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Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies

BMJ 2004; doi: https://doi.org/10.1136/bmj.37957.560278.EE (Published 23 January 2004) Cite this as: BMJ 2004;:bmj;bmj.37957.560278.EEv1

Data supplement

  • Nine tables of detailed results and list of excluded studies

    Table A Controlled singleton studies included in the review

    Table B Controlled twin studies included in the review

    Table C Preterm birth in singleton pregnancies after assisted versus natural conception

    Table D Preterm birth in twin pregnancies after assisted versus natural conception

    Table E Low and very low birth weight in singleton pregnancies after assisted versus natural conception

    Table F Low and very low birth weight in twin pregnancies after assisted versus natural conception

    Table G Small for gestational infants from singleton and twin pregnancies after assisted conception versus  ...

    Table H Caesarean section rates in singleton and twin pregnancies after assisted versus natural conceptions

    Table I Admissions to neonatal intensive care units after singleton and twin pregnancies from assisted versus ...

    References to studies examined, but excluded from the analyses
     

    Table A (Posted as supplied by authors) Controlled singleton studies included in the review
     

    Study
    Years
    Country
    No. of cases
    Type of cases*
    		Type of controls, matched for
    Matched studies**     
    Dhont et al. ’979
    1991-1995
    Belgium
    311
    1,2
    		Maternal age, parity, date of delivery (2 controls per case)
    Dhont et al. ’991†
    1992-1997
    Belgium
    3,048
    1,2
    		Maternal age, parity, fetal sex, date of delivery
    D’Souza et al.18
    1984-1991
    Great Britain
    150
    1
    		Maternal age, fetal sex, social class (controls are term babies)
    Isaksson et al.10
    1993-1999
    Finland
    69
    1,2
    		Maternal age, parity, year of delivery, mother’s residence (5 controls per case)
    Koivurova et al.19‡
    1990-1995
    Finland
    153
    1
    		Maternal age, parity, fetal sex, year of delivery, area of residence, social class
    Koudstaal et al.8
    before 1993
    Netherlands
    307
    1
    		Maternal age, parity, date of delivery
    Maman et al.20
    1989-1994
    Israel
    169
    1
    		Maternal age, parity, gestational age, (2.8 controls per case)
    Nuojua et al.21
    1991-1996
    Finland
    92
    4
    		Maternal age, parity, year of delivery, place of residence, smoking, occupation (3 controls per case)
    Petersen et al.22
    1986-1990
    Denmark
    70
    1
    		Maternal age, parity
    Reubinoff et al.7
    1983-1993
    Israel
    260
    1
    		Maternal age, parity, ethnic origin, location and date of delivery
    Tallo et al.12
    1988-1993
    United States
    62
    1
    		Maternal age, race, insurance type, fetal sex, date of delivery
    Tan et al.4
    1978-1987
    Great Britain
    494
    1
    		Maternal age
    Tanbo et al.5
    1985-1993
    Norway
    355
    1,3,4
    		Maternal age, parity
    Verlaenen et al.6
    1988-1994
    Belgium
    140
    1
    		Maternal age, parity, weight, height
    Non-matched studies     
    Addor et al.23
    1993-1994
    Switzerland
    113
    1,4
    		All women living in the canton of Vaud who gave birth to a singleton
    Frydman et al.24
    1981-1984
    France
    79
    1
    		All spontaneous singletons delivered at the same hospital in the same period
    Olivennes et al. ’9325
    1987-1989
    France
    164
    1
    		Natural singletons delivered at the same institution in the same period

    *Types of assisted conception studied: 1 = in-vitro fertilisation (IVF), 2 = intra-cytoplasmatic sperm injection (ICSI), 3 = gamete intra-fallopian transfer (GIFT), 4 = intra-uterine insemination (IUI).

    **One control per case unless specified otherwise.

    †Nine additional cases could not be matched accurately and are excluded from the analyses.

    ‡Only surviving infants were included.
     
     

    Table B (Posted as supplied by author) Controlled twin studies included in the review
     

