11/18/2008

EVIDENCE BASED IN ASSISTED REPRODUCTIVE TECHNOLOGY

Djaswadi Dasuki

WHAT IS EBM ?
Evidence-based medicine (EBM) is the integration of best research evidence with clinical expertise and patient values. Best research evidence is clinically relevant research often from 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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Clinical expertise is the ability to use our clinical skills and past experience to rapidly identify each patients unique health state and diagnosis, their individual risks and benefits of potential interventions, and their personal values and expectations. Patient values is unique preferences, concerns and expectations each patient brigns to a clinical encounter and which must be integrated into clinical decisions if they are to serve the patient.

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 in executing steps 1-4 and seeking ways to improve them both for next time.

Clinical problem

Defince important, searchable question Select most likely resource Design search strategy Summarize the evidence Apply the evidence Poor yield Select second most likely resource Design search strategy Summarize the evidence Apply the evidence

Figure General search strategy

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Table Level of evidence and grades of recommedations

Grade of recommedati on Level of evidence 1a Therapy/prevention aetiology/harm SR (with homogeneityd) of RCTs` Prognosis Diagnosis

A
1b

SR (with homogeneityd) of inception cohort studies; or a CPGe validated on a test set

SR (with homogeneityd) of level 1 diagnostic studies; or a CPG validate on a test set Idependent blind comparison of an appropdate patients Absolute SpPins and SnNoutsi

Individual RCT (with Individual narrow confidence interval) inception cohort study with 80% followfollow -up All or nonec All -or Allor-none case seriesh

1c

Grade of recommedati on

Level of evidence 2a

Therapy/prevention aetiology/harm SR (with homogeneityd) of cohort studies

Prognosis

Diagnosis

B
2b Individual cohort study (including lowlow-quality RCT; e.g. <80% followfollowup

SR (with homogeneityc) of either retrospective cohort studies or untreated control group in RCTs Retrospective cohort study or followfollow -up of untreated control patients in an RCT; Outcomes research

SR (with homogeneityd) of level 2 diagnostic studies

Independent blind comparison but either in nonnonconsecutive patients

2c

Outcomes research

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Grade of recommedati on

Level of evidence 3a 3b

Therapy/prevention aetiology/harm SR (with homogeneityd) of casecase-control studies Individual casecase-control study

Prognosis

Diagnosis

Independent blind comparison of an appropriate spectrum Case series (and poorpoor -quality prognostic cohort studies) Reference standard was not applied independently Expert opinion without explicit critical appraisal, or based on physiology

C
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Case series (and poorpoorquality cohort and casecasecontrol studies4 c

Expert opinion without Expert opinion explicity critical appraisal, without explicit or based on physiology critical appraisal,

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
Assisted hatching n/N Control n/N Weight (%) Odds Ratio (Fixed) 95% CI 1.57 [0.80, 3.10] 3.10 ] 1.08 [0.51, 2.29] 0.24 [0.03, 2.03] 0.91 [0.37, 2.26] 0.74 [0.25, 2.18] 3.58 [0.89,14.39 ] 1.19 [0.81, 1.73]
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Study

Cohen 1992A Hellebaut 1996 Hurst 1998 Lanzendorf 1998 Petersen 2005A

34/69 21/60 2/13 12/41 8/15

26/68 20/60 3/7 15/48 10/35

26.9 26.3 6.7 19.8 15.6

Petersen 2000B

9/40

3/40

4.7

Total (95% CI)

258

258

100.0

Comparison Clinical pregnancy, Outcome Clinical pregnancy rate per woman randomised: grouped by 1 st attempt and repeat attempts
Assisted hatching n/N Control n/N Weight (%) Odds Ratio (Fixed) 95% CI

Study

02 Repeat attempt at IVF or ICSI Antinori 1999A Carter 2003 Jelinkova 2002 Petersen 2005A Petersen 2005B RufasRufas -Sapir 2004 Sein 1995 Utsunomiya 1998 19/79 62/121 59/128 11/35 10/40 22/104 15/72 5/27 11/69 43/82 40/127 10/35 3/40 28/103 12/82 4/28 3.2 9.5 8.3 2.6 0.9 8.5 3.4 1.2 1.86 [0.81, 4.25] 0.95 [0.54, 1.67] 1.86 [1.12, 3.10] 1.15 [0.41, 3.19] 4.11 [1.04, 16.29] 0.72 [0.38, 1..36] 1.54 [0.67, 3.54] 1.36 [0.32, 5.73]

Subtotal (95% CI)

600

566

37.5

1.33 [1.02, 1.72]

Total events 203 (Assisted hatching), 151 (Control) Test for heterogeneity chichi-square= 9.95 df= df=7 7 p= p=0.19 0.19 I??= 29 29. .7% Test for overall effect z= 2.13 p= 0.03 0.03
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Study

Assisted hatching n/N

Control n/N

Weight (%)

Odds Ratio (Fixed) 95% CI

03 Mechanical Isiklar 1999 Laffoon 1999 RufasRufas -Sapir 2004 Stein 1995 16/22 9/28 22/104 15/72 10/22 10/28 28/103 12/82 1.0 2.6 8.5 3.4 3.20 [0.91, 11.27] 0.85 [0.28, 2.58] 0.72 [0.38, 1.36] 1.54 [0.67, 3.54]

