evaluation of new approaches

111
NARENDRA MALHOTRA M.D., F.I.C.O.G., F.I.C.M.C.H Prof. Dubrovick International university,croatia Indian FOGSI representative to FIGO President FOGSI (2008) Dean of I.C.M.U. (2008) Director Ian Donald School of Ultrasound National Tech. Advisor for FOGSI-G.O.I.—Mc Arthur Foundation EOC Course Hon Prof Ob Gyn at DMIMS,Sawangi,Advisor ART unit at MAMC & SMS Jaipur Editor od SAFOG journal Chairman publication committee of AOFOG Practicing Obstetrician Gynecologist at Agra. Special Interest in High Risk Obs., Ultrasound, Laparoscopy and Infertility, ART & Genetics Member and Fellow of many Indian and international organisations FOGSI Imaging Science Chairman (1996-2000) Awarded best paper and best poster at FOGSI : 5 times, Ethicon fellowship, AOFOG young gyn. award, Corion award, Man of the year award, Best Citizens of India award Over 30 published and 100 presented papers Over 50 guest lectures given in India & Abroad.Presented 10 orations. Organised many workshops, training programmes, travel seminars and conferences Editor 8 books, many chapters, on editorial board of many journals Editor of series of STEP by STEP books Revising editor for Jeatcoate’s Textbook of Gynaecology (2007) and DONALD OBS MANNUAL(2012) Very active Sports man, Rotarian and Social worker MALHOTRA HOSPITALS 84, M.G. Road, Agra-282 010 Phone : (O) 0562-2260275/2260276/2260277, (R) 0562-2260279, (M) 98370-33335; Fax : 0562-2265194 E-mail : [email protected] / [email protected] Website : www.malhotrahospitals.com Apollo Pankaj Hospitals, Agra Consultant for IVF at jalandhar,ludhiana,ambala,bhiwani,gwalior,allahabad,gorakhpur,udaipur,bariely,jaipur,delhi

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Page 1: Evaluation of new approaches

NARENDRA MALHOTRAM.D., F.I.C.O.G., F.I.C.M.C.H

• Prof. Dubrovick International university,croatia• Indian FOGSI representative to FIGO• President FOGSI (2008)• Dean of I.C.M.U. (2008)• Director Ian Donald School of Ultrasound• National Tech. Advisor for FOGSI-G.O.I.—Mc Arthur Foundation EOC Course• Hon Prof Ob Gyn at DMIMS,Sawangi,Advisor ART unit at MAMC & SMS Jaipur• Editor od SAFOG journal• Chairman publication committee of AOFOG• Practicing Obstetrician Gynecologist at Agra. Special Interest in High Risk Obs., Ultrasound, Laparoscopy and

Infertility, ART & Genetics• Member and Fellow of many Indian and international organisations• FOGSI Imaging Science Chairman (1996-2000)• Awarded best paper and best poster at FOGSI : 5 times, Ethicon fellowship, AOFOG young gyn. award, Corion

award, Man of the year award, Best Citizens of India award• Over 30 published and 100 presented papers• Over 50 guest lectures given in India & Abroad.Presented 10 orations.• Organised many workshops, training programmes, travel seminars and conferences• Editor 8 books, many chapters, on editorial board of many journals• Editor of series of STEP by STEP books• Revising editor for Jeatcoate’s Textbook of Gynaecology (2007) and DONALD OBS MANNUAL(2012)• Very active Sports man, Rotarian and Social worker

MALHOTRA HOSPITALS84, M.G. Road, Agra-282 010

Phone : (O) 0562-2260275/2260276/2260277, (R) 0562-2260279, (M) 98370-33335; Fax : 0562-2265194E-mail : [email protected] / [email protected]

Website : www.malhotrahospitals.comApollo Pankaj Hospitals, Agra

Consultant for IVF at jalandhar,ludhiana,ambala,bhiwani,gwalior,allahabad,gorakhpur,udaipur,bariely,jaipur,delhiNeapal & Bangladesh

Page 2: Evaluation of new approaches

NO DISCLOSURES NO CONFLICT OF INTREST

planet earth is getting heavier

Page 3: Evaluation of new approaches

  

Evaluation of New Approaches to

Female Contraception     

NARENDRA MALHOTRAJAIDEEP MALHOTRA

NEHARIKA MALHOTRA BORASAMIKSHA GUPTA

PARUL MITTALSHEMI BANSAL

KESHAV MALHOTRAwww.rainbowhospitals.org

INDIA

[email protected]

Page 4: Evaluation of new approaches

I come from AGRA city of Taj Mahal the biggest ever erection for a woman

THE

MTTBCMNMH

RAINBOW HOSPITALS

Page 5: Evaluation of new approaches

AGRA-BOSTONVIA

DELHI-LONDON

Page 6: Evaluation of new approaches
Page 7: Evaluation of new approaches

AS THE KNOWLEDGE OF REPRODUCTIVE PHYSIOLOGY GREW,NEWER METHODS TO CONTROL FERTILITY EVOLVED

population control has been practised from ancient timeswhen arabs used to insert pebbles in the uterus of female camels and various concoctions were used for douching just after and before intercourse

Page 8: Evaluation of new approaches

Antiquity: Ancient Egyptian women use a combination of cotton, dates, honey and acacia as a suppository, and it turns out fermented acacia really does have a 

spermicidal effect. The Bible and the Koran both refer to coitus interruptus (the withdrawal method).