    Study
    Years
    Country
    No. of cases
    Type of cases*
    		Type of controls, matched for
    Matched studies**     
    Dhont et al. ’979
    1991-1995
    Belgium
    230
    1,2
    		Maternal age, parity, date of delivery
    Dhont et al. ’991†
    1992-1997
    Belgium
    2,482
    1,2
    		Maternal age, parity, date of delivery
    Fitzsimmons et al.16
    1985-1996
    Canada
    112
    1,3,6
    		Maternal age, parity (two controls per case)
    Isaksson et al.10
    1993-1999
    Finland
    40
    1,2
    		Maternal age, parity, year of delivery, mother’s residence
    Koivurova et al.19‡
    1990-1995
    Finland
    103
    1
    		Maternal age, parity, fetal sex, year of delivery, area of residence, parity, social class
    Koudstaal et al.13
    before 1993
    The Netherlands
    192
    1
    		Maternal age, parity, date of delivery, zygosity
    Moise et al.11
    1990-1995
    Israel
    40
    1
    		Maternal age, parity, ethnic origin, only dizygotic twins (2 controls per case)
    Petersen et al.22
    1986-1990
    Denmark
    32
    1
    		Maternal age, parity
    Tallo et al.12
    1988-1993
    United States
    72
    1
    		Maternal age, race, insurance type, fetal sex, date of delivery, birth order
    Tan et al.4
    1978-1987
    Great Britain
    250
    1
    		Maternal age
    Non-matched studies     
    Addor et al.23
    1993-1994
    Switzerland
    52
    1,4
    		All women with naturally conceived twins living in the canton of Vaud
    Agustsson et al.14
    1990-1993
    Iceland, Scotland
    138
    1
    		All naturally conceived twin pregnancies in Iceland and the Tayside Region, Scotland
    Bernasko et al.26
    1990-1995
    United States
    210
    1,3
    		All naturally conceived twin deliveries in the database of Mount Sinai Medical Center
    Daniel et al.27
    1996-1997
    Israël
    208
    1,2
    		All naturally conceived twins at Tel Aviv Sourasky Medical Center
    Frydman et al.24
    1981-1984
    France
    22
    1
    		All naturally conceived twins delivered at the same hospital in the same period
    Lambalk et al.28
    1994-1996
    The Netherlands
    1,158
    1,5
    		Primiparous dizygotic (male-female) twin deliveries
    Olivennes et al. ’9617
    1988-1993
    France
    144
    1
    		Naturally conceived twin pregnancies managed and delivered in Clamart

    *Types of assisted conception studied: 1 = in-vitro fertilisation (IVF), 2 = intra-cytoplasmatic sperm injection (ICSI), 3 = gamete intra-fallopian transfer (GIFT), 4 = intra-uterine insemination (IUI), 5 = ovulation induction, 6 = clomiphene.

    **One control per case unless specified otherwise.

    †This paper also contains a subanalysis on 1,148 male-female twin infants matched for maternal age and parity, which is not included in this review.

    ‡Only surviving infants were included.
     
     

    Table C (Posted as supplied by author) Preterm birth in singleton pregnancies after assisted versus natural conception
     

    Study
    Assisted
    		 
    Spontaneous
    		 
    Relative risk (95% CI)
     
    n/N
    %
    		 
    n/N
    %
    		 
    Very preterm (<32 weeks) in matched studies
    Dhont et al. ‘991 *
    63/3,048
    2.1
    		 
    8/3,048
    0.3
    		 
    7.88
    (3.78 to 16.4)*
    Dhont et al. ‘979
    4/311
    1.3
    		 
    18/622
    2.9
    		 
    0.44
    (0.15 to 1.30)
    Koivurova et al.19 **
    3/153
    2.0
    		 
    3/287
    1.0
    		 
    1.88
    (0.38 to 9.18)
    Total very preterm (matched studies)
    70/3,512
    2.0
    		 
    29/3,957
    0.7
    		 
    3.27
    (2.03 to 5.28)
    Mildly preterm (32-36 weeks) in matched studies
    Dhont et al. ‘991 *
    281/3,048
    9.2
    		 
    117/3,048
    3.8
    		 
    2.40
    (1.95 to 2.96)*
    Dhont et al. ‘979
    22/311
    7.1
    		 
    47/622
    7.6
    		 
    0.94
    (0.57 to 1.52)
    Koivurova et al.19 **
    10/153
    6.5
    		 
    13/287
    4.5
    		 
    1.44
    (0.65 to 3.21)**
    Total mildly preterm (matched studies)
    313/3,512
    9.1
    		 
    177/3,957
    4.5
    		 
    2.05
    (1.71 to 2.47)
    Preterm (<37 weeks) in matched studies
    Dhont et al. ‘991 *
    344/3,048
    11.3
    		 
    125/3,048
    4.1
    		 
    2.75
    (2.26 to 3.36)*
    Dhont et al. ‘979
    26/311
    8.4
    		 
    65/622
    10.5
    		 
    0.80
    (0.52 to 1.23)
    Isaksson et al.10
    4/69
    5.8
    		 
    35/345
    10.1
    		 
    0.57
    (0.21 to 1.56)
    Koivurova et al.19 **
    13/153
    8.5
    		 
    16/287
    5.6
    		 
    1.52
    (0.75 to 3.08)**
    Koudstaal et al.8
    46/307
    15.0
    		 
    18/307
    5.9
    		 
    2.56
    (1.52 to 4.30)
    Nuojua et al.21
    8/92
    8.7
    		 
    14/276
    5.1
    		 
    1.71
    (0.74 to 3.96)
    Petersen et al.22
    5/70
    7.1
    		 
    3/70
    4.3
    		 
    1.67
    (0.41 to 6.71)
    Reubinoff et al.7
    23/260
    8.8
    		 
    10/260
    3.8
    		 
    2.30
    (1.12 to 4.74)
    Tallo et al.12
    6/62
    9.7
    		 
    1/62
    1.6
    		 
    6.00
    (0.74 to 48.4)
    Tan et al.4
    69/494
    14.0
    		 
    78/978
    8.0
    		 
    1.75
    (1.29 to 2.38)
    Tanbo et al.5
    53/355
    14.9
    		 
    61/643
    9.5
    		 
    1.57
    (1.12 to 2.22)
    Verlaenen et al.6
    16/140
    11.4
    		 
    2/140
    1.4
    		 
    8.00
    (1.87 to 34.2)
    Total preterm (matched studies)
    613/5,361
    11.4
    		 
    428/7,038
    6.1
    		 
    2.04
    (1.80 to 2.32)
    Preterm birth in non-matched studies
    Addor et al.23
    6/113
    5.3
    		 
    280/6,088
    4.6
    		 
    1.15
    (0.53-2.54)
    Olivennes et al. ’9325 †
    18/162
    11.1
    		 
    224/5,096
    4.4
    		 
    2.53
    (1.61-3.98) †
    Total preterm (non-matched studies)
    24/275
    8.7
    		 
    504/11,184
    4.5
    		 
    1.94
    (1.31-2.88)

    * Based on additional data obtained from the authors.

