. Jama 2001;258:2347

Patch: Efficacy

Number of women1,417

Woman-cycles of use2,440

Cumulative pregnancy rate1%

Shangold et al. Obstet Gynecol 2000;95:S36

History of Intrauterine Contraception

1909: Grafenberg develops ring-shaped IUD device

1962: 1st international conference on IUDs; designs for plastic spiral and plastic loop presented

1967: "T" shaped device developed

Richter R. Deutsche Med Wochenschr. 1909.; Grafenberg E. 1929.; Ishihama A. Yokohama Med Bull. 1959.; Oppenheimer W. Am J Obstet Gynecol. 1959.; Berelson B. 1964; Marguiles LC. 1962.; Lippes J. 1962.; Hubacher D, Cheng D. Contraception. 2004.

more…

History of Intrauterine Contraception (continued)

1980: LNG IUD tested in randomized clinical trials

1968: Contraceptive action of intrauterine copper reported

1976: Copper T 200 becomes first copper IUD

Lee NC. Obstet Gynecol. 1983.

History of Intrauterine Contraception (continued)

1988: Copper T 380 IUD available in the U.S.

2001: LNG IUD available in the U.S.

Today:Only 2% of US women use IUDs

Mosher WD, et al. 2004.

Comparison of Copper IUDsComparison of Copper IUDsComparison of Copper IUDsComparison of Copper IUDs

11stst Year Failure Year Failure per 100 womenper 100 women

Recommended Recommended

LifespanLifespan

TCu 380A 0.312 years

Multiload Cu 2501.23 years

Multiload Cu 3751.45 years

TCu 2002.33 years

Nova T3.35 years

Source: : FHI clinical trials, 1985-1989..Source: : FHI clinical trials, 1985-1989..

Dispelling Common Myths About IUDs• In fact, IUDs:

– Are not abortifacients– Do not cause ectopic pregnancies– Do not cause pelvic infection– Do not decrease the likelihood of future

pregnancies– Are not large in size

more…

Hubacher D, et al. N Engl J Med. 2001.; Stanwood NL, et al. Obstet Gynecol. 2002.Forrest JD. Obstet Gynecol Surv. 1996.; Lippes J. Am J Obstet Gynecol. 1999.

Dispelling Common Myths About IUDs (continued)

• In fact, IUDs:– Can be used by nulliparous women – Can be used by women who have had an

ectopic pregnancy– Do not need to be removed for PID treatment– Do not have to be removed if actinomyces-

like organisms (ALO) are noted on a Pap test

Duenas JL. Contraception. 1996.; Stanwood NL. Obstet Gynecol. 2002. Forrest JD. Obstet Gynecol Surv. 1996; Lippes J. Am J Obstet Gynecol. 1999. Otero-Flores JB. Contraception. 2003.; WHO. 2004.; Penney G. J Fam Plann Reprod Health Care. 2004.

Safety: IUDs Do Not Cause PID

• PID incidence for IUD users is similar to that of the general population

• Risk is increased only during the first month after insertion

• Preexisting STI at time of insertion, not the IUD itself, increases risk

Svensson L, et al. JAMA. 1984.Sivin I, et al. Contraception. 1991.Farley T, et al. Lancet. 1992.

Rate of PID by Duration of IUD Use

Adapted from Farley T, et al. Lancet. 1992.

1.6

9.25

<21 days of use 21 days - 8 years of use

Rate per 1,000 woman yearsN = 20,000 women

Risk of Fetal Abnormality

• IUD is extra-amniotic

• No increase in birth defects for copper IUD

Atrash HK, et al. 1994.Layde PM, et al. Fertil Steril. 1979.Simpson JL. Res Front Fertil Regul. 1985.

Safety: IUD Does Not Cause Infertility• IUD is not related to infertility

• Chlamydia is related to infertility

Tubal infertility by previous copper T IUD use and presence of chlamydia antibodies, nulligravid women

Hubacher D, et al. NEJM. 2001.

0,1

1

10

Odd

s R

atio

Fertility Rates in Parous Women After Discontinuation of Contraceptive

Pre

gnan

cies

(%

)

Months After Discontinuation

0

20

40

60

80

100

0 12 18 24 30 36 42

IUC

OC

Diaphragm

Other methods

Vessey MP, et al. Br Med J. 1983.Andersson K, et al. Contraception. 1992.Belhadj H, et al. Contraception. 1986.

