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Premium member Presentation Transcript CONTRACEPTIVE UPDATES: CONTRACEPTIVE UPDATES PG Student :- Dr Abhay Dhanorkar PG Guide :- Dr S arita Wadhva 4/10/2012 1Scope: Scope Introduction Definition History Reproductive rights Contraceptive scenario in India & Maharashtra Classification of contraceptives Barrier methods Oral Contraceptive Pills and Emergency Contraceptive Pills Injectable contraceptives Intrauterine device (IUDs) Sterilization Miscellaneous Advanced contraceptive methods in pipeline 4/10/2012 2contraceptive methods: contraceptive methods Preventive methods to help women avoid unwanted pregancies . Include all temporary and permanent measures to prevent pregnancy. 4/10/2012 3Aim of contraception: Aim of contraception Family planning to check the population growth, To prevent STDs like AIDS. To reduce the stress of pregnancy, labour & lactation in women suffering from heart disease etc. 4/10/2012 4HISTORY: HISTORY 3000BC 1500 1838 1916 1960 1960s 4/10/2012 5History contd…: History contd … 1992 1980s -1990s Today Today 1972 4/10/2012 6India – Some important landmarks: India – Some important landmarks 1951 - The National family planning program 1965 - Lippies loop introduced 1971 - MTP act 1977 - Family welfare programme 1978 - Child Marriage act 1992 - CSSM 1997 - RCH- I 2005 - RCH II 2007 - Nuvaring /NRHM Contraceptive usage has been rising gradually in India. In 1970 - 13% In 1997 - 35% In 2009 - 48% . 4/10/2012 7PowerPoint Presentation: The fertility rate in India has been in long-term decline from 5.7 in 1966 to 2.62 in 2011. 14 Indian states have dipped below the 2.1 According to the latest health ministry data Worst TFR in Bihar (3.9) Uttar Pradesh (3.7) MP (3.3) Jharkhand (3.2) Chhattisgarh (3) Uttaranchal (2.6) Assam (2.6) Gujarat (2.5) While achieved targeted TFR, Tamil Nadu (1.7) Kerala (1.7) Maharashtra (1.9) Delhi (1.9) West Bengal (1.9) Karnataka (2) 4/10/2012 8Reproductive Rights: Reproductive Rights To enable control over individual’s reproductive lives following rights are given. Reproductive health as a component of overall health. Reproductive decision-making for Voluntary choice of marriage, family formation Determination of the number, timing and spacing of one’s children Enable individuals to make free and informed choices free from discrimination based on gender Reproductive security, including freedom from sexual violence and coercion, and the right to privacy. 4/10/2012 9Contraceptive Scenario in India: Contraceptive Scenario in India The current trends in family planning in India shows High level of knowledge among eligible couples Low acceptance remains for spacing methods. Female sterilization remains the most widely used family planning method in spite of efforts to popularise male sterilization. 4/10/2012 10INDIA FACT SHEET, NFHS-3, 2005-06: INDIA FACT SHEET, NFHS-3, 2005-06 Family Planning Use - & Fertility – Smaller families -becoming the norm. Fertility has continued to decline NFHS-2 – 2.9 Children NFHS-3 – 2.7 Children. 14 states have reached replacement level or below replacement level fertility. Percentage of women with two daughters and no sons say they want no more children, NFHS-2 – 47% NFHS-3 – 64%. 4/10/2012 11PowerPoint Presentation: Declining fertility is due to Increased use of contraception - 43% to 49% between NFHS-2 and NFHS-3. Women ages 20-24 were married before the legal age of marriage of 18 years NFHS-2 - 50 % NFHS-3 - 47.4% Increase in median age at first birth from 19.8 to 19.2. 4/10/2012 12Key Indicators for India from NFHS-3: Key Indicators for India from NFHS-3 Marriage and Fertility NFHS -1 (1992-93) NFHS-2 (1998-99) NFHS 3 (2005-06) Urban Rural Women age 20-24 married by age 18 (%) 54.2 50.0 47.4 29.3 56.2 Men age 25-29 married by age 21 (%) NA NA 32.2 18.1 40.3 Total fertility rate (children per woman) 3.4 2.9 2.7 2.1 3.0 Women age 15-19 who were already mothers or pregnant at the time of the survey NA NA 16.0 8.7 19.1 Median age at first birth for women age 25-49 19.4 19.3 19.8 20.9 19.3 Married women with 2 living children wanting no more children 59.7 72.4 84.6 89.7 81.6 Two sons 71.5 82.7 89.9 92.1 88.6 One son, one daughter 66.0 76.4 87.0 92.8 85.3 Two daughters 36.9 47.0 64.1 74.7 54.4 4/10/2012 13Key Indicators for India from NFHS-3 contd…: Key Indicators for India from NFHS-3 contd … Family Planning (currently married women, age 15–49) Current use NFHS -1 (1992-93) NFHS-2 (1998-99) NFHS 3 (2005-06) Urban Rural Any method (%) 40.7 48.2 56.3 64.0 53.0 Any modern method (%) 36.5 42.8 48.5 55.8 45.3 Female sterilization (%) 27.4 34.1 37.3 37.8 37.1 Male sterilization (%) 3.5 1.9 1.0 1.1 1.0 IUD (%) 1.9 1.6 1.7 3.2 1.1 Pill (%) 1.2 2.1 3.1 3.8 2.8 Condom (%) 2.4 3.1 5.2 9.8 3.2 Total unmet need (%) 19.5 15.8 12.8 9.7 14.1 For spacing (%) 11.0 8.3 6.2 4.5 6.9 For limiting (%) 8.5 7.5 6.6 5.2 7.2 4/10/2012 14Key Indicators for Maharashtra from NFHS-3: Key Indicators for Maharashtra from NFHS-3 Marriage and Fertility NFHS -1 (1992-93) NFHS-2 (1998-99) NFHS 3 (2005-06) Urban Rural Women age 20-24 married by age 18 (%) 53.9 47.7 39.4 29.2 49.9 Men age 25-29 married by age 21 (%) NA NA 15.0 12.6 18.9 Total fertility rate (children per woman) 2.9 2.5 2.1 1.9 2.3 Women age 15-19 who were already mothers or pregnant at the time of the survey NA NA 13.8 9.3 18.2 Median age at first birth for women age 25-49 19.0 19.0 19.9 20.9 19.0 Married women with 2 living children wanting no more children 73.1 81.2 89.0 89.0 89.1 Two sons 81.7 93.5 95.5 93.1 97.5 One son, one daughter 79.2 85.3 92.8 91.5 94.2 Two daughters 37.6 41.4 55.1 69.2 36.5 4/10/2012 15Key Indicators for Maharashtra from NFHS-3 contd…: Key Indicators for Maharashtra from NFHS-3 contd … Family Planning (currently married women, age 15–49) Current use NFHS -1 (1992-93) NFHS-2 (1998-99) NFHS 3 (2005-06) Urban Rural Any method (%) 54.1 60.9 66.9 66.7 67.1 Any modern method (%) 52.9 59.9 64.9 64.0 65.8 Female sterilization (%) 40.3 48.5 51.1 44.2 57.5 Male sterilization (%) 6.2 3.7 2.1 1.0 3.2 IUD (%) 2.5 1.9 3.0 5.3 0.8 Pill (%) 1.4 1.7 2.4 3.6 1.3 Condom (%) 2.5 4.0 6.2 9.8 2.9 Total unmet need (%) 14.1 13.0 9.4 9.8 9.0 For spacing (%) 7.3 8.1 5.4 5.3 5.6 For limiting (%) 6.8 4.9 3.9 4.5 3.3 4/10/2012 16Need for Updates: Need for Updates The current unmet need for family planning is -12.8 % of which For spacing - 6.2 % and For Limiting births - 6.6 % Two important issues in catering to the unmet demand are Poor access to family planning services. Poor Quality of family planning services. 