    ** Only surviving infants.

    † Preterm in this study relates to <36 weeks.
     
     

    Table D (Posted as supplied by author) Preterm birth in twin pregnancies after assisted versus natural conception
     

    Study
    Assisted
    		 
    Spontaneous
    		 
    Relative risk (95% CI)
     
    n/N
    %
    		 
    n/N
    %
    		 
    Very preterm (<32 weeks)
    Matched studies        
    Dhont et al. ‘991*
    173/2,482
    7.0
    		 
    178/2,482
    7.2
    		 
    0.97
    (0.79 to 1.19)*
    Dhont et al. ‘979
    16/230
    7.0
    		 
    12/230
    5.2
    		 
    1.33
    (0.65 to 2.76)
    Koivurova et al.19 †
    2/103
    1.9
    		 
    11/103
    10.7
    		 
    0.18
    (0.04 to 0.80)†
    Total matched
    191/2,815
    6.8
    		 
    201/2,815
    7.1
    		 
    0.95
    (0.78 to 1.15)
    Non-matched studies        
    Bernasko et al.26
    22/210
    10.5
    		 
    56/558
    10.0
    		 
    1.04
    (0.65 to 1.67)
    Olivennes et al. ‘9617 **
    12/144
    8.3
    		 
    16/328
    4.9
    		 
    1.71
    (0.83 to 3.52)**
    Total non-matched
    34/354
    9.6
    		 
    72/886
    8.1
    		 
    1.20
    (0.82 to 1.78)
    Mildly preterm (32-36 weeks)
    Matched studies        
    Dhont et al. ‘991 *
    1,054/2,482
    42.5
    		 
    1,006/2,482
    40.5
    		 
    1.05
    (0.98 to 1.12)*
    Dhont et al. ‘979
    104/230
    45.2
    		 
    86/230
    37.4
    		 
    1.21
    (0.97 to 1.51)
    Koivurova et al.19 †
    43/103
    41.7
    		 
    34/103
    33.0
    		 
    1.26
    (0.88 to 1.81) †
    Total matched
    1,201/2,815
    42.7
    		 
    1,126/2,815
    40.0
    		 
    1.07
    (1.00 to 1.14)
    Non-matched studies        
    Olivennes et al. ‘9617 **
    44/144
    30.6
    		 
    114/328
    34.8
    		 
    0.88
    (0.66 to 1.17)**
    Preterm (<37 weeks)
    Matched studies        
    Dhont et al. ‘991 *
    1,227/2,482
    49.4
    		 
    1,184/2,482
    47.7
    		 
    1.04
    (0.98 to 1.10)*
    Dhont et al. ‘979
    120/230
    52.2
    		 
    98/230
    42.6
    		 
    1.22
    (1.01 to 1.49)
    Isaksson et al.10
    14/40
    35.0
    		 
    82/200
    41.0
    		 
    0.85
    (0.54 to 1.34)
    Koivurova et al19 †
    45/103
    43.7
    		 
    45/103
    43.7
    		 
    1.00
    (0.73 to 1.36) †
    Koudstaal et al.13
    98/192
    51.0
    		 
    80/192
    41.7
    		 
    1.23
    (0.99 to 1.52)
    Moise et al.11
    24/40
    60.0
    		 
    16/80
    20.0
    		 
    3.00
    (1.81 to 4.98)
    Petersen et al.22
    6/32
    18.8
    		 
    12/32
    37.5
    		 
    0.50
    (0.21 to 1.17)
    Tallo et al.12 †
    40/68
    58.8
    		 
    25/68
    36.8
    		 
    1.60
    (1.11 to 2.32)
    Tan et al.4
    146/250
    58.4
    		 
    22/42
    52.4
    		 
    1.11
    (0.82 to 1.52)
    Total matched
    1,722/3,437
    50.0
    		 
    1,566/3,429
    45.6
    		 
    1.07
    (1.02 to 1.13)
    Non-matched studies        
    Addor et al.23
    12/26
    46.2
    		 
    69/154
    44.8
    		 
    1.03
    (0.66 to 1.62)
    Olivennes et al. ‘9617 **
    56/144
    38.9
    130/328
    39.6
    0.98
    (0.77 to 1.25)**
    Total non-matched
    68/170
    40.0
    		 
    199/482
    41.3
    		 
    0.99
    (0.80 to 1.23)

    * Based on additional data obtained from the authors.

    ** Preterm relates to <36 weeks, very preterm to <31 weeks, and mildly preterm to 32-35 weeks; two cases were lost to follow-up.

