NEW RESEARCHES ON CONTRACEPTIVES,IUCD & STERILISATION: <ul><li>Candidate: Dr Shankar </li></ul><ul><li>Guide: Dr Pradeep G...
Testing Can Take Years <ul><li>Preclinical testing:  </li></ul><ul><ul><li>Evaluates safety of drug, device, or materials....
New Methods Covered in this Seminar: <ul><li>Barrier methods </li></ul><ul><li>Microbicides, Spermicidal </li></ul><ul><li...
Barrier method <ul><li>Condoms </li></ul><ul><ul><li>Male condom . </li></ul></ul><ul><ul><li>Female condom. </li></ul></u...
The polyurethane condom (Vs latex) <ul><li>Can be used in those with latex allergies </li></ul><ul><li>Pregnancy rates – 5...
Contd . <ul><li>New condoms according to WHO: </li></ul><ul><li>Polyurethane: Avanti, eZ.on, Supra. </li></ul><ul><li>Styr...
What is molecular condom? <ul><li>A smart vaginal drug delivery system. </li></ul><ul><li>A biologically responsive polyme...
New Female Condoms Are Designed For Better Fit and Lower Cost   <ul><li>FC2 Female Condom: </li></ul><ul><ul><li>Synthetic...
Contd . <ul><li>Brands in the market: </li></ul><ul><li>Femidom (polyurethane) </li></ul><ul><li>FC2(made up of nitrile) <...
Female condom – femidon, reality <ul><li>Loose soft fitting polyurethane sac – 15 cm long and 7 cm in diameter, flexible o...
Female condom – femidon, reality <ul><li>Disadvantages – Not as effective as male condom </li></ul><ul><li>Available in on...
Vaginal Barrier Methods Courtesy of the Cervical Barrier Advancement Society
Diaphragm-Like Devices: Easier to Use and Appropriate for Use with Microbicide <ul><li>Lea’s Shield® </li></ul><ul><ul><li...
New Cervical Caps Designed to Reduce Fitting Time <ul><li>FemCap ™ </li></ul><ul><ul><li>Silicone rubber device fits over ...
Contraceptive Sponges: No Fitting or Prescription Required   <ul><li>The Today Sponge ®   </li></ul><ul><ul><li>Discontinu...
Microbicides Jefferson Jackson Steele
Microbicides Can Reduce Transmission of HIV and other STIs <ul><li>Description:  Vaginally applied substances designed to ...
How Do Microbicides Work? <ul><li>Most microbicides under development act in one or more of the following ways: </li></ul>...
Microbicides with contraceptive action: <ul><li>Create physical barrier: cellulose sulfate, polystyrene sulfonate. </li></...
Spermicides: <ul><li>Inactivate or kill sperms. </li></ul><ul><li>Chemicals: nonoxynol-9, octoxynol-9, menfegol, benzalkon...
Oral combined contraceptives: <ul><li>Estrogen component: </li></ul><ul><li>MC-Ethinyl estradiol(EE). </li></ul><ul><li>Oc...
contd: <ul><li>Derivative of 17-hydroxy progesterone: </li></ul><ul><li>-Cyproterone acetate. </li></ul><ul><li>Spirolacto...
↓  EE DOSE: <ul><li>↓ EE dose from 50 to 30-35 µg- ↓ risk of MI, stroke, DVT. </li></ul><ul><li>↓  EE 30 to 20µg further ↓...
Regimens in OCP: <ul><li>Biphasic Vs Manophasic: </li></ul><ul><li>-Cochrane study : no evidence to say biphasic pills are...
Extended regimen: <ul><li>Similar efficacy. </li></ul><ul><li>Escape ovulation. </li></ul><ul><li>Shorter hormone free int...
Drospirenone <ul><li>New Progestin, now in India </li></ul><ul><li>Analogue of Spironolactone (3mg Drospirenone=25mg Spiro...
Continuous-Use Regimen Offers New Choice for Pill Users <ul><li>Reduces side effects associated with hormone withdrawal (m...
Extended Cycle Products <ul><li>21/2/5 regime   Mircette® ‐ 21 tab containing 20μg EE+ 0.15mg   desogestrel followed by 2 ...
Extended Cycle Products <ul><li>Continuous regimen </li></ul><ul><li>84/7 regimens     Seasonale®, Jolessa, Quasense   30...
Cochrane Review. Cochrane Library 2008 (3) Conclusions <ul><li>Extended use of COC </li></ul><ul><li>-Similar user satisfa...
Progesterone only pills(minipill): <ul><li>Plasma levels fall to baseline within 24 hours after intake,  must be taken at ...
Cerazette(Organon): <ul><li>Progesterone only pill -75 µgm Desogestrel, used daily. </li></ul><ul><li>Inhibit ovulation 97...
Mifeprestone as contraceptive: <ul><li>Sequential regimen: </li></ul><ul><li>-Mife + Norethisterone. </li></ul><ul><li>-Mi...
Injectables: Courtesy of Schering AG
Injectable contraceptives <ul><li>Progestogen only injectables: </li></ul><ul><ul><ul><li>DMPA -  im 150 mg every 3 months...
New Combined Injectables Offer Alternative to Progestin-only Injectables <ul><li>Description:  Monthly injections containi...
Combined Injectables Offer Advantages Over Progestin-Only Injectables <ul><li>Branded under names Cyclofem and Mesigyna. <...
New Subcutaneous DMPA Formulation Recently Approved <ul><li>DMPA-SC provides slower, more sustained absorption of the prog...
Contraceptive Implants Karen Tweedy-Holmes, Population Council
Implantables: progestin Trade name Unit  Duration of action: Levonorgestrel  Norplant 6 capsules 5 years. Etonegestrel Imp...
Implanon   ™ <ul><li>FDA approved July 2006 </li></ul><ul><li>Available worldwide since 1997 </li></ul><ul><ul><li>Approxi...
IMPLANON™ Rate-controlling membrane: (0.06 mm) 100% EVA 4 cm 2 mm Core: 40% ethylene vinyl acetate (EVA) 60% etonogestrel ...
Implanon   ™ <ul><li>Mechanism of action </li></ul><ul><ul><li>Prevents ovulation </li></ul></ul><ul><ul><li>Alters cervic...
Implanon ™  applicator
Implanon  ™ <ul><li>Easy to insert </li></ul><ul><ul><li>>85% less than 1 minute </li></ul></ul><ul><li>Easy to remove </l...
New Implants Have Fewer Rods than Norplant ® <ul><li>Description:  One or two progestin-releasing rods inserted just under...
New Implants: <ul><li>JEDELLE: </li></ul><ul><li>43 × 2.5 mm. </li></ul><ul><li>Each rod-75 µg LNG. </li></ul><ul><li>NEST...
BIODEGRADABLE IMPLANTS: <ul><li>Removal is not necessary. </li></ul><ul><li>LNG- Single capsule: </li></ul><ul><li>-phase ...
Vaginal Rings: Left: NuvaRing® (Organon). Right:Nestorone® vaginal ring.
In which way they are advantageous: <ul><li>Steroid absorption through vaginal route is rapid. </li></ul><ul><li>Constant ...
Combined Vaginal Rings Offer Better Cycle Control than Oral Contraceptives <ul><li>Prevent ovulation, thicken cervical muc...
Vaginal rings: <ul><li>NUVA RING </li></ul><ul><li>120 µg etonogestrel + 15 µg EE/day in ethylene vinyl acetate (EVA) copo...
Nuvaring ® <ul><li>Efficacy </li></ul><ul><ul><li>Perfect use  99% </li></ul></ul><ul><ul><li>Typical use  92% </li></ul><...
Progesterone only ring: <ul><li>Population council, NY has developed 2 progesterone only rings. </li></ul><ul><li>Both rel...
Transdermal Contraception Courtesy of Ortho McNeil Pharmaceutical
Transdermal Contraception Delivers Hormones Through the Skin <ul><li>Description:  Patches, sprays, or gels, applied weekl...
Combined Patches: A Good Alternative For Pill Users  <ul><li>User replaces patch weekly for three weeks, followed by one p...
Contd. <ul><li>Evra: </li></ul><ul><li>-releases 150µg norelgestromin & 20µg EE daily. </li></ul><ul><li>-FDA approval in ...
Contraceptive patches: Left: Evra (Ortho-McNeil). Right: Fidencia (Bayer-Schering-Pharma).
Contd. <ul><li>Women using patch are exposed to 60% more total estrogen than OC pill users. </li></ul><ul><li>Patch ,vagin...