4/10/2012 17Classification of contraceptive methods: Classification of contraceptive methods 4/10/2012 18Evaluation of contraceptive methods: Evaluation of contraceptive methods Contraceptive efficiency: It is the measurement of unplanned pregnancies even after the use of contraceptive measures. 1) Pearl Index : no. Of failures/100 woman-yr of exposure Failure rate/HWY= Total accidental pregnancies × 1200 total months of exposure 2) Life table analysis : calculates a failure rate for each month of use 4/10/2012 19I) Barrier methods: I) Barrier methods 4/10/2012 20Physical methods: Physical methods 1) condoms : Made up of fine latex sheath Most widely used barrier in males Highly effective if used correctly ADVANTAGE: Simple spacing method No side effects Easily available, safe & inexpensive Protects against STDs DISADVANTAGE: Chances of slip off and tear off Failure rate: 2-3/HWY 4/10/2012 21 Types of condoms: Types of condoms 1. Flavoured condoms 2. Dotted condoms 3. Super thin condoms It is transparent with a thin layer made of sheerlon material that acts like a second skin. It is highly effective against pregnancy and STDs. 4. Pleasure-shaped condoms It heightens sensitivity for both the partners. It has loose and enlarged tip. 5. Glow in the dark condoms When exposed to light for 30 seconds, it glows in the dark. It is non-toxic and has three layers. The inner and the outermost layers are made up of latex and the middle one contains a safe pigment that makes it glow. 4/10/2012 22Other Advances in Male Condoms: Other Advances in Male Condoms Desensitizing condoms with “climax control lubricant featuring benzocaine that helps prolong sexual pleasure and aids in prevention of premature ejaculation” ( Durex Performax , Trojan Extended Pleasure) Spermicidally lubricated condoms Distrubution of condoms: Health worker, Asha , Condom vending machine 4/10/2012 23PowerPoint Presentation: 4/10/2012 24Condom Applicator: Condom Applicator A South African designer invented : a condom that can be applied in less than four seconds. Dubbed Pronto, the condom aims to be quicker and easier to apply than conventional brands with the hopes of encouraging more people to use them. The condom is contained within a foil pack -- which also acts as the applicator. Crack the pack in half and slip the plastic applicator apart, then roll the condom down and snap the applicator off the condom -- all in one swift movement. Cost -Rs.33.95 per condom. British biotech company Futura Medical has created a new condom, -CSD500 -coated with a vasodilator gel. 4/10/2012 25PowerPoint Presentation: Strong, soft, transparent polyurethane sheath inserted in the vagina before sexual intercourse 15 cm long X 7 cm diameter There is silicone-based lubricant on the condom, but additional lubrication can be used. Has two flexible rings The outer ring , The larger, open ring stays outside the vagina, covering part of the perineum and labia during intercourse . The inner ring at the closed end of the condom eases insertion into the vagina, covering the cervix and holding the condom in place 4/10/2012 26PowerPoint Presentation: The female condom has been available since 1992 brand names, FC Female Condom, Aastha , Velvete,Reality , Femidom , Dominique, Femy , Myfemy , Protectiv ' and Care. 4/10/2012 27PowerPoint Presentation: Female condom instructions A new condom every time Make sure the condom is in place NO male condom with a female condom Inserted for up to 8 hours Wash your hands carefully with soap and water before inserting, or removing the female condom. 4/10/2012 28PowerPoint Presentation: Female Condoms How to insert the female condom ? 4/10/2012 29PowerPoint Presentation: How to remove the female condom ? To remove the condom, twist the outer ring and gently pull the condom out . Wrap the condom in the package or in tissue, and throw it in the garbage. Do not put it into the toilet . 4/10/2012 30Advantages of Female Condom: Advantages of Female Condom Female-controlled No medical condition limits use. More comfortable to men, less decrease in sensation than male latex condoms. Ease of use by men with erectile dysfunction. Offers greater protection as it covers both internal and external genitalia. Stronger (polyurethane is 40% more stronger than latex), and therefore there is less frequent breakage (1% compared to 4% for male condoms) Longer shelf-life under unfavourable storage conditions. CSWs found that the it allowed them to continue their job without interruption during menstruation. 4/10/2012 31Disadvantages of Female condom: Disadvantages of Female condom Difficulties in insertion and removal. Casues discomfort and inconvenience associated with use and movement of device during use. More expensive than male condoms. Failure rate – 21/HWY 4/10/2012 32Some Evidences of FC use: Some Evidences of FC use In a study in Alabama , 25% - Unable to correctly insert in first use 3% - Never able to do so despite additional instructions and multiple efforts. A study focused mainly on acceptability in 58 respondents from urban slums in Chennai and CSWs showed good acceptability in this group. Study conducted in the Andhra Pradesh, Kerala and Maharashtra, amongst 2 target groups, FSWs and eligible couples. For study period of 2 months, Usage levels were above 90% in both categories. 4/10/2012 33Physical methods contd...: Physical methods contd... 