    † Surviving infants only.


     

    Table E (Posted as supplied by author) Low and very low birth weight in singleton pregnancies after assisted versus natural conception
     

    Study
    Assisted
    		 
    Spontaneous
    		 
    Relative risk (95% CI)
     
    n/N
    %
    		 
    n/N
    %
    		 
    Birthweight < 1,500 g
    Matched studies        
    Dhont et al. ‘991
    72/3,048
    2.4
    		 
    10/3,048
    0.3
    		 
    7.20
    (3.72 to 13.9)
    Dhont et al. ‘979
    5/311
    1.6
    		 
    17/622
    2.7
    		 
    0.59
    (0.22 to 1.58)
    Isaksson et al.10
    1/69
    1.5
    		 
    4/345
    1.2
    		 
    1.25
    (0.14 to 11.0)
    Koivurova et al.19
    3/153
    2.0
    		 
    2/287
    0.7
    		 
    2.81
    (0.48 to 16.7)
    Tanbo et al.5
    14/355
    3.9
    		 
    15/643
    2.3
    		 
    1.69
    (0.83 to 3.46)
    Verlaenen et al.6
    5/140
    3.6
    		 
    1/140
    0.7
    		 
    5.00
    (0.59 to 42.3)
    Total matched
    100/4,076
    2.5
    		 
    49/5,085
    1.0
    		 
    3.00
    (2.07 to 4.36)
    Non-matched studies        
    Olivennes et al. ‘9325
    1/162
    0.6
    		 
    20/5,096
    0.4
    		 
    1.57
    (0.21 to 11.7)
    Total non-matched
    1/162
    0.6
    		 
    20/5,096
    0.4
    		 
    1.57
    (0.21 to 11.7)
    Birthweight 1,500 – 2,499 g
    Matched studies        
    Dhont et al. ‘991
    247/3,048
    8.1
    		 
    142/3,048
    3.8
    		 
    1.74
    (1.42 to 2.13)
    Dhont et al. ‘979
    19/311
    7.7
    		 
    53/622
    11.3
    		 
    0.72
    (0.43 to 1.19)
    Isaksson et al.10
    1/69
    1.4
    		 
    13/345
    3.8
    		 
    0.38
    (0.05 to 2.89)
    Koivurova et al.19
    6/153
    3.9
    		 
    7/287
    2.4
    		 
    1.61
    (0.55 to 4.70)
    Tanbo et al.5
    27/355
    7.6
    		 
    28/643
    4.4
    		 
    1.75
    (1.05 to 2.92)
    Verlaenen et al.6
    9/140
    6.4
    		 
    5/140
    3.6
    		 
    1.80
    (0.62 to 5.24)
    Total matched
    309/4,076
    7.6
    		 
    248/5,085
    4.9
    		 
    1.54
    (1.30 to 1.82)
    Non-matched studies        
    Olivennes et al. ’9325
    17/162
    10.5
    		 
    163/5,096
    3.2
    		 
    3.28
    (2.04 to 5.27)
    Total non-matched
    17/162
    10.5
    		 
    163/5,096
    3.2
    		 
    3.28
    (2.04 to 5.27)
    Birthweight < 2,500 g
    Matched studies        
    Dhont et al. ‘991
    319/3,048
    10.5
    		 
    162/3,048
    4.2
    		 
    1.97
    (1.64 to 2.36)
    Dhont et al. ‘979
    24/311
    7.7
    		 
    70/622
    11.3
    		 
    0.69
    (0.44 to 1.07)
    Isaksson et al.10
    2/69
    2.9
    		 
    17/345
    5.0
    		 
    0.59
    (0.14 to 2.49)
    Koivurova et al.19
    9/153
    5.9
    		 
    9/287
    3.1
    		 
    1.88
    (0.76 to 4.63)
    Koudstaal et al.8
    42/307
    13.7
    		 
    21/307
    6.8
    		 
    2.00
    (1.21 to 3.30)
    Nuojua et al.21
    8/92
    8.7
    		 
    17/276
    6.2
    		 
    1.41
    (0.63 to 3.16)
    Petersen et al.22
    11/70
    15.7
    		 
    0/70
    0.0
    		 
    23.0
    (1.38 to 382.9)
    Reubinoff et al.7
    29/260
    11.2
    		 
    30/260
    11.5
    		 
    0.97
    (0.60 to 1.56)
    Tallo et al.12
    3/62
    4.8
    		 
    3/62
    4.8
    		 
    1.00
    (0.21 to 4.76)
    Tan et al.4
    69/494
    14.0
    		 
    68/978
    6.9
    		 
    2.01
    (1.46 to 2.76)
    Tanbo et al.5
    41/355
    11.5
    		 
    43/643
    6.7
    		 
    1.73
    (1.15 to 2.60)
    Verlaenen et al.6
    14/140
    10.0
    		 
    6/140
    4.3
    		 
    2.33
    (0.92 to 5.90)
    Total matched
    571/5,361
    10.7
    		 
    446/7,038
    6.4
    		 
    1.70
    (1.50 to 1.92)
    Non-matched studies        
    Addor et al.23
    11/113
    9.7
    		 
