Recent Advances in Fertility Regulation

Professor PC Ho

Department of O&G

University of Hong Kong

Condom or sheathEspecially useful when coitus occurs

infrequently and at irregular intervals

Some protection against venereal disease

Coincident use of spermicides advisable

Intrauterine contraceptive deviceTwo types:

1. Inert e.g. Lippes

2. Bioactive e.g. copper T or 7 or levonorgestrel IUCD; need renewal every 3-5 years

Advantages of IUD

1. Highly effective

2. Little motivation

3. Non-coitus-related

4. Local effect

5. 90% conceive within 1 year of removal

New copper IUCD

Cu T 380 A

Cu T 220 CMultiload 250 & 375

Nova T

Prerferred over inert devices

Advantages of new copper IUCDs1. Smaller and easier to

insert

2. Less side effects

3. Lower pregnancy rate

<1/HWY

Complications of IUCD1. Expulsion

2. Bleeding

3. Pain

4. Perforation

5. Pelvic infection

6. Pregnancy

BleedingMost common complication

requiring removal; may present with:

1. Increased menstrual flow

2. Longer periods

3. Intermenstrual bleeding

Management of bleeding problems

1. May improve after several cycles2. NSAID3. Anti-fibrinolytic agents4. Oral iron5. Remove IUCD/Change to smaller

or LNG-IUCD

IUCD & ectopic pregnancy1. Does not increase overall risk of

ectopic pregnancy

2. Protects against IU pregnancy better than ectopic

3. Increased ectopic to intrauterine pregnancy ratio

Pelvic Inflammatory Disease

No significant increase in low risk women

IUCD related PID rare beyond 20 days

Contraindications1. Active or recent P.I.D.

2. Known or suspected pregnancy

3. Undiagnosed abnormal vaginal bleeding

4. Suspected/confirmed genital tract malignancy

5. Congenital uterine abnormality or fibroids that prevent proper placement

Levonorgestrel IUCD

• Contains levonorgestrel which is slowly released

• Highly effective – Pearl Index 0-0.2/HWY

• Ectopic preg rate – 0.02%/year

Levonorgestrel IUCD• Reduces menstrual blood loss but

there is a higher incidence of intermenstrual bleeding/spottingAmenorrhoea 16.1%Spotting 8.9%Meno/metrorrhagia 7.6%

(Siven & Stern 1994)

Levonorgestrel IUCD

• Incidence of PID lower than Nova-T

• Removal rates at 5 years due to PID–LNG 0.8/HWY–Nova T 2.2/HWY

» (Andersson et al 1994)

Modern combined oral contraceptives

• combination of oestrogen and progestogen taken daily for 21 days followed by an interval of 7 days

• Oestrogen - Ethinyl oestradiol 20 to 30 ug per tablet

• Progestogens: levonorgestrel;gestodene; desogestrel

• Failure rate < 0.1/HWY

OC pills - Side Effects

• Nausea & vomiting

• dizziness & headache

• breast tenderness

• fluid retention and weight gain

• Intermenstrual spotting/bleeding

– may disappear after a few cycles

Major complications of OC

• Increased risk of thromboembolism, cardiovascular diseases (CVA and myocardial infarction)

• Slightly increased risk of breast cancer and liver tumours (controversial - cervical cancer)

• Jaundice and liver dysfunction

COC - Absolute Contraindications

• Pregnancy

• Smoking in women over 35

• Past or present evidence of thromboembolic disorders

• Complicated valvular heart disease

• Focal migraine

• Liver tumours

COC - Absolute contraindications

• Acute liver disease or cirrhosis

• DM with vascular complications including hypertension

• Moderate or severe hypertension with BP > 160/100 mm Hg

• Hypertension with vascular disease

COC - Relative contraindications (Risks usually outweigh benefits)

• Mild hypertension 140-159/90-99 mm Hg

• History of hypertension when BP cannot be evaluated

• Chronic liver disease other than severe cirrhosis

• Symptomatic biliary tract disease

• Known hyperlipidaemia

Benefits of COC (I)

Reduction in risk of ovarian cancer

Reduction in risk of endometrial cancer

Menstrual benefits : Reduction in amount of blood loss mid-cycle pain menstrual irregularity premenstrual tension and dysmenorrhoea

Benefits of COC (II)

Reduction in PID

Protects against benign breast tumour

Possible benefits protection against ovarian cyst, uterine

fibroids and osteoporosis

Highly effective form of contraception and protects against ectopic pregnancy

Third generation progestogens

Desogestrel

Gestodene

Norgestimate

Better lipid profiles

Concerns on new progestogens

• Do they increase the risk of deep vein thrombosis?