2)diaphragm: Dutch cap / Fem caps Vaginal barrier Consists of a flexible ring made up of spring material to which a cup shaped synthetic rubber is attached Inserted into vagina over cervix A spermicidal jelly is always used Failure Rate: 6-12/HWY 4/10/2012 34Physical methods (c0ntd...): Physical methods (c0ntd...) 3) Cervical cap: smaller as compared to diaphragm Applied over cervix ADVANTAGE : Inexpensive, No medical consultation Total absence of risks and medical CIs DISADVANTAGE: Failures are quite common Chances of displacement high Cervicitis and local irritation Failure rate: 11/HWY 4/10/2012 35physical Methods (contd...): physical Methods (contd...) 4) VAGINAL SPONGE Trade name ‘TODAY’ Polyurethane foam sponge saturated with spermicide nonoxynol 9 (1gm) Less effective than diaphragm Failure Rate: 20-40/HWY in multiparous 9-20/HWY in nulliparous 4/10/2012 36Chemical barriers: Chemical barriers Spermicidal agents which can destroy sperms when applied in female genital tract They are available as Foams Creams. Jellies, Paste Suppositories Soluble films Common spermicidal agents Nanoynol-9 Octoxynol-3 Failure rate: 6/HWY 4/10/2012 37Chemical barriers (contd...): Chemical barriers (contd...) ADVANTAGES: Inexpensive Well tolerated Good protection DISADVANTAGES: High failure rate Must be used immediately before intercourse Mild burning and irritation If used alone, not most effective in preventing pregnancy 4/10/2012 38Intrauterine devices: Intrauterine devices 4/10/2012 39classification: classification 4/10/2012 40First generation iud: First generation iud They are inert or Nonmedicated devices made up of polyethylene Different shapes and sizes LIPPE’S LOOP: Double ‘S’ shaped device Made up polyethylene material Non toxic, non tissue reactive & extremely durable Small amount of Barium Sulphate is also added for radiological examination Available in 4 sizes A,B,C &D Failure rate: 3-5 / HWY 4/10/2012 41Second generation Iud: Second generation Iud Made up of metal - copper. EARLIER DEVICES Copper-7 Copper-T 200 NEWER DEVICES Variants of T device T copper 220C T copper 380A Nova T Multiload devices ML-Cu250 ML-Cu375 Failure rate: 0.8/HWY 4/10/2012 42Intra-uterine Contraception: Intra-uterine Contraception GyneFix - “frameless and flexible”= less pain and bleeding Non-biodegradable suture thread 6 Cu tubes (5mmx2.2mm) surface area 330mm 2 Special inserting device to anchor knot into fundal myometrium Suitable for nulliparous Expulsion less than other IUDs 4/10/2012 43Third generation iud: Third generation iud Hormone releasing IUD Progestastert Most commonly used T shaped device filled with 38mg of progesterone Releasing rate 65µg/day . Effective for 1 yr LNG-20 (Minera ) Releases 20µg of levonorgesterol . Effective for 5 yrs Effective rate 99% Failure rate: 0.2 / HWY 4/10/2012 44IUD: IUD IUD Mechanism of action of Iud 4/10/2012 45PowerPoint Presentation: IUD EFFECTIVENESS Progestasert 12-18 months CuT 200 4 yrs Nova T 5yrs CuT 380 A 10yrs Levonoregestrel 5 yrs 4/10/2012 46PowerPoint Presentation: ADVANTAGES OF IUDs: Safe, Effective, Reversible Inexpensive High continuation rate DISADVANTAGES OF IUDs: Heavy bleeding and pain Pelvic Inflammatory diseases Ectopic pregnancy May come out accidently if not properly inserted 4/10/2012 47PowerPoint Presentation: TIMING OF INSERTION: Inserted with a plunger Any time during women’s reproductive period Except in pregnancy Most ideal time is during or within 10 days of the beginning of menstruation t he diameter of cervical cavity is greatest at this time. 4/10/2012 48PowerPoint Presentation: IDEAL IUD CANDIDATE: Who has borne at least 1 child Has no history of PID Has normal menstrual periods Is willing to check IUD tail Has an access to follow up and treatment of potential problems Is in monogamous relationship 4/10/2012 49Hormonal methods: Hormonal methods 4/10/2012 50Classification of hormonal contraceptives: Classification of hormonal contraceptives 4/10/2012 51PowerPoint Presentation: May 9th, 1960 : US-FDA approved the The first Combined Oral Contraceptive Pill - Ladies Home Journal - 1990 Nothing else in the century – perhaps not even winning the right to vote – made such an immediate difference in women’s livesHormonal control of menstrual cycle: Hormonal control of menstrual cycle 4/10/2012 53Oral Contraceptives: Oral Contraceptives 4/10/2012 54Oral Contraceptive and Emergency Contraceptive Pills: Oral Contraceptive and Emergency Contraceptive Pills Combined oral contraceptive pills A. Monophasic pills 1. Standard dose pills 2. Low dose pills 3. Very low dose pills B. Multiphasic pills 1. Triphasic pills 2. Biphasic pills C. Progesterone only pills/ minipills 4/10/2012 55PowerPoint Presentation: Multiphasic pills These were developed with the aim of reducing the total monthly hormone intake while maintaining the efficacy . Biphasic pills: EE- 0.035 mg constant Low dose progesterone first 7 days High dose progesterone next 14 days. These have higher failure rates and are not available in India. 4/10/2012 56PowerPoint Presentation: Triphasic pills: EE- 0.03mg + LNG 0.05mg for 5 days EE- 0.03mg + LNG 0.075mg for 10 days EE- 0.03mg + LNG 0.125mg for 7 day These pills have fewer side effects like amenorrhoea , breakthrough bleeding and decreased incidence of acne. The drawbacks include errors in pill taking, increased failure and difficulty in postponing menstruation if required. 4/10/2012 57Absorption of oral preparations: 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 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 . 58 4/10/2012PowerPoint Presentation: Eg . MALA-D MALA-N Combined pills 4/10/2012 59Combined pills: Combined pills Composition : In early 1960s – Oestrogen - 100-200µg and Progesterone - 10mg Greater side effects Nowadays Oestrogen - 30-35µg and Progesterone - 0.05-0.15mg. Taken from 5 th to 25 th day of menstrual cycle, followed by a break of 7 days ( withdrawal bleeding ). Failure rate: 0.1/HWY 4/10/2012 60PowerPoint Presentation: Main type MALA-D: ( Levonorgestrol 0.15mg + EE 0.03mg) Packet of 28 tabs. 21 are white and 7 are brown coloured containing Ferrous Fumarate . MALA-N : ( Levonorgestrol 0.15mg + EE 0.03mg)Packet of 28 tabs. Govt Supply. Mechanism of action: Prevents ovulation Prevents implantation Makes cervical secretions thick Effectiveness 100% effective if taken correctly. 