Safety: IUDs May Be Used by HIV- Positive Women• No increased risk of

complications compared with HIV-negative women

• No increased cervical viral shedding

• WHO Category 2 rating

WHO. Medical Eligibility Criteria for Contraceptive Use. 2004. Morrison CS, et al. Brit J Obstet Gynaecol. 2001.Richardson B, et al. AIDS. 1999.

Safety: LNG IUD Does Not Increase Breast Cancer Risk

Backman T, et al. Obstet Gynecol. 2005.

Age Group (y)

LNG users: Incidence rate per 100,000

woman-years

Average Finnish population:

Incidence rate per 100,000 woman-

years

30–3427.225.5

35–3974.049.2

40–44120.3122.4

45–49203.6232.5

50–54258.5272.6

Safety: IUDs May Be Used in Nulligravid Women• No evidence of increased

infertility

• Risk of PID and subsequent infertility dependent on non-IUD factors

WHO. 2004.; Hubacher D, et al. NEJM. 2001.; Delbarge W, et al. Eur J Contracept Reprod Health Care. 2002.; Hov GG, et al. Contraception. 2007.Penney G, et al. J Fam Plann Reprod Health Care. 2004.

Screening: Appropriate Candidates for Intrauterine Contraception (continued)

Copper T IUD LNG IUD

Women who don’t want hormonal

contraception or want contraception for

more than 5 years

Women who request less menstrual flow

and/or who experience

dysmenorrhea or dysfunctional uterine

bleeding

Screening: Poor Candidates for Intrauterine Contraception • Known or suspected pregnancy

• Puerperal sepsis

• Immediate post septic abortion

• Unexplained vaginal bleeding

• Cervical or endometrial cancer

WHO. Medical Eligibility Criteria for Contraceptive Use. 2004.

more…

Screening: Poor Candidates for Intrauterine Contraception (continued)• Uterine fibroids that interfere with

placement

• Uterine distortion (congenital or acquired)

• Current PID

• Current purulent cervicitis, chlamydia, or gonorrhea

• Known pelvic tuberculosis

WHO. Medical Eligibility Criteria for Contraceptive Use. 2004.

IUD Insertion After Spontaneous or Induced Abortion• May be safely inserted immediately after

spontaneous or induced abortions

• Not recommended after septic abortion

Grimes D, et al. Cochrane Library. 2000.ParaGard label. 2006.WHO. 1983.

IUD for Postpartum Use

May be safely inserted in postpartum women

Treiman K, et al. Population Reports. 1995; Mishell DR, et al. Am J Obstet Gynecol. 1982; Kennedy KI, et al. In Hatcher RA, et al. Contraceptive Technology. 18th revised ed. 2004.

Copper T IUD LNG IUD

Within 48 hours postpartum

OR

After 4 weeks once uterus is involuted

6 weeks postpartum

IUD Use During Lactation

• Effectiveness not decreased

• Uterine perforation risk unchanged

• Expulsion rates unchanged

• Decreased insertional pain

• Reduced rate of removal for bleeding and pain

• LNG comparable to copper T in breastfeeding parametersChi I-C, et al. Contraception. 1989; Mirena label. 2006.Shaamash AH, et al. Contraception. 2005.

Checklist for STI Risk Assessment

Circle appropriate answerYesNo

Is the client < 25 years old? 1 0

Is she currently living apart from her husband or partner?

1 0

During the last year, has she had bleeding between periods or bleeding or spotting within 24 hours after sex?

1 0

Is her school education < secondary level?

1 0Morrison CS, et al. Contraception. 2007.

more…

Checklist for STI Risk Assessment (continued)

How many different sexual partners has she had during the last 3 months?

None

0One

> One

If she has had one or more partners, how often has she used a condom in the last 3 months?

Never used condoms01

Sometimes used condoms11

Always used condoms00Morrison CS, et al. Contraception. 2007.

Scoring STI Risk Assessment

Recommended action

Low cervical infection

population (<10%)

High cervical infection

population

(=10%)

Counsel/refer for IUD insertion without any reservations

If score is

0–2If score is 0

Consider presumptive treatment for chlamydia/ gonorrhea (if available) or counsel/refer to use another contraceptive

If score is 3+If score is 1+Morrison CS, et al. Contraception. 2006.