• Results are controversial and some of the results are probably due to the bias in the studies

• On the whole low dose OC pills are very safe; even if there is an increase in risk with new progestogens, the risk is small

Commonly asked questions

Are combined OC pills safe in women over the age of 35? Yes, if the woman is healthy and non-smoking

Can OC pills be used in women with uterine fibroids?Yes. OC pills do not induce growth of fibroids and may decrease bleeding in these women

(ACOG 2001)

Commonly asked questions

Can OC pills be used in SLE? In general, progestin-only methods should be used. Combined OC pills may be considered if SLE is stable and inactive with no thrombosis, nephropathy or antiphospholipid antibodies (ACOG, 2001)

Commonly asked questions

Can OC pills be used in women with fibrocystic breast changes, fibroadenoma, or a family history of breast cancer? Yes

Do women have to stop OC pills every few years?No

(ACOG 2001)

Depomedroxyprogesterone acetate (DMPA)

Disadvantages

1. High incidence of amenorrhoea or menstrual irregularity

2. Weight gain

3. Slow return of fertility after discontinuation

Advantages

1. Convenient - one injection/3 months

2. Can be used in women with contraindications to oestrogens

Monthly Injectables• Cyclofem – 25 mg DMPA amd 5 mg E2

cypionate• Mesigyna – 50 mg NET EN amd 5 mg E2

valerate• Perlutan – 150 mg

dihydroxyprogesterone acetophenide + 10 mg E2 enanthate

• Given monthly +/- 3 days

Monthly injectables

• Highly effective with pregnancy rates <1/HWY

• More regular cycle patterns 60-70% have regular cycles (compared to less than 10% in women on DMPA)

• Cannot be used for women with contra-indications for oestrogens

Progestogen implants

Capsules containing levonogrestrel implanted under skin

Low failure rate (<1/100WY)

Most common side effect: excessive bleeding and intermenstrual bleeding

Rapid return of fertility on removal

Minimal metabolic effects

The Implanon rod

Rate-controlling membrane (0.06 mm)

Core: 40% EVA60% etonogestrel

Membrane: 100% EVA

Core 2 m m

40 m m

(*Croxatto and Mäkäräinen, Contraception,1998,58,91S-97S) (**Sivin, Stud Fam Plann,1988,19,81-94)

Contraceptive efficacy

Implanon*

1-3 years

Norplant**

1st year

Norplant **

5th year

Cycles 73,429 157,729 10,855

Pregnancies 0 24 9

Pearl index 0(conf. int. 0.00-0.07)

0.2 1.1

(Affandi B. Contraception 1998;58:99S-107S)

Bleeding patterns

Bleeding patternImplanon

(N=169)Norplant

(N=163) P values

Amenorrhea 20.8% 4.4% < 0.0001

Infrequent B-S 26.1% 21.4% 0.099

Frequent B-S 6.0% 3.5% 0.14

Prolonged B-S 11.8% 8.5% 0.074

Complications (Comparative trials, meta-analysis)

Implanon

n/N %

Norplant

n/N %

Insertioncomplications 2/689 0.3 0/689 0

Removalcomplications 1/644 0.2 7/145 4.8

(Mascarenhas L. Contraception 1998:58:79S-83S.)