4/10/2012 61PowerPoint Presentation: Beneficial Effects with Combination Oral Contraceptives 100% effective in correct users. B eneficial effects on menorrhagia (anemia) , dysmenorrhea, ovulatory pain, acne and hirsutism P reventive effects on salpingitis, endometriosis, adenomyosis and myomas Lower the risk of endometrial, ovarian - (30-50%) and possibly colon cancer Preserves bone mineral density (3.3% > BMD in premenopausal females with OCP use May reduce the risk of ovarian cysts, rheumatoid arthritis , benign breast disease & Ectopic preg . May have protective effect against atherosclerosis . 4/10/2012 62PowerPoint Presentation: Untoward Effects with Combination Oral Contraceptives Cardiovascular effects hypertension in 5% users myocardial infarction Stroke ; ischemic or haemorrhagic DVT’s especially smokers >35, overweight and sedentary Cancers ( increase risk of) breast hepatocellular cervical Endocrin e and metabolic effect, impaires glucose tolerance and responses to glucose challenge Breast tenderness, Weight gain, Headache and migraine Special infections, HIV, HPV 4/10/2012 63Contraindications to OCP Use: Contraindications to OCP Use Absolute Contraindications Cancer of breast and Genitals H/O venous thromboembolism Vascular disease- CAD or CVD Liver disease ( i.e. Viral hepatitis, cirrhosis) Pregnancy Congenital hyperlipidaemia Relative Contraindications Age above 40 yrs. Smoking and age above 35 yrs HTN with SBP>160, DBP>99 Chronic renal diseases Epilepsy , Migraine Hyperlipidemia LDL>160 DM with secondary complications Infrequent bleeding, Amenorrhoea . 4/10/2012 64PowerPoint Presentation: Postpartum women - not breastfeeding can start combined hormonal methods at 3 weeks (MEC category 2 ). Women who have additional risk factors for venous thromboembolism (VTE) generally should not start combined hormonal methods until 6 weeks after childbirth, depending on the number, severity, and combination of the risk factors (MEC category 2/3). These additional risk factors include Previous VTE Thrombophilia Caesarean delivery Blood transfusion at delivery Postpartum hemorrhage Pre- eclampsia Obesity Smoking 4/10/2012 65PowerPoint Presentation: Women with deep vein thrombosis who are established on anticoagulant therapy generally can use progestin-only contraceptives (MEC category 2) but not combined hormonal methods (MEC category 4). 4/10/2012 66PowerPoint Presentation: Women with systemic lupus erythematosus generally can use any contraceptive except that: (a) A woman with positive (or unknown) antiphospholipid antibodies should not use combined hormonal methods (MEC category 4) and generally should not use progestin-only methods (MEC category 3). (b) A woman with severe thrombocytopenia generally should not start a progestin-only injectable (MEC category 3). 4/10/2012 67Progesterone only pills: Progesterone only pills Minipill or Micropill. Composition: Low dosage of progesterone, mainly Norgestrel 0.075mg Dosage: One tab daily throughout the menstrual cycle It is mainly given in older women in whom combined pills are C/I as in CVDs Efficacy 96-98% Failure rate:0.5/HWY 4/10/2012 68Pop (contd...): Pop (contd...) Mechanism of action: Makes cervical mucosa thick – action starts in 2-4 hrs last for 24hrs. Decreases the motility of Fallopian tubes. Prevent pregnancy without preventing ovulation, as ovulation occurs in 20-30% women. Suitable for Lactating women Smokers above 35 yrs old Estrogen sensitive women Disadvantages: Higher risk of neoplasia in women taking POP than in women on Combined Pills Poor control of cycle. 4/10/2012 69 Progesterone only contraceptives: Progesterone only contraceptives Types Norethindrone 350 mcg ( Micronor / Noriday ) Levonorgestrel 75 mcg ( Neogest ) Norgestrel 30 mcg ( Microval / Norgestone ) Ethynodiol diacetate 500 mcg ( Femulen ) Desogestrel 75 mcg ( Cerazette ).Post coital pills: Post coital pills Morning after pills types . Levonorgestrel only , combined form,mifepristone. Dosage: 1 st tab within 72hrs of intercourse 2 nd tab after 12 hrs of 1 st tab In WHO multicentric randomized trial- within 120 hours of exposure to unprotected sex, a single dose of LNG 1.5 mg is as effective as 2 doses given 12 hours apart. Indications : Contraceptive failure Rape Unprotected intercourse. Failure Rate: 2/HWY 4/10/2012 71Post coital pills (contd...): Post coital pills (contd...) Mechanism of action: Hypermotility of fallopian tube Hypermotility of uterus hence no implantation and fertilization Disadvantages: Nausea and vomiting. Next period may start earlier or later Do not protect against STI & HIV 4/10/2012 72ECP OCP : ECP OCP After taking emergency contraceptive pills (ECPs) She can start COCs the day after she finishes taking the ECPs. There is no need to wait for her next monthly bleeding to start her pills. A new COC user should begin a new pill pack. A continuing user who needed ECPs due to pill-taking errors can continue where she left off with her current pack. All women will need to use a backup method for the first 7 days of taking pills. 4/10/2012 73PowerPoint Presentation: 4/10/2012 74Instructions for missed pill: Instructions for missed pill 4/10/2012 75Once a month (long acting) pill: Once a month (long acting) pill In this method a long acting oestrogen ( Quinestro l) + short acting progesterone is given But the results are highly disappointing. 