Levonorgestrel Intrauterine System (LNG IUS)

32 m

m Steroid reservoirlevonorgestrel 20 mcg/day

Approved December 2000

LNG IUS: Characteristics

• High efficacy

• Long-term reversible method

• Reduction in menstrual blood loss

• Low systemic levels of LNG

• Early spotting common

• Foreign body in the uterus

• Expulsions

• Requires professional insertion

LNG IUS: Mechanism of Action

• Fertilization inhibition:– Cervical mucus thickened

– Sperm motility and function inhibited

– Endometrium suppressed

– Weak foreign body reaction induced

– Ovulation inhibited (in some cycles)

Jonsson et al. Contraception 1991;43:447Videla-Rivero et al. Contraception 1987;36:217

LNG IUS: Efficacy

• Overall failure rate 0.14 per 100 woman-years

• Gross cumulative five-year rate is 0.71 per 100 women

Andersson et al. Contraception 1994;49:56Luukkainen et al. Contraception

1987;36:169

LNG IUS: EfficacyFive-Year Cumulative Pregnancy Rates per 100 Women by Age and

IUD Type

0 0,1 0,1 0,2

2,9

1,5

0,80,6

0

0,5

1

1,5

2

2,5

3

<=25 26 - 30 31 - 35 36+

Age (Years)

LNG IUS

Nova T

Luukkainen and Toivonen. Contraception 1995;52:269

LNG IUS: Comparison to Sterilization

Andersson et al. Contraception 1994;49:56Peterson et al. Am J Obstet Gynecol

1996;174:1161

5-year gross cumulative failure rate per 100 women

0,5

1,41,3

0,6

0

1

2LNG IUS

Nova T

All Sterilization

Post PartumSalpingectomy

LNG IUS: Return to Fertility

0

20

40

60

80

100

3 6 9 12MonthsC

um

ula

tive

pre

gn

an

cy r

ate

(%

)

LNG IUS

Copper IUD

Andersson et al. Contraception 1992;46:575Belhadj et al. Contraception 1986;34:261

Plasma Concentrations of Levonorgestrel

0

1000

2000

3000

4000

5000

6000

7000

Pla

sma

con

cen

trat

ion

s (p

g/m

L)

LNG IUS Implant Mini-pill Combined OCs

Nilsson et al. Acta Endocrinol 1980;93:380Diaz et al. Contraception 1987;35:551

LNG IUS: Endometrial Effect

Days of cycle

Months

Changes in the endometrium during normal menstrual cycle

Ovulation

LNG IUS: Endometrial Effect

Days of cycle

Months

Endometrium in “resting state” with LNG IUS

Ovulation

Pakarinen et al. Fertil Steril 1997;68:59

LNG IUS: Early Spotting

• Endometrial suppression effect is not immediate

• Takes three months for full effect on the endometrium

• Spotting is common during this time

Silverberg et al. Int J Gynecol Pathol 1986;5:235

LNG IUS: Number of Bleeding Days

Luukkainen and Toivonen. 1992;90

Days

0

2

4

6

0 4 8 12 16 20 24

Months

Copper IUD

LNG IUS

LNG IUS: Bleeding Patterns

• 20 % of women will have no bleeding at all after 12 months

Pekonen et al. J Clin Endocrinol Metab 1992;75:660Luukkainen et al. Contraception 1987;36:169

LNG IUS: Non-contraceptive Therapeutic Uses

• Alternative to hysterectomy– Cancelled hysterectomy: 80 % LNG IUS

vs. 9 % normal care

• Treatment of menorraghia– 97 % decrease in menstrual blood loss

(MBL)

Hurskainen et al. Lancet. 2001 Jan 27;357:273Andersson and Rybo. Br J Obstet Gynaecol. 1990 Aug;97:690

LNG IUS: Non-contraceptive Therapeutic Uses (cont)

• Hormone replacement therapy (HRT)– Days of bleeding/spotting at 12 months:

2 LNG IUS vs. 6 oral LNG

• Adjuvant therapy for tamoxifen users– Decidual change in endometrium of all

women with LNG IUS

Barrington and Bowen-Simpkins. Br J Obstet Gynaecol. 1997 May;104:614

Gardner et al. Lancet. 2000 Nov 18;356:1711

US Preventive Services Task Force Ratings

LNG IUS FindingStrength of conclusion

Increases concentration of hemoglobin

A

Effective treatment for menorraghia

A

Well-accepted alternative to hysterectomy

B

Hubacher and Grimes. Obstet Gynecol Surv 2002 Feb;57:120

US Preventive Services Task Force Ratings (cont)

