FutureFuture methodsmethods ofof fertilityfertility regulationregulation

CatherineCatherine ddd’Arcangues,’’ArcanguesArcangues,, Ph.D.,Ph.D., M.D.M.D.

DepartmentDepartment ofof ReproductiveReproductive HealthHealth andand ResearchResearch WorldWorld HealthHealth OrganizationOrganization CDA/Paris/SEP 04/ 1 Department of reproductive health and research Département santé et recherche génésiques Department of reproductivehealth and research 2. 1. 3. 2. 1. 3. • • • • New targets forcontraception New Improvement ofexisting methods New Improvement ofexisting methods New targets forcontraception Mode ofaction Efficacy, side manufacturing process, cost Efficacy, side Mode ofaction manufacturing process, cost approches approches - - effects, durationofaction, effects, durationofaction, éatmn at trcecegénésiques etrecherche santé Département

CDA/Paris/Sep 04/ 2 1. 1. Department of reproductivehealth and research Improvement Improvement of of existing existing éatmn at trcecegénésiques etrecherche santé Département methods methods

CDA/Paris/Sep 04/ 3 Department of reproductivehealth and research Copper-releasing Intra Intra - - uterine uterine devices devices éatmn at trcecegénésiques etrecherche santé Département L evonorgestrel-releasing

CDA/Paris/Sep 04/ 4 Also • • • Department of reproductivehealth and research Swing: copper-releasing Copper (CDB-2914) IUD releasing Intra Intra under development: IUD releasing - - uterine uterine a devices devices indomethacin with éatmn at trcecegénésiques etrecherche santé Département coil r eceptor stem modulator

CDA/Paris/Sep 04/ 5 Department of reproductivehealth and research • • • • • • Nestorone Implanon Jadelle Implanon Jadelle Nestorone pure , 1 etonogestrel levonorgestrel pure progestogen, 1 Contraceptive implants Contraceptive implants : : : : : : , 1 , 1 , 2 , 2 rod rod rods rods , 3 , 3 éatmn at trcecegénésiques etrecherche santé Département rod rod , 5 , 5 years years , 2 , 2 years years years years

CDA/Paris/Sep 04/ 6 InjectablesInjectables (1)(1)

ImprovedImproved pharmacokineticpharmacokinetic profileprofile :: •• BiodegradableBiodegradable microspheresmicrospheresmicrospheres::: ,norethisterone, norgestimatenorgestimatenorgestimate,,, progesteroneprogesterone •• ControlledControlled particleparticle sizesize distributiondistributiondistribution::: DDMPA,MPA, levonorgestrellevonorgestrellevonorgestrel butanoatebutanoate DecreasedDecreased sidesideside-effects--effectseffects :: ••MonolithicMonolithic macrocrystalsmacrocrystalsmacrocrystals::: progesterone,progesterone, 171717-beta---betabeta-- ,estradiol, testosteronetestosterone combinedcombined forfor onceonceonce-a-month--aa--monthmonth administrationadministration CDA/Paris/SEP 04/ 7 Department of reproductive health and research Département santé et recherche génésiques Safer deliverysystem : • Department of reproductivehealth and research Safer deliverysystem : • ( disposable syringes in non Provision of ( disposable syringes in non Provision of Uniject Uniject - - reusable reusable , , Soloshot Soloshot Cyclofem Cyclofem Injectables (2) Injectables (2) ) ) éatmn at trcecegénésiques etrecherche santé Département

CDA/Paris/Sep 04/ 8 Contraceptive vaginal rings

•• ProgestogenProgestogen onlyonly (for continuous use) - Progering - Silesia (3 months) - nestorone - Pop.C. (12 months)

•• EstrogenEstrogen--progestogenprogestogen (3 weeks in /1 week out) - Nuvaring - Organon (1 month) - nestorone/EE - Pop.C. (12 months) CDA/Paris/SEP 04/ 9 Department of reproductive health and research Département santé et recherche génésiques • • • • Department of reproductivehealth and research Patch Patch Patch Patch – – – – – – – – – – nestorone levonorgestrel EVRA Schering gestodene levonorgestrel EVRA norgestimate nestorone Schering releasing releasing releasing releasing : : Transdermal Transdermal norelgestromin ) ) ( ( 50 50 also also µ µ + + g g an estrogen a progestogen: an estrogen a progestogen: being being ethinyl ethinyl + + ethinyl ethinyl developed developed 150 150 estradiol estradiol estradiol 18 estradiol 18 systems systems µ µ éatmn at trcecegénésiques etrecherche santé Département g g and and + + ethinyl ethinyl as agel as agel a progestogen: a progestogen: µ µ g estradiol 20 g estradiol 20 and and ( ( Angeliq Angeliq a spray) a spray) - - µ µ g g