4/10/2012 76Male pills: Male pills The hormones which reduce sperm count tend to reduce testosterone levels hence they affect potency and libido Gossypol: 2,2′-bis-(Formyl-1,6,7-trihydroxy-5-isopropyl-3-methylnaphthalene) Cotton seed derivative Causes azoospermia and severe oligospermia Toxic Use for 6 months leads to complete sterility 4/10/2012 77PowerPoint Presentation: Estrogenic Effects Ovulation is inhibited in part by follicle stimulating hormone (FSH) and lutenizing hormone (LH) suppression. Therefore the pituitary does not release hormones to stimulate the ovary Secretions of the uterus are altered Ovum transport is accelerated 4/10/2012 78 Oestrogenic and progestrogenic effect & side effectsPowerPoint Presentation: Estrogen component of OCP’s Ethinyl estradiol (20-50 mcg) Estrogen Mediated Side Effects of OCP’s Nausea Bloating Breast tenderness Vascular Headaches HTN DVT/ Leg Pain 4/10/2012 79PowerPoint Presentation: Progestational effects Ovulation is inhibited in part by inhibition of lutenizing hormone (LH) A thickened cervical mucus is created inhibiting sperm transport Implantation is inhibited Ovum transport may be slowed Activation of enzymes that permit the sperm to penetrate the ovum may be inhibited 4/10/2012 80PowerPoint Presentation: Progestin component of OCP’ s Pregnanes Estranes Gonanes Progestin Mediated Side Effects of OCP’s Poor control of cycle Increase chances of neoplasm. Lipid Abnormalities: lowers high density lipoproteins (HDL) 4/10/2012 81PowerPoint Presentation: Categorizations of Progestins Progestins 19-nortestosterone Estranes Gonanes Norethindrone Norethindrone acetate Ethynodiol diacetate Norgestrel Levonorgestrel Norgestimate Desogestrel Gestodene Drospirenone 17 α - spirolactone Pregnanes Medroxy-progesterone acetate Cyproterone acetate Chlormadinone acetate Progesterone 4/10/2012 82The drugs known to have a clinically significant impact on contraceptive efficacy: The drugs known to have a clinically significant impact on contraceptive efficacy Rifampicin Griseofulvin , Some anticonvulsants Topiramate , Barbiturates , Carbamazepine , P rimidone Ritonovir . 83 4/10/2012PowerPoint Presentation: Women with AIDS who are treated with ritonavir - protease inhibitors, generally should not use combined hormonal methods or progestin-only pills (MEC cat 3). These ARV drugs may make these contraceptive methods less effective. These women can use progestin-only injectables , implants, and other methods. Women taking only other classes of ARVs can use any hormonal method. 4/10/2012 84PowerPoint Presentation: Women with chronic hepatitis or mild cirrhosis of the liver can use any contraceptive method (MEC cat 1). Women taking medicines for seizures or rifampicin generally can use implants. 4/10/2012 85Quick Start (also for ring, patch, Depo): Quick Start (also for ring, patch, Depo ) If negative pregnancy test: swallow first pill under direct observation during visit (regardless of menstrual day). Give Emergency Contraception if indicated (and usually Quick Start the next day). Use back-up with condoms for 1 week. Repeat pregnancy test if no withdrawal bleed, or follow-up pregnancy test in 2-4 weeks. Women prefer it. (81%- 97%) Higher initiation/continuance rates. No bleeding differences based on day of initiation. 4/10/2012 86Quick Start contd…: Quick Start contd … Very low pregnancy rates in first cycle with quick start even if recent unprotected intercourse (3% or lower). Consider the impact on initiation rate: 100% with observed quick start. About 75% if pills dispensed (even lower if RX only) Hormonal contraceptives are not teratogenic (or abortifacients ) even if pregnancy does occur. 4/10/2012 87Oral Contraceptives: Extended Use Counseling on Safety: Oral Contraceptives: Extended Use Counseling on Safety Standard/traditional pill is 21 days active pills and 7 days placebo (21/7 regimen) Monthly withdrawal bleeding is designed to make the pill cycle feel “natural” But, there is no ovulation on the pill And, no menstrual lining “build up” 4/10/2012 88Perceived Benefits of Menstruation : Perceived Benefits of Menstruation Myths about monthly menstruation Necessary for “cleansing the system” A “natural” state A symbol of femininity, fertility, and youth A sign a woman is not pregnant Address safety concerns of the patient (her parents or partner) before prescribing extended OCPs. 4/10/2012 89Who might benefit from reduced frequency of menstruation? : Who might benefit from reduced frequency of menstruation? Women with menstrual-related disorders dysmenorrhea , menorrhagia , menstrual migraines, cyclic breast pain… Athletes Women in the military Developmentally delayed women Any woman who chooses to bleed less frequently 4/10/2012 90Seasonale: Seasonale 30 mcg EE and 150 mcg Levonorgestrel 84 active pills then 7 days placebo 4 menses per year Generic version Nordette / Levlen also available. 4/10/2012 91Seasonique: Seasonique Extended biphasic regimen 84 tablets Levonorgestrel - 0.15mg & ethinyl estradiol - 0.03 mg Then 7 tablets 0.01 mg ethinyl estradiol Method failure rate 0.64% Potentially decrease estrogen withdrawal side effects and PMS symptoms . 4/10/2012 92Lybrel: Lybrel 1 st Continuous Oral contraceptive 20 mcg ethinyl estradiol & 90 mcg levonorgestrel Given daily. No hormone free break 60% amenorrhea rate at 1 year Increased breakthrough bleeding/spotting Return to menses by 90 days 4/10/2012 93PowerPoint Presentation: 4/10/2012 94PowerPoint Presentation: Femcon Fe ( norethindrone 0.4mg and ethinyl estradiol 35mcg chewable and ferrous fumarate tablets) Chewable birth control Spearmint flavored LoEstrin 24 Fe ( Norethindrone acetate 1mg & Ethinyl Estradiol 20 mcg ) 24 hormone days with only 4 placebo days 4/10/2012 95Depot preparations: Depot preparations 4/10/2012 96PowerPoint Presentation: Depot preparations 4/10/2012 97Injectable contraceptives: Injectable contraceptives Classification 4/10/2012 98Progesterone only injectables: Progesterone only injectables Dmpa : Dose: 150mg IM every 3 months. MOA: suppresses ovulation Advantage: doesn’t affect lactation, useful in postpartum period. Can be used in the multiparae of age >35yr NET-en: Dose: 200mg IM every 2 months Both DMPA & NET-EN are given in 1 st 5 days of menstrual cycle. They are given deep IM in gluteus maximus 4/10/2012 99New formulation of DMPA (Uniject): New formulation of DMPA ( Uniject ) Prefilled, singleuse syringe could be particularly They contain a special formulation of DMPA, called DMPA-SC (104 mg). Short needle meant for subcutaneous injection Useful to provide DMPA in the community. Injections by appropriately trained community health workers is safe, effective, and acceptable. 