Extended vs. cyclic use of transdermal patch: <ul><li>Conclusions – extended regimen </li></ul><ul><li>Effective for delay...
Spray-On Contraceptives: A New Technique For Hormone Delivery <ul><li>A new progestin-only spray(Nestorone)The Metered Dos...
Gene-Based Approaches Promise Dramatic Change in Contraception <ul><li>Target the genes or proteins involved in sperm and ...
Intrauterine Devices Courtesy of Berlex
Three Main IUDs Are Used Currently Copper-bearing IUDs Hormonal IUD   TCu-380A Multiload-375 LNG-IUD
New IUDs Make Insertion and Removal Easier and Reduce Side Effects <ul><li>Description : Progestin-releasing IUDs and IUDs...
One of the Most Effective Methods of Contraception <ul><li>Women who become pregnant during first year of use: </li></ul><...
New Progestin-Releasing Mirena IUS Offers Many Advantages Over Cu-IUDs <ul><li>Approved in 2000 for 5 years of use. Availa...
Levonorgestrel-releasing intrauterine systems:  Left: Mirena®; Right: “Small Mirena®”.
Mirena/ LNG 20/ Levonova <ul><li>Polydimethyl siloxane T frame </li></ul><ul><li>Capsule on the stem – 52 mg LNG </li></ul...
Mirena/ LNG 20/ Levonova <ul><li>Non contraceptive uses </li></ul><ul><ul><li>Menorrhagia </li></ul></ul><ul><ul><li>Proge...
Other LNG-IUS: <ul><li>FEMILIS(Contrel): </li></ul><ul><li>-Shorter sidearms. </li></ul><ul><li>-Initial study show good c...
Flexi Gard/ Cu fix IUD/ Gynefix <ul><li>Frameless IUD, 3 cm long </li></ul><ul><li>6 Copper sleeves (300 sq mm of Cu) stru...
Flexi Gard/ Cu fix IUD/ Gynefix <ul><li>Knot is pushed 9 to 10 mm into myometrium of fundus by a special stylet </li></ul>...
Silverlily and Goldlily IUDs: <ul><li>Both devices provide good protection </li></ul><ul><li>against unwanted pregnancy </...
Other IUD under research: <ul><li>Swing: Cu releasing with coil stem. </li></ul><ul><li>IUD with a progesterone receptor m...
WHO Guidance Allows More Women to Use IUDs World Health Organization, 2004    PID Purulent cervicitis,  chlamydia, or gono...
New Male Contraceptives Courtesy of Shepherd Medical
What can be? <ul><li>Inhibition of sperm production: </li></ul><ul><li>Inhibition of sperm maturation: </li></ul><ul><li>B...
Which male contraceptives  are closest to market? <ul><li>Three methods are in clinical trials: </li></ul><ul><li>RISUG(Re...
Inhibitors of spermatogenesis: <ul><li>Hormonal : </li></ul><ul><li>Testosterone derivative: testosterone enanthate(TE),te...
Hormonal methods <ul><li>LH stimulates Tes production in Leydig cells </li></ul><ul><li>FSH stimulates spermatid productio...
Hormones: <ul><li>No such preparations  are available. </li></ul><ul><li>All these inhibit LH & FSH. </li></ul><ul><li>Azo...
MHCs – What are they? <ul><li>Supra-physiological dose of testosterone suppresses testicular production of testosterone an...
MHCs – How are they reversed? <ul><li>Stop treatment, hormones begin rebound, spermatogenesis reinitiates </li></ul><ul><l...
MHCs – Side effects <ul><li>Similar to side effects experienced by women on hormonal contraceptives  </li></ul><ul><li>Mil...
nonhormonal : <ul><li>GOSSYPOL: </li></ul><ul><li>-disequiterpene aldehyde derivative from seed,stem,root of the cotton pl...
Interesting leads - Adjudin <ul><li>Non-toxic lonidamine analog </li></ul><ul><li>Disrupts cellular bridges between sperma...
Interesting leads – RAR antagonist <ul><li>Retinoic acid required for sperm production </li></ul><ul><li>1 week of RAR ant...
Contd. <ul><li>Inhibition of sperm maturation: </li></ul><ul><li>-Antiandrogens, Alpha-chlorohydrin. </li></ul><ul><li>-tr...
Male sterilization: <ul><li>Surgical vasectomy. </li></ul><ul><li>No-scalpel vasectomy. </li></ul><ul><li>Fascial interpos...
Vasectomy: resection and electrocauterisation
Vasectomy: resection and ligation: A) resection, folding and ligation; B) resection and ligation; C) resection and interfa...
No-scalpel vasectomy: <ul><li>By Dr Shungiang in China in 1974. </li></ul><ul><li>As compared to surgical vasectomy: </li>...
<ul><li>A polymer gel of styrene maleic anhydride mixed with dimethyl sulphoxide injected into the vasa deferentia </li></...
RISUG – How effective is it? <ul><li>Extremely effective (>99%) </li></ul><ul><li>200+ men have been treated with RISUG  2...
<ul><li>Transient, painless scrotal swelling which resolves with no intervention within 2 weeks </li></ul><ul><li>Prostate...
RISUG – How is it reversed? <ul><li>Reversal proven in monkeys after 1½ years of use, all had normal sperm count within 3 ...
The IVD – What is it? <ul><li>US design in Phase I trials: dual silicone plugs inserted into the vas block sperm </li></ul...
IVD – How effective is it? <ul><li>US design awaiting completion of trial; past designs 90-100% effective </li></ul><ul><l...
IVD – Side effects <ul><li>Similar to “no scalpel vasectomy”, but less frequent and less severe </li></ul><ul><li>10% repo...
Female Sterilization <ul><li>Interrupts the patency of fallopian tubes thereby preventing fertilization </li></ul><ul><li>...
Laparoscopic Sterilization: <ul><li>Performed as outpatient: </li></ul><ul><li>Bipolar Cautery: bipolar cutting current of...
Sterilization by laparotomy: <ul><li>Pomeroy technique. </li></ul><ul><li>Irving technique. </li></ul><ul><li>Uchida techn...
What is Essure? <ul><li>A new method of female hysteroscopic sterilisation. </li></ul><ul><li>Marketed and sold by  </li><...
Contd .  <ul><li>Inner coil-stainless steal. </li></ul><ul><li>Outer coil nickel-titanium alloy. </li></ul><ul><li>Polyeth...
contd. <ul><li>Placement failure-16%. </li></ul><ul><li>If correctly placed-tubal occlusion in 99.5% at 12months. </li></u...
What is Adiana? <ul><li>By Hologic Inc, USA. </li></ul><ul><li>A two step process. </li></ul><ul><li>Controlled thermal da...
Contd. <ul><li>OVABLOCK : Method of inserting a rubber tube in both fallopian tubes. </li></ul><ul><li>QUINACRINE  :chemic...
female sterilisation techniques.  Left: Upper figure: Essure; Lower figure: Adiana Right: Ovabloc (www.ovabloc.com/ovabloc...
<ul><li>To see  laparoscopic surgeries  in Gynae  logon to </li></ul><ul><li>www.youtube.com </li></ul><ul><li>and </li></...
 
<ul><li>For  queries mail me at </li></ul><ul><li>pkgarg_in2004@yahoo.com  </li></ul>
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New Researches On Contraceptives,Iucd & Sterilisation

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NEW RESEARCHES ON CONTRACEPTIVES,IUCD & STERILISATION
pradeep garg aiims new delhi

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  • Duration of use: TCu-380A: up to 10 years, and may be extended to 12 years Multiload-375: up to 5 years Levonorgestrel-releasing IUD (LNG-IUD): up to 5 years, and maybe longer The U.S. Agency for International Development (USAID) supplies the TCu-380A to developing-country programs. The two other major donors of contraceptives, the United Nations Population Fund (UNFPA) and the International Planned Parenthood Federation (IPPF), provide both the TCu-380A and the Multiload-375. The LNG-IUD, marketed under the brand names Mirena ® and, in some European countries, Levonova ® , has been sold in Europe since 1990. Its high cost and the need to train providers in a new insertion technique have discouraged USAID from distributing it.
