Number of embryos for transfer following in vitro fertilisation or intra‐cytoplasmic sperm injection

Mohan S Kamath; Mariano Mascarenhas; Richard Kirubakaran; Siladitya Bhattacharya

doi:10.1002/14651858.CD003416.pub5

Número de embriones a transferir después de la fertilización in vitro o de la inyección intracitoplasmática de espermatozoides

Appendices

Appendix 1. Cochrane Gynaecology and Fertility specialised register search strategy

PROCITE platform

Searched 16 March 2020

Keywords CONTAINS "Number of blastocysts" or "number of blastocysts transferred" or "number of embryos" or "number of embryos transferred" or "triple embryos transfer" or "single blastocyst transfer" or "single embryo transfer" or "single vs multiple" or "single vs multiple transfer" or "double embryo transfer" or "triple embryos transfer" or "three embryos transfer" or "SET" or "two embryos" or Title CONTAINS "Number of blastocysts" or "number of blastocysts transferred" or "number of embryos" or "number of embryos transferred" or "triple embryos transfer" or "single blastocyst transfer" or "single embryo transfer" or "single vs multiple" or "single vs multiple transfer" or "double embryo transfer" or "triple embryos transfer" or "three embryos transfer" or "SET" or "two embryos"
AND
Keywords CONTAINS "ivf" or "ICSI" or "subfertility" or Title CONTAINS "ivf" or "ICSI" or "subfertility"
(1250 records)

Appendix 2. CENTRAL Register of Studies Online (CRSO) search strategy

Web platform

Searched 16 March 2020

#1 MESH DESCRIPTOR Embryo Transfer EXPLODE ALL TREES 1072
#2 (Embryo* adj5 Transfer*):TI,AB,KY 3969
#3 (blastocyst* adj5 Transfer*):TI,AB,KY 472
#4 #1 OR #2 OR #3 4087
#5 (one adj2 embryo*):TI,AB,KY 136
#6 (single adj2 embryo*):TI,AB,KY 295
#7 (single adj2 blastocyst*):TI,AB,KY 119
#8 (one adj2 blastocyst*):TI,AB,KY 32
#9 (two adj2 embryo*):TI,AB,KY 238
#10 (double adj2 embryo*):TI,AB,KY 224
#11 (double adj2 blastocyst*):TI,AB,KY 2
#12 (two adj2 blastocyst*):TI,AB,KY 46
#13 (three adj2 embryo*):TI,AB,KY 109
#14 (triple adj2 embryo*):TI,AB,KY 3
#15 (triple adj2 blastocyst*):TI,AB,KY 0
#16 (three adj2 blastocyst*):TI,AB,KY 3
#17 (multiple adj2 blastocyst*):TI,AB,KY 3
#18 (multiple adj2 embryo*):TI,AB,KY 41
#19 (SET or DET or TET):TI,AB,KY 26970
#20 (SBT or DBT or TBT):TI,AB,KY 756
#21 (four adj2 embryo*):TI,AB,KY 39
#22 (four adj2 blastocyst*):TI,AB,KY 1
#23 #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 28576
#24 #4 AND #23 882

