This document provides information on emergency contraceptives, including their evolution and current practices. It discusses various emergency contraceptive methods such as the Yuzpe regimen, levonorgestrel pills, mifepristone, copper IUDs, and the recently approved ulipristal acetate. It summarizes the mechanisms of action, effectiveness, appropriate timing, side effects, limitations and safety considerations of the different emergency contraceptive options. The document concludes that emergency contraception can effectively reduce unintended pregnancies and abortions if provided correctly and in a timely manner after unprotected intercourse.
2. DR ALKA MUKHERJEE
MBBS DGO FICOG FICMCH PGDCR PGDMLS MA(PSY)
Director & Consultant At Mukherjee Multispecialty Hospital
MMC ACCREDITATED SPEAKER
MMC OBSERVER MMC MAO – 01017 / 2016
Present Position
Director of Mukherjee Multispecialty Hospital
Hon.Secretary INTERNATIONAL COUNCIL FOR HUMAN RIGHTS
Hon.Secretary NARCHI NAGPUR CHAPTER (2018-2020)
Hon.Secretary AMWN (2018-2021)
Hon.Secretary ISOPARB (2019-2021)
Life member, IMA, NOGS, NARCHI, AMWN & Menopause Society,
India, Indian medico-legal & ethics association(IMLEA), ISOPRB,
HUMAN RIGHTS
Founder Member of South Rapid Action Group, Nagpur.
On Board of Super Specialty, GMC, IGGMC, AIIMS Nagpur,
NKPSIMS, ESIS and Treasury, Nagpur for “ WOMEN SEXUAL
HARASSMENT COMMITTEE.”
mukherjeehospital@yahoo.com
www.mukherjeehospital.com
https://www.facebook.com/
Mukherjee Multispeciality
https://www.instagram.com/
Achievement
Winner of NOGS GOLD MEDAL – 2017-18
Winner of BEST COUPLE AWARD in Social
Work - 2014
APPRECIATION Award IMA - MS
Past Position
Organizing joint secretary ENDO-GYN
2019
Vice President IMA Nagpur (2017-2018)
Vice President of NOGS(2016-2017)
Organizing joint secretary ENDO-GYN
Organizing secretary AMWICON – 2019
PREZ ELECT NOGS NARCHI
3. FERTILE PERIOD
A woman’s fertile period is
considered to be the six
consecutive days ending with
(and including) the day of
ovulation
Wilcox AJ et al. New England Journal of
Medicine. 1995
5. The choice of the contraceptive method is
influenced –
• demographic,
• cultural,
• economic, and
• social factors
• India was the first country in the world to adopt an official
population policy
• India’s population currently is 1.31 billion.
• contraceptive prevalence in the country is only 56% as per the
WHO global health statistics 2012
5646
Contraceptive
Prevalence In…
Populatio
n using
Contrace
ptives
methods
6. UNINTENDED PREGNANCY - 15·6 million abortions took place
in India in 2015 , giving an abortion rate of 47 per 1000 women
aged 15–49
• Each year, approximately 85 million women (41 %) in the
world face an unintended pregnancy , more than one in
seven of these cases occurs in India
• 46 million unwanted pregnancies end in abortion each
year, 20 million of which are unsafe.
• 25·8 million pregnancies (54%)
resulted in births
• 33% of pregnancies ended in induced
abortions, and 14% of pregnancies
ended in a miscarriage
• The rate of unintended pregnancy
was estimated at 70 pregnancies per
1000 women aged 15–49 years
7. WHAT IS EMERGENCY CONTRACEPTION ??
• Emergency contraception (EC) is a method of contraception
used as an emergency step taken before menstruation is
missed, to prevent pregnancy following Unprotected Sexual
Intercourse(UPSI) or expected failure of contraception
• They are popularly also called as ‘Morning after pill’ or
“postcoital oral contraceptives.”