  • Sources: TCu-380A effectiveness: United Nations Development Program, 1997 LNG-IUD effectiveness: Luukkainen, 1987; Sivin, 1984 TCu-380A vs. LNG-IUD comparative study: World Health Organization, 2003
  • Changes to the WHO guidance now allow women with STIs other than gonorrhea, chlamydia, or purulent cervicitis to have IUDs inserted. Purulent cervicitis is an infection of the cervix with a pus-like discharge from the opening of the cervix. It may be a sign of a gonorrhea or chlamydial infection. There is concern that a woman at very high individual risk of gonorrhea or chlamydia may currently have gonorrhea or chlamydia but without any immediate symptoms. Only laboratory testing would detect these silent infections, and in many places these tests are not available. If a woman lives in a setting with a high prevalence of STIs but she herself is not at increased risk of STIs, then she generally can have an IUD inserted (category 2). WHO Medical Eligibility Criteria Classification: Category 1: Use the method in any circumstances. Category 2: Generally use the method. Category 3: Use of the method not usually recommended unless other more appropriate methods are not available or not acceptable. Category 4: Method not to be used. When clinical judgment is limited, interpretation of Categories 1 and 2: Yes (Use the method.) (shown in green in the chart on this slide) Categories 3 and 4: No (Do not use the method.) (shown in red in the chart on this slide)
  • New Researches On Contraceptives,Iucd & Sterilisation

    1. 1. NEW RESEARCHES ON CONTRACEPTIVES,IUCD & STERILISATION: <ul><li>Candidate: Dr Shankar </li></ul><ul><li>Guide: Dr Pradeep Garg </li></ul><ul><li>Co-guide: Dr Pushparaj </li></ul><ul><li>(Date:20-08-2009). </li></ul>
    2. 2. Testing Can Take Years <ul><li>Preclinical testing: </li></ul><ul><ul><li>Evaluates safety of drug, device, or materials. </li></ul></ul><ul><li>US FDA Clinical trials: </li></ul><ul><ul><li>Phase I: (1-2 years) Determines safe dosage and side effects. </li></ul></ul><ul><ul><li>Phase II: (1-2 years) Evaluates initial effectiveness. </li></ul></ul><ul><ul><li>Phase III: (2-4 years) Confirms effectiveness, monitors side effects and safety. </li></ul></ul><ul><ul><li>Phase IV: (Ongoing) Postmarketing studies after US FDA approval evaluate risks, benefits, and optimal use. </li></ul></ul>
    3. 3. New Methods Covered in this Seminar: <ul><li>Barrier methods </li></ul><ul><li>Microbicides, Spermicidal </li></ul><ul><li>Oral contraceptives </li></ul><ul><li>Injectables </li></ul><ul><li>Implants </li></ul><ul><li>Vaginal rings </li></ul><ul><li>Transdermal patches </li></ul><ul><li>Gene-based approaches </li></ul><ul><li>IUDs </li></ul><ul><li>Male contraceptives </li></ul><ul><li>Sterilization </li></ul>
    4. 4. Barrier method <ul><li>Condoms </li></ul><ul><ul><li>Male condom . </li></ul></ul><ul><ul><li>Female condom. </li></ul></ul><ul><li>Occlusive caps </li></ul><ul><ul><li>Vaginal diaphragm. </li></ul></ul><ul><ul><li>Cervical cap. </li></ul></ul><ul><ul><li>Vault cap. </li></ul></ul><ul><ul><li>Vinule cap. </li></ul></ul><ul><li>Vaginal sponge. </li></ul><ul><li>Spermicide. </li></ul>
    5. 5. The polyurethane condom (Vs latex) <ul><li>Can be used in those with latex allergies </li></ul><ul><li>Pregnancy rates – 5.4% with latex condoms and 9% with polyurethane condoms </li></ul><ul><li>Advantages :More resistant to heat & oxidation </li></ul><ul><li>Thinner material </li></ul><ul><li>Can be used with any lubricant </li></ul><ul><li>Disadvantages: Higher risk of breakage during use ,Lesser protection against STI, Costlier. </li></ul><ul><ul><ul><ul><ul><li>Cochrane database systemic review 2006 </li></ul></ul></ul></ul></ul>
    6. 6. Contd . <ul><li>New condoms according to WHO: </li></ul><ul><li>Polyurethane: Avanti, eZ.on, Supra. </li></ul><ul><li>Styrene based plastic: </li></ul><ul><li>- Tactylon, Unique, Unisex </li></ul><ul><li>Recent developments are on “invisible condom” & the “spray-on condom” . </li></ul><ul><li>WHO-2006. </li></ul>
    7. 7. What is molecular condom? <ul><li>A smart vaginal drug delivery system. </li></ul><ul><li>A biologically responsive polymer liquid at room temp-turns into gel when come in contact to tissue at body temp. </li></ul><ul><li>This gel is Ph sensitive, when come in contact to semen-liquifies & releases entrapped antivirals in to the semen. </li></ul><ul><li>J Reprod Med End-2007. </li></ul>
    8. 8. New Female Condoms Are Designed For Better Fit and Lower Cost <ul><li>FC2 Female Condom: </li></ul><ul><ul><li>Synthetic latex model. </li></ul></ul><ul><ul><li>Expected to become available in developing countries. </li></ul></ul><ul><li>VA Feminine condom: </li></ul><ul><ul><li>First latex model. </li></ul></ul><ul><ul><li>-marketed in Western Europe, Brazil, India, and South Africa. </li></ul></ul><ul><ul><li>WHO-2006 </li></ul></ul><ul><li>The PATH Woman’s Condom: </li></ul><ul><ul><li>Designed for near-universal fit. </li></ul></ul><ul><ul><li>High user satisfaction in clinical trials. </li></ul></ul>Courtesy of PATH
    9. 9. Contd . <ul><li>Brands in the market: </li></ul><ul><li>Femidom (polyurethane) </li></ul><ul><li>FC2(made up of nitrile) </li></ul><ul><li>V-Armour (made of latex). </li></ul><ul><li>Four times more expensive than male condom. </li></ul>
    10. 10. Female condom – femidon, reality <ul><li>Loose soft fitting polyurethane sac – 15 cm long and 7 cm in diameter, flexible outer polyurethane ring covering the vulva and a second smaller flexible inner ring to aid insertion and retention. </li></ul><ul><li>Typical failure rate is 21% (5% when used correctly). </li></ul><ul><li>Only female controlled method protecting from HIV and other STD. </li></ul>
    11. 11. Female condom – femidon, reality <ul><li>Disadvantages – Not as effective as male condom </li></ul><ul><li>Available in one size only </li></ul><ul><li>Labeled for single use </li></ul><ul><li>After washing drying & relubricating 10 times, some deterioration was noted but all devices remained within USFDA product specification limits </li></ul><ul><ul><ul><ul><ul><li>Contraception 2000. </li></ul></ul></ul></ul></ul><ul><li>Slight increase in holes after 7 cycles of washing, drying & relubricating. </li></ul><ul><li>Contraception-2003. </li></ul>
    12. 12. Vaginal Barrier Methods Courtesy of the Cervical Barrier Advancement Society
    13. 13. Diaphragm-Like Devices: Easier to Use and Appropriate for Use with Microbicide <ul><li>Lea’s Shield® </li></ul><ul><ul><li>Silicone rubber cup-shaped device covers cervix. One way valve allows cervical secretions and air to pass out. </li></ul></ul><ul><ul><li>Available in several countries. </li></ul></ul><ul><li>SILCS contraceptive </li></ul><ul><ul><li>Silicone device covers cervix. Special shape makes insertion and removal easy. </li></ul></ul><ul><ul><li>Currently under development. </li></ul></ul>Courtesy of the Cervical Barrier Advancement Society Courtesy of PATH
    14. 14. New Cervical Caps Designed to Reduce Fitting Time <ul><li>FemCap ™ </li></ul><ul><ul><li>Silicone rubber device fits over cervix and blocks sperm. </li></ul></ul><ul><ul><li>Comes in three sizes; a provider must check the fit. </li></ul></ul><ul><li>Ovès ™ </li></ul><ul><ul><li>Disposable cervical cap made of silicone. </li></ul></ul><ul><ul><li>Comes in three sizes; a provider must check the fit. </li></ul></ul><ul><ul><li>Effectiveness has not yet been established. </li></ul></ul>Courtesy of the Cervical Barrier Advancement Society Courtesy of the Cervical Barrier Advancement Society
    15. 15. Contraceptive Sponges: No Fitting or Prescription Required <ul><li>The Today Sponge ® </li></ul><ul><ul><li>Discontinued in 1994 but recently re-released in Canada. </li></ul></ul><ul><ul><li>Effectiveness: 13 to 16 pregnancies per 100 users in the first year as typically used </li></ul></ul><ul><ul><li>Contain 1gm of nonoxynol-9. </li></ul></ul><ul><ul><li>Use for 24 hr. </li></ul></ul><ul><ul><li>(JRME-2007) </li></ul></ul><ul><li>Protectaid ® </li></ul><ul><ul><li>New polyurethane foam sponge, packed with spermicide gel F-5 ® . </li></ul></ul><ul><ul><li>Manufacturer plans to apply for US FDA approval. </li></ul></ul><ul><ul><li>Effectiveness: 23 pregnancies per 100 users in one year as typically used. </li></ul></ul><ul><ul><li>(JRME-2007). </li></ul></ul>
