Study ID

Randomisation method

Concealed allocation

Design

Total Pt randomised

Drop‐outs

Cancelled cycles

Intention to treat

Power calculation

1.

IUI versus Timed intercourse both in natural cycle

1 study

Bhattacharya 2008

Computer generated randomisation scheme

Central telephone system

Parallel

334 unexplained (386 total)

Total: 2
(0.6%) in IUI + NC

Approximately 3% in the IUI group

Yes

Yes

2.

IUI versus Timed intercourse both in stimulated cycle

7 studies

Agarwal 2004

Random number table

Sealed opaque envelopes

Parallel

140

Total 19%
IUI+OH: 37%
TI+OH: 1%

Not clear

Possible, but not representative: unbalanced groups

No

Arcaini 1996

Not clear

Not clear

Parallel

68

Total: 14 (20.6%)

16 of 231 (7%)

Yes

No

Chung 1995

Blocked randomisation scheme

Numbered sealed envelopes

Parallel

100

Total: 12 (12%)

17 of 257 (6.6%)

Yes, possible

No

Crosignani 1991

Not clear

Not clear

Crossover

90

Not clear

Not clear

Not possible

No

Janko 1998

Not clear

Not clear

Parallel

72

Not clear

Not clear

Yes, possible

No

Karlstrom 1993

Not clear

Not clear

Parallel

79
a 39
b 40

Not clear

Not clear

Not possible

No

Melis 1995

Computer generated random number list

Numbered sealed envelopes

Parallel

108

Total: 5 (4.6%)

Not clear

Not possible

No

3.

IUI in natural cycle versus IUI in stimulated cycle

Arici 1994

Random number table

Computer system utilising locked files

Crossover

26

1st cycle: 0 (0%)
Total: 16 (62%)

Not clear

Yes, possible

No

Goverde 2000

Computer generated randomisation schedule

Numbered, masked and sealed envelopes

Parallel

120

Not clear

Not clear

Not clear

Yes

Guzick 1999

Computer generated permuted block procedure

Computer system utilising locked files

Parallel

211 unexplained
932 total

72 (15.5%)

130 (5.6%)

Not possible

No

Murdoch 1991

Random number sequence

Sequentially numbered opaque sealed envelopes

Parallel

39

Total: 5 (13%)

30 of 111 (27%)
(10 cancelled because no treatment in weekend available)

Yes, possible

No

4.

IUI with OH versus TI in natural cycle

1 study

Deaton 1990

Not clear

Not clear

Crossover
(after 4 cycles)

51

Not clear

Not clear

Not possible

No

Steures 2006

Computer generated randomisation sequence in balanced blocks

Opaque sealed envelopes

Parallel

253

Not clear

63 (14%)

Yes

Yes

5.

IUI in natural cycle versus TI with OH

No studies

Bhattacharya 2008

Computer generated randomisation scheme

Central telephone system

Parallel

342 unexplained

(387 total)

Total: 4

2 in both groups

Approximately 4% in clomiphene group

Yes

Yes

Study ID

Age distribution

Subfertility years

Prim/Sec infertility

Previous treatment

Stimulation Method

Single insemination

1.

IUI versus Timed intercourse both in natural cycle

1 study

Bhattacharya 2008

TI+NC: 32 (±3.4) IUI+NC: 32 (±3.7)
(TI is expectant management)

TI+NC: 30 (25 ‐ 38)
IUI+NC:30 (25 ‐ 40)
_{months (Inter quartile range)}

Mixed

117/386 (30%)
Secondary

Not stated

No stimulation

Single

2.