• largely underutilized in India, which if taken correctly can
reduce the risk of an unintended pregnancies which in turn
will reduces 8% maternal mortality
• 90% of abortion-related and 20% of pregnancy-related
morbidity and mortality can be prevented
https://www.acog.org/patient-
resources/faqs/contraception/emergency-contraception
9. INDICATIONS FOR EMERGENCY
CONTRACEPTION
ECPs are indicated when:
• no contraceptive was used;
• a contraceptive was used incorrectly;
• A contraceptive was used correctly but was
immediately observed to have failed
FSRH, Emergency Contraception March 2017
10. Common situations in which ecps may be needed by a woman
who is using a routine contraceptive method
11. CLINICAL CONSIDERATIONS
Recommendations as to which ECP to use depends on
a number of factors, including :
• timing of presentation after unprotected sexual
intercourse, patient factors (such as obesity,
allergies, and concurrent medications), cost, and
availability
12. TIMING OF UNPROTECTED SEXUAL
INTERCOURSE
Timing of unprotected
sexual intercourse
• While all methods are highly
effective within 72 hours of
unprotected sexual
intercourse
• eg. LNG can be administered
before 72 hours and after, it
is less effective, and is not
currently labeled for use as
such
• The copper IUD does not
decrease in efficacy over the
120 hours
Patient factors
- Weight
While BMI 30
kg/m2 is not
considered a
contraindication
to ECPs selection
of a method may
vary
Eg. LNG is metabolized
by the CYP3A4
microsomal system,
medications which
induce the CYP3A4 eg.
Antifungals and
Antiepileptic drugs
may decrease levels of
LNG
Patient
factors -
Concomitant
medications
13. YUZPE METHOD
• Oldest form of post-coital emergency contraception
• This method involves taking two pills each containing 50 µg of
ethinylestradiol and 0.50 mg of levonorgestrel or 1 .5 mg
levonorgestrel within the first 72 hours .
This treatment is repeated 12 hours later
• The Yuzpe method works by delaying or inhibiting ovulation,
when utilized during the first half of the menstrual cycle
• It is only effective if follicles are not already well developed
• The crude failure rate is 1-5 per 100 woman-months while the
true reduction in pregnancy risk is over 75
14. EFFICACY OF YUZPE REGIMEN
• After a single act of unprotected sexual intercourse, the Yuzpe
regimen fails in about 2 of women who use it correctly (1.9%, 95
CI 1.4–2.4 %)
• The crude failure rate is 1-5 per 100 woman-months while the
true reduction in pregnancy risk is over 75
• It means, if 100 women have intercourse in the mid 2 weeks of
their cycle, approximately 8 will become pregnant. Use of
emergency contraceptive pills would reduce this number to 2
women (a 75 reduction)
• Side effects with 50% of women develop nausea, and 20%
develop vomiting - Antiemetic medications
• Changes in menstrual bleeding, mastalgia and increased risk of
venous thromboembolism are observed
Kubba AA. Eur. J Contracept. Reprod. Health Care 1997
15. LEVONORGESTREL (LNG)- progestin-only pill licensed
• Single dose oral tablet of LNG (1.5 mg) or two doses ( 0.75 mg each – 12
hours apart) to be taken within 72 hours of unprotected I/C
• Suppresses LH - delays or inhibits ovulation, In order to be effective, it
must be administered before the LH surge begins. LNG is less effective
when given closer to the time of ovulation
• Thickens cervical mucus
• Efficacy of 1.5 mg of LNG may decrease among patients weighing more
than 70 kg or with a BMI greater than 26 kg/m2, with a four-fold risk of
pregnancy in obese women compared to women with a normal BMI
• In such cases needs doubling the dose to 3.0 mg, but effect is not well
documented
Haeger et al. Contraception and Reproductive Medicine (2018) 3:20
Mini pills
16. EFFECTS OF LEVONORGESTREL
• A further advantage of the levonorgestrel-only is the absence
of ethinylestradiol – safe in arterial or venous thrombosis in
the past
• Nausea (23%) and vomiting (5.6%), fatigue, dizziness,
headache, and mastalgia,
• Disruption in the menstrual cycle pattern - When LNG is
taken in the preovulatory stage of menses, the length of the
cycle may be abbreviated; in the peri- and postovulatory
phases, cycle length is unaffected, but the duration of
bleeding is elongated in the subsequent cycle
17. MIFEPRISTONE
• Mifepristone, an anti-progestin synthetic steroid emergency
contraceptive option within 120 hours of UPSI at much lower
doses (10 to 50 mg)
• MOA - as an EC - pre-implantation, hence not considered an
abortifacient here
• Dual mode of action:
A. During the follicular phase, it delays the estrogen rise, LH
surge, and ovulation, thus lead to inhibition of ovulation
B. After ovulation, mifepristone inhibits endometrial
development, thus preventing implantation
. Effective even in obese women.