    292/6,088
    4.8
    		 
    2.03
    (1.14 to 3.60)
    Olivennes et al. ’9325
    18/162
    11.1
    		 
    183/5096
    3.6
    		 
    3.09
    (1.96 to 4.89)
    Total non-matched
    29/275
    10.5
    475/11,184
    4.2
    2.58
    (1.80 to 3.68)


     

    Table F (Posted as supplied by author) Low and very low birth weight in twin pregnancies after assisted versus natural conception
     

    Study
    Assisted
    		 
    Spontaneous
    		 
    Relative risk (95% CI)
     
    n/N
    %
    		 
    n/N
    %
    		 
    Birthweight < 1,500 g
    Matched studies        
    Dhont et al. ‘991
    166/2,482
    6.7
    		 
    196/2,482
    7.9
    		 
    0.85
    (0.69 to 1.03)
    Dhont et al. ‘979
    14/230
    6.1
    		 
    14/230
    6.1
    		 
    1.00
    (0.49 to 2.05)
    Isaksson et al.10
    2/40
    5.0
    		 
    16/200
    7.5
    		 
    0.63
    (0.15 to 2.61)
    Koivurova et al.19 †
    1/103
    1.0
    		 
    5/103
    4.9
    		 
    0.20
    (0.02 to 1.68)
    Moise et al.11
    10/40
    25.0
    		 
    3/80
    3.8
    		 
    6.67
    (1.94 to 22.88)
    Total matched
    193/2,895
    6.7
    		 
    234/3,095
    7.6
    		 
    0.89
    (0.74 to 1.07)
    Non-matched studies        
    Daniel et al.27
    26/208
    12.5
    		 
    21/242
    8.7
    		 
    1.44
    (0.84 to 2.48)
    Olivennes et al. ‘9617
    22/144
    15.3
    		 
    34/328
    10.4
    		 
    1.47
    (0.89 to 2.43)
    Total non-matched
    48/352
    13.6
    55/570
    9.6
    1.46
    (1.01 to 2.11)
    Birthweight 1,500 – 2,499 g
    Matched studies        
    Dhont et al. ‘991
    1,182/2,482
    47.6
    		 
    1,157/2,482
    46.6
    		 
    1.02
    (0.96 to 1.08)
    Dhont et al. ‘979
    114/230
    49.6
    		 
    112/230
    48.7
    		 
    1.02
    (0.85 to 1.23)
    Isaksson et al.10
    16/40
    40.0
    		 
    78/200
    38.5
    		 
    1.03
    (0.68 to 1.56)
    Koivurova et al.19 †
    46/103
    44.7
    		 
    42/103
    40.8
    		 
    1.10
    (0.80 to 1.50)
    Moise et al.11
    18/40
    45.0
    		 
    44/80
    55.0
    		 
    0.82
    (0.55 to 1.22)
    Total matched
    1,376/2,895
    47.5
    		 
    1,433/3,095
    46.3
    		 
    1.02
    (0.97 to 1.08)
    Non-matched studies        
    Daniel et al.26
    105/208
    50.5
    		 
    106/242
    43.8
    		 
    1.15
    (0.95 to 1.40)
    Olivennes et al. ‘9617
    120/144
    83.3
    		 
    276/328
    84.1
    		 
    0.99
    (0.91 to 1.08)
    Total non-matched
    225/352
    63.9
    382/570
    67.0
    1.05
    (0.96 to 1.15)
    Birthweight < 2,500 g
    Matched studies        
    Dhont et al. ‘991
    1,348/2,482
    54.3
    		 
    1,353/2,482
    54.5
    		 
    1.00
    (0.95 to 1.05)
    Dhont et al. ‘979
    128/230
    55.6
    		 
    126/230
    54.8
    		 
    1.02
    (0.86 to 1.20)
    Isaksson et al.10
    18/40
    45.0
    		 
    92/200
    46.0
    		 
    0.98
    (0.67 to 1.42)
    Koivurova et al.19 †
    47/103
    45.6
    		 
    47/103
    45.6
    		 
    1.00
    (0.74 to 1.35)
    Koudstaal et al.13
    117/192
    60.9
    		 
    85/192
    44.3
    		 
    1.38
    (1.13 to 1.67)
    Moise et al.11
    28/40
    70.0
    		 
    47/80
    58.8
    		 
    1.19
    (0.91 to 1.57)
    Petersen et al.22
    12/32
    37.5
    		 
    15/32
    46.9
    		 
    0.80
    (0.45 to 1.43)
    Tallo et al.12 †
    48/68
    70.6
    		 
    29/68
    42.6
    		 
    1.66
    (1.21 to 2.27)
    Tan et al.4
    132/250
    52.8
    		 
    16/42
    38.1
    		 
    1.39
    (0.93 to 2.07)
    Total matched
    1,878/3,437
    54.6
    		 
    1,810/3,429
    52.8
    		 
    1.03
    (0.99 to 1.08)
    Non-matched studies        
    Addor et al.23
    26/52
    50.0
    		 
    166/308
    53.9
    		 
    0.93
    (0.69 to 1.24)
    Bernasko et al.26 *
    148/206
    71.8
    		 
    324/548
    59.1
    		 
    1.22
    (1.09 to 1.36)
    Daniel et al.27
    131/208
    63.0
    		 
    127/242
    52.5
    		 
    1.20
    (1.02 to 1.41)
    Olivennes et al. ‘9617
    142/144
    98.6
    		 
    310/328
    94.5
    		 
    1.04
    (1.01 to 1.08)
    Total non-matched
    447/610
    73.3
    		 
    927/1,426
    65.0
    		 
    1.12
    (1.06 to 1.19)

    * Infants of 2 mothers in the study group and 5 in the control group were excluded because of stillbirth of one or both twins.

