4-Pres-Sardjito-Prof. Dr. Djaswadi Dasuki_ M.ph._ PhD._ SpOG

7/28/2019 4-Pres-Sardjito-Prof. Dr. Djaswadi Dasuki_ M.ph._ PhD._ SpOG

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EVIDENCE BASED IN

ASSISTED REPRODUCTIVE

TECHNOLOGY

Djaswadi Dasuki

1

WHAT IS EBM ?

Best research evidence is clinically relevant research oftenfrom the basic sciences of medicine, but especially from

patient-centered clinical research into the accurary and

precision of diagnostic tests, the power of prognostic

markers, and the efficacy and safety of therapeutic,

rehabilitative, and preventive regiments.

2

Evidence-based medicine (EBM) is the integration of bestresearch evidence with clinical expertise and patientvalues.


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Clinical expertise is the ability to use our clinical skills and

past experience to rapidly identify each patients uniquehealth state and diagnosis, their individual risks and

benefits of potential interventions, and their personal values

and expectations.

Patient values is unique preferences, concerns andexpectations each patient brigns to a clinical encounter and

which must be integrated into clinical decisions if they are

to serve the patient.

3

HOW DO WE ACTUALLY PRACTICE EBM ?

Step 1 converting the need for information (about

prevention, diagnosis, prognosis, prognosis, therapy,

causation, etc.) into an answerable question.

Step 2 tracking down the best evidence with which to

answer that question.

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Step 3 critically appraising that evidence for its validity,

impact, and applicability. Step 4 integrating the critical appraisal with our clinical

expertise and with our patients unique biology, values and

circumstances.

Step 5 evaluating our effectiveness and efficiency inexecuting steps 1-4 and seeking ways to improve them

both for next time.

5

Clinical problem

6

Defince important,Defince important,searchable questionsearchable question

Select most likelySelect most likelyresourceresource

Design searchDesign searchstrategystrategy

Summarize theSummarize theevidenceevidence

Apply the evidenceApply the evidence

Select second mostSelect second mostlikely resourcelikely resource

Design searchDesign searchstrategystrategy

Summarize theSummarize theevidenceevidence

Apply the evidenceApply the evidence

Pooryield

Figure General search strategy


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Table Level of evidence and grades of recommedations

Grade ofGrade of

recommedatirecommedationon

Level ofLevel of

evidenceevidence

Therapy/preventionTherapy/prevention

aetiology/harmaetiology/harm

PrognosisPrognosis DiagnosisDiagnosis

AA

1a1a SR (with homogeneitySR (with homogeneitydd) of) ofRCTs`RCTs`

SR (withSR (withhomogeneityhomogeneitydd) of) ofinception cohortinception cohortstudies; or astudies; or aCPGCPGee validatedvalidatedon a test seton a test set

SR (withSR (withhomogeneityhomogeneitydd) of) oflevel 1 diagnosticlevel 1 diagnosticstudies; or a CPGstudies; or a CPGvalidate on a testvalidate on a testsetset

1b1b Individual RCT (withIndividual RCT (withnarrow confidence interval)narrow confidence interval)

IndividualIndividualinception cohortinception cohortstudy withstudy with 80%80%followfollow--upup

Idependent blindIdependent blindcomparison of ancomparison of anappropdateappropdatepatientspatients

1c1c All or noneAll or nonecc AllAll--oror--none casenone caseseriesserieshh

Absolute SpPinsAbsolute SpPinsand SnNoutsand SnNoutsii

7

Grade ofGrade of

recommedatirecommedationon

Level ofLevel of

evidenceevidence

Therapy/preventionTherapy/prevention

aetiology/harmaetiology/harm


BB

2a2a SR (wi th homogenei tyd)SR (with homogeneityd)of cohort studiesof cohort studies

SR (withSR (withhomogeneityc)homogeneityc)of eitherof eitherretrospectiveretrospectivecohort studiescohort studiesor untreatedor untreatedcontrol group incontrol group inRCTsRCTs

SR (withSR (withhomogeneityd)homogeneityd)of levelof level 22diagnosticdiagnosticstudiesstudies

2b2b Individual cohort studyIndividual cohort study(including low(including low--qualityqualityRCT; e.g.