    16. 16. Microbicides Jefferson Jackson Steele
    17. 17. Microbicides Can Reduce Transmission of HIV and other STIs <ul><li>Description: Vaginally applied substances designed to reduce transmission of HIV and other STIs. Some function as spermicides to provide contraceptive protection. </li></ul><ul><li>How they work: Boost body’s defense against infection, damage or hinder disease pathogens, or prevent virus replication. </li></ul><ul><li>Effectiveness: Expected to be 50-60% effective. </li></ul><ul><li>(John Hopkins manual-2008) </li></ul>
    18. 18. How Do Microbicides Work? <ul><li>Most microbicides under development act in one or more of the following ways: </li></ul><ul><ul><li>Vaginal defense enhancers: Boost body’s natural defenses against infection. </li></ul></ul><ul><ul><li>Surfactants: Damage and disable disease pathogens to prevent them from causing infection. </li></ul></ul><ul><ul><li>Entry and fusion inhibitors: Bind to disease pathogens or to healthy cells before pathogens can invade them. </li></ul></ul><ul><ul><li>Replication inhibitors: Prevent viruses from replicating in cells that they have entered. </li></ul></ul><ul><ul><li>(John Hopkins manual-2008) </li></ul></ul>
    19. 19. Microbicides with contraceptive action: <ul><li>Create physical barrier: cellulose sulfate, polystyrene sulfonate. </li></ul><ul><li>↑ vaginal defense mechanism: Buffer-Gel, Acidform. </li></ul><ul><li>Surfactant products: Acyl carnitine analogues. </li></ul><ul><li>Block attachment of HIV to target cell: naphthyl urea derivative. </li></ul><ul><li>Under investigation: Carraguard :- prevents HIV transmission. </li></ul><ul><li>WHO-2007 </li></ul><ul><li>JRME-2007. </li></ul>
    20. 20. Spermicides: <ul><li>Inactivate or kill sperms. </li></ul><ul><li>Chemicals: nonoxynol-9, octoxynol-9, menfegol, benzalkonium chloride. </li></ul><ul><li>Applied 10-15 min before sexual act. </li></ul><ul><li>No douching within 8hrs. </li></ul><ul><li>Typical failure rate 15-21%. </li></ul><ul><li>J Rprod Med End-2007. </li></ul>
    21. 21. Oral combined contraceptives: <ul><li>Estrogen component: </li></ul><ul><li>MC-Ethinyl estradiol(EE). </li></ul><ul><li>Occasionally – Mestranol. </li></ul><ul><li>Under trial: Estradiol(E2),Estetrol(E4). </li></ul><ul><li>E4 is 18 times less potent than EE. </li></ul><ul><li>Progesterone component: </li></ul><ul><li>19-nortestosterone: </li></ul><ul><li>1 st generation: norethisterone, norethisterone acetate, lynestrenol, ethinodiol diacetate . </li></ul><ul><li>2 nd generation: levonorgestrel. </li></ul><ul><li>3 rd generation: desogestrel, gestodene, norgestimate. </li></ul>BJOG-2008.
    22. 22. contd: <ul><li>Derivative of 17-hydroxy progesterone: </li></ul><ul><li>-Cyproterone acetate. </li></ul><ul><li>Spirolactone derivative: Drospirenone. </li></ul><ul><li>Progesterone only pill:(Minipill): </li></ul><ul><li>Norethindrone-0.350mg(Micronor). </li></ul><ul><li>Levonorgestrel-0.075mg(Neogest). </li></ul><ul><li>Norgestrel-0.030mg(Microval). </li></ul><ul><li>Desogestrel-0.075mg(Cerazette). </li></ul>
    23. 23. ↓ EE DOSE: <ul><li>↓ EE dose from 50 to 30-35 µg- ↓ risk of MI, stroke, DVT. </li></ul><ul><li>↓ EE 30 to 20µg further ↓ risk of DVT. </li></ul><ul><li>20 Vs >20 µg pill: </li></ul><ul><li>-more disruption of bleeding pattern. </li></ul><ul><li>-more chance of discontinuation. </li></ul><ul><li>Cochrane Database Syst Rev-2006. </li></ul>
    24. 24. Regimens in OCP: <ul><li>Biphasic Vs Manophasic: </li></ul><ul><li>-Cochrane study : no evidence to say biphasic pills are better than monophasic. </li></ul><ul><li>-so monophasic pills are better choice. </li></ul><ul><li>Biphasic Vs Triphasic: </li></ul><ul><li>-no enough evidence to say triphasic > biphasic for birth control, bleeding pattern or staying on pill. </li></ul><ul><li>Cochrane Database Syst Rev-2006. </li></ul>
    25. 25. Extended regimen: <ul><li>Similar efficacy. </li></ul><ul><li>Escape ovulation. </li></ul><ul><li>Shorter hormone free interval. </li></ul><ul><li>↓ break through bleeding. </li></ul><ul><li>↓ pelvic pain, breast tenderness </li></ul><ul><li>NETA 1mg/EE 20mcg(24 vs 21d) is well tolerated & similar efficacy. </li></ul><ul><li>(Contraception-2007). </li></ul>
    26. 26. Drospirenone <ul><li>New Progestin, now in India </li></ul><ul><li>Analogue of Spironolactone (3mg Drospirenone=25mg Spironolactone) </li></ul><ul><li>Can increase Serum potassium </li></ul><ul><li>Has no estrogenic or androgenic activity </li></ul><ul><li>Antiovulatory and antimineralocorticoid activity </li></ul><ul><li>Avoid in: long term use of NSAIDs, other K + -sparing diuretics, K + supplementation, ACE inhibitors, etc. </li></ul><ul><li>Some evidence of effectiveness > placebo for Premenstrual dysphoric disorder (PMDD) </li></ul><ul><li>Common preparations : Yasmin, Tarana, Janya, Dronis, Rasmin </li></ul><ul><li>Yasmin = 30 mcg E 2 + 3 mg Drospirenone (21/7) Dronis /Yaz = 20 mcg E 2 + 3 mg drospirenone (24/4). </li></ul>
    27. 27. Continuous-Use Regimen Offers New Choice for Pill Users <ul><li>Reduces side effects associated with hormone withdrawal (migraines, heavy or painful monthly bleeding). </li></ul><ul><li>Breakthrough bleeding is more likely, but diminishes after 8 or 9 months of use. </li></ul><ul><li>Seasonale ® is packaged specifically for continuous use and is US FDA approved. </li></ul><ul><ul><li>Users take pill every day for 84 days (12 weeks) and then take a hormone-free pill for 7 days. </li></ul></ul><ul><ul><li>( Contraception-2008 ) </li></ul></ul>
    28. 28. Extended Cycle Products <ul><li>21/2/5 regime Mircette® ‐ 21 tab containing 20μg EE+ 0.15mg desogestrel followed by 2 placebo tab followed by 5 tab containing 10μg EE. </li></ul><ul><li>Kariva™ ‐ 21 tab containing 20μg EE+ 0.15mg desogestrel followed by 2 placebo tab followed by 5 tab containing 10μg EE. </li></ul><ul><li>24/4 regimens Yaz® ‐ 20μg EE+ 3 mg drospirenone. </li></ul><ul><li>Loestrin® 24 ‐ 24 tab containing 20μg EE+ 1 mg norethindrone acetate followed by 4 tab containing 75mg ferrous fumarate. </li></ul>
    29. 29. Extended Cycle Products <ul><li>Continuous regimen </li></ul><ul><li>84/7 regimens  Seasonale®, Jolessa, Quasense 30μg EE + LNG 0.15mg </li></ul><ul><li>S easonique ‐ 84 tab containing 30μg EE+ 0.15mg LNG followed by 7 tabs of 10μg EE </li></ul><ul><li>Lybrel - 365 tab containing 20μg EE+ 90μg LNG (28 day pack) </li></ul>
    30. 30. Cochrane Review. Cochrane Library 2008 (3) Conclusions <ul><li>Extended use of COC </li></ul><ul><li>-Similar user satisfaction, discontinuation rates, </li></ul><ul><li>compliance </li></ul><ul><li>-May improve menstruation related symptoms </li></ul><ul><li>-Bleeding patterns equivalent or improved </li></ul><ul><li>relatively to cyclic use </li></ul><ul><li>Questions to address: long-term efficacy, safety </li></ul><ul><li>Extended COC use is a reasonable approach for </li></ul><ul><li>women without contraindications to COC. </li></ul>
    31. 31. Progesterone only pills(minipill): <ul><li>Plasma levels fall to baseline within 24 hours after intake, must be taken at the same time daily. </li></ul><ul><li>Dose delay > 3 hours - Backup X 48 hours. </li></ul><ul><li>Failure rate: Typically used-3-10%. </li></ul><ul><li>Irregular bleeding - Main reason for discontinuation </li></ul><ul><li>Minimal effects on milk production </li></ul><ul><li>↑ P rolactin release- ↑ Milk production </li></ul><ul><li>No effect on infant growth or development. </li></ul>
    32. 32. Cerazette(Organon): <ul><li>Progesterone only pill -75 µgm Desogestrel, used daily. </li></ul><ul><li>Inhibit ovulation 97% after 7 months of use. </li></ul><ul><li>Minimum effects on lipid & carbohydrate metabolism. </li></ul><ul><li>Useful in lactating mothers & perimenopausal. </li></ul><ul><li>Safety margin – 12 hrs </li></ul><ul><li>Pearl index – 0.14. </li></ul><ul><li>Disadvantages – Irregular bleeding, amenorrhea. </li></ul>BJOG-2008.