Appendix 3. MEDLINE search strategy

OVID platform

Searched from 1946 to 16 March 2020

1 Embryo Transfer/ (15557)
2 (Embryo$ adj5 Transfer$).tw. (18859)
3 (blastocyst$ adj5 transfer$).tw. (2479)
4 exp embryo, mammalian/ or exp blastocyst/ (93114)
5 or/1‐4 (112678)
6 (two adj2 embryo$).tw. (3566)
7 (double adj2 embryo$).tw. (643)
8 DET.tw. (1117)
9 (three adj2 embryo$).tw. (1944)
10 (triple adj2 embryo$).tw. (45)
11 TET$.tw. (450651)
12 (two adj2 blastocyst$).tw. (273)
13 (double adj2 blastocyst$).tw. (34)
14 (three adj2 blastocyst$).tw. (122)
15 (triple adj2 blastocyst$).tw. (4)
16 DBT.tw. (2494)
17 TBT.tw. (1746)
18 (one adj2 embryo$).tw. (2295)
19 (single adj2 embryo$).tw. (2109)
20 SET.tw. (510321)
21 (one adj2 blastocyst$).tw. (236)
22 (single adj2 blastocyst$).tw. (388)
23 SBT.tw. (2058)
24 (four adj2 embryo$).tw. (962)
25 (four adj2 blastocyst$).tw. (80)
26 FET.tw. (3167)
27 FZET.tw. (0)
28 (multiple$ adj2 embryo$).tw. (727)
29 (multiple$ adj2 blastocyst$).tw. (22)
30 (quadruple adj2 embryo$).tw. (5)
31 (quadruple adj2 blastocyst$).tw. (1)
32 or/6‐31 (972810)
33 5 and 32 (9191)
34 randomized controlled trial.pt. (501858)
35 controlled clinical trial.pt. (93575)
36 randomized.ab. (473201)
37 placebo.tw. (211687)
38 clinical trials as topic.sh. (190393)
39 randomly.ab. (329293)
40 trial.ti. (215152)
41 (crossover or cross‐over or cross over).tw. (83825)
42 or/34‐41 (1305981)
43 exp animals/ not humans.sh. (4678649)
44 42 not 43 (1200138)
45 33 and 44 (479)

Appendix 4. Embase search strategy

OVID platform

Searched from 1980 to 16 March 2020

1 Embryo Transfer/ (29832)
2 (Embryo$ adj5 Transfer$).tw. (29099)
3 (blastocyst$ adj5 transfer$).tw. (4752)
4 exp embryo, mammalian/ or exp blastocyst/ (28866)
5 or/1‐4 (59994)
6 (two adj2 embryo$).tw. (4269)
7 (double adj2 embryo$).tw. (999)
8 DET.tw. (1537)
9 (three adj2 embryo$).tw. (2348)
10 (triple adj2 embryo$).tw. (65)
11 TET$.tw. (473237)
12 (two adj2 blastocyst$).tw. (406)
13 (double adj2 blastocyst$).tw. (102)
14 (three adj2 blastocyst$).tw. (161)
15 (triple adj2 blastocyst$).tw. (5)
16 DBT.tw. (3402)
17 TBT.tw. (2248)
18 (one adj2 embryo$).tw. (3129)
19 (single adj2 embryo$).tw. (3734)
20 SET.tw. (649215)
21 (one adj2 blastocyst$).tw. (410)
22 (single adj2 blastocyst$).tw. (896)
23 SBT.tw. (3782)
24 (four adj2 embryo$).tw. (1078)
25 (four adj2 blastocyst$).tw. (105)
26 FET.tw. (4510)
27 FZET.tw. (0)
28 (multiple$ adj2 embryo$).tw. (1063)
29 (multiple$ adj2 blastocyst$).tw. (46)
30 (quadruple adj2 embryo$).tw. (7)
31 (quadruple adj2 blastocyst$).tw. (1)
32 or/6‐31 (1140425)
33 5 and 32 (11074)
34 Clinical trial/ (956829)
35 Randomized controlled trials/ (175321)
36 Random Allocation/ (82227)
37 Single‐Blind Method/ (36164)
38 Double‐Blind Method/ (142855)
39 Cross‐Over Studies/ (50639)
40 Placebos/ (277114)
41 Randomi?ed controlled trial$.tw. (222841)
42 RCT.tw. (36001)
43 Random allocation.tw. (1981)
44 Randomly allocated.tw. (34385)
45 Allocated randomly.tw. (2509)
46 (allocated adj2 random).tw. (810)
47 Single blind$.tw. (24170)
48 Double blind$.tw. (199664)
49 ((treble or triple) adj blind$).tw. (1107)
50 Placebo$.tw. (298020)
51 Prospective Studies/ (480306)
52 or/34‐51 (2020914)
53 Case study/ (67370)
54 Case report.tw. (394310)
55 Abstract report/ or letter/ (1084934)
56 or/53‐55 (1536415)
57 52 not 56 (1964442)
58 animal/ (1323785)
59 human/ (20095580)
60 58 not 59 (958622)
61 57 not 60 (1932644)
62 33 and 61 (1211)