LNG IUS FindingStrength of conclusion

Prevents anemiaA

Can be used as a vehicle for hormone replacement therapy (HRT)

A

Mitigates tamoxifen-induced endometrial effects

B

Hubacher and Grimes. Obstet Gynecol Surv 2002 Feb;57:120

LNG IUS: Possible Complications

SymptomsConsider

Return of menstruationExpulsion

Fever/chillsInfection

Continuous bleeding and/or pain after first month post-insertion

Perforation, infection, or partial expulsion

LNG IUS: Possible Complications (cont)

SymptomsConsider

Irregular bleeding and/or pain in every cycle

Dislocation or perforation

Missing stringDislocation or perforation

LNG IUS: Potential Contraindications

• Pregnancy or suspicion of pregnancy

• Active cervical or endometrial infections

• Uterine anomaly

• Complete list included in the package labeling

LNG IUS: Potential Complications• Expulsions

– Most occur during the first six months after insertion

– The five-year cumulative expulsion rate is 4.9 per 100 women

• Perforations– Occur at the time of insertion– Rare events, fewer than one per thousand

Andersson et al. Contraception 1994;49:56

LNG IUS: The Inserter

LNG IUS: Insertion

• Different insertion technique than other intrauterine contraception

–New, one-handed insertion

–Requires hands-on training

• Efficacy and user continuation dependent on skillful insertion

LNG IUS: Counseling

• Efficacy

• Return to fertility

• Side effects

• Changes in bleeding patterns

• Non-contraceptive health benefits

• Safety

• Insertion and follow-up

LNG IUS Counseling: Efficacy

• High efficacy

–In clinical studies failure rate about that of female and male sterilization

• Continuous contraception for up to five years

LNG IUS Counseling: Side Effects• Possible hormonal side effects

– Mood changes

– Acne

– Headache

– Breast tenderness

– Nausea

• No reported weight gain

Mean Weight Change After Five Years

2,5 2,4

0

0,5

1

1,5

2

2,5

3

Wei

gh

t g

ain

in k

g

Andersson et al. Contraception 1994;49:56

Nova T LNG IUS

LNG IUS Counseling: Changes in Bleeding

• Bleeding characteristics:

• 1 – 4 mo frequent spotting

• 1 – 6 mo reduced duration and amount of bleeding

• Reduction in menstrual blood loss

• After 12 mo, about 20 % have no bleeding

Pakarinen et al. Fertil Steril 1997;68:59

LNG IUS Counseling: Absence of Bleeding• Local effect

– No proliferation of endometrium

• This is expected. It is not a sign of:

– Pregnancy

– Ovarian or pituitary dysfunction

– Menopause

• Rapid return to menstruation after removal

LNG IUS Counseling: Health Benefits

• Reduction of– Duration and amount of bleeding

– Ectopic pregnancies

– Menstrual pain

• Increase of– Hemoglobin

– Iron storageLuukkainen et al. Contraception 1987;36:169

LNG IUS Counseling: Safety

• > Ten years experience in Europe

• > Two million users world wide

• Few serious side effects

• Highly effective

• Does not prevent acquisition of STDs

–Condoms advised for women at risk

LNG IUS Counseling: Insertion

• Steps in the insertion process

–Pelvic and speculum exam

–Sensations produced by tenaculum

–Paracervical anesthesia, if needed

–Sensations of IUS as it is inserted

–Measures you will take for her comfort

LNG IUS Counseling: Post-Insertion• Schedule a follow-up visit at 1 – 3

months post-insertion

–Check for partial or complete expulsion

–Address any questions or concerns

LNG IUS: Therapeutic Possibilities• Range of non-contraceptive benefits,

including:

–Treatment of heavy menstrual bleeding

–Endometrial protection for women receiving estrogen replacement therapy

LNG IUS: Treatment of Heavy Bleeding

Andersson and Rybo. Br J Obstet Gynaecol 1990;97:690

0

100

200

300

400

Before treatment

3 6 12

Months of useMen

str

ual b

lood

loss (

ml)

