V.N.PrilepskayV.N.Prilepskay., А.А.., А.А.KuzeminKuzemin,,Т.А.Т.А.NazarenkoNazarenko, Т.М., Т.М.AstakhovaAstakhova

Research Centre of ObstetricsResearch Centre of Obstetrics, , Gynecology & Gynecology & Perinatology Moscow,RussiaPerinatology Moscow,Russia

Mifepriston in emergencyMifepriston in emergencycontraceptioncontraception

ММifepristonifepriston

Synthetic steroidSynthetic steroid, , derivative of nortetisteron derivative of nortetisteron with antigestagen activitywith antigestagen activity..

Main indication for the use in medical abortionMain indication for the use in medical abortion

Additional indicationsAdditional indications:: Treatment of uterine leiomyomaTreatment of uterine leiomyoma Emergency contraceptionEmergency contraception

Three regimens were studied for emergency Three regimens were studied for emergency contraception during contraception during 120120 hrs after unprotected hrs after unprotected

coituscoitus

Single dose of Mifepriston Single dose of Mifepriston – 10– 10mgmg Single dose of levonorgestrel Single dose of levonorgestrel – 1,5 м– 1,5 мgg Two doses of levonorgestrel with an interval Two doses of levonorgestrel with an interval

of of 1212 hrs hrs

Exclusion criteria:Exclusion criteria:

Other methods of contraception used at the Other methods of contraception used at the momentmoment

Pospartum periodPospartum period Adrenal insufficiencyAdrenal insufficiency Thromboses in Thromboses in ааnamnesisnamnesis Severe diabetes mellitusSevere diabetes mellitus Genital massesGenital masses

Study design included four visitsStudy design included four visits

1.1. ScreeningScreening

2.2. On days 7-8 after the intended menstruation On days 7-8 after the intended menstruation onsetonset

3.3. On days On days 7-8 7-8 of the following menstrual cycleof the following menstrual cycle

4.4. Two months later the Two months later the 3-3-rdrd visitvisit

Drawbacks:Drawbacks:

1.1. Small number of casesSmall number of cases

2.2. Absence of control groupAbsence of control group

Main directions in the study of Main directions in the study of emergency contraception:emergency contraception:

Objective :improvement of emergency methodsObjective :improvement of emergency methods1.1. Creation of international consortium on emergency Creation of international consortium on emergency

contraceptioncontraception..2.2. Enhancement of the WHO studies on that themeEnhancement of the WHO studies on that theme..3.3. Study of efficacy and comparison of different methods Study of efficacy and comparison of different methods

(Youzpe method, levonorgestrel and mifepriston in (Youzpe method, levonorgestrel and mifepriston in different doses).different doses).

4.4. Prolongation of an interval after an unprotected coitus Prolongation of an interval after an unprotected coitus ((from from 72 72 ttо 120 о 120 hrshrs).).

Inclusion criteria:Inclusion criteria:

Unprotected coitus not more than Unprotected coitus not more than 72 72 hrs thrs tоо visitvisit..

Reproductive ageReproductive age Regular menstrual cycle during the last Regular menstrual cycle during the last

three monthsthree months None of psychic pathologyNone of psychic pathology Patient”s consentPatient”s consent

Results:Results:

No pregnanciesNo pregnancies in any of in any of 3030 patients patients.. Side effects inSide effects in 5 (16%) 5 (16%) patients onpatients on 2 2 –– 3 3 visits in visits in

the form of long the form of long ((in average up to in average up to 4646 days days) ) or or postponed cyclespostponed cycles- 34-36 - 34-36 daysdays..

By the By the 4 4 visit cycle was regylar in all patientsvisit cycle was regylar in all patients None of any other side effectsNone of any other side effects

V.N.PrilepskayV.N.Prilepskay., А.А.., А.А.KuzeminKuzemin,Т.А.,Т.А.NazarenkoNazarenko, , Т.М.Т.М.AstakhovaAstakhova 2004.2004.

Clinical TrialsClinical Trials

Clinical trials os these indications were carried Clinical trials os these indications were carried out in Russia for the first time at the out in Russia for the first time at the Research center of Obstetrics, Gynecology Research center of Obstetrics, Gynecology and Perinatology of the Russian Academy of and Perinatology of the Russian Academy of Medical Sciences.Medical Sciences.