Appendix 5. PsycINFO search strategy

OVID platform

Searched from 1806 to 16 March 2020

1 exp Infertility/ or exp Reproductive Technology/ (3474)
2 (Embryo$ adj5 Transfer$).tw. (175)
3 (blastocyst$ adj5 transfer$).tw. (6)
4 or/1‐3 (3551)
5 (two adj2 embryo$).tw. (41)
6 (double adj2 embryo$).tw. (16)
7 DET.tw. (166)
8 (three adj2 embryo$).tw. (15)
9 (triple adj2 embryo$).tw. (0)
10 (two adj2 blastocyst$).tw. (0)
11 (three adj2 blastocyst$).tw. (0)
12 (one adj2 embryo$).tw. (34)
13 (single adj2 embryo$).tw. (30)
14 (four adj2 embryo$).tw. (9)
15 or/5‐14 (300)
16 4 and 15 (24)

Appendix 6. CINAHL search strategy

EBSCO platform

Searched from 1961 to 16 March 2020

S47 S23 AND S46 219
S46 S45 NOT S44 634,392
S45 S24 OR S25 OR S26 OR S27 OR S28 OR S29 OR S30 OR S31 OR S32 OR S33 OR S34 OR S35 OR S36 OR S37 OR S38 663,188
S44 S42 NOT S43 168,310
S43 MH (human) 2,045,086
S42 S39 OR S40 OR S41 191,371
S41 TI (animal model*) 2,899
S40 MH (animal studies) 111,330
S39 MH animals+ 87,856
S38 AB (cluster W3 RCT) 327
S37 MH (crossover design) OR MH (comparative studies) 259,647
S36 AB (control W5 group) 100,230
S35 PT (randomized controlled trial) 87,859
S34 MH (placebos) 11,654
S33 MH (sample size) AND AB (assigned OR allocated OR control) 3,787
S32 TI (trial) 100,205
S31 AB (random*) 284,114
S30 TI (randomised OR randomized) 98,224
S29 MH cluster sample 4,074
S28 MH pretest‐posttest design 39,788
S27 MH random assignment 57,798
S26 MH single‐blind studies 13,185
S25 MH double‐blind studies 43,656
S24 MH randomized controlled trials 91,194
S23 S4 AND S22 873
S22 S5 OR S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20 OR S21 3,454
S21 TX TBT or TX DBT 796
S20 TX TET or TX DET 1,244
S19 TX (single N2 embryo*) 453
S18 TX (single N2 blastocyst*) 114
S17 TX (one N2 blastocyst*) 39
S16 TX (double N2 blastocyst*) 4
S15 TX (two N2 blastocyst*) 29
S14 TX (three N2 blastocyst*) 22
S13 TX (four N2 blastocyst*) 13
S12 TX (multiple N2 blastocyst*) 3
S11 TX (multiple N2 embryo*) 170
S10 TX (four N2 embryo*) 102
S9 TX (triple N2 embryo*) 5
S8 TX (three N2 embryo*) 247
S7 TX (one N2 embryo*) 270
S6 TX (double N2 embryo*) 98
S5 TX (two N2 embryo*) 329
S4 S1 OR S2 OR S3 3,283
S3 TX (blastocyst* N5 Transfer*) 401
S2 TX (Embryo* N5 Transfer*) 3,191
S1 (MM "Embryo Transfer") 1,122

Figure 1

Study flow diagram.

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Figure 2

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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Figure 3

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Figure 4

Forest plot of comparison: 2 Repeated SET (mixed policies) versus multiple ET in a single cycle, outcome: 2.1 Cumulative live birth.

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Figure 5

Forest plot of comparison: 2 Repeated SET (mixed policies) versus multiple ET in a single cycle, outcome: 2.2 Multiple pregnancy.