    33. 33. Mifeprestone as contraceptive: <ul><li>Sequential regimen: </li></ul><ul><li>-Mife + Norethisterone. </li></ul><ul><li>-Mife + MPA. </li></ul><ul><li>-Mife (Day 1-15) + Nomegestrel acetate (Day 16-28). </li></ul><ul><li>Continuous regimen: </li></ul><ul><li>-1-10 mg/day. </li></ul><ul><li>Weekly use: </li></ul><ul><li>-5-50mg. </li></ul><ul><li>Monthly use: </li></ul><ul><li>-Mife 200mg 2days after the LH peak. </li></ul><ul><li>Emergency Contraception: </li></ul><ul><li>-Mife 10mg. </li></ul>WHO-2006.
    34. 34. Injectables: Courtesy of Schering AG
    35. 35. Injectable contraceptives <ul><li>Progestogen only injectables: </li></ul><ul><ul><ul><li>DMPA - im 150 mg every 3 months . </li></ul></ul></ul><ul><ul><ul><li>sc 104 mg 3 monthly– effective, ↓irregular bleeding, ↑amenorrhea. </li></ul></ul></ul><ul><ul><ul><li>Norethisterone enanthate(NET-EN )– 200mg im every 2 months. </li></ul></ul></ul><ul><li>Combined injectables – Once a month: </li></ul><ul><ul><ul><li>Cyclofem: DMPA 25 mg + Estradiol cypionate 5 mg. </li></ul></ul></ul><ul><ul><ul><li>Mesigyna : NET EN 50 mg + Estradiol valerate 5 mg. </li></ul></ul></ul><ul><li>Under research: </li></ul><ul><ul><ul><li>LNG butanoate – 5 to 10 mg – 3 to 6 monthly </li></ul></ul></ul><ul><ul><ul><li>DMPA-Sc: “Depo-Sub Q Provera”. </li></ul></ul></ul>
    36. 36. New Combined Injectables Offer Alternative to Progestin-only Injectables <ul><li>Description: Monthly injections containing a progestin and an estrogen. </li></ul><ul><li>How they work: Injected estrogen and progestin prevent ovulation, thicken cervical mucus, and suppress endometrial growth. </li></ul><ul><li>Effectiveness: 0.1 to 0.4 pregnancies per 100 women per year. </li></ul><ul><li>WHO-2006. </li></ul>
    37. 37. Combined Injectables Offer Advantages Over Progestin-Only Injectables <ul><li>Branded under names Cyclofem and Mesigyna. </li></ul><ul><li>Irregular bleeding patterns less common and decrease with length of use. </li></ul><ul><li>Women can become pregnant as soon as six weeks after discontinuation. </li></ul><ul><li>Community health workers or women themselves can administer using Uniject, a single-use, prefilled, nonreusable syringe. </li></ul>BJOG-2008.
    38. 38. New Subcutaneous DMPA Formulation Recently Approved <ul><li>DMPA-SC provides slower, more sustained absorption of the progestin than conventional DMPA. </li></ul><ul><li>Available only in a pre-filled Uniject syringe. </li></ul><ul><li>Amenorrhea 55% at 12 months of use. </li></ul>Courtesy of PATH Contraception-2004.
    39. 39. Contraceptive Implants Karen Tweedy-Holmes, Population Council
    40. 40. Implantables: progestin Trade name Unit Duration of action: Levonorgestrel Norplant 6 capsules 5 years. Etonegestrel Implanon 1 rod 3 years. Nestrone Elcometrine 1 capsule 6 months. Nestrone Elcometrine 1 rod 2 years. Norgestrol Unilant/ Surplant 1 rod 1 year Levonorgestrel Jedelle/Norplant II 2 rods 5 years
    41. 41. Implanon ™ <ul><li>FDA approved July 2006 </li></ul><ul><li>Available worldwide since 1997 </li></ul><ul><ul><li>Approximately 3 million implants inserted since 1998 </li></ul></ul><ul><li>Single rod implant (As opposed to six for Norplant) </li></ul><ul><ul><li>68mg 3-keto-desogestrel (etonogestrel) </li></ul></ul><ul><ul><li>Achieve ovulatory inhibitory levels within 8 hours of insertion </li></ul></ul><ul><ul><li>JRME-2007. </li></ul></ul>
    42. 42. IMPLANON™ Rate-controlling membrane: (0.06 mm) 100% EVA 4 cm 2 mm Core: 40% ethylene vinyl acetate (EVA) 60% etonogestrel (68 mg) Release Rate : 60  g/day to 70  g/d initially then decreases to 25  g/d to 30  g/d by end of third year <ul><li>IMPLANON™ is not radio-opaque </li></ul>
    43. 43. Implanon ™ <ul><li>Mechanism of action </li></ul><ul><ul><li>Prevents ovulation </li></ul></ul><ul><ul><li>Alters cervical mucous </li></ul></ul><ul><li>Efficacy – Highly effective </li></ul><ul><ul><li>.38 pregnancies/100 women years </li></ul></ul><ul><ul><li>No data in women over 130% of ideal body weight </li></ul></ul>
    44. 44. Implanon ™ applicator
    45. 45. Implanon ™ <ul><li>Easy to insert </li></ul><ul><ul><li>>85% less than 1 minute </li></ul></ul><ul><li>Easy to remove </li></ul><ul><ul><li>One rod </li></ul></ul><ul><ul><li>Different material than Norplant - doesn’t stimulate fibrosis </li></ul></ul><ul><ul><li>1.7% experience difficulty with removal </li></ul></ul>
    46. 46. New Implants Have Fewer Rods than Norplant ® <ul><li>Description: One or two progestin-releasing rods inserted just under the skin. </li></ul><ul><li>How they work: Progestin released under the skin thickens the cervical mucus, prevents ovulation in many cycles, and suppresses endometrial growth. </li></ul><ul><li>Effectiveness: 0.3 to 1.1 pregnancies per 100 women in the first year of use as typically used. </li></ul>
    47. 47. New Implants: <ul><li>JEDELLE: </li></ul><ul><li>43 × 2.5 mm. </li></ul><ul><li>Each rod-75 µg LNG. </li></ul><ul><li>NESTORONE: </li></ul><ul><li>Only in Brazil. </li></ul><ul><li>Effective up to 2 years. </li></ul><ul><li>Can be given to lactation. </li></ul><ul><li>NOMEGESTREL ACETATE (Uniplant): </li></ul><ul><li>One rod-1000µg/day. </li></ul><ul><li>For 1 year. </li></ul><ul><li>Under trial. </li></ul>BJOG-2008
    48. 48. BIODEGRADABLE IMPLANTS: <ul><li>Removal is not necessary. </li></ul><ul><li>LNG- Single capsule: </li></ul><ul><li>-phase II trial going on. </li></ul><ul><li>-release LNG from polymer:caprolactone. </li></ul><ul><li>-life span- 1 year. </li></ul><ul><li>Norethisterone (85%) + Cholesterol(15%) mixed by a heat fusion technique. </li></ul>BJOG-2008
    49. 49. Vaginal Rings: Left: NuvaRing® (Organon). Right:Nestorone® vaginal ring.