4/10/2012 100PowerPoint Presentation: A woman may have a repeat injection of DMPA up to 4 weeks late. (Previous guidance said that she could have her DMPA reinjection up to 2 weeks late.) The guidance for reinjection of NET-EN remains at up to 2 weeks late. 4/10/2012 101PowerPoint Presentation: Side effects: Disruption of normal menses Amenorrhoea Contraindications: Breast cancer Genital cancer Undiagnosed uterine bleeding Suspected malignancy Lactating women Failure rate: 0.3/HWY 4/10/2012 102Combined injectables: Combined injectables Containing long-acting progesterone with short action estrogen 25 mg DMPA + 15 mg estradiol cypionate ( Cyclofem ) and 50 mg NET-EN + 5 mg estrdiol valerate ( Mesigyna ) Given once a month and produce a menstruation like pattern. The trials are currently taking place in India. MOA : Suppression of ovulation A lteration of cervical and endometrial secretions. C/I : Pregnancy, °\ Thromboembolytic disorders C erebrovascular disease ° Coronory artery disease M igraine ° Breast cancer DM 4/10/2012 103Subdermal implant: Subdermal implant Norplant For long term contraception. Has 6 capsules containing 35mg each of norgestrel. Norplant R2 – contains rods of norgestrel. Contraception is achieved in 24hrs & lasts for 5-6 yrs Disadvantage: Surgical procedure Failure Rate: 0.1/HWY 4/10/2012 104IMPLANON/ Jadellen: IMPLANON/ Jadellen A flexible plastic single flexible rod 4cm long x 2mm diameter Contains 68mg ETONOGESTREL, an active metabolite of desogestrel Effective for 3 years Release of etonogestrel 60-70ug/day in first 5-6 weeks 35-45ug/day end of year 1 30-40ug/day end of year 2 25-30ug/day end of year 3 4/10/2012 105Implanon: Implanon Benefits reliable long term contraception Improvement in menorrhagia and dysmenorrhoea Beneficial effect on acne in 59% No adverse effects on bone mass No significant effect on lipids, haemostasis or liver function Adverse side effects Bleeding pattern altered: Amenorrhoea 20% Infrequent - 26% Frequent - 6% Prolonged - 12% Weight gain of >10% in 21% - no change from reference group Hormonal ‘nuisance’ effects eg breast pain, headache, libido decrease, dizziness, nausea Other (<2.5%) alopecia , depression,change in libido 4/10/2012 106The Patch (OrthoEvra): The Patch ( OrthoEvra ) The ORTHO EVRA patch is a thin & plastic patch that sticks to the skin. The sticky part of the patch contains the hormones: norelgestromin (progestin) and ethinyl estradiol (estrogen). Weekly for 3wks then patch free 1 week. These hormones are absorbed continuously through the skin and into the bloodstream. 4/10/2012 107Vaginal ring (Nuvaring): 108 Vaginal ring ( Nuvaring ) Etonorgestrel 120mcg + Ethinylestradiol 15mcg daily Use for three weeks with a withdrawal week Inhibits ovulation Cycle control good Effective – Pearl index 1.8 Non-latex Implanted intravaginally The progesterone is absorbed slowly through the vaginal mucosa. Store 2-8 degrees; if room temperature, up to 4-12 NuvaRing is 98% effective when used correctly. Effectiveness: Overall perfect use failure rate 0.3%, typical use failure rate 8% 108 4/10/2012Nonsteroidal contraceptive drugs: Nonsteroidal contraceptive drugs Centchroman : Non steroidal OCD developed by CDRI Lucknow contains Ormeloxifene 30mg Trade name ‘ Saheli ’ Dose : 30mg twice a week for 12 weeks followed by once in a week MOA : Suppression of Corpus Leuteum functions Interferes with motility of fallopian tube hence no implantation. Advantages : Normal Menstruation Complete reversibility on withdrawal 4/10/2012 109Post conceptional methods Classification: Post conceptional methods Classification 4/10/2012 110Menstrual regulation: Menstrual regulation No legal restriction Aspiration of uterine content within 6-14 days of missed period Cervical dilatation needed in nullipara Early complications : Bleeding, Uterine perforation and trauma. Late complications : Tendency to abortion or premature births, infertility, menstrual disorders, ectopic pregnancy & Rh isoimmunisation 4/10/2012 111Menstrual induction: Menstrual induction Based on disturbing the normal progesteron - prostaglandin balance by IU application of 1.5mg solution or 2.5-5mg pellet of prostaglandin F 2. Causes sustained uterine contraction for 7 min. followed by cyclical contraction for 3- 4 hrs. Bleeding starts and continues for 7-8 days. 4/10/2012 112Oral abortifacient: Oral abortifacient Mifepristone + Misoprostol – 95% successful in terminating pregnancies upto 9 weeks. Commonly used regimen Mifepristone 200mg oral on day 1 followed by Misoprostol 800mcg vaginally immediately or 6 -8 hrs later. Other regimen is Mifepristone 600mg oral on day 1 followed by Misoprostol 400mcg orally on day 3 Follow up visit is must within 14 days for clinical and/or USG examination 4/10/2012 113abortion: abortion Definition: Termination of pregnancy before the foetus becomes viable LEGALISATION Medical termination of pregnancy act 1971 1) Conditions under which abortion is done Medical Eugenic Humanitarian Socio-economic In failure of contraceptive device 4/10/2012 114PowerPoint Presentation: 2) Who can perform abortion? If < 12 weeks 1 RMP having experience in OB-GYN If > 12 weeks -20 weeks then 2 RMP opinion 3) Where can abortion be done? Place approved by civil surgeon. 4/10/2012 115PowerPoint Presentation: METHODS Dilatation and Curettage : cervix is dilated with dilators and implanted ovum is removed by doing curettage of endometrium Vaccum Aspiration : Implanted ovum is removed by applying suction PG Administration : PGE1 ( misoprostol ) PGF2 ( carboprost ),PGE2 ( Dinoprost ) Intrauterine instillation : Intraamniotic – Hypertonic urea (40%) , saline (20%) Extraamniotic – Ethacrydine lactate 4/10/2012 116Miscellaneous methods: Miscellaneous methods Abstinence Coitus Interruptus : failure rate 25/HWY Safe period/rhythm period/ calendar method Basis: ouvulation from 12 th -16 th day before onset of menses Calculation: 1 st day of fertile period = shortest cycle-18days Last day of fertile period = longest cycle-10days 4/10/2012 117PowerPoint Presentation: Drawbacks : Irregular cycle so difficult to predict Only for educated and responsible couples Programmed Sex High Failure rate 9/HWY Complication : Embryonic Abnormalities, Ectopic Pregnancy 4/10/2012 118PowerPoint Presentation: 4) Natural family planning method : Basis: same as calendar method but here the women employs self recognition of certain signs and symptoms associated with ovulation. Basal Body temperature method Cervical mucous method Symptothermic : It is based on the observation of changes in different body signs : cervical secretions, basal body temperature and the position of the opening of the cervix. 