Coordinator of the trial was academican Coordinator of the trial was academican Vladimir I.KulakovVladimir I.Kulakov

A total ofA total of 30 30 women were investigated. women were investigated.

MifepristonMifepriston ( (tabletstablets10 м10 мgg) ) (М(Мir-Pharmir-Pharm))

As a means of emergency contraception it As a means of emergency contraception it was registered in Russia inwas registered in Russia in 2004 2004 after after clinical trials and was approved for clinical clinical trials and was approved for clinical practicepractice..

Indications for emergency Indications for emergency contraceptioncontraception

Absence of any contraception in regular Absence of any contraception in regular sexual contactssexual contacts

Rupture of condomRupture of condom IUD expulsion during the cycle of the studyIUD expulsion during the cycle of the study Sexual abuseSexual abuse

Age fromAge from 18 18 till till 33 лет, 33 лет, mean agemean age 23,8+ 23,8+/-/-1,7.1,7.

Methods of studyMethods of study

1.1. ClinicalClinical ( (anamnesis data, examinations etcanamnesis data, examinations etc.).)

2.2. Blood testsBlood tests,,urine testsurine tests, , biochemical testsbiochemical tests

3.3. Bacterioscopy of vaginal dischargeBacterioscopy of vaginal discharge

4.4. Tests for genital infectionsTests for genital infections,,IVFIVF..

5.5. Sonography of pelvis minor with Doppler modesSonography of pelvis minor with Doppler modes..

6.6. Tests for CG in blood.Tests for CG in blood.

7.7. InterrogationInterrogation

No pregnanciesNo pregnancies

А) А) verified by ultrasonographyverified by ultrasonography

В) В) verified by tests for Chorionic gonadotropin verified by tests for Chorionic gonadotropin in blood plasmain blood plasma

General criterion of is a number of General criterion of is a number of pregnancies/number of women using pregnancies/number of women using MifepristonMifepriston

Major parameters of effficiencyMajor parameters of effficiency

ObjectivesObjectives

To assess efficacy and safety of a low-dose To assess efficacy and safety of a low-dose mifepristonemifepristone(10мг) (10мг) in emergency in emergency contraceptioncontraception..

ConclusionConclusion

««Mifepriston retards ovulation that mean Mifepriston retards ovulation that mean prolonged cycle and later onset of the prolonged cycle and later onset of the following menstruationfollowing menstruation»»

ConclusionConclusion

««The per cent of pregnancies occuringThe per cent of pregnancies occuring in the in the following cycle after Mifepriston used for following cycle after Mifepriston used for emergency contraception is high in case of emergency contraception is high in case of unprotected coitusunprotected coitus (22%), (22%),that determines the that determines the necessity to use contraception or continencenecessity to use contraception or continence.».»

ConclusionConclusion

««All three regimens are very efficient for emergency All three regimens are very efficient for emergency contraception and prevents a high per cent of pregnancies contraception and prevents a high per cent of pregnancies if taken during the first if taken during the first 55 days days.».»

((Randomized double blind study in Randomized double blind study in 15 15 family planning clinics family planning clinics in in 10 с10 сountriesountries (4136 (4136 healthy women with regylar healthy women with regylar menstrual cyclemenstrual cycle)).)).

Helene von Hertzen et al. Lancet 2002, 360:1803-10Helene von Hertzen et al. Lancet 2002, 360:1803-10

Further investigationsFurther investigations

Comparison of Mifepriston effect in the dose Comparison of Mifepriston effect in the dose of of 10 м10 мgg in different regimens of usein different regimens of use: 72 : 72 and and 120 120 hrs after unprotected coitushrs after unprotected coitus..

Intended designIntended design::

150150 patients in each group patients in each group

ConclusionConclusion

Results of the study tesify of a high effect of Results of the study tesify of a high effect of a single dosea single dose

Of Of ММifepristonifepriston (10 мг) (10 мг) as a method of as a method of emergency contraception and rather good emergency contraception and rather good tolerance of ittolerance of it..

Most typical side effect Most typical side effect ((inin 6 6 patiens, patiens, 20 %) –20 %) –is menstrual disoders during the first two is menstrual disoders during the first two cycles after the witgdrawal of itcycles after the witgdrawal of it..

Thank you for your attentionThank you for your attention