    50. 50. In which way they are advantageous: <ul><li>Steroid absorption through vaginal route is rapid. </li></ul><ul><li>Constant release rate. </li></ul><ul><li>Method is under woman’s control. </li></ul><ul><li>First pass metabolism & GI absorption is bypassed. </li></ul><ul><li>Can remove the ring for 2hrs if feels uneasy. </li></ul>
    51. 51. Combined Vaginal Rings Offer Better Cycle Control than Oral Contraceptives <ul><li>Prevent ovulation, thicken cervical mucus, and suppress endometrial growth. </li></ul><ul><li>Fewer bleeding problems than combined oral contraceptives. </li></ul><ul><li>NuvaRing ® approved for use in Europe, the US, Brazil, and Chile. </li></ul><ul><li>Nestorone ® + EE in clinical trial stage, is intended for use specifically in developing countries. </li></ul>
    52. 52. Vaginal rings: <ul><li>NUVA RING </li></ul><ul><li>120 µg etonogestrel + 15 µg EE/day in ethylene vinyl acetate (EVA) copolymer ring. </li></ul><ul><li>Use ring × 3wks, then 1wk free. </li></ul><ul><li>Side effects: </li></ul><ul><li>-Leucorrhoea, vaginal discomfort, vaginitis. </li></ul><ul><li>-FB sensation,expulsion. </li></ul><ul><li>Nestorone ring </li></ul><ul><li>150µg nestorone + 15µg EE/day. </li></ul><ul><li>Effective up to 12 months. </li></ul><ul><li>Phase-3 trials going on. </li></ul>BJOG-2008.
    53. 53. Nuvaring ® <ul><li>Efficacy </li></ul><ul><ul><li>Perfect use 99% </li></ul></ul><ul><ul><li>Typical use 92% </li></ul></ul><ul><li>Continuation – 1 year </li></ul><ul><ul><li>68% </li></ul></ul><ul><li>Usage </li></ul><ul><ul><li>3 weeks in/ 1 week out </li></ul></ul><ul><ul><li>Consider continuous use </li></ul></ul><ul><ul><li>Out <3 hours OK </li></ul></ul>
    54. 54. Progesterone only ring: <ul><li>Population council, NY has developed 2 progesterone only rings. </li></ul><ul><li>Both release natural progesterone . </li></ul><ul><li>PROGERING : Used during lactation. </li></ul><ul><li>FERTIRING : Used in IVF. </li></ul><ul><li>J Reprod Med End-2007. </li></ul>
    55. 55. Transdermal Contraception Courtesy of Ortho McNeil Pharmaceutical
    56. 56. Transdermal Contraception Delivers Hormones Through the Skin <ul><li>Description: Patches, sprays, or gels, applied weekly or daily. </li></ul><ul><li>How they work: Patches release estrogen and progestin through the skin, preventing ovulation, thickening the cervical mucus, and suppressing endometrial growth. </li></ul><ul><li>Effectiveness: Patches—0.8 to 1.3 pregnancies per 100 women in the first year. </li></ul><ul><li>BJOG-2008. </li></ul>
    57. 57. Combined Patches: A Good Alternative For Pill Users <ul><li>User replaces patch weekly for three weeks, followed by one patch-free week. </li></ul><ul><li>Similar effectiveness to oral contraceptives (OCs). </li></ul><ul><li>In clinical trials, women liked the patch as much as OCs. </li></ul><ul><li>Ortho Evra® the only patch on the market . </li></ul>Courtesy of Ortho McNeil Pharmaceutical
    58. 58. Contd. <ul><li>Evra: </li></ul><ul><li>-releases 150µg norelgestromin & 20µg EE daily. </li></ul><ul><li>-FDA approval in 2001. </li></ul><ul><li>-applied weekly×3wks,one week gap. </li></ul><ul><li>Fidencia: </li></ul><ul><li>-Gestodene + EE </li></ul><ul><li>-Availability by 2010. </li></ul><ul><li>Under trial: </li></ul><ul><li>-Nestorone patch. </li></ul>J Reprod Med End-2007
    59. 59. Contraceptive patches: Left: Evra (Ortho-McNeil). Right: Fidencia (Bayer-Schering-Pharma).
    60. 60. Contd. <ul><li>Women using patch are exposed to 60% more total estrogen than OC pill users. </li></ul><ul><li>Patch ,vaginal ring ,pill users- same pregnancy rate. </li></ul><ul><li>Patch user : Breast discomfort,BTB > pill users. </li></ul><ul><li>3% discontinue due to local allergic reaction. </li></ul><ul><li>Other adverse effects are more/less same. </li></ul><ul><li>Cochrane Database-2007. </li></ul>
    61. 61. Extended vs. cyclic use of transdermal patch: <ul><li>Conclusions – extended regimen </li></ul><ul><li>Effective for delaying withdrawal bleeding </li></ul><ul><li>high satisfaction </li></ul><ul><li>Low adverse events </li></ul><ul><li>Few discontinuation due to bleeding </li></ul><ul><li>Not enough data on long-term efficacy, tolerability and safety </li></ul><ul><li>Cochrane study-2008. </li></ul>
    62. 62. Spray-On Contraceptives: A New Technique For Hormone Delivery <ul><li>A new progestin-only spray(Nestorone)The Metered Dose Transdermal System- is absorbed into the skin, then diffuses into bloodstream. </li></ul><ul><li>Suppress ovulation-83%. </li></ul><ul><li>Phase III clinical trials underway in Australia. </li></ul>Karen Tweedy-Holmes, Population Council Contraception-2007
    63. 63. Gene-Based Approaches Promise Dramatic Change in Contraception <ul><li>Target the genes or proteins involved in sperm and egg development. </li></ul><ul><li>In women: target molecules to prevent ovulation. </li></ul><ul><li>In men: prevent sperm from penetrating an egg’s outer layer. </li></ul><ul><li>Unlikely to cause side effects. </li></ul><ul><li>At least 10 years away from reaching the market. </li></ul>
    64. 64. Intrauterine Devices Courtesy of Berlex
    65. 65. Three Main IUDs Are Used Currently Copper-bearing IUDs Hormonal IUD TCu-380A Multiload-375 LNG-IUD
    66. 66. New IUDs Make Insertion and Removal Easier and Reduce Side Effects <ul><li>Description : Progestin-releasing IUDs and IUDs without the conventional T-shaped frame. </li></ul><ul><li>How they work : Stimulate a sterile inflammatory response in the uterine cavity that is toxic to sperm. Progestin-releasing IUDs also thicken cervical mucus and suppress endometrial growth. </li></ul><ul><li>Effectiveness: 0.1 to 2.5 pregnancies per 100 women in the first year of use. </li></ul>Contraception-2008
    67. 67. One of the Most Effective Methods of Contraception <ul><li>Women who become pregnant during first year of use: </li></ul><ul><ul><li>TCu-380A: 3 to 8 per 1,000 (0.3% to 0.8%) </li></ul></ul><ul><ul><li>LNG-IUD: 1 to 3 per 1,000 (0.1% to 0.3%) </li></ul></ul><ul><li>Comparable to effectiveness of female sterilization </li></ul><ul><li>LNG-IUD is more effective than TCu-380A. </li></ul><ul><li>Contraception-2008. </li></ul>
    68. 68. New Progestin-Releasing Mirena IUS Offers Many Advantages Over Cu-IUDs <ul><li>Approved in 2000 for 5 years of use. Available in over 100 countries. </li></ul><ul><li>More effective than many Cu-IUDs. </li></ul><ul><li>Over time causes less bleeding than Cu-IUDs. </li></ul><ul><li>Can use to treat heavy, prolonged bleeding or painful menstrual cramps. </li></ul>Courtesy of Berlex
    69. 69. Levonorgestrel-releasing intrauterine systems: Left: Mirena®; Right: “Small Mirena®”.