CDA/Paris/Sep 04/ 10 • • • • observation from abstinence/protection cycle " Standard method observation abstinence/protection from cycle " Standard method Department of reproductivehealth and research Two Two cycle cycle days day days day , , based based days days 19. 19. " " day day method method Natural Natural 8 to 8 to on on , , based based methods methods on cervical mucus on cervical mucus éatmn at trcecegénésiques etrecherche santé Département

CDA/Paris/Sep 04/ 11 • • • • • • • • Department of reproductivehealth and research Quinacrine Ovabloc Adiana Essure Quinacrine Ovabloc Adiana Essure Female Female sterilization sterilization éatmn at trcecegénésiques etrecherche santé Département

CDA/Paris/Sep 04/ 12 Department of reproductivehealth and research Styrene-based Polyurethane: p Male condoms Male condoms lastic: Tactylon, Unique, Unisex Avanti, eZ.on,Supra éatmn at trcecegénésiques etrecherche santé Département

CDA/Paris/Sep 04/ 13 Femidom Department of reproductivehealth and research • • • Under development: Female Female plastic natural polyurethane (Reddy, other) (PATH) latex condoms condoms éatmn at trcecegénésiques etrecherche santé Département V-Amour

CDA/Paris/Sep 04/ 14 Department of reproductivehealth and research Lea's Lea's valve Shield Shield New New ® ® diaphragms diaphragms éatmn at trcecegénésiques etrecherche santé Département SILCS SILCS

CDA/Paris/Sep 04/ 15 Department of reproductivehealth and research Ov Ov è è s s New cervicalcaps New cervicalcaps éatmn at trcecegénésiques etrecherche santé Département FemCap FemCap ™ ™

CDA/Paris/Sep 04/ 16 Department of reproductivehealth and research 2. 2. New New approaches approaches éatmn at trcecegénésiques etrecherche santé Département

CDA/Paris/Sep 04/ 17 • • • • • • • • derivatives cellulose sulfate, sperm and by vagina Products Products Surfactant Products derivatives cellulose sulfate, sperm and vagina by Products Surfactant Products Products Department of reproductivehealth and research maintaining maintaining sperm sperm Microbicides with contraceptiveaction Microbicides with contraceptiveaction ): ): : : e.g. e.g. e.g. e.g. which which that which which that . . products products - - Sulfated Sulfated BufferGel zona BufferGel zona create create natural natural block increase block increase polystyrene polystyrene pellucida pellucida : : a e.g. a e.g. and and attachment attachment protective acidity protective and acidity and vaginal vaginal acylcarnitine acylcarnitine sulfonated sulfonated Acidform Acidform fusion fusion sulfonate sulfonate ( ( which which éatmn at trcecegénésiques etrecherche santé Département defense defense physical physical of of : : e.g. e.g. . HIV to . HIV to polymers polymers immobilises immobilises analogs analogs . . naphthyl naphthyl mechanisms mechanisms barrier barrier target target , , , C31G. , C31G. such such urea urea in in cells cells the the as as

CDA/Paris/Sep 04/ 18 Other corpus luteum embryonic Their Most advanced goal is Department of reproductivehealth and research targets: - antigen - + squalene/mannide + muramyl + diphtheria the hCG m olecules C t rophoblastic β -terminal to generate Chain: whole (FA-1), sperm and z immunocontraceptives ona pellucida d Immunocontraceptives Immunocontraceptives on sperm the ipeptide toxoid p ortion c ontinued cells, necessary antibodies as carrier o as adjuvant monooleate r the s p urface, e.g. rotein (permanent effect production of 109-145 amino against (SP-10), LDH-C4 are based éatmn at trcecegénésiques etrecherche santé Département (4:1) asemulsifying f or maintainance fe hCG rtilin progesterone: (PH-30), fertilisation s on ovaries) a on hCG ecreted cid s equence : b of

y agent the o f

CDA/Paris/Sep 04/ 19 • • • • • • • • • • Sequential Emergency contraception: 10mg Monthly Weekly Continuous Emergency contraception: 10mg Monthly Weekly Continuous Sequential – – – – – Department of reproductivehealth and research Mifepristone Mifepristone Mifepristone Mifepristone use: 2,5to 50mgdoses use: 2,5to 50mgdoses Anti Anti use: 200 mg2 use: 200 mg2 regimen regimen regimen regimen - - (days + + + + progestins progestins Norethisterone Norethisterone Medroxyprogesterone 1 -15) +nomegestrolacetate : 0,1to10 mg/ : 0,1to10 mg/ days days for contraception for contraception after after éatmn at trcecegénésiques etrecherche santé Département the the acetate day acetate day LH LH peak peak ( days 16-28)