Marions L. Obstet Gynecol. 2002
18. SIDE EFFECTS OF MIFEPRISTONE
• Side effects : nausea, vomiting, headache, dizziness, fatigue,
mastalgia, lower abdominal pain, and diarrhea
• Studies indicate that a larger dose of mifepristone correlates with
a longer delay to menses
• Absolute contraindications :
i. Chronic adrenal failure,
ii. Steroid therapy,
iii. Severe asthma,
iv. Bleeding disorders,
v. Known hypersensitivity to prostaglandins or mifepristone, and
vi. Porphyria.
19. COPPER IUD
• The most effective form of emergency contraception, which is
inserted within 5 day of UPSI without change in efficacy
• Advantage providing ongoing contraception for up to 10 years
• MOA - inhibition of fertilization as the copper ions released -
toxic effect on sperm and ova - their mobility and viability
• Even if fertilization occur - implantation prevented - the
inflammatory response in the endometrium
• Both PRE-FERTILISATION and POST-FERTILISATION action
• Side effects – painful insertion process & menorrhagia
• Absolute contraindications - pregnancy undiagnosed vaginal
bleeding, malignant gestational trophoblastic disease, copper
allergy Australian family physician. 2017 Oct;46(10):722.
20. LIMITATIONS
• Despite The Long-term Contraceptive Benefits Of The
Copper IUCDs – Underutilized
• FACTORS: contribute to the relatively low use of the copper
IUCD as a form of EC
a) The Necessity Of IUCD Placement By A Trained Health Care
Provider,
b) High Up-front Costs,
c) Lack Of Provider And
d) Patient knowledge regarding the IUCD’ s effectiveness and
use as a form of EC
21. FACTORS AFFECTING ECP USE
• Successful use of emergency contraception requires accurate
knowledge about the different EC methods by both
providers and patients, prescriptions when necessary for
obtaining ECPs, and access to the different methods
• Unfortunately, despite awareness of the availability of
emergency contraception, knowledge about timing, and
appropriateness continues to be an issue
22. OCCASIONALLY, MEDIA COVERAGE HAS PORTRAYED ECP USE IN
A NEGATIVE MANNER
They wrote:
• Often the male partner
does not bring the pills and
this puts woman at more
risk
• Youngsters are using
emergency pills too often
• These pills should be sold
only on a doctor's
prescription
23. CONCLUSIONS
• The available methods for emergency contraception in INDIA
are: Yuzpe regimen, high dose levonorgestrel, copper IUD
• The treatment must begin within the first 72 h after
unprotected intercourse (for hormonal regimens)
• The Yuzpe regimen fails in about 2% of women who use it
correctly. Levonorgestrel was slightly, but not significantly
more effective than the Yuzpe regimen in preventing
pregnancy
• The earlier emergency contraceptive treatment - started -
more effective - Mifepristone in low dose (unavailable in
India) and
• Copper-releasing IUD are highly effective but it need to be
administered and followed-up by highly qualified health care
providers
24. NEW EC - ULIPRISTAL ACETATE 30 MG
Therapeutic indications:
Emergency contraception within 120 hours (5 days) of
unprotected sexual intercourse or contraceptive failure
For example:
- UPSI : Unprotected sexual intercourse
- Failure of condom : breakage ,slippage etc.
-Missed pill , patch , ring, injection , IUD expulsion etc.
Ulipristal acetate is a derivative of 19-norprogesterone
It is a selective progesterone- receptor modulator (SPRM)
25. DRUG APPROVAL
• In Europe since 2009, In USA by FDA since 2010 , In Australia, approved
since March 2016
• In India, approved by DCGI in 2020
MOA: UPA has an inhibitory effect on ovulation when administered during
the follicular phase
• The treatment consists of one tablet to be taken orally as soon as
possible, but no later than 120 hours (5 days) after UPSI or contraceptive
failure
• If vomiting occurs within 3 hours of the tablet intake, another tablet
should be taken
• If a woman’s menstrual period is late or in case of symptoms of
pregnancy, pregnancy should be excluded before the tablet is
administered
26. • The route of administration is oral, metabolism occurs in the liver
• The mono-demethylated metabolite is pharmacologically active
• The active terminal half-life after 30 mg single dose is estimated to
be 32.4 ± 6.3 hours, 90% of the excretion is with feces
27. DRUG INTERACTIONS - Ulipristal Acetate 30 mg
• UPA’s effectiveness - Reduced when taken concomitantly with
drugs like barbiturates, carbamazepine, phenytoin,
griseofulvin, and rifampin.