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Grade ofGrade ofrecommedatirecommedati

onon

Level ofLevel ofevidenceevidence

Therapy/preventionTherapy/preventionaetiology/harmaetiology/harm


3a3a SR (wi th homogenei tyd)SR (with homogeneityd)of caseof case--control studiescontrol studies

3b3b Individual caseIndividual case--controlcontrolstudystudy

IndependentIndependentblindblindcomparison ofcomparison ofan appropriatean appropriatespectrumspectrum

CC44 Case series (and poorCase series (and poor--

quality cohort and casequality cohort and case--control studies4control studies4 cc

Case series (andCase series (andpoorpoor--qualityqualityprognosticprognosticcohort studies)cohort studies)

ReferenceReferencestandard wasstandard wasnot appliednot appliedindependentlyindependently

DD

55 Expert opinion withoutExpert opinion withoutexplicity critical appraisal,explicity critical appraisal,or based on physiologyor based on physiology

Expert opinionExpert opinionwithout explicitwithout explicitcriticalcriticalappraisal,appraisal,

Expert opinionExpert opinionwithout explicitwithout explicitcriticalcriticalappraisal, orappraisal, orbased onbased onphysiologyphysiology

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Assisted hatching on assited conception (IVF & ICSI)

Objectives

To determine whether assited hatching (AH) of embryos

facilitates live births and clinical pregnancy and whether it

impacts on negative outcomes (such as multiple pregnancy

and miscarriage).

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Comparison live birth rate, Outcome live birth per woman randomised

StudyStudy AssistedAssistedhatchinghatchingn/Nn/N

ControlControln/Nn/N

WeightWeight(%)(%)

Odds RatioOdds Ratio(Fixed)(Fixed)95% CI95% CI

Cohen 1992ACohen 1992A 34/6934/69 26/6826/68 26.926.91.57 [0.80,1.57 [0.80,

3.103.10]]

Hellebaut 1996Hellebaut 1996 21/6021/60 20/6020/60 26.326.31.08 [0.51,1.08 [0.51,

2.29]2.29]

Hurst 1998Hurst 1998 2/132/13 3/73/7 6.76.70.24 [0.03,0.24 [0.03,

2.03]2.03]

Lanzendorf 1998Lanzendorf 1998 12/4112/41 15/4815/48 19.819.80.91 [0.37,0.91 [0.37,

2.26]2.26]

Petersen 2005APetersen 2005A 8/158/15 10/3510/35 15.615.60.74 [0.25,0.74 [0.25,

2.18]2.18]

Petersen 2000BPetersen 2000B 9/409/40 3/403/40 4.74.7

3.583.58[0.89,14.39[0.89,14.39

]]

1.19 [0.81,1.19 [0.81,

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Comparison Clinical pregnancy, Outcome Clinical pregnancy rate per woman

randomised: grouped by 1 st attempt and repeat attempts

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StudyStudyAssistedAssistedhatchinghatching

n/Nn/N


WeightWeight(%)(%)

Odds Ratio (Fixed)Odds Ratio (Fixed)95% CI95% CI

0202 Repeat attempt at IVF or ICSIRepeat attempt at IVF or ICSI

Antinori 1999AAntinori 1999A 19/7919/79 11/6911/69 3.23.2 1.86 [0.81, 4.25]1.86 [0.81, 4.25]

Carter 2003Carter 2003 62/12162/121 43/8243/82 9.59.5 0.95 [0.54, 1.67]0.95 [0.54, 1.67]

Jelinkova 2002Jelinkova 2002 59/12859/128 40/12740/127 8.38.3 1.86 [1.12, 3.10]1.86 [1.12, 3.10]