5) Lactation 4/10/2012 119Lactational Amenorrhea Method Algorithm: Lactational Amenorrhea Method Algorithm 4/10/2012 120Standard Days Method: Standard Days Method Identifies days 8-19 of the cycle as fertile Is appropriate with menstrual cycles between 26 and 32 days long Helps a couple plan or prevent pregnancy by knowing which days they should or should not have unprotected sex. It is used with CycleBeads , a color-coded string of beads to help a woman: Track her cycle days Know when she is fertile Monitor her cycle lengthTerminal methods: Terminal methods 4/10/2012 122vasectomy: vasectomy NSV 4/10/2012 123PowerPoint Presentation: Failure Rate: 0.15/HWY (due to mistaken identification of vas) COMPLICATIONS: Operative Sperm granules Spontaneous recanalisation Autoimmune response Psychological response 4/10/2012 124No scalpel vas occlusion: No scalpel vas occlusion METHODS Elastomer plugs : Gets hardened and plugs the vas SHUG : preformed silicon rubber plug is inserted. RISUG : Reversible Inhibition of Sperm Under Guidance 4/10/2012 125Tubectomy: Tubectomy Failure rate: 0.5/HWY 4/10/2012 126Approaches to the fallopian tubes, surgical procedures, timing of procedure,and related occlusion techniques: Approaches to the fallopian tubes, surgical procedures, timing of procedure,and related occlusion techniques 4/10/2012 127Tubal inserts (no incision): Tubal inserts (no incision) 4/10/2012 1281.New Male Pill: 1.New Male Pill The pill contains desogestrel as well as testosterone. B locks the production of sperm while maintaining male characteristics and sex drive. It must be taken daily. 100% effective and completely reversible in preliminary clinical trials . In clinical trials, all of the participants’ sperm counts dropped to zero, which means that the male pill would be more effective than the condom and even the female pill. 4/10/2012 1292. CatSper Blocker: 2. CatSper Blocker Sperm rely on calcium ions in sperm- tail for mobility and fertilization. Humans -ion-channel gene - CatSper . Blocking CatSper action - effective form of birth control. Men or women could take this potential CatSper “blocker” because it could be made to act ”wherever sperm are present.” Active only in fully developed sperm, which means blocking or boosting its action could have few or no side effects. 4/10/2012 1303. Spray On -Contraceptive: 3. Spray On -Contraceptive Australian biotech company Acrux has come up with a world first — a contraceptive spray for women. Metered Dose Transdermal System (MDTS) to administer a pre-set dose of the Nestorone to the skin (forearm) every 14 days. The fast-drying spray gradually absorbed into the bloodstream. Suitable for Breastfeeding mothers Who cannot tolerate contraceptive pills with oestrogens . Leaves no visible residue & less irritation than patches. Because it does not have to be taken at the same time every day, it will suit women who often forget to take the Pill. 4/10/2012 1314. Adjudin “The male Patch”: 4. Adjudin “The male Patch” Adjudin ( 2,4-dichlorobenzyl- 1H-indazole-3-carbohydrazide) is non-hormonal male contraceptive drug, which acts by blocking the maturation of sperm in the testes, but without affecting testosterone production. Normal spermatogenesis returned in 95% within 210 days after the drug had been discontinued. The oral dose effective for contraception is so high that there have been side effects in the muscles and liver, therefore the drug is being manufactured as implant or patch for males. 4/10/2012 1325. Contraction Inhibitor Pill “Dry Orgasm”: 5. Contraction Inhibitor Pill “Dry Orgasm” 2 different types of smooth muscle in vasa deferentia longitudinal muscle fibers and circular muscle fibers. W hen segments of vasa deferentia were exposed to phenoxybenzamine or thioridazine , the longitudinal smooth muscle fibers did not contract. The circular smooth muscles did, causes , clamping the vas shut. Thioridizine’s side effects were so extreme( hives, difficult breathing;,swelling of face) that the manufacturer discontinued it in 2005, the common side effects of phenoxybenzamine are dizziness , fast heartbeat & stuffy nose. 4/10/2012 1336. Anti-Fertility Vaccines: 6. Anti-Fertility Vaccines Contraceptive vaccine either target Gamete production (GRH, FSH and LH) Gamete function (ZP) Gamete outcome ( hCG ). CVs targeting gamete function are better choices but induce oophoritis affecting sex steroids. Antisperm antibody-mediated immunoinfertility provides a naturally occurring model to indicate how an antisperm vaccine will work in humans. The hCG vaccine is the first vaccine to undergo clinical trials in humans. Both the efficacy and the lack of immunotoxicity have been reasonably well demonstrated for this vaccine. 4/10/2012 1347. R.I.S.U.G: 7. R.I.S.U.G Reversible Inhibition of Sperm Under Guidance ( RISUG ), developed at IIT Kharagpur in India by Dr. Sujoy K Guha . It is currently undergoing clinical trials in India. RISUG is a non-hormonal injectable contraceptive composed of SMA (styrene maleic anhydride) mixed with DMSO (solvent dimethylsulfoxide ). Partially blocks the vasa deferentia and destructs the sperm The differential charge from the gel ruptures the sperm’s cell membrane, stopping the sperm before they can even start their journey to the egg. R eversals by multiple injection of dimethyl sulfoxide or sodium bicarbonate – and several months to reverse. 