            

Page 9: Evaluation of new approaches

BIRTH CONTROL & PLANNED PARENTHOOD

1914-1921 Activist Margaret Sanger coins the term “birth control,” opens first birth control clinic in Brownsville, Brooklyn, and starts the American Birth Control League, the precursor to Planned Parenthood.1951 Sanger and Pincus meet at a dinner party in New York; she persuades him to work on a birth control pill.

1952 The race is on. Pincus tests progesterone in rats and finds it works. He meets gynecologist John Rock, who has already begun testing chemical contraception in women. Frank Colton, chief chemist at the pharmaceutical company Searle, also independently develops synthetic progesterone

Page 10: Evaluation of new approaches

Introduction

• Despite of the wide spread availability of a cafeteria of contraceptive choices the world still sees

• a 49% rate of unintended pregnancies • a 22.5% rate of unintended births• a 26.5% rate of elective abortions in the U.S.

• In the developing world this figure may be much higher

0

10

20

30

40

50

60

1 2 3

Series1

Page 11: Evaluation of new approaches

POPULATION EXPLOSION THE “BOMB” HAS EXPLODED IN

DEVELOPING COUNTRIES

                                             

POLPULATION CONTROL EXPRESS HAS DERAILED

Page 12: Evaluation of new approaches

UN/WORLD BANKAccording to projections of the UnitedNations (UN) and the World Bank, 80–90 % of population growth until 2025will occur in developing countries; 50 %of population growth is based on increasinglife expectancy attributed toe. g. better medical care, 17 % of couplesare wishing for more than two childrenand 33 % of the population growth stemsfrom unwanted pregnancies.

www.unfpa.orgWHO www.who.int/reproductivehealth/en UN : The world at six billion www.u.n.org

Page 13: Evaluation of new approaches

IS THERE STILL HOPE TO CONTROL POPULATION ???

• WELL YES AND NO ?• NO BECAUSE THE BATTLE IS LOST….• YES BECOS WE CAN STILL HOPE TO STABILSE THE

POPULATION GROWTH BY USE OF NEWER CONTRACEPTIVE METHODS(SPECIALLY EDUCATING AND EMPOWERING WOMEN TO USE NEWER METHODS)

Page 14: Evaluation of new approaches

Female contraception has given a new meaning to control of reproduction to a woman.

Various female contraceptive methods have flooded the market today and the choice for the user and also for the provider sometimes has become difficult.

This presentation aims to evaluate the various newer approaches to female contraception in Global settings.

 

Page 15: Evaluation of new approaches

Today a basket of contraceptive choices available to women and various studies have shown that today even in the educated and developed world the first year failure rates are much higher in typical users than perfect users

Page 16: Evaluation of new approaches

What do women want from an ideal contraceptive method?

• Highly effective

• Prolonged duration of action

• Rapidly reversible

• Privacy of use

• Protection against STD

• Easily accessible

Page 17: Evaluation of new approaches

WHY NEWER CONTRACEPTION ? “Newer”, innovations are needed,and the

obvious answer is because ‘the pill’ will not work if not taken (for many reasons) and hormones are not suitable to all women and what may be good for some, may not be suitable to everyone

Page 18: Evaluation of new approaches

WELL THIS IS AN EDITORIAL IN JAN 2013

Page 19: Evaluation of new approaches

The newer research being done in the world by only two major pharmaceuticals who can afford research

  

Generics are mainly produced by One .To find one new substance more than 5000 drugs need to be tested over 10–15 years, costing 400–800 million US Dollars.The other three have stopped the research in the field of contraception

Page 20: Evaluation of new approaches

The newer methods make a formidable list of additions to the

current choices• Newer Pills• Newer Barrier methods• Implants• Patches• Rings• Injectables• Microbicides• I.U.C.D.’s(Intrauterine Uterine Devises)• Transcervical Sterilization• Male hormonal contraception• Gene based approaches• Immune contraception• Anti Progesterone• Surgeryless Contraception• New Fertility awareness based methods

Page 21: Evaluation of new approaches

EVALUATION OF NEWER METHODS HOW??