IUI versus Timed intercourse both in stimulated cycle

7 studies

Agarwal 2004

IUI+OH: 29.52 (±3.65)
TI +OH: 28,83 (±4,76)

IUI+OH: 4.91(±2.72)
TI+OH: 4.93 (±3.27)

Mixed
32/113 (28%) secondary

No

CC 50‐150 mg

Single

Arcaini 1996

IUI+OH: 34.6 (±4.9)
TI+OH: 33.4 (±4.7)

IUI+OH: 4.2 (±1.6)
TI+OH: 3.9 (±2.3)

Mixed
7/68 (10%) secondary

Not stated

High dose: CC100mg and hMG 75‐225IU

Double

Chung 1995

IUI+OH: 31.8 (±3.1)
TI+OH: 32.1 (±4.0)

IUI+OH: 4.7 (±2.0)
TI+OH: 5.3 (±2.6)

Not clear

Not stated

hMG 150IU starting dose and GnRHa

IUI: Single
TI: Double

Crosignani 1991

< 38 yrs

> 3 yrs

Not clear

Probably

Not stated

Not stated

Janko 1998

Not stated

> 3 yrs

Not clear

Not stated

hMG (10 amp per cycle)

Not stated

Karlstrom 1993

32 (range 21‐38)

5 (range 2‐14)

Mixed
49/148 (33%) secondary (incl Pt in DIPI groups)

No

hMG (low dose step up) 75 IU starting dose OR CC 100mg

IUI: Single
TI: Double

Melis 1995

33.1 (±5.2)

4.3 (±1.4)

Not clear

Yes, all patients

High dose: FSH 225IU

Single

3.

IUI in natural cycle versus IUI in stimulated cycle

Arici 1994

33 (range 24‐41)

3.5 (range 1‐15)

Not clear

No

CC 50 mg

IUI+NC: Double
IUI+OH: Single

Goverde 2000

IUI+NC: 31.6 (±3.7)
IUI+OH: 31.7 (± 3.9)

IUI+NC: 3.9 (±1.7)
IUI+OH: 4.2 (±1.9)

Mixed
13.5% secondary

Not stated

hMG 75IU starting dose

Single

Guzick 1999

IUI+NC: 32 (±4)
IUI+OH: 32 (±4)
<40 yrs

IUI+NC: 3.8 (±2.6)
IUI+OH: 3.5 (±2.2)

Mixed
40% secondary

No

FSH 150IU

Single

Murdoch 1991

IUI+NC: 30.5 (±3.1) IUI+OH: 30.1 (±2.9)

IUI+NC: 5.7 (±2.4)
IUI+OH: 5.1 (±1.9)

Mixed
5/34 (15%) secondary

No

hMG (low dose) 75IU + GnRHa

IUI+OH: Single
IUI+NC: till USS evidence of ovulation

4.

IUI with OH versus TI in natural cycle

1 study

Deaton 1990

33 (±4.0)

3.5 (±1.7)

Mixed
21/51 (41%) secondary

Not stated

CC 50 mg

Single

Steures 2006

IUI+OH: 33 (±3.4)
TI+NC: 33 (±3.1)
(TI is expectant management)

IUI+OH: 2.0 (±0.5)
TI+NC: 1.9 (±0.5)

Mixed
58/253 (23%) secondary

Not stated

FSH 37‐150 IU or CC 50‐150 mg

Not stated

5.

IUI in natural cycle versus TI with OH

Bhattacharya 2008

TI+OH: 32 (±3.5) IUI+NC: 32 (±3.7)

TI+OH: 30 (24 ‐ 38)
IUI+NC: 30 (25 ‐ 40)
_{months (Inter quartile range)}

Mixed
109/387 (28%)

Not stated

CC 25‐50 mg

Single

* Mean age in years (± SD) or range

* Mean duration in years (± SD) or range

* Daily dose

Analysis

Number of studies

OR

95% CI

Heterogeneity (P)

I² (%)

LIVE BIRTH RATE

Main analysis
(All cycles, by ITT, fixed effect, Agarwal 2004 excluded)

2

1.59

0.88 ‐ 2.88

0.06

71.7

Not by ITT

2

1.46

0.80 ‐ 2.66

0.06

71

Random effect

2

1.65

0.52 ‐ 5.23

0.06

71.7

Agarwal 2004 included

3

0.81

0.51 ‐ 1.28

0.0002

88.2

PREGNANCY RATE

Main analysis
(All cycles, by ITT, fixed effect, Agarwal 2004 excluded)