Petersen 2005APetersen 2005A 11/3511/35 10/3510/35 2.62.6 1.15 [0.41, 3.19]1.15 [0.41, 3.19]

Petersen 2005BPetersen 2005B 10/4010/40 3/403/40 0.90.9 4.11 [1.04, 16.29]4.11 [1.04, 16.29]

RufasRufas--Sapir 2004Sapir 2004 22/10422/104 28/10328/103 8.58.5 0.72 [0.38, 1..36]0.72 [0.38, 1..36]

Sein 1995Sein 1995 15/7215/72 12/8212/82 3.43.4 1.54 [0.67, 3.54]1.54 [0.67, 3.54]

Utsunomiya 1998Utsunomiya 1998 5/275/27 4/284/28 1.21.2 1.36 [0.32, 5.73]1.36 [0.32, 5.73]

Subtotal (95% CI)Subtotal (95% CI) 600600 566566 37.537.5 1.33 [1.02, 1.72]1.33 [1.02, 1.72]

Total eventsTotal events 203203 (Assisted hatching),(Assisted hatching), 151151 (Control)(Control)Test for heterogeneity chiTest for heterogeneity chi--square=square= 99..9595 df=df=77 p=p=0.190.19 I??=I??= 2929..77%%Test for overall effect z=Test for overall effect z= 22..1313 p= 0p= 0.03.03


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StudyStudyAssistedAssistedhatchinghatching

n/Nn/N


WeightWeight(%)(%)

Odds Ratio (Fixed)Odds Ratio (Fixed)95% CI95% CI

0303 MechanicalMechanical

Isiklar 1999Isiklar 1999 16/2216/22 10/2210/22 1.01.0 3.20 [0.91, 11.27]3.20 [0.91, 11.27]

Laffoon 1999Laffoon 1999 9/289/28 10/2810/28 2.62.6 0.85 [0.28, 2.58]0.85 [0.28, 2.58]

RufasRufas--Sapir 2004Sapir 2004 22/10422/104 28/10328/103 8.58.5 0.72 [0.38, 1.36]0.72 [0.38, 1.36]

Stein 1995Stein 1995 15/7215/72 12/8212/82 3.43.4 1.54 [0.67, 3.54]1.54 [0.67, 3.54]

Subtotal (95% CI)Subtotal (95% CI) 226226 235235 15.515.5 1.09 [0.71, 1.66]1.09 [0.71, 1.66]

Total eventsTotal events 6622 (Assisted hatching),(Assisted hatching), 6060 (Control)(Control)Test for heterogeneity chiTest for heterogeneity chi--square=square= 5.275.27 df=df=33 p=p=0.150.15 I??=I??= 43.143.1%%Test for overall effect z=Test for overall effect z= 0.380.38 p=p= 0.70.7Total (95% CI)Total (95% CI) 14591459 14301430 100.0100.0 1.29 [1.10, 1.52]1.29 [1.10, 1.52]Total eventsTotal events 524524 (Assisted hatching),(Assisted hatching), 430430 (Control)(Control)Test for heterogeneity chiTest for heterogeneity chi--square=square= 28.4128.41 df=df=2323 p=p=0.200.20 I??=I??= 19.1%19.1%Test for overall effect z=Test for overall effect z= 3.113.11 p=p= 0.0020.002

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Laporoscopic Surgery For Subfertility AssociatedWith Endometriosis

Objectives

To assess the efficacy of laparoscopic surgery in

the treatment of subfertility associated with

endometriosis. The review aims to compare

outcomes of laparoscopic surgical interventions

compared to no treatment or medical treatment with

regard to improved fertility.