- Reduced when taken concomitantly with
Acid-suppressive drugs, such as PPI, H2 blocker, and antacids
• UPA’s effectiveness - Increased with CYP3A4 inhibitors such
as itraconazole and ketaconazole
28. Hormonal contraception use after
administration of Ullipristal acetate
Ulipristal acetate: an update for Australian GPs. Australian family physician. 2017
May;46(5):301.
29. SIDE EFFECTS
• Headache
• Abdominal pain
• Nausea
• Dysmenorrhea
• Fatigue
• Dizziness
• Delayed menses by 2.1
days
*https://www.medscape.com/viewarticle/926833
EMA (European Medicines Agency's )
states that the single-dose ulipristal
acetate 30 mg
emergency contraceptive does not
have concerns of liver injury*
30. SAFETY
• No teratogenic effects or birth
defects have been associated with
UPA taken by a woman who does
not realize she is already pregnant
• No adverse outcomes associated
with breastfeeding after taking
UPA, American guidelines
discourages mothers avoid giving
breastmilk in the 24 h following
consumption of UPA , while
European guidelines suggest a 7-
day window before resuming
breastfeeding an infant following
the ingestion of UPA
Haeger KO. Contracept Reprod Med. 201
CONTRAINDICATIONS
• Hypersensitivities to
UPA
• Severe liver disease,
owing to metabolism
in liver
• Known or suspected
pregnancy
31. EFFECTS ON OVULATION
With a follicle’s diameter of 14 –
16mm
The lead follicle stops growing
and was replaced by a new
lead follicle
With leading follicle’s diameter ≥18
mm
Follicular rupture is delayed
for at least 5-6 days, until
sperm from the UPSI for which
EC was taken are no longer
viable
Brache et al., 201
32. Aim : This study was designed to determine the capacity of
ulipristal acetate (UPA) 30mg, a selective progesterone receptor
modulator developed for EC, to block follicular rupture when
administered with a follicle of ≥18 mm.
33. RESULT
Inhibition of follicular rupture at 5 days after treatment
administration, stratified by LH status at time of treatment
34. A single dose of 30 mg UPA administered
immediately before ovulation (either before
the LH surge or when the LH surge has already
begun) significantly delays or inhibits
subsequent follicular rupture in comparison to
placebo-treated cycles
AUTHORS CONCLUDED…
35. Raw data from three pharmacokinetic studies with similar
methodology were pooled to allow direct comparison of UPA, LNG
and LNG + meloxicam's ability to prevent ovulation when
administered orally in the advanced follicular phase, with a leading
follicle of ≥18 mm
• Study : LNG 1.5 mg Vs Placebo
• Study 2 : LNG 1.5 mg Vs LNG 1.5 mg + Meloxicam 15 mg
• Study 3 : UPA 30 mg Vs Placebo
36. Survival analysis of time to follicular rupture from
treatment intake to the fifth day after treatment
Dominant Follicle Persisting
for at least 5 days after
Treatment (%)
1. UPA : 58.8 %
2. LNG : 14.6%
3. LNG + Melox : 38.7%
4. Placebo : 4%
The median time from treatment to
rupture was 6 days during the UPA
cycles versus 2 days in the LNG cycles
Brache V. Contraception. 2013
37. EFFICACY DIFFERENCE BETWEEN LEVONORGESTREL AND ULIPRISTAL
ACETATE : PROPORTION OF UNRUPTURED DOMINANT FOLLICLES AT 5 DAYS
AFTER TREATMENT ACCORDING TO LH STATUS AT TIME OF INTAKE
Treatment before LH Surge Onset
Treament after LH Surge onset but before
LH Peak
UPA 100% 78.60%
LNG 25% 14%
100%
78.60%
25%
14%
0%
20%
40%
60%
80%
100%
120%
Subjectswithoutfollicularrupture(%)
Inhibition of follicular rupture at 5 days after
treatment administration, stratified by LH status at
time of treatment.