10

1.68

1.13 ‐ 2.50

0.40

4.7

Not by ITT

10

1.63

1.09 ‐ 2.43

0.39

5.5

Random effect

10

1.71

1.11‐ 2.63

0.40

4.7

Agarwal 2004 included

11

1.09

0.77 ‐ 1.54

0.001

65.4

Adequate methodology
(Chung 1995, Melis 1995)

2

1.70

0.96 ‐ 3.02

0.06

71.7

Previous treatment excluded
(Melis 1995 excluded)

9

2.00

1.26 ‐ 3.20

0.50

0

Calculated data excluded
(Janko 1998 excluded)

9

1.69

1.11 ‐ 2.59

0.31

15.2

Trials including pt with endometriosis excluded
(Karlstrom 1993 excluded)

8

1.81

1.19 ‐ 2.76

0.42

1.7

Duration of subfertility at least 3 years

7

1.67

1.05 ‐ 2.66

0.37

7.1

Duration of treatment: First cycle only

7

1.48

0.71 ‐ 3.11

0.48

0

Duration of treatment: 1 ‐ 3 Cycles

9

1.54

1.00 ‐ 2.38

0.38

6.5

Duration of treatment: > 3 Cycles

1

2.62

0.98 ‐ 6.98

NA

NA

Ovarian hyperstimulation: Clomiphene

1

0.30

0.03 ‐ 2.93

NA

NA

Ovarian hyperstimulation: Gonadotropins

4

1.68

1.03 ‐ 2.75

0.32

15.2

ADVERSE EVENTS

Multiple pregnancy rate

4

1.46

0.55 ‐ 3.87

0.76

0

Miscarriage rate
(similar results with Agarwal 2004 included)

2

1.66

0.56 ‐ 4.88

0.52

0

Ectopic pregnancy rate (only 1 event)

3

3.06

0.12 ‐ 76.95

NA

NA

OHSS rate

2

2.75

0.11 ‐ 69.83

NA

NA

Analysis

Number of studies

OR

95% CI

Heterogeneity (p)

I2 (%)

LIVE BIRTH RATE

Main analysis
(All cycles, by ITT, fixed effect)

4

2.07

1.22 ‐ 3.50

0.55

0

Not by ITT

4

2.02

1.19 ‐ 3.42

0.53

0

Random effect

4

2.08

1.22 ‐ 3.54

0.55

0

Cross over trials excluded
(Arici 1994 excluded)

3

2.02

1.18 ‐ 3.45

0.39

0

Adequate Methodology
(Guzick 1999 excluded, Randomisation not per unexplained pt)

3

1.69

0.83 ‐ 3.44

0.47

0

Endometriosis (Arici 1994, Guzick 1999 excl)

2

1.57

0.75 ‐ 3.32

0.29

9.4

Ovarian hyperstimulation: Clomiphene

1

3.75

0.29 ‐ 47.99

NA

NA

Ovarian hyperstimulation: Gonadotropins

3

2.02

1.18 ‐ 3.45

0.39

0

Duration of treatment: First cycle only

1

3.75

0.29 ‐ 47.99

NA

NA

PREGNANCY RATE

Main analysis (PR+LB)
(All cycles, by ITT, fixed effect)

4

2.14

1.26 ‐ 3.61

0.44

0

Pregnancy rates only
(All cycles, by ITT, fixed effect)

2

1.74

0.38 ‐ 8.01

0.13

55.6

Not by ITT

4

2.08

1.23 ‐ 3.52

0.41

0

Random effect

4

2.14

1.25 ‐ 3.64

0.44

0

Duration of treatment: First cycle only

4

2.14

1.26 ‐ 3.61

0.44

0

ADVERSE EVENTS

Multiple pregnancy rate

2

3.0

0.11 ‐ 78.27

NA

NA

Miscarriage rate

1

5.21

0.19 ‐ 141.08

NA

NA

Ectopic pregnancy rate

3

6.48

0.33 ‐ 127.09

NA

NA

OHSS rate

3

No events

NA

NA