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Figure 6

Forest plot of comparison: 2 Single versus multiple (in a single cycle), outcome: 2.1 Live birth.

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Figure 7

Funnel plot of comparison: 3 Single versus multiple (in a single cycle), outcome: 3.1 Live birth.

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Figure 8

Forest plot of comparison: 2 Single versus multiple (in a single cycle), outcome: 2.2 Multiple pregnancy.

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Analysis 2.1

Comparison 2: Repeated SET (mixed policies) versus multiple ET in a single cycle, Outcome 1: Cumulative live birth

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Analysis 2.2

Comparison 2: Repeated SET (mixed policies) versus multiple ET in a single cycle, Outcome 2: Multiple pregnancy

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Analysis 2.3

Comparison 2: Repeated SET (mixed policies) versus multiple ET in a single cycle, Outcome 3: Clinical pregnancy rate

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Analysis 2.4

Comparison 2: Repeated SET (mixed policies) versus multiple ET in a single cycle, Outcome 4: Miscarriage

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Analysis 3.1

Comparison 3: Single versus multiple embryo transfer (in a single cycle), Outcome 1: Live birth

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Analysis 3.2

Comparison 3: Single versus multiple embryo transfer (in a single cycle), Outcome 2: Multiple pregnancy

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Analysis 3.3

Comparison 3: Single versus multiple embryo transfer (in a single cycle), Outcome 3: Clinical pregnancy rate

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Analysis 3.4

Comparison 3: Single versus multiple embryo transfer (in a single cycle), Outcome 4: Miscarriage

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Analysis 4.1

Comparison 4: Double embryo transfer versus more than two embryos transferred, Outcome 1: Live or cumulative live birth

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Analysis 4.2

Comparison 4: Double embryo transfer versus more than two embryos transferred, Outcome 2: Multiple pregnancy

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Analysis 4.3

Comparison 4: Double embryo transfer versus more than two embryos transferred, Outcome 3: Clinical pregnancy

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Summary of findings 1. Repeated single embryo transfer (mixed policies) versus multiple embryo transfer in a single cycle of IVF or ICSI

Outcomes		*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
Repeated single embryo transfer (mixed policies) versus multiple embryo transfer in a single cycle of IVF or ICSI
Patient or population: transfer following in vitro fertilisation or intracytoplasmic sperm injection Setting: clinic Intervention: repeated single (mixed policies) Comparison: multiple embryo transfer
Outcomes		Risk with multiple embryo transfer	Risk with repeated single (mixed policies)	Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
Cumulative live birth	pooled	420 per 1000	399 per 1000 (344 to 462)	RR 0.95 (0.82 to 1.10)	985 (4 RCTs)	⊕⊕⊝⊝ LOW ¹
Cumulative live birth	SET + 1 FET versus DET (×1) (cleavage stage)	421 per 1000	392 per 1000 (333 to 459)	RR 0.93 (0.79 to 1.09)	878 (3 RCTs)	⊕⊕⊝⊝ LOW ¹
Cumulative live birth	SET (×2) versus DET (×1) (cleavage stage)	407 per 1000	464 per 1000 (285 to 755)	RR 1.14 (0.70 to 1.84)	107 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{1 2}
Multiple pregnancy	pooled	127 per 1000	18 per 1000 (11 to 30)	Peto odds ratio 0.13 (0.08 to 0.21)	985 (4 RCTs)	⊕⊕⊕⊝ MODERATE ³
Multiple pregnancy	SET + 1 FET versus DET (×1) (cleavage stage)	128 per 1000	19 per 1000 (12 to 31)	Peto odds ratio 0.13 (0.08 to 0.22)	878 (3 RCTs)	⊕⊕⊕⊝ MODERATE ³
Multiple pregnancy	SET (×2) versus DET (×1) (cleavage stage)	111 per 1000	15 per 1000 (4 to 63)	Peto odds ratio 0.12 (0.03 to 0.54)	107 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{2 3 4}
Clinical pregnancy rate	pooled	515 per 1000	489 per 1000 (432 to 556)	RR 0.95 (0.84 to 1.08)	943 (3 RCTs)	⊕⊕⊝⊝ LOW ¹
Miscarriage rate	pooled	76 per 1000	149 per 1000 (71 to 289)	Peto odds ratio 2.14 (0.93 to 4.95)	282 (2 RCTs)	⊕⊕⊝⊝ LOW ^{3 4}
*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect
¹ Very serious risk of bias, downgraded by 2 levels: high risk or unclear risk of bias for allocation concealment, high risk of bias for performance bias due to lack of blinding. ² Serious risk of indirectness, downgraded by 1 level: single centre study. ³ Serious risk of bias, downgraded by 1 level: high risk or unclear risk of bias for allocation concealment. We did not downgrade for performance bias as it is unlikely, that any change in clinician's behaviour due to knowledge of group allotment will influence outcomes such as multiple pregnancy or miscarriage rates. ⁴ Serious risk of imprecision, downgraded by 1 level: wide confidence interval.