Post-coital contraceptionEmergency -

intercourse unexpectedrapefailure of barrier methods

Regular - not a good method because of high failure rate and side effects

Yuzpe regimen

2 tablets of OC pills(100 g EE 1 mg norgestrel)within 72 hours of coitusAnother 2 tablets 12 hours laterPregnancy rates 0.2% - 2.6%Nausea 50% Vomiting 20-25%

Randomised comparison of Yuzpe regimen with LNG

Yuzpe LNG

No of subjects 424 410

Pregnancy rates

whole group 3.5% 2.9%

No further

coitus 2.7% 2.4%

Ho & Kwan 1993

46.5

22.4 23.1

36.8

20.8

4.2

16.1

2.7

18.5

23.9

15.9

3.4

0

10

20

30

40

50

Nause

a

Vomiti

ng

Dizzin

ess

Fatigu

e

Breas

t ten

dernes

sIM

B

Inci

den

ce o

f si

de

effe

cts

(%) YUZPE

LNG

*

*

*

Group Number ofGroup Number of Observed Observed Pregnancy Pregnancy womenwomen pregnancies rate (%) pregnancies rate (%) 95% CI 95% CI

YuzpeYuzpe 979 979 3131 3.23.2 (2.2, 4.5) (2.2, 4.5) LNG LNG 976 976 1111 1.11.1 (0.6, 2.0) (0.6, 2.0)

Relative risk (RR) of pregnancy for LNG compared with Yuzpe:Relative risk (RR) of pregnancy for LNG compared with Yuzpe:

RRRR 95% CI 95% CI

0.360.36 (0.18, 0.70)(0.18, 0.70) WHO 1998WHO 1998

*

Pregnancy ratesPregnancy rates

50.5

18.8 20.216.7

28.5

23.1

5.6

16.8

11.2

16.9

0

10

20

30

40

50

60

Nausea Vomiting Headache Dizziness Fatigue

Inci

denc

e of

sid

e ef

fect

s (%

)YUZPELNG

*

**

*

Pregnancy rates by further acts of intercourse

Further Acts of intercourse

No Yes

Yuzpe 1.9% 5.3%

LNG 0.8% 1.6%

ConclusionsConclusions

• The LNG regimen is more effective than The LNG regimen is more effective than the Yuzpe regimen.the Yuzpe regimen.

• It is better tolerated.It is better tolerated.

• With both regimens, earlier treatment is With both regimens, earlier treatment is more effective.more effective.

Mifepristone (RU 486)• Antiprogestin which blocks the

action of progesterone • Used in inducing abortions• Highly effective in emergency

contraception even at a very low dose (10 mg) which does not cause abortion

Post-coital insertion ofCopper I.U.C.D.

Advantages:

1. Highly effective pregnancy rate

<0.1%

2. Can be used 5 days after intercourse

3. Continued contraception

Disadvantages:

Bleeding; pain; infection

Emergency Contraception

1. Effective and safe methods are now available but they are underutilized

2. Need to remove barriers- Education- Improve access

TOP in first trimester1. Surgical methods

Suction evacuation

2. Medical method (<9 wks)

Mifepristone (RU486) + PG

Regimen of medical abortion with mifepristone and PG analogue

Mifepristone PG analogue Follow up

48h

2 weeks

Medical abortion with mifepristone & PG

• For TOP up to 9 weeks

• Misoprostol is commonly used now

• Complete abortion rate over 95%

• The process resembles miscarriage: abdominal pain, bleeding and expulsion of products of conception

Complicationsof Sterilization1. Complications due to laparoscopy

or laparotomy - visceral damage; bleeding; wound complications including pain and infection

2. Failure (about 1 in 200 lifetime risk)

3. Ectopic pregnancy

Mortality rate 1 in 10,000

VasectomyAdvantages

1. Simple and quick operation requiring less skill

2. Local anaesthesia

3. Less complication

4. Easier to reverse

Disadvantage

Not immediately effective - 2 negative semen tests at 8 and 12 weeks

Long term health risks of vasectomy

Men can be reasssured that there is no substantial long-term health risk associated with vasectomy but they should be informed about the possibility of chronic testicular pain after vasectomy. The pain is generally mild and only rarely requires further medical or surgical intervention.

RCOG 1999

Other new developments

• Hormonal patch

• Vaginal rings

• Male pills