CDA/Paris/Sep 04/ 20 Department of reproductivehealth and research • • • • • • • • • • Prevent fertilization Modify sperm function Prevent sperm deposition Prevent spermtransport Prevent spermproduction Prevent fertilization Modify sperm function Prevent sperm deposition Prevent spermtransport Prevent spermproduction MALE CONTRACEPTION MALE CONTRACEPTION METHODS FOR METHODS FOR éatmn at trcecegénésiques etrecherche santé Département

CDA/Paris/Sep 04/ 21 Department of reproductivehealth and research Hormonal controlof spermproduction Hormonal controlof spermproduction TL SPERMATOZOIDS TESTES TESTES BRAIN BRAIN GnRH H éatmn at trcecegénésiques etrecherche santé Département PITUITARY F S H

CDA/Paris/Sep 04/ 22 Department of reproductivehealth and research • • • • Methods to Methods to Immunological, basedonantibodies against Hormonal Hormonal Immunological, basedonantibodies against – – – – – – GnRH, LH, FSH,theirreceptors progestogen orGnRHanalogue+ Testosterone esters progestogen orGnRHanalogue+ testosterone Testosterone esters GnRH, LH, FSH,theirreceptors supress supress sperm production sperm production éatmn at trcecegénésiques etrecherche santé Département

CDA/Paris/Sep 04/ 23 - - Percutaneous vas occlusion Fascial No scalpelvasectomy - - Department of reproductivehealth and research or e.g. silicone plugs non e.g. sclerosing or e.g. silicone plugs non e.g. sclerosing Reversible, with Permanent, with Reversible, with Permanent, with resins resins - - polyurethane methylcyanoacrylate polyurethane methylcyanoacrylate sclerosing sclerosing Methods formale sterilization Methods formale sterilization interposition : e.g. : e.g. agents agents maleic maleic agents agents : : anhydride /styrene : anhydride /styrene : , , éatmn at trcecegénésiques etrecherche santé Département

CDA/Paris/Sep 04/ 24 Department of reproductivehealth and research 3. 3. New New targets targets éatmn at trcecegénésiques etrecherche santé Département

CDA/Paris/Sep 04/ 25 Possible targets

•• GametogenesisGametogenesis •• SpermSperm motilitymotility •• SpermSperm capacitationcapacitation •• AcrosomalAcrosomal reactionreaction •• FollicularFollicular developmentdevelopment •• ImplantationImplantation CDA/Paris/SEP 04/ 26 04/ CDA/Paris/SEP Department of reproductive health and research Département santé et recherche génésiques Department of reproductivehealth and research éatmn at trcecegénésiques etrecherche santé Département

CDA/Paris/Sep 04/ 27 Department of reproductivehealth and research • • • • • • • • • • • • antagonists. antibodies against LIF,IL Change in endometrial receptivity: LIFantagonists; Inhibitors of fusionofspermwith Inhibitors oftestis Inhibitors of Lonidamine from fumagillin antagonists. Inhibitors of fusionofspermwith Inhibitors oftestis Inhibitors of Lonidamine antibodies against LIF,IL Change in endometrial receptivity: LIFantagonists; from fumagillin Anti Anti - - seminiferous seminiferous angiogenic angiogenic Some Some ). ). epididymal analogues: depleteimmature germcells epididymal analogues: depleteimmature germcells of of agents ( agents ( - - specific enzymes(GST, SAC) the specific enzymes(GST, SAC) the epithelium. epithelium. more more proteins: proteins: magainin magainin - - 11, ortheIL 11, ortheIL promising promising éatmn at trcecegénésiques etrecherche santé Département zona eppin zona eppin analogues, analogues, - - pellucida pellucida 11 receptor; 11 receptor; and cystatin and cystatin leads leads : GnRH : GnRH - - ebaf ebaf 11 11 . .

CDA/Paris/Sep 04/ 28 for thedevelopment ofnewtechnologies for thedevelopment ofnewtechnologies For women tobenefitfromthese newtechnologies, • • • • • • • • Department of reproductivehealth and research they need better access toeducation andincome and ofnew generationsofwomen andmen Access in resource different religious andsocio Perspectives ofusers andpotentialusers,of Industry involvement Cost andtime(10 and ofnew generationsofwomen andmen different religious andsocio Perspectives ofusers andpotentialusers,of Industry involvement Cost andtime(10 Access in resource and tohave greater decision-making power. Challenges Challenges - - 15 years,US$200 15 years,US$200 - - poor settings (cost,technology) poor settings (cost,technology) éatmn at trcecegénésiques etrecherche santé Département - - cultural backgrounds, cultural backgrounds, - - 300 million) 300 million)

CDA/Paris/Sep 04/ 29 Department of reproductivehealth and research éatmn at trcecegénésiques etrecherche santé Département

CDA/Paris/Sep 04/ 30 Department of reproductivehealth and research éatmn at trcecegénésiques etrecherche santé Département

CDA/Paris/Sep 04/ 31