    † Surviving infants only.


     

    Table G (Posted as supplied by author) Small for gestational infants from singleton and twin pregnancies after assisted conception versus natural conceptions*
     

    Study*
    Assisted
    		 
    Spontaneous
    		 
    Relative risk (95% CI)
     
    n/N
    %
    		 
    n/N
    %
    		 
    Singletons
    Matched studies        
    Koudstaal et al.8
    50/307
    16.3
    		 
    24/307
    7.8
    		 
    2.08
    (1.31 to 3.30)
    Maman et al.20
    13/169
    7.7
    		 
    36/469
    7.7
    		 
    1.00
    (0.54 to 1.84)
    Reubinoff et al.7
    33/260
    12.7
    		 
    34/260
    13.1
    		 
    0.97
    (0.62 to 1.52)
    Tallo et al.12
    1/62
    1.6
    		 
    1/62
    1.6
    		 
    1.00
    (0.06 to 15.63)
    Tan et al.4
    64/494
    13.0
    		 
    89/978
    9.1
    		 
    1.42
    (1.05 to 1.93)
    Verlaenen et al.6
    15/140
    10.7
    		 
    7/140
    5.0
    		 
    2.14
    (0.90 to 5.09)
    Total matched
    176/1,432
    12.3
    		 
    191/2,216
    8.6
    		 
    1.40
    (1.15 to 1.71)
    Non-matched studies        
    Addor et al.23
    6/113
    5.3
    		 
    371/6,088
    6.1
    		 
    0.87
    (0.40 to 1.91)
    Olivennes et al. ’9325
    18/162
    11.1
    		 
    301/5,096
    5.9
    		 
    1.88
    (1.20 to 2.95)
    Total non-matched
    24/275
    8.7
    		 
    672/11,184
    6.0
    		 
    1.46
    (0.98 to 2.15)
    Twins
    Matched studies        
    Koudstaal et al.13
    51/192
    26.6
    		 
    49/192
    25.5
    		 
    1.04
    (0.74 to 1.46)
    Moise et al.11
    12/40
    30.0
    		 
    15/80
    18.8
    		 
    1.60
    (0.83 to 3.09)
    Tallo et al.12 †
    13/68
    19.1
    		 
    7/68
    10.3
    		 
    1.86
    (0.79 to 4.37)
    Tan et al.4
    58/250
    23.2
    		 
    6/42
    14.3
    		 
    1.62
    (0.75 to 3.52)
    Total matched
    134/550
    24.4
    		 
    77/382
    20.2
    		 
    1.27
    (0.97 to 1.65)
    Non-matched studies        
    Addor et al.23
    16/52
    30.8
    		 
    92/308
    29.9
    		 
    1.03
    (0.66 to 1.60)
    Bernasko et al.26 **
    26/206
    12.6
    		 
    68/548
    12.4
    		 
    1.02
    (0.67 to 1.55)
    Olivennes et al. ‘9617
    26/144
    18.1
    		 
    75/328
    22.9
    		 
    0.79
    (0.53 to 1.18)
    Total non-matched
    68/402
    16.9
    235/1,184
    19.8
    0.93
    (0.73 to 1.18)

    * Different weight for gestational age curves were used as references in these studies. Koudstaal et al.8,13 and Verlaenen et al.6used the reference curve of Kloosterman, Reubinoff et al.7 and Tan et al.4 the Gairdner and Pearson standard growth charts, Olivennes et al.17, 25 the Leroy and Lefort curve, and Moise et al.11 and Tallo et al.12 the Colorado Intrauterine Growth Charts. Maman et al.20, Addor et al.23 and Bernasko et al.26 did not report what standard charts were used.

    ** Infants of 2 mothers in the study group and 5 in the control group were excluded from the report because of stillbirth of one or both twins.

    † Surviving infants only.


     

    Table H (Posted as supplied by author) Caesarean section rates in singleton and twin pregnancies after assisted versus natural conceptions
     

    Study
    Assisted
    		 
    Spontaneous
    		 
    Relative risk (95% CI)
     
    n/N
    %
    		 
    n/N
    %
    		 
    Singletons
    Matched studies        
    Dhont et al. ‘991
    647/3,048
    21.2
    		 