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Laparoscopic surgery versus diagnostic laparoscopy, Outcome ongoing

pregnancy at 20 weeks or live birth

StudyStudy

LaparoscLaparoscopicopic

surgerysurgeryn/Nn/N


WeightWeight(%)(%)

PetoPeto Odds RatioOdds Ratio95% CI95% CI

Gruppo Italiano 1999Gruppo Italiano 1999 10/5110/51 10/4510/45 20.720.7 0.85 [0.32, 2.28]0.85 [0.32, 2.28]

Marcoux 1997Marcoux 1997 50/17250/172 29/16929/169 79.379.3 1.95 [1.18, 3.22]1.95 [1.18, 3.22]

Total (95% CI)Total (95% CI) 223223 214214 100.0100.0 1.64 [1.05, 2.57]1.64 [1.05, 2.57]

Total eventsTotal events 6060 ((Laparoscopic surgeryLaparoscopic surgery),), 3939 (Control)(Control)Test for heterogeneity chiTest for heterogeneity chi--square=square= 2.142.14 df=df=11 p=p=0.140.14 I??=I??= 53.453.4%%Test for overall effect z=Test for overall effect z= 2.172.17 p=p= 0.030.03

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Laparoscopic surgery versus diagnostic laparoscopiy, Outcome pregnancy

StudyStudyTreatmentTreatment

n/Nn/NControlControl

n/Nn/NWeightWeight

(%)(%)PetoPeto Odds RatioOdds Ratio

95% CI95% CI

Gruppo Italiano 1999Gruppo Italiano 1999 12/5112/51 13/4513/45 20.820.8 0.76 [0.31, 1.88]0.76 [0.31, 1.88]

Marcoux 1997Marcoux 1997 63/17263/172 37/16937/169 79.279.2 2.03 [1.28, 3.24]2.03 [1.28, 3.24]

Total (95% CI)Total (95% CI) 223223 214214 100.0100.0 1.66 [1.09, 2.51]1.66 [1.09, 2.51]

Total eventsTotal events 7575 ((Treatment surgeryTreatment surgery),), 5050 (Control)(Control)Test for heterogeneity chiTest for heterogeneity chi--square=square= 3.573.57 df=df=11 p=p=0.060.06 I??=I??= 72.072.0%%Test for overall effect z=Test for overall effect z= 2.382.38 p=p= 0.020.02

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In Vitro Fertilisation For Unexplained Subfertility

Objectives

The aim of this review is to determine, in the context of

unexplained infertility, whether IVF improves the probability of

live-birth compared with (1) expectant management, (2)

clomiphene citrate (CC), (3) intrauterine insemination (IUI) alone,

(4) IUI with controlled ovarian stimulation, and (5) gamete

intrafallopian transfer (GIFT).

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Comparison IVF Versus Expectant Management, Outcome Pregnancy rate

per woman

StudyStudyIVFIVFn/Nn/N

ExpectantExpectantManagementManagement

n/Nn/N

WeightWeight(%)(%)

Odds RatioOdds Ratio (Fixed)(Fixed)95% CI95% CI

Hughes 2004Hughes 2004 12/2412/24 3/273/27 38.238.2 8.00 [1.89, 33.85]8.00 [1.89, 33.85]

Soliman 1993Soliman 1993 1/211/21 2/142/14 61.861.8 0.30 [0.02, 3.67]0.30 [0.02, 3.67]

Total (95% CI)Total (95% CI) 4545 4141 100.0100.0 3.24 [1.07, 9.80]3.24 [1.07, 9.80]

Total eventsTotal events 1313 ((IVFIVF),), 55 ((Expectant ManagementExpectant Management))Test for heterogeneity chiTest for heterogeneity chi--square=square= 44.97.97 df=df=11 p=p=0.030.03 I??=I??= 79.979.9%%Test for overall effect z=Test for overall effect z= 2.082.08 p=p= 0.040.04

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Comparison IVF versus GIFT, Outcome Pregnancy rate per woman

StudyStudyIVFIVFn/Nn/N

GIFTGIFTn/Nn/N

WeightWeight(%)(%)

Odds RatioOdds Ratio (Fixed)(Fixed)95% CI95% CI

Raneiri 1995Raneiri 1995 17/3417/34 12/3512/35 52.152.1 1.92 [0.73, 5.05]1.92 [0.73, 5.05]