4/10/2012 1358. Hydrothermal Male Control: 8. Hydrothermal Male Control Methods used include Hot water applied to the scrotum Heat generated by ultrasound Artificial cryptorchidism (holding the testicles inside the abdomen) using specialized briefs. Raising the body temperature above 42 degrees Celsius initiates certain processes, resulting in cells disability. It is called Heat Shock Factor (HSF).It disable sperm cells. Hot water bath (about 46.7 degrees Celsius)for 45 minutes daily for 3 weeks - simple wet heating - ensure up to 6 months of male infertility. ultrasound method - the testicles are heated with the help of ultrasound - only two procedures 48 hours - temporary infertility for up to 10 months. 4/10/2012 1369. Biodegradable Time Releasing Contraceptive Implant: 9. Biodegradable Time Releasing Contraceptive Implant In pipeline is a biodegradable contraceptive Implant that does not require surgical removal, consists of long-acting contraceptive capsule-type implant- CaproF . 4/10/2012 13710. SILCS Diaphragm: 10. SILCS Diaphragm The SILCS diaphragm is a silicone barrier contraceptive device . Its dome is filled with BufferGel that acts both as a spermicide and microbicide that not only immobilizes the sperms but also kills them and fights infections. It avoids the need for many sizes and a pelvic exam for a correct fit; it is designed as a “one size fits most” device. T he new device is being evaluated for comfort and ease-of-use in studies, underway in the Dominican Republic, South Africa, Thailand, and the United States. 4/10/2012 13811. Injectable silicone plugs : 11. Injectable silicone plugs O ften used by men in China as a potential alternative to vasectomy. There are two tested types of injected plugs: Medical-grade polyurethane (MPU) M edical-grade silicone rubber (MSR). The polymer (special ingredient) is injected directly into the vasa deferentia , Once injected, the polymer solidifies in place, forming a flexible plug. The procedure takes less than 30 minutes under local anesthesia. It is easier to reverse. It takes 2 to 4 years after the reversal procedure. 4/10/2012 13912.Essure: 12.Essure The Essure procedure involves placing a small & flexible device called a Micro- insert into each fallopian tubes. The Micro- inserts are made from materials that have been well studied and used successfully in the heart and other parts of the human body for many years. Once the Micro-inserts are in place, body tissue grows into the Micro- inserts, blocking the fallopian tubes. 4/10/2012 140References: References Contraceptive Updates, Reference Manual for Doctors 2009, by MOHFW & UNFPA,India . WHO - Medical eligibility criteria for contraceptive use – 4th ed 2009. WHO, Family Planning A GLOBAL HANDBOOK FOR PROVIDERS Update 2011 “Guidelines for administration of emergency contraceptive pills by medical officers,” Research Studies and Standard Division, Department of Family Welfare, Government of India, June 2009. The essentials of Contraceptive Technology, a handbook for clinic staff, John Hopkins Population Information Program, 2010 Projestin Only Injectables : Fact Sheet. UNFPA India, 2004 Guidelines for IUDs for medical officers, research studies and standard division, Department of Family Welfare, Government of India - June 2007 4/10/2012 141References contd…: References contd … Westhoff C, Heartwell S, Edwards S. Initiation of Oral Contraceptives Using a Quick Start Compared With a Conventional Start: A Randomized Controlled TrialObstet Gynecol. 2007 Jun;109(6):1270-1276. Jick SS et al. Risk of non fatal VTE in women using a contraceptive transdermal patch and oral contraceptives containing 35 mcg EE and norgestimate . Contraception 2006;73(3):223-8. Sheng J et al. The LNG-IUS study on adenomyosis : a 3–year follow-up study on the efficacy and side effects of the use of levonorgestrel intrauterine system for the treatment of dysmenorrhea associated with adenomyosis . Contraception. 2009 Mar;79(3):189-93. Grimes DA et al. Cochrane systematic reviews of IUD trials: lessons learned. Contraception. 2007 Jun;75(6 Suppl ):S55-9. Lethaby AE et al. Progesterone or progestogen -releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst Rev. 2005 Oct 19;(4) K.Park , Text book of preventive and social medicine,contraceptive methods pp.457-474,21st edition,Bhanot publication,Jabalpur , India. 4/10/2012 142PowerPoint Presentation: Trussell J. Contraceptive efficacy. In Hatcher RA, Trussell J. Stewart F, et al Contraceptive Technology: 17th Revised Edition. New York. NY: Ardent Media, 1998. Jick SS, Jick H. The contraceptive patch in relation to ischaemic stroke and acute myocardial infarction. Pharmacotherapy, 2007, 27:218-220. Elkind -Hirsch KE, Darensbourg C, Ogden B et al. Contraceptive vaginal ring use for women has less adverse metabolic effects than an oral contraceptive. Contraception, 2007, 76:348-356. World Health Organization. Emergency Contraception. Fact Sheet No. 244, October 2005. Available at: http://who.int/mediacent/factsheets/fs244/en/print.html 4/10/2012 143 References contd …References contd…: Allen RH, Goldberg AB, Grimes DA. Expanding access to intrauterine contraception. American Journal of Obstetrics and Gynecology 2009;201(5):456-61. Grimes DA, Lopez LM, Schulz KF, Immediate post-partum insertion of intrauterine devices Review, published in The Cochrane Library2010, Issue 5. Rajesh K.Naz , Satish K.Gupta , Jagdish C.Gupta , Recent advances in contraceptive vaccine development: a mini-review Human Reproduction 2005;vol.20,(12): 3271–3283. Amobi , NI, J Guillebaud , AV Kaisary , E Turner and IC Smith (2002) “Discrimination by SZL49 between contractions evoked by noradrenaline in longitudinal and circular muscle of human vas deferens.” British Journal of Pharmacology 136(1):127-35. http://www.who.int/reproductionhealth/publications/family_planning/ http://www.pillwatch.com/info/male-contraception-what-to-choose.html http://www.smashinglists.com/10-advanced-methods-of-birth-control-in-pipeline/ http://www.fsrh.org/admin/uploads/630_NuvaringProductReview240309.pdf 4/10/2012 144 References contd …PowerPoint Presentation: 4/10/2012 145 Thank you!!!PowerPoint Presentation: 4/10/2012 146PowerPoint Presentation: 4/10/2012 147 You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.