    70. 70. Mirena/ LNG 20/ Levonova <ul><li>Polydimethyl siloxane T frame </li></ul><ul><li>Capsule on the stem – 52 mg LNG </li></ul><ul><li>20 μg LNG per day </li></ul><ul><li>Failure rate is 0.1 to 0.4 per 100 women in first year </li></ul><ul><li>Effective for 5 years </li></ul><ul><li>↓ MBL, amenorrhea, protection from ectopic </li></ul>
    71. 71. Mirena/ LNG 20/ Levonova <ul><li>Non contraceptive uses </li></ul><ul><ul><li>Menorrhagia </li></ul></ul><ul><ul><li>Progestin component of HRT </li></ul></ul><ul><ul><li>Treatment of endometrial hyperplasia </li></ul></ul><ul><ul><li>Adjuvant therapy with tamoxifen </li></ul></ul><ul><ul><li>Endometriosis associated pelvic pain. </li></ul></ul><ul><ul><li>J Reprd Med End-2007. </li></ul></ul>
    72. 72. Other LNG-IUS: <ul><li>FEMILIS(Contrel): </li></ul><ul><li>-Shorter sidearms. </li></ul><ul><li>-Initial study show good clinical study. </li></ul><ul><li>-no comparative effectiveness studies. </li></ul><ul><li>Contraception-2005. </li></ul><ul><li>FIBROPLANT(Contrel): </li></ul><ul><li>-Frameless IUS with EVA delivery system. </li></ul><ul><li>-Two versions available:releasing 14 & 20 µg LNG/day. </li></ul><ul><li>- Life span-5yrs. Contraception-2003. </li></ul>
    73. 73. Flexi Gard/ Cu fix IUD/ Gynefix <ul><li>Frameless IUD, 3 cm long </li></ul><ul><li>6 Copper sleeves (300 sq mm of Cu) strung on a surgical polypropylene nylon thread knotted at the upper end </li></ul><ul><li>Pearl index 2.5 </li></ul>
    74. 74. Flexi Gard/ Cu fix IUD/ Gynefix <ul><li>Knot is pushed 9 to 10 mm into myometrium of fundus by a special stylet </li></ul><ul><li>Risk of perforation </li></ul><ul><li>Minigyne fix – 2 cm long with 4 copper sleeves. As effective as Gynefix </li></ul>
    75. 75. Silverlily and Goldlily IUDs: <ul><li>Both devices provide good protection </li></ul><ul><li>against unwanted pregnancy </li></ul><ul><li>Relevant termination rates are low </li></ul><ul><li>Continuation rates are high </li></ul><ul><li>(first year figures: Silverlily 86.3%, Goldlily 88.2% ) </li></ul><ul><li>Using alloy of Cu/Ag and Cu/Au provides a </li></ul><ul><li>new possibility in intrauterine contraception </li></ul><ul><li>(longer life span, less side effects ) </li></ul><ul><li>Copper/noble metal alloys may create a new generation of IUDs. </li></ul><ul><li>Contraception-2008 </li></ul>
    76. 76. Other IUD under research: <ul><li>Swing: Cu releasing with coil stem. </li></ul><ul><li>IUD with a progesterone receptor modulator:(CBD-2914). </li></ul><ul><li>Copper IUD releasing Indomethacin or other PG synthetase blockers/inhibitors. </li></ul><ul><li>Six Copper IUD with modification in shape:CuSafe-300,Fincoid-350,Gynefix,Intracervical Fixing Device, </li></ul><ul><li>Sof-T, MultiLoad Mark II. </li></ul>WHO-2007
    77. 77. WHO Guidance Allows More Women to Use IUDs World Health Organization, 2004   PID Purulent cervicitis, chlamydia, or gonorrhea Other STIs HIV AIDS Clinically well on ART Not well on or not taking ART Condition Exists Before Insertion Do not insert (Category 4) Do not insert (Category 4) Generally can insert (Category 2) Generally can insert (Category 2) Generally can insert (Category 2) Usually do not insert (Category 3) Condition Develops After Insertion Generally can keep her IUD while being treated (Category 2) Generally can keep her IUD while being treated (Category 2) Generally can keep her IUD while being treated (Category 2) Generally can keep her IUD (Category 2) Generally can keep her IUD (Category 2) At High Individual Risk for Condition NA Usually do not insert (Category 3) NA Generally can insert (Category 2) NA NA
    78. 78. New Male Contraceptives Courtesy of Shepherd Medical
    79. 79. What can be? <ul><li>Inhibition of sperm production: </li></ul><ul><li>Inhibition of sperm maturation: </li></ul><ul><li>Blockage of sperm transport. </li></ul><ul><li>Prevention of sperm deposition. </li></ul><ul><li>Modification of sperm function & prevention of fertilization. </li></ul>
    80. 80. Which male contraceptives are closest to market? <ul><li>Three methods are in clinical trials: </li></ul><ul><li>RISUG(Reversible inhibition of sperm under guidance) </li></ul><ul><li>The Intra Vas Device (IVD) </li></ul><ul><li>Male hormonal contraceptives </li></ul><ul><li>Two interesting pre-clinical leads: </li></ul><ul><li>Adjudin </li></ul><ul><li>RAR antagonist </li></ul><ul><li>Int J Andro-2008. </li></ul>
    81. 81. Inhibitors of spermatogenesis: <ul><li>Hormonal : </li></ul><ul><li>Testosterone derivative: testosterone enanthate(TE),testosterone bucinate(TB),testosterone undecanoate(TU). </li></ul><ul><li>Progestogen: DMPA,LNG,desogestrel. </li></ul><ul><li>Antiandrogen & progestogen: CPA. </li></ul><ul><li>Immunological: Abs against GnRH,FSH,LH & their receptors. </li></ul><ul><li>Nonhormonal : Gossypol, triptolide, Adjudin. </li></ul>
    82. 82. Hormonal methods <ul><li>LH stimulates Tes production in Leydig cells </li></ul><ul><li>FSH stimulates spermatid production when Tes is present </li></ul><ul><li>Blood-testis barrier regulates internal testes environment </li></ul>
    83. 83. Hormones: <ul><li>No such preparations are available. </li></ul><ul><li>All these inhibit LH & FSH. </li></ul><ul><li>Azoospermia 40-60% cases. </li></ul><ul><li>Effect is reversible. </li></ul><ul><li>Trials going on: </li></ul><ul><li>LNG implants(160µgm/day)+Inj TE 200mg wkly. </li></ul><ul><li>Desogestrel 300µg+ testosterone pellets. </li></ul><ul><li>Norethisterone enanthate 200mg+TU 1000mg 8wkly. (Cochrane Review:2008) </li></ul>
    84. 84. MHCs – What are they? <ul><li>Supra-physiological dose of testosterone suppresses testicular production of testosterone and halts spermatogenesis </li></ul><ul><li>May include a progestin for faster, more complete suppression </li></ul><ul><li>No orally available testosterone; delivery via implants, depot injections, transdermal gels and patches </li></ul>
    85. 85. MHCs – How are they reversed? <ul><li>Stop treatment, hormones begin rebound, spermatogenesis reinitiates </li></ul><ul><li>Meta analysis showed all formulations reliably reversible within 3-5 months </li></ul><ul><li>Minimum 2½ month recovery due to lag for production of mature sperm </li></ul>The Lancet -2006.
    86. 86. MHCs – Side effects <ul><li>Similar to side effects experienced by women on hormonal contraceptives </li></ul><ul><li>Mild weight gain, increase in lean muscle mass, acne </li></ul><ul><li>Drop in HDL cholesterol level with some androgens </li></ul><ul><li>No prostate over-stimulation observed in studies up to 18 months </li></ul><ul><li>The Lancet-2006. </li></ul>
    87. 87. nonhormonal : <ul><li>GOSSYPOL: </li></ul><ul><li>-disequiterpene aldehyde derivative from seed,stem,root of the cotton plant. </li></ul><ul><li>-↓sprmatogenesis, ↓sperm motility. </li></ul><ul><li>-gossypol formic acid,gossypol acetic acid. </li></ul><ul><li>-SE: hypokalemic paralysis-1%. </li></ul><ul><li>TRIPTOLIDE: </li></ul><ul><li>-isolated from the plant-T.wilfordii. </li></ul><ul><li>-current trial going on. </li></ul>
    88. 88. Interesting leads - Adjudin <ul><li>Non-toxic lonidamine analog </li></ul><ul><li>Disrupts cellular bridges between spermatids and Sertoli cells </li></ul><ul><li>Clever targeted delivery by attaching Adjudin to a modified FSH </li></ul><ul><li>Population Council researchers working to improve delivery method and bring down production costs </li></ul>Nature Medicine -2006,Int J Andro-2008.