Summary of findings 1. Repeated single embryo transfer (mixed policies) versus multiple embryo transfer in a single cycle of IVF or ICSI

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Summary of findings 2. Single compared to multiple embryo transfer in a single cycle following IVF or ICSI

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
Single compared to multiple embryo transfer in a single cycle following in vitro fertilisation or intracytoplasmic sperm injection
Patient or population: transfer following in vitro fertilisation or intracytoplasmic sperm injection Setting: clinic Intervention: single embryo transfer Comparison: multiple embryo transfer (in a single cycle)
Outcomes	Risk with multiple (in a single cycle)	Risk with Single	Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
Live birth	463 per 1000	310 per 1000 (273 to 347)	RR 0.67 (0.59 to 0.75)	1904 (12 RCTs)	⊕⊕⊝⊝ LOW ¹
Multiple pregnancy	151 per 1000	28 per 1000 (21 to 38)	Peto odds ratio 0.16 (0.12 to 0.22)	1952 (13 RCTs)	⊕⊕⊕⊝ MODERATE ²
Clinical pregnancy	547 per 1000	383 per 1000 (350 to 421)	RR 0.70 (0.64 to 0.77)	1860 (10 RCTs)	⊕⊕⊝⊝ LOW ¹
Miscarriage rate	72 per 1000	69 per 1000 (46 to 99)	Peto odds ratio 0.96 (0.66 to 1.42)	1560 (7 RCTs)	⊕⊕⊝⊝ LOW ^2,3
*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect
¹ Very serious risk of bias, downgraded by 2 levels: unclear or high risk for allocation concealment, high risk for performance bias due to lack of blinding in majority of the included studies. ² Serious risk of bias, downgraded by 1 level: high risk or unclear risk of bias for allocation concealment. We did not downgrade for performance bias as it is unlikely, that any change in clinician's behaviour due to knowledge of group allotment will influence outcomes such as multiple pregnancy or miscarriage rates. ³ Serious risk of imprecision, downgraded by 1 level: wide confidence interval.

Summary of findings 2. Single compared to multiple embryo transfer in a single cycle following IVF or ICSI

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Table 1. Prognostic factors in included studies