• Efficacy• Side Effects• Easy use• Compliance• Duration of action• Manufacturing Process• Costs• Newer mode of actions• Additional non-contraceptive benefits• Applicable to masses and acceptance

Page 22: Evaluation of new approaches

WHO fertility control in the future will focus on

1. Improvement of existing methods: efficacy, side effects, duration of action, manufacturing process, costs2. New approaches: more selective mode of action3. New targets for contraception

Page 23: Evaluation of new approaches

INNOVATIONS FOR MODERN CONTRACEPTIVE METHOD

Modern contraceptive methods have surprisingly only a short history and has been dominated by the innovations in the “pill” and to some extent “other hormonal methods”. These innovations have mainly targeted

• Tinkering with the pill contents• Tinkering with the pill dosage• Tinkering with the routes of administration of

hormonal contraception

Page 24: Evaluation of new approaches
Page 25: Evaluation of new approaches

News about 3rd gen OCPs with

• Contain progestins desogestrel or gestodene do have increased risk of VTE– LOE=2a

• Odds of developing a VTE with 3rd gen OCP was 70% higher than with 2nd gen OCPs

Page 26: Evaluation of new approaches

Increased Risk of OCP Failure in Obese Women

• Study showed women with BMI> 27 had 60% increased pregnancy risk compared to women with BMI of 21 or less

• Biologic reasons may include: – higher BMR– induction of hepatic enzymes– increased sequestration of hormones in adipose

Holt,VL et al. OB/GYN Jan 2005;105:46-52

Page 27: Evaluation of new approaches

OCP recommendation for Women >70 kg

• Consider using OCPs with at least 50 mcg ethinyl estradiol to avoid contraceptive failure.

• LOE=2b

Page 28: Evaluation of new approaches

Reality of Non-compliance with OCPs

• Top 3 reasons for missing pills were:– Being away from home– Forgetting to take the pill– Not having a new pack in time for a new menstrual cycle

• Monthly diary cards completed by 141 women over age 18• 2/3 of pill users missed at least one pill in 3 mos study• Almost 50% of users missed 2 or more pills in study

Journal of Midwifery& Women’s Health 2005;50:380-5

Page 29: Evaluation of new approaches

New Oral Contraceptives (OCs) Offer Continuous Use and

New Progestin Formulations

• Description: Continuous-use products and pills containing new progestins.

• How they Work: Continuous pill use reduces menstrual cycles to four per year. New progestins may reduce side effects.

• Effectiveness: 6-8 pregnancies per 100 women in the first year. Continuous-use OCs may be more effective.

Page 30: Evaluation of new approaches
Page 31: Evaluation of new approaches

Drospirenone• Preliminary data suggest efficacy for ACNE /PMDD• Improved QOL indicators(non contraceptive benefits)• Reduced premenstrual sxs from 23% to 11%• Study used only 4 days of placebo instead of 7 days for 64

women in placebo-controlled crossover• May be as efficacious as SSRI

Contraception 2005;72:414-21

Page 32: Evaluation of new approaches

Importance of 24 days regimen in OCs?

With lower doses of EE & progestins used in recent OC pills , EE & progestions are cleared from the circulation 2-3 days after the

active pill is discontinued Due to several hormone-free days FSH & LH level start rising It causes unscheduled uterine bleeding (intermittent bleeding &

spotting) & ovulation too

Page 33: Evaluation of new approaches

So the call for the time is to reduce the pill free days from 7 to 4 i.e 24 +4 regimen

Page 34: Evaluation of new approaches

Benefits of the 24+4 regimen increased ovulation inhibition during the HFI

• The increases in levels of LH and FSH, observed with the 7-day HFI, were reduced by shortening the HFI to 3 or 4 days

LHOC 1 2 3 4 5 6 7 OC

0

2

4

6

8

10

FSHOC 1 2 3 4 5 6 7 OC

****

****

**

7-day HFI3- or 4-day HFI

mIU

/mL

**p<0.01  **p<0.01

LH = Luteinizing hormone; FSH = Follicle-stimulating hormone:HFI = Hormone-free interval; OC = Oral contraceptive

Post hoc comparisons of cycles

**p<0.01

Willis SA, et al. Contraception 2006;74:10–3

Page 35: Evaluation of new approaches

Benefits of the 24+4 regimen increased ovulation inhibition during the HFI

• Levels of estradiol and inhibin-B, representing ovarian responseto gonadotropin increases, that were observed with the 7-day HFI was reduced by shortening the HFI

OC 1 2 3 4 5 6 7 OC0

20

40

60

80

pg/m

L

Inhibin-B

OC 1 2 3 4 5 6 7 OC

** *

****

****

Estradiol

7-day HFI3- or 4-day HFI

*p<0.05  **p<0.01

Means for 2 cycles in 12 subjects

Post hoc comparisons of cycles

Willis SA, et al. Contraception 2006;74:10–3

 HFI = Hormone-free interval; OC = Oral contraceptive

Page 36: Evaluation of new approaches

Benefits of the 24+4 regimenreduced hormonal fluctuations

• The shorter HFI with the 24/4-day regimen results in less pronounced estradiol fluctuations compared with a 21/7-day regimen

• This may reduce hormone-withdrawal symptoms by creating more stable hormone levels

Klipping C et al. Contraception 2008;78:16–25

21+7 with drsp ® 24+4 with drsp ® 

3 5 8 11 14 17 20 23 26

Estrad

iol levels (pg/mL)

Cycle days

0

10

20

30

40

Page 37: Evaluation of new approaches

Benefits of the 24+4 regimencontinuous drospirenone activity

• 24+4 with drsp ® regimen provides 3 extra days of antimineralocorticoid and antiandrogenic activity per 28-day cycle relative to conventional 21+7 day OCs