Tanbo 1990Tanbo 1990 16/3516/35 11/4211/42 47.947.9 2.37 [0.91, 6.18]2.37 [0.91, 6.18]

Total (95% CI)Total (95% CI) 6969 7777 100.0100.0 2.14 [1.08, 4.22]2.14 [1.08, 4.22]

Total eventsTotal events 3333 ((IVFIVF),), 2323 ((GIFTGIFT))Test for heterogeneity chiTest for heterogeneity chi--square=square= 0.090.09 df=df=11 p=p=0.760.76 I??=I??= 0.00.0%%Test for overall effect z=Test for overall effect z= 2.082.08 p=p= 0.040.04

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Gonadotrophin Therapy For Ovulation Induction InSubfertility Associated With Polycystic Ovary Syndrome

Objectives

To determine the effectiveness of urinary-derived

gonadotrophins as ovulation induction agents in patients with

PCOS trying to conceive. In particular, to assess the effectiveness

of

(1) different gonadotrophin preparation, (2) the addition of a

gonadotrophin-releasing hormone agonist (GnRH-a) to

gonadotrophin stimulation and (3) different modalities of

gonadotrophin administration.

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Comparison FSH versus hMG, Outcome Pregnancy rate (per cycle)

StudyStudyIncreasingIncreasingwith hMGwith hMG

n/Nn/N

IncreasedIncreasedwith FSHwith FSH

n/Nn/N

WeightWeight(%)(%)


01 without GnRH01 without GnRH--a (patient randomiseda (patient randomised--paralel data)paralel data)

Gadir 1990Gadir 1990 10/11410/114 15/11915/119 38.338.3 0.67 [0.29, 1.54]0.67 [0.29, 1.54]

Homburg 1990Homburg 1990 3/233/23 3/423/42 8.78.7 2.00 [0.35, 11.43]2.00 [0.35, 11.43]

Sagle 1991Sagle 1991 5/355/35 5/405/40 15.015.0 1.16 [0.31, 4.38]1.16 [0.31, 4.38]

Seibel 1985Seibel 1985 1/111/11 3/123/12 5.95.9 0.35 [0.04, 2.86]0.35 [0.04, 2.86]

SubtSubtotal (95% CI)otal (95% CI) 183183 213213 67.967.9 0.82 [0.44, 1.53]0.82 [0.44, 1.53]

Total eventsTotal events 1919 ((Increased with hMGIncreased with hMG),), 2323 ((Inreased with FSHInreased with FSH))Test for heterogeneity chiTest for heterogeneity chi--square=square= 2.142.14 df=df=33 p=p=0.540.54 I??=I??= 0.00.0%%Test for overall effect z=Test for overall effect z= 0.610.61 p=p= 0.50.5

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StudyStudyIncreasingIncreasingwith hMGwith hMG

n/Nn/N

IncreasedIncreasedwith FSHwith FSH

n/Nn/N

WeightWeight(%)(%)


0044 with GnRHwith GnRH--a (patients randomiseda (patients randomised--parallel data)parallel data)

HomburgHomburg 19901990 3/273/27 2/302/30 7.97.9 1.731.73 [[0.280.28,, 10.6710.67]]

JacobsJacobs 19871987 2/192/19 2/162/16 6.26.2 0.830.83 [[0.110.11,, 6.496.49]]

SubtSubtotal (95% CI)otal (95% CI) 4646 4646 14.114.1 1.251.25 [[0.320.32,, 4.894.89]]

Total events 5 (Total events 5 (Increased with hMGIncreased with hMG), 4 (), 4 (Inreased with FSHInreased with FSH))Test for heterogeneity chiTest for heterogeneity chi--square=square= 0.270.27 df=df=33 p=0.60p=0.60 I??=I??= 0.00.0%%Test for overall effect z= 0.32 p= 0.7Test for overall effect z= 0.32 p= 0.7

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THANK YOU

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Documents

4-Pres-Sardjito-Prof. Dr. Djaswadi Dasuki_ M.ph._ PhD._ SpOG