    496/3,048
    16.3
    		 
    1.30
    (1.17 to 1.45)
    D’Souza18
    40/150
    26.7
    		 
    19/150
    12.7
    		 
    2.11
    (1.28 to 3.46)
    Isaksson et al.10
    17/69
    24.6
    		 
    70/345
    20.3
    		 
    1.21
    (0.76 to 1.93)
    Koudstaal et al.8
    51/307
    16.6
    		 
    40/307
    13.0
    		 
    1.27
    (0.87 to 1.87)
    Maman et al.20
    80/169
    47.3
    		 
    93/469
    19.8
    		 
    2.39
    (1.87 to 3.04)
    Nuojua et al.21
    23/92
    25.0
    		 
    69/276
    25.0
    		 
    1.00
    (0.66 to 1.50)
    Reubinoff et al.7
    109/260
    41.9
    		 
    40/260
    15.4
    		 
    2.73
    (1.98 to 3.75)
    Tan et al.4
    232/494
    47.0
    		 
    235/978
    24.0
    		 
    1.95
    (1.69 to 2.26)
    Tanbo et al.5
    100/355
    28.2
    		 
    125/643
    19.4
    		 
    1.45
    (1.15 to 1.82)
    Verlaenen et al.6
    16/140
    11.4
    		 
    10/140
    7.1
    		 
    1.60
    (0.75 to 3.40)
    Total matched
    1,315/5,084
    25.9
    		 
    1,197/6,616
    18.1
    		 
    1.54
    (1.44 to 1.66)
    Non-matched studies        
    Frydman et al.24
    37/79
    46.8
    		 
    597/3,841
    15.5
    		 
    3.01
    (2.36 to 3.85)
    Olivennes et al. ‘9325
    47/162
    29.0
    		 
    749/5,096
    14.7
    		 
    1.97
    (1.54 to 2.53)
    Total non – matched
    84/241
    34.9
    		 
    1,346/8,937
    15.1
    		 
    2.33
    (1.95 to 2.79)
    Twins
    Matched studies        
    Dhont et al. ‘991
    559/1,241
    45.0
    		 
    457/1,241
    36.8
    		 
    1.22
    (1.11 to 1.35)
    Isaksson et al.10
    12/20
    60.0
    		 
    68/100
    68.0
    		 
    0.88
    (0.60 to 1.29)
    Koudstaal et al.13
    38/96
    39.6
    		 
    29/96
    30.2
    		 
    1.31
    (0.89 to 1.94)
    Moise et al.11
    13/20
    65.0
    		 
    21/40
    52.5
    		 
    1.24
    (0.80 to 1.92)
    Tan et al.4
    80/125
    64.0
    		 
    13/21
    61.9
    		 
    1.03
    (0.72 to 1.48)
    Total matched
    702/1,502
    46.7
    		 
    588/1,498
    39.3
    		 
    1.21
    (1.11 to 1.32)
    Non-matched studies        
    Agustsson et al.14
    45/69
    65.2
    		 
    259/453
    57.2
    		 
    1.14
    (0.94 to 1.38)
    Bernasko et al.26
    53/105
    50.5
    142/279
    50.9
    0.99
    (0.79 to 1.24)
    Daniel et al.27
    45/104
    43.3
    		 
    41/121
    33.9
    		 
    1.28
    (0.92 to 1.78)
    Frydman et al.24
    8/11
    72.7
    		 
    26/58
    44.8
    		 
    1.62
    (1.02 to 2.57)
    Lambalk et al.28
    181/480
    37.7
    		 
    192/613
    31.3
    		 
    1.20
    (1.02 to 1.42)
    Olivennes et al. ‘9617
    39/72
    54.2
    		 
    71/164
    43.3
    		 
    1.25
    (0.95 to 1.65)
    Total non- matched
    371/841
    44.1
    731/1,688
    43.3
    1.17
    (1.06 to 1.29)


     

    Table I (Posted as supplied by author) Admissions to neonatal intensive care units after singleton and twin pregnancies from assisted versus natural conceptions
     

    Study
    Assisted
    		 
    Spontaneous
    		 
    Relative risk (95% CI)
     
    n/N
    %
    		 
    n/N
    %
    		 
    Singletons
    Matched studies        
    Dhont et al. ‘991
    638/3,048
    20.9
    		 
    506/3,048
    16.6
    		 
    1.26
    (1.13 to 1.4)
    Dhont et al. ‘979
    30/311
    9.6
    		 
    61/622
    9.8
    		 
    0.98
    (0.65 to 1.49)
    Isaksson et al.10
    1/69
    1.5
    		 
    0/345
    0.0
    		 
    14.8
    (0.61 to 360)
    Koivurova et al.19 †
    20/153
    13.1
    		 
    30/287
    10.5
    		 
    1.25
    (0.74 to 2.13)
    Nuojua et al.21
    2/92
    2.2
    		 
    18/276
    6.5
    		 
    0.33
    (0.08 to 1.41)
    Reubinoff et al.7
    9/260
    3.5
    		 
    5/260
    1.9
    		 
    1.80
    (0.61 to 5.30)
    Tanbo et al.5
    42/355
    11.8
    		 
    40/643
    6.2
    		 
    1.90
    (1.26 to 2.87)
    Verlaenen et al.6
    23/140
    16.4
    		 
    14/140
    10.0
    		 
    1.64
    (0.88 to 3.06)
    Total matched
    765/4428
    17.3
    		 
    674/5,621
    12.0
    		 
    1.27
    (1.16 to 1.40)
    Non-matched studies        
    Addor et al.23
    7/113
    6.2
    		 
