Capri, c'est IUI. ESHRE Capri guidelines on IUI

<strong>ESHRE</strong> CAMPUS 2009ARTIFICIAL INSEMINATION: AN UPDATEGenk, December 13-15, 2009Intrauterine insemination discussed bythe <strong>ESHRE</strong> <strong>Capri</strong> Workshop GroupM. Aboulghar (Egypt), D.T. Baird (UK), J. Collins (Canada),P.G. Crosignani (Italy), P. Devroey (Belgium),E. Diczfalusy (Sweden), K. Diedrich (Germany),J.L.H. Evers (The Netherlands), B.C.J.M. Fauser (The Netherlands),L. Fraser (UK), J.P.M. Geraedts (The Netherlands),L. Gianaroli (Italy), A. Glasier (UK), C.B. Lambalk (The Netherlands),E. Somigliana (Italy), A. Sunde (Norway), B. Tarlatzis (Greece),A. Van Steirteghem (Belgium)

MAIN INDICATION FOR <strong>IUI</strong>:UNEXPLAINED INFERTILITYCategories of unexplained infertility:• 20% of couples after the initial work-up• 20-40% of couples with mild male subfertility• 50% of those in whom conventional treatmentshave failed

LIVE BIRTH RATE PER COUPLEFOLLOWING <strong>IUI</strong> WITH OR WITHOUTOVARIAN STIMULATION(Verhulst et al., 2006)

PREGNANCY RATES ASSOCIATED TO <strong>IUI</strong>:THREE LARGE CLINICAL STUDIESStudy Rate x cycle (%)Women Pregnancy Twin TripletstreatedNo.Guzick et al., 1999 932 12 20 7(RCT)Gleicher et al., 2000 1494 13 20 9(retrospective)Dickey et al., 2005 2272 19 19 4(retrospective)

THE RISK OF MULTIPLEPREGNANCY• Perinatal mortality: 7 times higher for tripletsand 5 times higher for twins(Fisk and Trew, Lancet 1999)• Cerebral palsy: 48 times more frequent in tripletsand 8 times in twins(Petterson et al., B.M.J., 1993)

FEWER TRIPLETS WITH LOWER DOSE FSH(≤ ≤ 75 IU/DAY) AND CYCLE CANCELLATIONStudy PR per cycle Triplets/All pregnanciesBalasch et al., 1994 12.8% 0/12Cohlen et al., 1998 13.2% 0/21Sengoku et al., 1999 14.3% 0/7Goverde et al., 2000 8.7% 0/31Ragni et al., 2004 20.0% 0/13Gerli et al., 2004 12.3% 0/17Papageorgiou et al., 2004 10.4% 1/266Tur et al., 2005 A 10.1% 1/149Tur et al., 2005 B 14.0% 5/207Ragni et al., 2006 9.2% 0/116Total - 7/839Studies with cancellationcriteria 10.2% 2/613

THEORIESOLDNEW• The higher the number of released oocytesthe higher the chance of conception• High ovarian responsivity reflects therelease of higher quality oocytes

<strong>IUI</strong>: NUMBER OF STIMULATEDFOLLICLES VS PREGNANCY RATEMeta-analysis of 11599 cyclesFollicleNo.% increase of PR vsmonofollicular cycles2 1.63 2.0(Van Rumste et al., H. R.U., 2008)

ONE OR MORE FOLLICLESFOR <strong>IUI</strong> CYCLES?• If the growth of 1-2 follicles would beassociated with the expected fecundity,mono-ovulation will be the goal for thefuture <strong>IUI</strong>• There is a need of RCTs

<strong>IUI</strong>: CLINICAL CONDITIONSAFFECTING SUCCESS RATES• Age of the female partner• Duration of subfertility• Abnormal spermiogram(Steures et al., 2004)

PREMATURE LH SURGE DURING FSHSTIMULATION WITH AND WITHOUTANTAGONISTS• Patients: 203 women with unexplained infertility• Mild ovarian stimulation: median FSH dose 550-600 IUGroup A BAntagonist Ganirelix PlaceboCycles 103 100LH surge % 3.9 28.0Ongoing PR % 12.6 12.0• Premature luteinization is one of the consequencesof the poor quality follicle(Lambalk et al., HR, 21, 632-639, 2006)

ONGOING P.R. PER COUPLE WITHONE CYCLE OF FSH/<strong>IUI</strong> WITH ANDWITHOUT GnRH ANTAGONISTNNT: 20 antagonist cycles for one additional pregnancy

LUTEAL SUPPORT: IS IT NECESSARYIN STIMULATED <strong>IUI</strong> CYCLES?• Luteal support is necessary during inductionof ovulation in hypophysectomized patients• Women undergoing <strong>IUI</strong> stimulated cycles arenot totally hypogonadotropic• Exogenous HCG persists for at least 10 daysand at that time the embryo is secreting theendogenous hormone

<strong>IUI</strong>: FACTORS INVOLVED IN BALANCINGEFFICACY AND SIDE EFFECTS• The chance of spontaneous pregnancy• Ovarian stimulation aimed to the growth ofone or more follicles• Cycle cancellation if there are more than twodominant follicles

PREGNANCY RATE PER CYCLE ANDNUMBER NEEDED TO TREAT(NNT) PER CYCLETreatment Pregnancy rate NNT 95 % CI Sourceper cycle<strong>IUI</strong> 5 32 (12-46) Guzick et al., 1999,Steures et al., 2007FSH/<strong>IUI</strong> 12 11 (9-16) Guzick et al., 1999IVF 31 4 (3-7) Hughes et al., 2004

IVF MAKE-UP FOR THE BIRTHSLOST BY POSTPONING CONCEPTIONWoman’s ageIVF make-upFrom 30 to 35 50%From 35 to 40 30%(The <strong>ESHRE</strong> <strong>Capri</strong> Workshop Group, HRU, 11, 261-276, 2005)

PREGNANCY RATES FOLLOWING <strong>IUI</strong>COMBINED WITH OVARIAN STIMULATIONUSING EITHER ANTI-ESTROGEN OR FSHPrior to IVF, <strong>IUI</strong> with clomiphene stimulation is cheap andmany couples will conceive(Cantineau et al., 2007)

CONCLUSIONS - 1• In good prognosis couples, the live birth rateis better without treatment• <strong>IUI</strong> is widely used with infertility diagnosesother than bilateral tubal obstruction, severemale infertility and severe ovulation defects• The good success rate recently associatedwith mild stimulated <strong>IUI</strong> cycles must beconfirmed by large trials

CONCLUSIONS - 2• Prevention of premature LH surges andluteal phase support do not appear majorrequirements in <strong>IUI</strong> cycles• Although <strong>IUI</strong> treatment is cheaper andless demanding IVF is the most effectivetreatment for infertility• There is a need for management trialsto evaluate the order of treatment andoverall effectiveness of treatment strategiesin more clinical and cost settings.