Subtotal (95% CI)

226

235

15.5

1.09 [0.71, 1.66]

Total events 62 (Assisted hatching), 60 (Control) Test for heterogeneity chichi-square= 5.27 df= df=3 3 p= p=0.15 0.15 I??= 43.1 43.1% % Test for overall effect z= 0.38 p= 0.7 Total (95% CI) 1459 1430 100.0 Total events 524 (Assisted hatching), 430 (Control) Test for heterogeneity chichi-square= 28.41 df= df=23 23 p= p=0.20 0.20 I??= 19.1% Test for overall effect z= 3.11 p= 0.002

1.29 [1.10, 1.52]

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Laporoscopic Surgery For Subfertility Associated With 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
Laparosc opic surgery n/N 10/51 50/172

Study

Control n/N

Weight (%)

Peto Odds Ratio 95% CI

Gruppo Italiano 1999 Marcoux 1997

10/45 29/169

20.7 79.3

0.85 [0.32, 2.28] 1.95 [1.18, 3.22]

Total (95% CI)

223

214

100.0

1.64 [1.05, 2.57]

Total events 60 (Laparoscopic surgery), surgery), 39 (Control) Test for heterogeneity chichi-square= 2.14 df= df=1 1 p= p=0.14 0.14 I??= 53.4 53.4% % Test for overall effect z= 2.17 p= 0.03

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Laparoscopic surgery versus diagnostic laparoscopiy, Outcome pregnancy

Study

Treatment n/N

Control n/N

Weight (%)

Peto Odds Ratio 95% CI

Gruppo Italiano 1999 Marcoux 1997

12/51 63/172

13/45 37/169

20.8 79.2

0.76 [0.31, 1.88] 2.03 [1.28, 3.24]

Total (95% CI)

223

214

100.0

1.66 [1.09, 2.51]

Total events 75 (Treatment surgery), surgery), 50 (Control) Test for heterogeneity chichi-square= 3.57 df= df=1 1 p= p=0.06 0.06 I??= 72.0 72.0% % Test for overall effect z= 2.38 p= 0.02

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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
Study IVF n/N Expectant Management n/N Weight (%) Odds Ratio (Fixed) 95% CI

Hughes 2004 Soliman 1993

12/24 1/21

3/27 2/14

38.2 61.8

8.00 [1.89, 33.85] 0.30 [0.02, 3.67]

Total (95% CI)

45

41

100.0

3.24 [1.07, 9.80]

Total events 13 (IVF IVF), ), 5 (Expectant Management) Management) Test for heterogeneity chichi-square= 4.97 df= df=1 1 p= p=0.03 0.03 I??= 79.9 79.9% % Test for overall effect z= 2.08 p= 0.04

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Comparison IVF versus GIFT, Outcome Pregnancy rate per woman

Study

IVF n/N

GIFT n/N

Weight (%)

Odds Ratio (Fixed) 95% CI

Raneiri 1995 Tanbo 1990 Total (95% CI)

17/34 16/35 69

12/35 11/42 77

52.1 47.9 100.0

1.92 [0.73, 5.05] 2.37 [0.91, 6.18] 2.14 [1.08, 4.22]

Total events 33 (IVF IVF), ), 23 (GIFT GIFT) ) Test for heterogeneity chichi-square= 0.09 df= df=1 1 p= p=0.76 0.76 I??= 0.0 0.0% % Test for overall effect z= 2.08 p= 0.04

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Gonadotrophin Therapy For Ovulation Induction In Subfertility 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)

Study Increasing with hMG n/N Increased with FSH n/N Weight (%) Peto Odds Ratio 95% CI

01 without GnRHGnRH-a (patient randomisedrandomised-paralel data) Gadir 1990 Homburg 1990 Sagle 1991 Seibel 1985 10/114 3/23 5/35 1/11 15/119 3/42 5/40 3/12 38.3 8.7 15.0 5.9 0.67 [0.29, 1.54] 2.00 [0.35, 11.43] 1.16 [0.31, 4.38] 0.35 [0.04, 2.86]

Subtotal Subt otal (95% CI)

183

213

67.9

0.82 [0.44, 1.53]

Total events 19 (Increased with hMG), hMG), 23 (Inreased with FSH) FSH) Test for heterogeneity chichi-square= 2.14 df= df=3 3 p= p=0.54 0.54 I??= 0.0 0.0% % Test for overall effect z= 0.61 p= 0.5

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Study

Increasing with hMG n/N

Increased with FSH n/N

Weight (%)

Peto Odds Ratio 95% CI

04 with GnRHGnRH-a (patients randomisedrandomised-parallel data) Homburg 1990 Jacobs 1987 3/27 2/19 2/30 2/16 7.9 6.2 1.73 [0.28 0.28, , 10.67 10.67] ] 0.83 [0.11 0.11, , 6.49 6.49] ]

Subtotal Subt otal (95% CI)

46

46

14.1

1.25 [0.32 0.32, , 4.89 4.89] ]

Total events 5 (Increased (Increased with hMG), hMG), 4 (Inreased (Inreased with FSH) FSH) Test for heterogeneity chichi-square= 0.27 df= df=3 3 p=0.60 I??= 0.0 0.0% % Test for overall effect z= 0.32 p= 0.7

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THANK YOU

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