Blode H, et al. Eur J Contracept Reprod Health Care 2000;5:256–64

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 Days

Drospire

none

 level

Extends into the 

4 day hormone-

free interval

3 extra days of drospirenone

Cycle 2

28-day presence™

Cycle 1

Page 38: Evaluation of new approaches

More Ovulation Inhibition 24+4 with drsp® has less follicular development even with ‘missed pills’ compared to 21+7 with drsp®M

Klipping et al, Contraception 2008

Hoogland Scores range from 1 to 6, 1 meaning no follicular activity, 6 meaning ovulation

Percentage of women with follicular development: Hoogland Scores 4-6

0

20

40

60

80

2nd Cycle "Missed Pill Cycle"

% of study

 pop

ulati

on

24+4 with drsp® 21+7 with drsp®

Page 39: Evaluation of new approaches

How effective is 24+4 with drsp®?

• 24+4 with drsp® has proven its excellent contraceptive efficacy in clinical trials

• Pearl Index*• 0.80 (upper one-sided 97.5% CI of 1.30) for typical use

• 0.41 (upper one-sided 97.5% CI of 0.85) for perfect use

This corresponds to more than 99% contraceptive protection

*The total number of unplanned pregnancies which occurred per 100 woman-years of use;  CI = confidence interval; Anttila L, et al. Int J Gynecol Obstet. 2009;107(suppl 2):s622

Page 40: Evaluation of new approaches

Significant reduction in acne lesions with 24+4 with drsp® : pooled data

*p<0.0001 vs. placebo

Koltun W, et al. Int J Gynecol Obstet 2009;107(suppl 2):s620

-60

-50

-40

-30

-20

-10

0Cycle 1 Cycle 3 Cycle 6

Percen

tage re

ducti

on in

 total lesion 

coun

t from baseline

24+4 with drsp®  Placebo

24+4 with drsp®  was associated with a greater reduction from baseline in total lesion counts versus placebo

Page 41: Evaluation of new approaches

Significant improvement in individual items with 24+4 with drsp 

1. a) Depressed; b) Hopeless;c) Worthless, guilty

2. Anxious, tense

3. a) Mood swings; b) Feel sensitive

4. a) Angry, irritable; b) Conflicts

5. Diminished interest

6. Difficulty concentrating

7. Tired, fatigued

8. a) Increased appetite;b) Food cravings

9. a) Slept more; b) Trouble sleeping

10. Overwhelmed, lack of control

11. a) Breast tenderness; b) Breast swelling; c) Bloated sensation;d) Headache;  e) Muscle pain

Pearlstein TB, et al. Contraception. 2005;72:414–21;Bayer Schering Pharma AG, data on file (protocol number 305141)

Item number

Chan

ge from

 baseline

1

*

24+4 with drsp®  Placebo 

2

*

3

*

4

*

5

*

6

*

7

*

8

*

9

*

10

*

11

*-3.5

-1.5

-1.0

-0.5

0.0

3.0

-2.5

-2.0

11 items of Daily Record of Severity of Problems:

*p<0.05 vs. placebo; decrease = improvement

Page 42: Evaluation of new approaches

24+4 with drsp®

now available in India

Page 43: Evaluation of new approaches

VTE associated with COC use: a class effect

CLASS EFFECT:

the risk of VTE is increased during COC use

– The risk of VTE during COC use is lower than during pregnancy and childbirth

Page 44: Evaluation of new approaches

Continuous-Use Regimen Offers New Choice for Pill Users

• Reduces side effects associated with hormone withdrawal (migraines, heavy or painful monthly bleeding).

• Breakthrough bleeding is more likely, but diminishes after 8 or 9 months of use.

• Seasonale® is packaged specifically for continuous use and is US FDA approved.– Users take pill every day for 84 days (12 weeks) and then take a hormone-free pill for 7 days.

Page 45: Evaluation of new approaches

Annual (365 days) Regimen – Lybrel

• Approved by FDA on 5/22/2007.• A low dose pill (20mcg ethinyl estradiol / 90mcg levonorgestrel) taken daily for 364 days without a placebophase or pill free interval.

• 13 dispenses of 28 active yellow pills.

Page 46: Evaluation of new approaches

Progestogen only pills, progesterone only injectables,

contraceptive patches and implants which are more popular in the developing countries

and why?

Page 47: Evaluation of new approaches

PICs: Other Benefits

• Do not affect breast feeding• Few side effects• No supplies needed by the client• Can be provided by trained non-medical

staff• Contain no estrogen• Do not interfere with intercourse

Page 48: Evaluation of new approaches

Effective, daily regimen of COCs is burdensome for many women

66%

72%

75%

0% 50% 100%

Is taken monthly

Effective with lowdose of hormone

Non-daily regimen

Percent of women

Thompson M. Sexuality, Reproduction and Menopause 2006;4:74–79

Women’s rating of ‘very desirable/absolutely essential’ for contraceptive attributes

