recent advances in fertility regulation professor pc ho department of o&g university of hong...
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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