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
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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.
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Evidence-based medicine (EBM) is the integration of bestresearch evidence with clinical expertise and patientvalues.
7/28/2019 4-Pres-Sardjito-Prof. Dr. Djaswadi Dasuki_ M.ph._ PhD._ SpOG
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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.
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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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7/28/2019 4-Pres-Sardjito-Prof. Dr. Djaswadi Dasuki_ M.ph._ PhD._ SpOG
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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.
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Clinical problem
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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
7/28/2019 4-Pres-Sardjito-Prof. Dr. Djaswadi Dasuki_ M.ph._ PhD._ SpOG
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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
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Grade ofGrade of
recommedatirecommedationon
Level ofLevel of
evidenceevidence
Therapy/preventionTherapy/prevention
aetiology/harmaetiology/harm
PrognosisPrognosis DiagnosisDiagnosis
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.
7/28/2019 4-Pres-Sardjito-Prof. Dr. Djaswadi Dasuki_ M.ph._ PhD._ SpOG
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Grade ofGrade ofrecommedatirecommedati
onon
Level ofLevel ofevidenceevidence
Therapy/preventionTherapy/preventionaetiology/harmaetiology/harm
PrognosisPrognosis DiagnosisDiagnosis
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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7/28/2019 4-Pres-Sardjito-Prof. Dr. Djaswadi Dasuki_ M.ph._ PhD._ SpOG
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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
ControlControln/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
7/28/2019 4-Pres-Sardjito-Prof. Dr. Djaswadi Dasuki_ M.ph._ PhD._ SpOG
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StudyStudyAssistedAssistedhatchinghatching
n/Nn/N
ControlControln/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
ControlControln/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(%)(%)
PetoPeto Odds RatioOdds Ratio95% CI95% CI
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(%)(%)
PetoPeto Odds RatioOdds Ratio95% CI95% CI
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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