Page 49: Evaluation of new approaches

Women Prefer Monthly Contraceptive Compared With A Daily Pill Regimen

80%

84%

85%

77% 78% 79% 80% 81% 82% 83% 84% 85% 86%

Consider switchingto minimize

estrogen exposure

Prefer convenienceof a monthly option

to a daily pill

Prefer monthlyoption with a lowerdose of hormones

Percent of women

Synovate Healthcare. Hormonal Contraceptive Claim Test survey data – ExUS, 2009

Page 50: Evaluation of new approaches

change of routes of hormonal contraceptives

NEWER DELIVERY ROUTES

Page 51: Evaluation of new approaches

Comparison of New Contraceptive Methods

Monthly injectable Implant

Intrauterine system Ring Patch

Efficacious Yes Yes Yes Yes Yes

Office Visits 1 monthInsertion &

removalInsertion &

removalRx Rx

Easily reversible

Yes Yes Yes Yes Yes

Dosing frequency

1 month 3-5 yrs 5 yrsEvery 4 weeks

Weekly

User-controlled

No No No Yes Yes

Discreet Yes Sometimes Yes Yes Sometimes

www.contraceptiononline.org

Page 52: Evaluation of new approaches

INJECTABLE CONTRACEPTIVESProgestin – Only Injectables      - Norethindrone enanthate (NET-EN)      - Depot-medroxyprogestrone acetate         (DMPA).           

    

- 150mg of DMPA via deep intramuscular injecton in gluteal region / deltoid muscle.

- Depo-SubQ Provera 104- 104mg of DMPA via subcutaneous injection into anterior thigh or abdomen.

- Duration of protection : 3 months (13 weeks). - Pearl index of 0.3-0.8 with typical use.

Page 53: Evaluation of new approaches

New Subcutaneous DMPA Formulation Recently Approved

• DMPA-SC provides slower, more sustained absorption of the progestin than conventional DMPA.

• Available only in a pre-filled Uniject syringe.

Page 54: Evaluation of new approaches

New Combined Injectables Offer Alternative to Progestin-only

Injectables

• Description: Monthly injections containing a progestin and an estrogen.

• How they work: Injected estrogen and progestin prevent ovulation, thicken cervical mucus, and suppress endometrial growth.

• Effectiveness: 0.1 to 0.4 pregnancies per 100 women per year.

Page 55: Evaluation of new approaches

Combined Injectables Offer Advantages Over Progestin-Only Injectables

• Irregular bleeding patterns less common and decrease with length of use.

• Women can become pregnant as soon as six weeks after last injection.

• Community health workers or women themselves can administer using Uniject, a single-use, prefilled, nonreusable syringe.

Page 56: Evaluation of new approaches

Contraceptive Injection: Lunelle

Intramuscular injection q 28-30 days

25 mg medroxyprogesterone acetate/ 5 mg estradiol cypionate

Rapid return to fertility

Better efficacy than OCPs

Adverse events are similar to OCPs

Greater than 90% of users would recommend to a friend

Kaunitz AM, et al. Contraception. 1999;60:179-187.

Page 57: Evaluation of new approaches

Contraceptive Implants

Page 58: Evaluation of new approaches

New Implants Have Fewer Rods than Norplant®

• Description: One or two progestin-releasing rods inserted just under the skin.

• How they work: Progestin released under the skin thickens the cervical mucus, prevents ovulation in many cycles, and suppresses endometrial growth. 

• Effectiveness: 0.3 to 1.1 pregnancies per 100 women in the first year of use as typically used. 

Page 59: Evaluation of new approaches

New Implants Offer Several Improvements Over Norplant

• Levonorgestrel implants:– Deliver same daily dose as Norplant– Effective for up to 5 years– Two rods instead of six capsules – Easier to insert and remove than Norplant. Insertions take less than five minutes. 

• Etonogestrel implants:– Single rod provides at least 3 years of protection against pregnancy. Users have few if any ovulatory cycles. 

• Nestorone implants:– Single rod designed specifically for breastfeeding     women. 

Page 60: Evaluation of new approaches

Intrauterine Devices

Page 61: Evaluation of new approaches

New Frameless Design May Reduce Some Side Effects

• Several copper cylinders strung together are anchored into the uterus. 

• May cause less pain and bleeding 

• Requires different insertion technique

• Less likely to be expelled when inserted correctly.

Page 62: Evaluation of new approaches

New Progestin-Releasing Lng -IUS Offers Many Advantages Over Cu-IUDs

• Approved in 2000 for 5 years of use. Available in over 100 countries.

• More effective than many Cu-IUDs. 

• Over time causes less bleeding than Cu-IUDs.

• Can use to treat heavy, prolonged bleeding or painful menstrual cramps.

Page 63: Evaluation of new approaches

Levonorgestrel Intrauterine System: LNG-IUS

• Releases 20 g of levonorgestrel per 24 hrs

• Duration: 5 years• Packaged with sterile

inserter• High efficacy-Pearl Index of 0.1

• Cheaper Indian version now available for 1/3 the costs

www.contraceptiononline.orgLahteenmaki P, et al. Steroids. 2000;65:693-697.