LNG IUS: Percentage Reduction of Menstrual Blood Loss

-100

-75

-50

-25

0

LNG IUS

Placebo

ProstaglandinSynthetase Inhibitor

Combination OCs

Milsom et al. Am J Obstet Gynecol 1991;164:879

LNG IUS vs. Endometrial Resection

500

400

300

200

100

0

Baseline 6 months 12 months

Crosignani et al. Obstet Gynecol 1997;90:257

Pic

tori

al b

lood

loss

assessm

en

t ch

art

score

Levonorgestrel intrauterine systemEndometrial resection

LNG IUS as Alternative to Hysterectomy

Lahteenmaki et al. BMJ 1998;316:1122

0

10

20

30

40

50

60

70

LNG IUS Medical Therapies

Perc

ent

Women Canceling Hysterectomy

LNG IUS: Hormone Replacement• Prevention of endometrial hyperplasia

from estrogen therapy

• “Local is logical”

• Oral progestins can cause depression

• LNG IUS avoids systemic side effects of oral progestins

Girdler et al. J Womens Health Gend Based Med 1999;8:637

LNG IUS: Hormone Replacement

• Bleeding is the most common reason why women discontinue HRT

• LNG IUS suppresses endometrium

• 83 – 88 % have no bleeding/ spotting at 12 months

• 82 % continuation rate at three years

Ettinger. Menopause 1999;6:273 Suhonen et al. Acta Obstet Gynecol Scand 1997;76:145

General Discussion

• New methods are coming to U.S. market

• This should translate into more

contraceptive choices, fewer unintended

pregnancies

• These new methods share the common

advantage of not requiring daily attention

Intrauterine Contraception in the U.S.

LNG IUSCopper IUD

20 mcg

levonorgestrel/daycopper ions

Approved for

5 years

Approved for

10 years

Approved 2000Approved 1988

PID Incidence Rate for All IUDs by Time Since Insertion

Farley et al. Lancet 1992;339:785

0

2

4

6

8

1 2 3 4 5 6 7 8 9 10 11 12

Month (first year)

2 3 4 5 6 7 8

Year

Time Since Insertion

Combined WHO clinical trial data for all IUDs - 22,908 IUD insertions(per 1,000 woman-years)

Dispelling Myths:Intrauterine Contraception• Infections are a frequent problem

• Prevents implantation

• Women are not interested in intrauterine contraception

Prophylactic Antibiotics?

• Any risk of infection associated with the IUD relates to insertion

• One woman in 1,000 will develop PID in the first three months

• Meta-analysis has not shown any overall benefit of prophylactic antibiotics

Grimes and Schulz. Contraception 1999;60:57 Walsh et al. Lancet 1998;351:1005

Myth: IUD Prevents Implantation• Most evidence now suggests that all

IUDs induce a foreign body reaction that is spermicidal, preventing fertilization

• Today’s intrauterine contraceptives have other mechanisms of action that prevent fertilization

Alvarez et al. Fertil Steril 1988;49:768

Use of Contraception by U.S. Women Physicians

0

20

40

Sterilization IUD Pills

% o

f Wom

en U

sing

Met

hod

Women MDs General Population

Frank. Obstet Gynecol 1999;94:666

Incidence* of Ectopic Pregnancy

LNG IUS0.20

Copper IUD0.34

No method1.20-1.60

All U.S. women2.00

* Per 1,000 woman-yearsAndersson et al. Contraception 1994;49:56

Sivin. Stud Fam Plann 1983;14:57

Summary

• LNG IUS bleeding patterns:– 1 – 4 mo frequent spotting

– 1 – 6 mo reduced duration and amount of bleeding

– > 12 mo, about 20 % have no bleeding

• Treatment of heavy menstrual bleeding and endometrial protection with HRT

Gynefix- Frameless IUD

• Developed 1994 in Belgium- available in Europe and UK

• Frameless IUD-copper tubes on a thread with a knot to anchor to the fundus

• Reduced risk of expulsion, pain & heavy bleeding

• Progestogen device in development

Female Barrier Contraception- Diaphragms and Caps

• Rubber barriers placed into the vagina to cover the cervix prior to sex

• Sperm remain in vagina where acid conditions kill the sperm in a few hours- need to remain inside for 6 hours.