UPA LNG
38. COMPARISON OF THE MECHANISMS OF
ACTION OF UPA AND LNG
*Brache V, Hum Reprod. 2010
An intact follicle was found in almost 60% of
cases on the fifth day after treatment, whereas
follicular rupture occurred on average 6 days
(from 4 to 10 days) after taking UPA
39. Ullipristal Acetate Prevents Ovulation More
Effectively Than Levonorgestrel
UPA works on the most
fertile days, i.e. just before
ovulation, during the LH
surge (pre-peak), when
levonorgestrel is no more
effective
Contraception. 2013 Nov 1;88(5):611-8.
Physiological LH Surge
40. EFFECTS ON THE FALLOPIAN TUBE
• The fallopian tube - Some studies have suggested that
progesterone may suppress ciliary beating frequency (CBF)
and muscular contraction in the fallopian tube
• UPA in contrast to this enhances CBF and frequency in
Fallopian tube
• Alters tubal environment, resulting/embryo transfer which
may minimal risk of ectopic pregnancy with the use of UPA
Li et al., 2010
41. Ulipristal Acetate Taken 48–120 Hours After
Intercourse for Emergency Contraception
• Pregnancy rate of 2.1% (95% confidence interval 1.4 – 3.1%).
1,241 women were evaluated, 26 were pregnant
• ADRs were mild or moderate (headache, nausea, and
abdominal pain)
• Cycle length increased a mean of 2.8 days, whereas the
duration of menstrual bleeding did not change
Ulipristal acetate is effective and well tolerated for emergency
contraception 48–120 hours after unprotected intercourse
P Fine et al. Obstetrics & Gynecology. 2010
42. Ulipristal acetate versus levonorgestrel for emergency
contraception: a randomised non-inferiority trial and meta
analyis
Aim : Efficacy and safety of ullipristal acetate with levonorgestrel for emergency contraception
• Randomized, multicenter, non-inferiority trial
• 2221 women were randomly assigned to receive a single, supervised dose of 30 mg
ulipristal acetate (n=1104) or 1·5 mg levonorgestrel (n=1117) orally
Glasier A et al. Lancet 2010
UPA is 2.5 times
more effective
than LNG
Pregnancy rates per 1000 women in the first 24 hours after unprotected sex
55 with no
intervention 23 with LNG
9 with
UPA
43. EFFICACY DIFFERENCE BETWEEN
LEVONORGESTREL AND ULIPRISTAL ACETATE
Administration Levonorgestrel
Ulipristal
acetate
Odds ratio (95%
CI)*
Within 24 hours 2.5% 0.9% 0.35 (0.11, 0.93)
Within 72 hours 2.2% 1.4% 0.58 (0.33, 0.99)
Within 120 hours 2.2% 1.3% 0.55 (0.32, 0.93)
Percentage of pregnancies in according to time from
unprotected sex to administration of emergency
contraception
Mazza D.Australian family physician. 2017.
44. AUTHORS CONCLUDED ….
Ulipristal acetate provides women and
health-care providers with an effective
alternative for emergency contraception
that can be used up to 5 days after
unprotected sexual intercourse
46. Faculty of sexual and reproductive healthcare
(fsrh) guidance 2017
• Ulipristal acetate has been demonstrated to be more
effective than levonorgestrel and should be considered as
the first-line oral emergency contraception option
• Ulipristal acetate remains an effective EHC option regardless
of a woman’s weight or BMI
FSRH Guideline (March 2017)
47. Interventions for emergency contraception
The studies compared 25 different interventions of different
types of emergency contraception.