Study author and year	Age Eligibility criteria (mean participant age, where stated)	Duration of infertility	Previous failed cycle	Frozen cycles	Prim/Sec infertility	FSH	Quality of embryo
Prados 2015	Under 38 years (mean age 33)	Mean 2.6 to 3.2 years	First IVF/ICSI cycle.	Frozen cycles included	Not stated	Not stated	Good
Gerris 1999	less than 34 years	Average duration of infertility 3.5 years.	First IVF/ICSI cycle.	Not included	Unclear	Not mentioned	Good
Heijnen 2006	38 to 45 years (mean age 41)	Average duration of infertility in DET group was 3.7(± 2.5) and in TET group was 3.2(± 2.4) years	First cycle and previous successful cycle	Not included	Yes	Not mentioned	Good
Komori 2004	Not stated	Not stated	Not stated	Not stated	Not stated	Not stated	Good
Lukassen 2005	< 35 years (mean age 30 to 31)	Not stated	First IVF/ICSI cycle or after previous successful cycle .	Not included	Yes	FSH < 10IU/L.	Good
Martikainen 2001	various, no age criteria, ranged between 22 to 40 years (mean age 31)	Not stated	women who had / not had more than 1 previous failed treatment.	Frozen cycles included	Yes, but not mentioned	Not mentioned	good
Mostajeran 2006	Not stated	Not stated	Not stated	Not stated	Not stated	Not stated	Good
Thurin 2004	< 36 years (mean age 31)	0 to 12 years	First or second IVF cycle	Frozen cycles included	Yes	Not mentioned	Good, blastocysts included
Thurin 2005 Unpublished trial, pilot study, part of a thesis	≥ 36 years	0 to 12 years	First or second IVF/ICSI cycle	Frozen cycles included	Yes	Not mentioned	At least 2 good‐quality embryos available
van Montfoort 2006	Various ages, no criteria (mean age 33)	SET‐ 3.3 ± 1.8, DET‐ 3.3 ± 2.1 years	First IVF cycle	Not included	Yes	Not mentioned	Good
Vauthier‐Brouzes 1994	≤ 35 years	Not mentioned	First or previous successful cycle	Frozen cycles included	Yes	Not mentioned	good
ASSETT 2003 unpublished trial	Female age < 35 if no previous ART pregnancy, < 40 if previous ART pregnancy.	Not mentioned	First or previous successful cycle	Frozen cycles included	Yes	Not mentioned	At least 4 good‐quality embryos or at least 3 if previous ART pregnancy successful
ECOSSE 2006 unpublished trial	≤ 37 years	Not mentioned	First or second cycle of treatment	Frozen cycles included	Yes	Not mentioned	4 or more good quality embryos available at the time of embryo transfer
Abuzeid 2017	< 35 years	SET ‐ 2.6 ± 1.6 years DET ‐ 3.2 ± 2.4 years	No more than 1 previous ART failure	Frozen cycles performed but not included in the analysis	Yes	Mentioned	At least 2 good‐quality blastocysts were available,
Clua 2015	oocyte donor recipients aged 18‐50 years	not mentioned	Undergoing first or second synchronised oocyte donation cycle	Frozen cycles performed but not included in the analysis	Not mentioned	Not mentioned	Minimum of 5 embryos with at least 2 good‐quality embryos on day 3 after oocyte retrieval
López‐Regalado 2014b	< 38 years	SET ‐ 3.1 ± 1.1 DET ‐ 3.1 ± 1.0	First or second cycle with previous attempt with positive pregnancy test	Frozen cycles included	Not mentioned	Not mentioned	good

Table 1. Prognostic factors in included studies

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Comparison 2. Repeated SET (mixed policies) versus multiple ET in a single cycle

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Cumulative live birth Show forest plot	4	985	Risk Ratio (M‐H, Fixed, 95% CI)	0.95 [0.82, 1.10]

2.1.1 SET + 1 FET versus DET (x1) (cleavage stage)	3	878	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.79, 1.09]
2.1.2 SET (x2) versus DET (x1) (cleavage stage)	1	107	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.70, 1.84]
2.2 Multiple pregnancy Show forest plot	4	985	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.13 [0.08, 0.21]

2.2.1 SET + 1 FET versus DET (x1) (cleavage stage)	3	878	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.13 [0.08, 0.22]
2.2.2 SET (x2) versus DET (x1) (cleavage stage)	1	107	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.12 [0.03, 0.54]
2.3 Clinical pregnancy rate Show forest plot	3	943	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.87, 1.12]