Page 64: Evaluation of new approaches

RINGS

Page 65: Evaluation of new approaches

New Contraceptive Rings• Developed by the

Population Council• Sponsored by USAID,

NICHD, WHO

• One year vaginal ring• Releases progesterone

receptor (PR) modulator

• Dual-protection ring • Anti-retroviral agents• Contraceptive steroids

Delivers Nesterone/EE 150/15 µg/day13 cycles with 3 weeks on reinsert after 1 week

Page 66: Evaluation of new approaches

Vaginal Ring:

Roumen FJ, et al. Hum Reprod. 2001;16:469-475. www.contraceptiononline.org

Vaginal ring releases 15 g of ethinyl estradiol and 120 g of etonogestrel daily

Worn for 3 out of 4 weeks

Self insertion and removal

Pregnancy rate 0.65 per 100 woman–years

Page 67: Evaluation of new approaches

Vaginal Ring Cycle Control and Tolerability

• Good cycle control

– Irregular bleeding was rare (2.6% - 6.4% of evaluable cycles)

– Withdrawal bleeding occurred (97.9% - 99.4% of evaluable cycles)

• Well tolerated and well accepted by users and their partners (only 5% of partners objected to use)

www.contraceptiononline.org

Roumen FJ, et al. Hum Reprod. 2001;16:469-475.

Page 68: Evaluation of new approaches

0

10

20

30

40

Incid

en

ce o

f Ir

r eg

ula

r b

leed

ing

(%

)

Bjarnadottir RI, et al. Am J Obstet Gynecol. 2002;186:389-395.

Vaginal Ring Compared to OC:Irregular Bleeding

Cycle Number

NuvaRing

Combined oral contraceptive

1 2 3 4 5 6

*

*P<0.001 for COC vs NuvaRing

www.contraceptiononline.org

Page 69: Evaluation of new approaches

Most women who try the vaginal ring report being very satisfied 

42%30%

34%61%

0%

20%

40%

60%

80%

100%

NuvaRing® users Pill users

Percenta

ge o

f w

om

en

Patient satisfaction with the vaginal ring versus a pill

Very satisfied

Very satisfied

Satisfied Satisfied

91%

76%

Page 70: Evaluation of new approaches

Reasons for satisfaction with vaginal ring

The 3 most frequently mentioned responses were:

• Monthly administration (54%)

• Low hormonal dose (31%)

• Ease of use (27%)

Roumen et al. Eur J Contracept Reprod Health Care 2006;11:14-22

92 95 96

7 4 32 1 10

25

50

75

100

Cycle 3 Cycle 6 Cycle 13

Pro

po

rtio

n o

f u

se

rs (

%)

(Very) Satisfied

Neutral

(Very) Dissatisfied

Page 71: Evaluation of new approaches

Would women recommend Vaginal Ring to others?

97

75

0

25

50

75

100

Women who completed thestudy

Women who discontinuedthe study

Prop

ortio

n of

use

rs (%

)

Agree

Dieben T, et al. Obstet Gynecol 2002;100:585-593

Page 72: Evaluation of new approaches

PATCHES

Page 73: Evaluation of new approaches

Contraceptive Patch:

• Patch contains 6 mg norelgestromin and 0.75 mg ethinyl estradiol

• Delivers continuous systemic doses of hormones

– 150 µg norelgestromin (NGMN)– 20 µg ethinyl estradiol (EE)

• Direct comparisons to oral contraceptive delivery doses cannot be made

Per day

www.contraceptiononline.org

Page 74: Evaluation of new approaches

Transdermal Contraceptive Patch

• 3-patch system– Apply 1 patch each week for 3 weeks– Apply each patch the same day of the week

• 1 week is patch-free

Week 1 Week 2 Week 3 Week 4

Patch #1

Patch #2

Patch #3

28-day cycle

Patch-free

Week 5

Start next cycle

28-day cycle

Abrams et al. J Clin Pharmacol. 41:1232, 2001Smallwood et al. Obstet Gynecol. 98:799, 2001

Page 75: Evaluation of new approaches

Transdermal Contraceptive PatchEfficacy & Cycle Control

Estrogen-progesterone patch with 7 day patches for 3 weeks, followed by a patch free week

Randomised study in 812 Vs OCs in 605• Pearl Index marginally lower than OCs• Higher breakthrough bleeding in first 2 cycles• More site reactions, mastalgia & dysmenorrhoea• Perfect compliance in 88.2% with patch & 77.7% with

OCs

                                                                                 Creasy, JAMA, 285:2347, 2001

Page 76: Evaluation of new approaches

Sites Of Application

- Buttocks- Upper outer arm- Back- Lower abdomen or- Upper torso excluding

breast

Page 77: Evaluation of new approaches

News about Patch

• FDA updated labelling since product exposes women to higher levels of estrogen than most OCPs– 60% more estrogen than 35 microgram estrogen

pill• May increase risk of thrombotic disease• FDA monitoring safety data closely• Lawyers already jumping on the band wagon

Page 78: Evaluation of new approaches

Patch Compared to OC: Adverse Events

Audet MC, et al. JAMA. 2001;285:2347-2354.