What do Authors have to say about UPA:
• Ulipristal acetate (UPA) is more effective than levonorgestrel
• UPA users were probably more likely to resume menstruation
after the expected date
Cochrane Database of Systematic
Reviews 2019, Issue 1. Art. No.:
CD001324
48. SUMMARY
• Ulipristal Acetate (UPA) is a selective progesterone- receptor
modulator (SPRM)
• UPA is the only EHC to work up to the point of ovulation
• It is 2.5 times more effective than levonorgestrel
• UPA is metabolized predominantly by CYP3A4
• Most common side effect of UPA is headache
• FSRH recommends UPA as first-line oral emergency
contraceptive and effective regardless of a woman’s BMI
Notas del editor
Although the time of ovulation may be difficult to predict, the fertile window extends from 5 days before ovulation (the lifespan of a sperm within the female genitourinary (GU) tract) to the day of ovulation (after which time the ovum deteriorates)4 (Fig. 1). The highest rates of conception begin 2 days before and continue up to the day of ovulation.
Unlike the pills described below, the mechanism of the copper IUD is somewhat different. Pre-fertilization effects are prominent.
The copper composition can be toxic to both the ovum and the sperm.
Additionally, the foreign body induces a chronic inflammatory response, leading to release of cytokines and integrins. These inflammatory markers cause both a spermicidal effect and inhibit implantation even if fertilization does occur.
Ulipristal acetate is taken as a single 30 mg dose as soon as possible after unprotected intercourse, but has continuing efficacy up to five days later (120 hours), compared with 72 hours for levonorgestrel ECP.
Ulipristal acetate became available as an ECP in the European Union in 2009. This was followed by its release in the US in 2010. In March 2016, it became available in Australia as a Schedule 4 (prescription) item but, following approval by the Therapeutic Goods Administration (TGA),7 from 1 February 2017 it has become a Schedule 3 (pharmacist only) item, available over the counter
The concomitant administration of medicinal products that tend to increase gastric pH may also decrease the drug’s efficacy
Since both UPA and progestin-based contraceptives bind to progesterone receptors, patients are advised to wait for at least 5 days between the administration of UPA and starting/resuming a hormonal contraceptive
Patients should also be advised to undertake a pregnancy test three weeks after commencement of the hormonal contraception
It is recommended to use of barrier protection (e.g., a condom) until the patient’s next menstrual cycle
It is not appropriate to insert a hormonal IUD if a woman has received ulipristal acetate in that cycle
A bridging method should be offered until pregnancy can be excluded
While repeated use of UPA within the same cycle is safe, it may not be suitable for use as an ongoing, regular method because users are likely to ovulate at some point and therefore be at risk for pregnancy
UPA has an inhibitory effect on ovulation when administered during the follicular phase. In particular, during the mid-follicular phase, with follicles between 14 and 16 mm in diameter, a single dose between 10 and 100 mg produced a delay in follicular rupture and suppression of plasma levels of estradiol (Stratton et al. 2000). On the other hand, when women with follicles larger than 18 mm in diameter took the pill, a delay in follicular rupture occurred between 5 and 6 days in 59% of the cases (Brache et al. 2010)
When UPA was administered before the onset
of the LH surge,, follicle rupture had not occurred within 5 days in 8/8 (100%) and after the onset but before the LH peak 11/14 [78.6%;
95% CI cycles, . In contrast, when UPA was given after the LH peak, follicle rupture inhibition was only observed in
1/12 [8.3%; 95% CI (0.2–38.5)] cycles.
study demonstrates that UPA can significantly delay follicular rupture when given immediately before ovulation. This
new generation EC compound could possibly prevent pregnancy when administered in the advanced follicular phase, even if LH levels have
already begun to rise, a time when levonorgestrel EC is no longer effective in inhibiting ovulation.
By the time the follicle reaches 18–20 mm (ovulation should occur within 48 h), ovulation is prevented by levonorgestrel in only 12% of cycles, whereas ulipristal acetate prevents ovulation in 60% of cycles, therefore potentially preventing pregnancy in substantially more women than levonorgestrel.
Ulipristal acetate delays ovulation by at least five days when given before the onset of the luteinising hormone (LH) surge in 100% of cycles; in comparison, levonorgestrel only achieves this in 25% of cycles.8 When administered once the LH surge has commenced, but before it peaks, ulipristal acetate delays ovulation in 79% of cycles, whereas levonorgestrel delays ovulation in only 14% of cycles.8 Once the LH surge has reached its peak, neither ulipristal acetate nor levonorgestral has any effect on ovulation.
Observations:
Fig. 1 illustrates the difference between groups in AUC0–48 of total LNG
Fig. 2 illustrates the similarity between groups in mean AUC0–48 for UPA