2.3.1 SET + 1 FET versus DET (x1) (cleavage stage)	2	836	Risk Ratio (M‐H, Fixed, 95% CI)	0.97 [0.84, 1.11]
2.3.2 SET (x2) versus DET (x1) (cleavage stage)	1	107	Risk Ratio (M‐H, Fixed, 95% CI)	1.18 [0.81, 1.71]
2.4 Miscarriage Show forest plot	2	282	Peto Odds Ratio (Peto, Fixed, 95% CI)	2.14 [0.93, 4.95]

2.4.1 SET + 1 FET versus DET (x1) (cleavage stage)	1	175	Peto Odds Ratio (Peto, Fixed, 95% CI)	2.86 [0.85, 9.67]
2.4.2 SET (x2) versus DET (x1) (cleavage stage)	1	107	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.65 [0.52, 5.23]

Comparison 2. Repeated SET (mixed policies) versus multiple ET in a single cycle

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Comparison 3. Single versus multiple embryo transfer (in a single cycle)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Live birth Show forest plot	12	1904	Risk Ratio (M‐H, Fixed, 95% CI)	0.67 [0.59, 0.75]

3.1.1 SET (x1) versus DET (x1) (cleavage stage)	11	1704	Risk Ratio (M‐H, Fixed, 95% CI)	0.67 [0.59, 0.76]
3.1.2 SET (x1) versus DET (x1) (blastocyst stage)	2	200	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.51, 0.84]
3.2 Multiple pregnancy Show forest plot	13	1952	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.16 [0.12, 0.22]

3.2.1 SET (x1) versus DET (x1) (cleavage stage)	11	1704	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.16 [0.11, 0.22]
3.2.2 SET (x1) versus DET (x1) (blastocyst stage)	3	248	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.18 [0.09, 0.36]
3.3 Clinical pregnancy rate Show forest plot	10	1860	Risk Ratio (M‐H, Fixed, 95% CI)	0.70 [0.64, 0.77]

3.3.1 SET (x1) versus DET (x1) (cleavage stage)	8	1612	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.62, 0.78]
3.3.2 SET (x1) versus DET (x1) (blastocyst stage)	3	248	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.62, 0.88]
3.4 Miscarriage Show forest plot	7	1560	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.96 [0.66, 1.42]

3.4.1 SET (x1) versus DET (x1) (cleavage stage)	6	1460	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.96 [0.65, 1.43]
3.4.2 SET (x1) versus DET (x1) (blastocyst stage)	1	100	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.00 [0.24, 4.21]

Comparison 3. Single versus multiple embryo transfer (in a single cycle)

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Comparison 4. Double embryo transfer versus more than two embryos transferred

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Live or cumulative live birth Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1.1 DET (x1) versus TET (x1)	1	45	Risk Ratio (M‐H, Fixed, 95% CI)	0.48 [0.14, 1.68]
4.1.2 DET (x1) versus four embryo transfer (x1)	1	56	Risk Ratio (M‐H, Fixed, 95% CI)	0.53 [0.27, 1.05]
4.1.3 DET (x2) versus TET (x2)	1	45	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.37, 1.92]
4.1.4 DET (x3) versus TET (x3)	1	45	Risk Ratio (M‐H, Fixed, 95% CI)	0.86 [0.43, 1.71]
4.2 Multiple pregnancy Show forest plot	3		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

4.2.1 DET versus TET	2	343	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.36 [0.14, 0.93]
4.2.2 DET versus four embryo transfer	1	56	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.46 [0.11, 1.88]
4.3 Clinical pregnancy Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.3.1 DET (x1) versus TET (x1)	2	343	Risk Ratio (M‐H, Fixed, 95% CI)	0.75 [0.53, 1.06]
4.3.2 DET (x1) versus four embryo transfer (x1)	1	56	Risk Ratio (M‐H, Fixed, 95% CI)	0.76 [0.47, 1.26]

Comparison 4. Double embryo transfer versus more than two embryos transferred

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Número de embriones a transferir después de la fertilización in vitro o de la inyección intracitoplasmática de espermatozoides

Appendices

Appendix 1. Cochrane Gynaecology and Fertility specialised register search strategy