Patch (n=812) OC (n=605)

OverallTreatment

limiting OverallTreatment

limiting

Breast discomfort

19% 1.0% 6% 0.2%

Headache 22% 1.5% 22% 0.3%

Application site reaction

20% 2.6% NA NA

Nausea 20% 1.8% 18% 0.8%

Abdominal pain 8% 0.2% 8% 0.3%

Dysmenorrhea 13% 1.5% 10% 0.2%

Page 79: Evaluation of new approaches

Spray-On Contraceptives: A New Technique For Hormone Delivery

• Daily progestin-only spray-on is absorbed into the skin, then diffuses into bloodstream.

• Phase I clinical trials underway in Australia.

Page 80: Evaluation of new approaches

Contraceptive Gel

Clinical trial of Nestorone gel is applied to the skin daily for 3 months, suppressed ovulation in 83% of participants.

Page 81: Evaluation of new approaches

The need… Every year, an estimated :• 20 million unsafe abortions occur• 80,000 deaths result from

complications of unsafe abortions• 287,000 maternal deaths occur from

complications of pregnancy and birth

TIMELY AND PROPER USE OF EMERGENCY CONTRACEPTION TO PREVENT UNWANTED PREGNANCY CAN SAVE MANY LIVES AND REDUCE MENTAL TORTURE

Page 82: Evaluation of new approaches

Emergency Contraception… is it enough?

• There are safe methods to prevent pregnancy after unprotected sex

• How long ago did you have unprotected sex?

• Could you have been exposed to STIs/HIV?

Page 83: Evaluation of new approaches

Emergency Contraception• Reduce risk of pregnancy

– Use even up to 5 days after unprotected intercourse

– More effective the sooner taken• Consider giving pt advance supply at annual PE/pap

– Pregnancy Risk reduced by 75-89%, if taken within 72 hrs

Page 84: Evaluation of new approaches

Types of Emergency Contraception

Progestin-only Oral Contraceptive Pills : (Emergency Contraceptive Pill) containing levonorgestrel

Combined Oral Contraceptive Pills : containing ethinyl estradiol and levonorgestrel (Use only pills brands containing these Hormones)

Insertion of IUCD Anti-progestins

(Mifepristone(RU486- 1st gen.Progestrone Receptor Modulator)

Page 85: Evaluation of new approaches

TWO TABLETS (0.75 mg Levonorgestrel each)

TAKEN AS A SINGLE DOSE WITHIN 120 HOURS (5 days) OF EXPOSURE

IS EQUALLY EFFECTIVE

WHO multicentric randomized trial, Lancet 2002,360:1803-10

Page 86: Evaluation of new approaches

IUCD

Inserted within 5 days of unprotected exposure• mechanical interference with implantation • Copper is blastocidal• Can be continued as regular method• Lowest failure rate--less than 1 %

Page 87: Evaluation of new approaches

ANTIPROGESTERONES

• Mifepristone(RU486)1st generation Progestrone Receptor Modulator

• inhibits progesterone• prevents implantation• interrupts early pregnancy• As EC 10 mg single dose within 5 days is

highly effective

Page 88: Evaluation of new approaches

Luteinizing HormoneLuteinizing Hormone

Follicular phase Surge Luteal phase

Synergize with FSH to support estrogen production

LH

Theca cell

Estrogens

FSH

Cholesterol

AndostendioneAromatization

Supporting corpus luteum

formation

Progesterone

Production

• Cumulus oophorus maturation

• Follicular rupture and oocyte expulsion

Resumption of oocyte meiosis

GV

GVB

Page 89: Evaluation of new approaches

Yuzpe Regimen <72 h Propose treatment

Menstruation Follicular phase

Preovulatory period

Mid-luteal phase

Late luteal phase

Bleeding

GnRh antagonist

Page 90: Evaluation of new approaches

Emergency contraception should prevent pregnancy in 100%

GnRH antagonist as one single injunction seems to do the work properly

GnRh Antagonist as EC

Highly effective - Avoid pregnancy

Free of side effects…….

Easy administered

Affordable

Page 91: Evaluation of new approaches

Condom Effectiveness vs Heterosexual HIV Transmission

• Study showed 80% reduction in HIV incidence with consistent use for all vaginal intercourse– LOE=1a

Page 92: Evaluation of new approaches

Female Condom: “Reality”

Page 93: Evaluation of new approaches

New Female Condoms Are Designed For Better Fit and Lower Cost 

• FC2 Female Condom:– Synthetic latex model.– available in developing 

countries in 2005.• VA Feminine condom:

– First latex model.– marketed in Western 

Europe, Brazil, India, and South Africa in 2005.

• The PATH Woman’s Condom:– Designed for near-

universal fit.– High user satisfaction 

in clinical trials. 

Page 94: Evaluation of new approaches

Vaginal Barrier Methods

Page 95: Evaluation of new approaches

Summary of Barrier MethodsContraceptive Technology,18th Revised edition, by Robert Hatcher, MD.

Page 96: Evaluation of new approaches

New Cervical Caps Designed to Reduce Fitting Time

• FemCap™– Silicone rubber device

fits over cervix and blocks sperm.

– Comes in three sizes; a provider must check the fit.