    89. 89. Interesting leads – RAR antagonist <ul><li>Retinoic acid required for sperm production </li></ul><ul><li>1 week of RAR antagonist treatment blocks sperm production for 3 months </li></ul><ul><li>100% effective, no observable side effects, fully reversible </li></ul><ul><li>Researchers at Columbia University testing in other animal models </li></ul><ul><li>IntJ Andro-2008. </li></ul>
    90. 90. Contd. <ul><li>Inhibition of sperm maturation: </li></ul><ul><li>-Antiandrogens, Alpha-chlorohydrin. </li></ul><ul><li>-trials going on in Germany. </li></ul><ul><li>Inhibition of sperm transport: </li></ul><ul><li>Condoms: previously discussed </li></ul><ul><li>Sterilization: </li></ul>
    91. 91. Male sterilization: <ul><li>Surgical vasectomy. </li></ul><ul><li>No-scalpel vasectomy. </li></ul><ul><li>Fascial interposition. </li></ul><ul><li>Percutaneous vas occlusion. </li></ul><ul><li>-Permanent: with sclerosing agent-eg: methylcyanoacrylate, polyurethane. </li></ul><ul><li>- Reversible: with non sclerosing agent- eg : silicone plug, or resins :e.g. maleic anhydride styrene. </li></ul><ul><li>WHO-2006. </li></ul>
    92. 92. Vasectomy: resection and electrocauterisation
    93. 93. Vasectomy: resection and ligation: A) resection, folding and ligation; B) resection and ligation; C) resection and interfascial positioning.
    94. 94. No-scalpel vasectomy: <ul><li>By Dr Shungiang in China in 1974. </li></ul><ul><li>As compared to surgical vasectomy: </li></ul><ul><li>-Less bleeding, infection & pain during and after the procedure. </li></ul><ul><li>-Takes less time. </li></ul><ul><li>-Faster return to sexual activity. </li></ul><ul><li>Cochrane Database-2007. </li></ul>
    95. 95. <ul><li>A polymer gel of styrene maleic anhydride mixed with dimethyl sulphoxide injected into the vasa deferentia </li></ul><ul><li>Partially blocks the lumen and disrupts passing sperm </li></ul><ul><li>Now in Phase III clinical trials in India </li></ul>RISUG – What is it? Contraception-1998.
    96. 96. RISUG – How effective is it? <ul><li>Extremely effective (>99%) </li></ul><ul><li>200+ men have been treated with RISUG 2 pregnancies: 1 due to improper delivery, 1 due to marital infidelity </li></ul><ul><li>Long-lasting </li></ul><ul><li>The first clinical trial volunteers received RISUG in 1992; Informal follow-up visits show they still have effective contraception today </li></ul>Contraception-1998.
    97. 97. <ul><li>Transient, painless scrotal swelling which resolves with no intervention within 2 weeks </li></ul><ul><li>Prostate indicators all healthy after 8 years of RISUG use in Phase II trial volunteers </li></ul><ul><li>Zero clinical trial attrition to date </li></ul>RISUG – Side effects Contraception-2005.
    98. 98. RISUG – How is it reversed? <ul><li>Reversal proven in monkeys after 1½ years of use, all had normal sperm count within 3 months of reversal </li></ul><ul><li>Sodium bicarbonate solution </li></ul><ul><li>Multiple injections and reversals effective in monkeys </li></ul><ul><li>Not yet (formally) tested in men </li></ul>Sources: Lohiya (2000) Int J of Andrology 23(1): 36-42. Lohiya (2005) Contraception 71(3): 214-26. Contraception-2005.
    99. 99. The IVD – What is it? <ul><li>US design in Phase I trials: dual silicone plugs inserted into the vas block sperm </li></ul><ul><li>Chinese design has completed Phase II trials: single urethane stent filled with nylon mesh allows vasal fluid to pass but traps sperm </li></ul>Int J Andro-2008.
    100. 100. IVD – How effective is it? <ul><li>US design awaiting completion of trial; past designs 90-100% effective </li></ul><ul><li>Chinese design 100% effective, no pregnancies in 123 couples in 1 year </li></ul><ul><li>Like vasectomy, effective after 3 months </li></ul><ul><li>Sperm count required to confirm </li></ul>
    101. 101. IVD – Side effects <ul><li>Similar to “no scalpel vasectomy”, but less frequent and less severe </li></ul><ul><li>10% reported mild pain, 3% developed granulomas </li></ul><ul><li>No spontaneous reversal, no congestive epididymitis </li></ul><ul><li>Higher satisfaction rate than NSV </li></ul>Int J Andrology -2008.
    102. 102. Female Sterilization <ul><li>Interrupts the patency of fallopian tubes thereby preventing fertilization </li></ul><ul><li>Failure rate: Depends on method used - </li></ul><ul><li>ranges from 0.8-3.7% </li></ul><ul><li>May be performed through a minilaparotomy </li></ul><ul><li>incision , laparoscopically, or transcervically. </li></ul>
    103. 103. Laparoscopic Sterilization: <ul><li>Performed as outpatient: </li></ul><ul><li>Bipolar Cautery: bipolar cutting current of 25 </li></ul><ul><li>watts to cauterize the tube. </li></ul><ul><li>Fallope Ring: Silastic band that ligates a knuckle </li></ul><ul><li>of tube. </li></ul><ul><li>Hulka clip: Spring-loaded clip applied to isthmic </li></ul><ul><li>portion of the tube. </li></ul><ul><li>Filshe: Titanium with silicone rubber clip applied </li></ul><ul><li>to isthmic portion of the tube. </li></ul>
    104. 104. Sterilization by laparotomy: <ul><li>Pomeroy technique. </li></ul><ul><li>Irving technique. </li></ul><ul><li>Uchida technique. </li></ul><ul><li>Parkland technique. </li></ul><ul><li>Madlener technique. </li></ul><ul><li>Kroener’s technique (Fimbriectomy). </li></ul>
    105. 105. What is Essure? <ul><li>A new method of female hysteroscopic sterilisation. </li></ul><ul><li>Marketed and sold by </li></ul><ul><li>Conceptus, Inc. </li></ul><ul><li>Approved by FDA </li></ul><ul><li>on Nov. 4th, </li></ul><ul><li>2002. </li></ul>
    106. 106. Contd . <ul><li>Inner coil-stainless steal. </li></ul><ul><li>Outer coil nickel-titanium alloy. </li></ul><ul><li>Polyethylene terephthalate fibres woven around inner coil. </li></ul><ul><li>Device inserted through 5F gauge hysteroscope. </li></ul><ul><li>Fibrosis occurs in & around the microcoil producing permanent sterilisation. </li></ul><ul><li>Placement confirmed-USG/X-ray after 3months. </li></ul>
    107. 107. contd. <ul><li>Placement failure-16%. </li></ul><ul><li>If correctly placed-tubal occlusion in 99.5% at 12months. </li></ul><ul><li>A pregnancy rate of 1.2/1000 has been reported. </li></ul><ul><li>BJOG-2008. </li></ul>
    108. 108. What is Adiana? <ul><li>By Hologic Inc, USA. </li></ul><ul><li>A two step process. </li></ul><ul><li>Controlled thermal damage of the endosalpinx followed by insertion of a biocompatible matrix plug with in the tubal lumen. </li></ul><ul><li>J Minim Invasive Gynecol-2005. </li></ul>
    109. 109. Contd. <ul><li>OVABLOCK : Method of inserting a rubber tube in both fallopian tubes. </li></ul><ul><li>QUINACRINE :chemical sterilisation by this polymerising agent leads to occlusion of both the tubes. </li></ul><ul><li>J Reprod Med Endo-2007. </li></ul>
    110. 110. female sterilisation techniques. Left: Upper figure: Essure; Lower figure: Adiana Right: Ovabloc (www.ovabloc.com/ovabloc-de/eingriff.html)
    111. 111. <ul><li>To see laparoscopic surgeries in Gynae logon to </li></ul><ul><li>www.youtube.com </li></ul><ul><li>and </li></ul><ul><li>type </li></ul><ul><li> pradeep aiims </li></ul>
    112. 113. <ul><li>For queries mail me at </li></ul><ul><li>pkgarg_in2004@yahoo.com </li></ul>
    113. 114. THANK YOU

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