• Use of spermicide is controversial• Failure rates anything from 5-20%-rates

lower in older women and experienced users

• Need to be individually fitted• Last approximately 2 years• Size needs to be checked if weight

gain, failure, or pregnancy• Affected by oil based vaginal lubricants

and treatments eg Antifungal creams and pessaries

Barriers-The Female Condom

• Lubricated, loose fitting polyurethane sheath with 2 flexible rings - one size fits all

• Lines the vagina and covers some of the vulva

• Effectiveness: 85-95%

The Female Condom

• Advantages– Contraception and STI protection– Can be used with oil based products– Better heat transmission– Stronger than latex– Less “constriction” for partner– Does not need erection before use– May provide better protection against herpes

and HPV • Disadvantages

– Harder to dispose of than male condom– Requires careful insertion and practise– Not yet widely available

Latex male condoms

• Cornerstone of safer sex-must be used every time to provide maximal protection

• Can be used with other methods of contraception- “Double Dutch”

• Affected by oil based lubricants and vaginal medications like antifungals

Polyurethane Male Condom

• Stronger and thinner than latex condoms

• Better heat transmission

• Can safely be used with oil-based lubricants

• Can be used by those with latex allergies

Permanent Contraception-• Inner wire/outer coil with

synthetic fibre between• Inserted into uterine ends of

Fallopian tubes through hysteroscope under LA

• Growth of fibroblasts causes scarring and permanent closure of the tubes -irreversible

Sterilization: Tubal Ligation MethodsMethods for accessing the fallopian

tubes

• Laparotomy

• Mini-laparotomy

• Vaginal posterior colpotomy

• Laparoscopy

• Hysteroscopy

Tubal Sterilization: FDA-Approved Methods

• Partial salpingectomy• Clips• Silicone rings• Electrocoagulation• Micro-insert

The most widely used occlusion methods are typically performed on the isthmic portion of the fallopian tube:

Electrocoagulation

Uterotubal Junction Device

Hossenian, 1976

Intra-tubal DeviceHamou, 1982

Hysteroscopic Sterilization Techniques

Chemical

Hysteroscopic Sterilization Techniques (continued)

P-Block DeviceBrundin, 1981

OvaPlug1981

Transcervical Sterilization Methods

EndoscopeEfficiency

ContinuousFlow

Technology

AdvancedCardiologyTechnology

Transcervical Sterilization: Advantages to the Provider

• Outpatient procedure

• No general or regional anesthesia

• Women with certain medical conditions may be eligible

Transcervical Sterilization: Disadvantages to the Provider• Special equipment and training

needed for insertion

• Some women may not be candidates

• Uncertainty still exists about long-term effectiveness and insurance coverage

Transcervical Sterilization: Advantages to the Patient• No incision

• Absence of a scar preserves privacy

• Less invasive

• Less discomfort

• Faster recovery

• Efficacy

Transcervical Sterilization: Disadvantages to the Patient• Another contraceptive method is

required for three months after insertion

• Non-reversible; some women may experience regret

New Tubal Occlusion Method:Micro-Insert Tubal Occlusion

(Essure®)• FDA approval in November 2002

• Only FDA approved hysteroscopic method of tubal sterilization available

• Placement of micro-inserts into proximal fallopian tubes

Micro-Insert: Design

ARHP. Clinical Proceedings. May 2002.

Micro-Insert length = 4 cm

Inner Coil Material: Stainless Steel

Fiber Material: PET

Dynamic Expanding Superelastic Outer Coil Material: Nitinol

Micro-Insert: Mechanism of Action• Expansion of outer coil for acute anchoring

• Space filling/mechanical blockage of tubal lumen

• Tubal occlusion by tissue in-growth into and around the micro-insert

• Long-term nature of tissue response not known beyond 24 months

Essure® Prescribing Information

Male Hormonal Contraception

• Recent trials at Andrology Clinic, Concord Hospital

• Depo Provera plus testosterone implants 3 monthly

• Very low sperm count (less than 1 million per ml) in all men on trial - 80% had no sperm

• Few side-effects• Similar regime using an oral

progestogen and testosterone implants being trialed in UK

• Implants and testosterone also being trialed

The Introduction of a New Contraceptive Method to the Market

• New contraceptive methods usually considered newsworthy

• Consumers increasingly well informed around options and their rights to informed choice

• The growing number of options available makes it increasingly difficult for health practitioners to do justice to the pros and cons of each method in the available time.

Contraceptive Counselling

• The trend to an increase in available contraceptive options seems likely to continue along with an acceptance that the consumer has a right to accurate, comprehensive and balanced information from their health provider

• Any clinician attempting to counsel a patient around contraceptive choice will need to put this counselling within the broader context of the person’s past experiences, cultural background and belief systems

• A person will rarely persist with a contraceptive method they do not feel is right for them - they will simply feel their practitioner has not heard them

• In the area of contraception the clinician is often the adviser, sometimes the supplier, but, if they have any sense at all, never the decider.