• Ovès™– Disposable cervical cap made of 

silicone. – Comes in three sizes; a provider 

must check the fit. – Effectiveness has not yet been 

established.

Page 97: Evaluation of new approaches

Contraceptive SpongesNo Fitting or Prescription Required 

• The Today Sponge® – Discontinued in 1994

but recently re-released in Canada.

– Effectiveness: 13 to 16 pregnancies per 100 users in the first year as typically used.

• Protectaid®

– New polyurethane foam sponge, packed with spermicide gel F-5®. 

– Manufacturer plans to apply for US FDA approval.

– Effectiveness: 23 pregnancies per 100 users in one year as typically used. 

Page 98: Evaluation of new approaches

Microbicides Can Reduce Transmission of HIV and other STIs

• Description: Vaginally applied substances designed to reduce transmission of HIV and other STIs. Some function as spermicides to provide contraceptive protection.

• How they work: Boost body’s defense against infection, damage or hinder disease pathogens, or prevent virus replication.

• Effectiveness: First microbicides expected to be 50-60% effective.

Page 99: Evaluation of new approaches

Why Are Microbicides So Promising?

• Could save many lives by protecting against HIV infection.– If 20% of people in high-risk groups used a 60% effective

microbicide, 2.5 million lives would be saved in the first three years of use.

– Could lead to considerable savings in public health expenditures.

• Women could control microbicide use.– Women could protect themselves against STIs when they

cannot use condoms, perhaps without needing the cooperation of their partners.

Page 100: Evaluation of new approaches

Microbicide Studies Explore User Preferences

• Acceptability studies conducted around the world found that women and men have great interest in using microbicides.– Women would prefer a microbicide to be an

odorless, colorless cream placed in the vagina with applicator.

– Most women, but few men, would prefer a formulation offering dual protection against both pregnancy and STIs.

Page 101: Evaluation of new approaches

New Fertility Awareness-Based Methods Provide Simplified Ways to Track Fertile Days

• Description: Tracking a woman’s fertility and avoiding unprotected sex on fertile days using colored beads or secretion diary.

• How they work: Avoiding unprotected intercourse during days identified as probably fertile.

• Effectiveness: Standard Days Method™—12 pregnancies per 100 women per year. TwoDay Method™—14 pregnancies per 100 women per year.

Page 102: Evaluation of new approaches

Standard Days Method Tracks Fertility with CycleBeads™

• Color-coded beads indicate fertile days.

• Works best for women who:– Have cycles between 26

and 32 days long and,– Most likely ovulate

between days 8 and 19 of the fertile period.

Page 103: Evaluation of new approaches

New Sterilization Techniques Offer Alternative to Surgery

• Description:  Procedures that prevent pregnancy permanently by reaching and blocking the fallopian tubes though the vagina and uterus.

• How they work:  Blocks egg from descending from a fallopian tube.

• Effectiveness: 0.2 to 2 pregnancies per 100 women in the first year of use.

Page 104: Evaluation of new approaches

Transcervical Female Sterilization New Sterilization Methods are Safer

• Essure®: A spring-like device scars and plugs the fallopian tubes.

• Quinacrine: A chemical compound scars and blocks fallopian tubes.

• The Adiana Procedure: A plastic implant is inserted into a lesion in the fallopian tubes. Tissue grows into the plug and blocks the fallopian tubes. 

Page 105: Evaluation of new approaches

Gene-Based Approaches Promise Dramatic Change in Contraception

• Target the genes or proteins involved in sperm and egg development.

• In women: target molecules to prevent ovulation.

• In men: prevent sperm from penetrating an egg’s outer layer.

• Unlikely to cause side effects.• At least 10 years away from reaching the

market.

Page 106: Evaluation of new approaches

The 21st century has brought many many new innovations in women health care including a new era of contraceptive choices. This, has and is, sometimes confusing to the user, provider and the prescriber. 

Page 107: Evaluation of new approaches

66

5 7 6

16

0

10

20

30

40

50

60

70

COC IUD Barrier Other No preference

Users’ opinion of best contraceptive method (baseline)

% o

f w

omen

Page 108: Evaluation of new approaches

“Technology made large populations possible and large populations make technology indispensable” 

Page 109: Evaluation of new approaches

Contraception Resources• Contraceptive Technology,18th Revised edition, by Robert Hatcher, MD

and website at:http://www.managingcontraception.com/cmanager/publish/

• Managing Contraception Pocket Guide by Robert Hatcher, MD • Planned Parenthood section on birth control options:

http://www.plannedparenthood.org/pp2/portal/medicalinfo/birthcontrol/

• Best Method For Me: http://www.bestmethodforme.com/survey/index.php

• Ortho Personalized Birth Control Selector: http://www.orthowomenshealth.com/birthcontrol/selector/index.html

• EC Info: NOT-2-LATE.com at: http://ec.princeton.edu/info/contrac.html

Page 110: Evaluation of new approaches

WELCOME TO INDIA IFFS 2016

Page 111: Evaluation of new approaches

thank you

“Contraceptives should be used at every conceivable occasion.”