    273/6,088
    4.5
    		 
    1.38
    (0.67 to 2.86)
    Total non-matched
    7/113
    6.2
    		 
    273/6,088
    4.5
    		 
    1.38
    (0.67 to 2.86)
    Twins
    Matched studies        
    Dhont et al. ‘991
    1,727/2,482
    69.6
    		 
    1,682/2,482
    67.8
    		 
    1.03
    (0.99 to 1.07)
    Dhont et al. ‘979
    98/230
    42.6
    		 
    60/230
    26.1
    		 
    1.63
    (1.25 to 2.13)
    Isaksson et al.10
    4/40
    10.0
    		 
    16/200
    7.5
    		 
    1.25
    (0.44 to 3.54)
    Koivurova et al.19 †
    39/103
    37.9
    		 
    46/103
    44.7
    		 
    0.85
    (0.61 to 1.18)
    Moise et al.11
    16/40
    40.0
    		 
    23/80
    28.8
    		 
    1.39
    (0.83 to 2.32)
    Total matched
    1,884/2,895
    65.1
    		 
    1,827/3,095
    59.0
    		 
    1.05
    (1.01 to 1.09)
    Non-matched studies        
    Addor et al.23
    14/52
    26.9
    		 
    38/308
    12.3
    		 
    2.18
    (1.27 to 3.74)
    Agustsson et al.14
    126/138
    91.3
    736/906
    81.2
    1.12
    (1.06 to 1.19)
    Bernasko et al.26 *
    96/206
    46.6
    		 
    200/548
    36.5
    		 
    1.28
    (1.06 to 1.53)
    Daniel et al.27
    93/208
    44.7
    		 
    75/242
    30.9
    		 
    1.44
    (1.13 to 1.84)
    Total non-matched
    329/604
    54.5
    1,049/2,004
    52.3
    1.26
    (1.16 to 1.36)

    * Infants of 2 mothers in study group and 5 in the control group excluded because of stillbirth of one or both twins.

    † Denominators include only surviving infants.


     

    (Posted as supplied by author) References to studies examined, but excluded from the analyses (with reasons for their exclusion)

    Australian in vitro fertilisation collaborative group. High incidence of preterm births and early losses in pregnancy after in vitro fertilisation. BMJ 1985; 291:1160-63. (overlap with Saunders et al. and no control group)

    Australian In-Vitro Fertilization Collaborative Group. In-vitro fertilization pregnancies in Australia and New Zealand, 1979-1985. Med J Aust 1988;148:429-36. (overlap with Saunders et al. and no control group)

    MRC Working Party on Children Conceived by In Vitro Fertilisation. Births in Great Britain resulting from assisted conception, 1978-87. BMJ 1990;300:1229-33. (no control group)

    FIVNAT (French In Vitro National). Pregnancies and births resulting from in vitro fertilization: French national registry, analysis of data 1986 to 1990. Fertil Steril 1995;64:746-56. (no control group)

    Andrews MC, Muasher SJ, Levy DL, Jones HW, Jr., Garcia JE, Rosenwaks Z et al. An analysis of the obstetric outcome of 125 consecutive pregnancies conceived in vitro and resulting in 100 deliveries. Am J Obstet Gynecol 1986;154:848-54. (no separate data for singleton and twin pregnancies)

    Beral V, Doyle P, Tan SL, Mason BA, Campbell S. Outcome of pregnancies resulting from assisted conception. Br Med Bull 1990;46:753-68. (no control group)

    Bergh T, Ericson A, Hillensjo T, Nygren KG, Wennerholm UB. Deliveries and children born after in-vitro fertilisation in Sweden 1982-95: a retrospective cohort study. Lancet 1999;354:1579-785. (no control group)

    Brandes JM, Scher A, Itzkovits J, Thaler I, Sarid M, Gershoni-Baruch R. Growth and development of children conceived by in vitro fertilization. Pediatrics 1992;90:424-9. (no specific obstetric data)

    Callahan TL, Hall JE, Ettner SL, Christiansen CL, Greene MF, Crowley WF, Jr. The economic impact of multiple-gestation pregnancies and the contribution of assisted-reproduction techniques to their incidence. N Engl J Med 1994;331:244-9. (no specific obstetric data)

    Cohen J, Mayaux MJ, Guihard-Moscato ML. Pregnancy outcomes after in vitro fertilization. A collaborative study on 2342 pregnancies. Ann N Y Acad Sci 1988;541:1-6. (no control group)

    Doyle P, Beral V, Maconochie N. Preterm delivery, low birthweight and small-for-gestational-age in liveborn singleton babies resulting from in-vitro fertilization. Hum Reprod 1992;7:425-8. (no numerical data for the control group reported to be "the general population of England and Wales")

    Friedler S, Mashiach S, Laufer N. Births in Israel resulting from in-vitro fertilization/embryo transfer, 1982-1989: National Registry of the Israeli Association for Fertility Research. Hum Reprod 1992;7:1159-63. (no control group)

    Ghazi HA, Spielberger C, Kallen B. Delivery outcome after infertility--a registry study. Fertil Steril 1991;55:726-32. (no separate data for singleton and twin pregnancies and no control group)

    Gissler M, Malin SM, Hemminki E. In-vitro fertilization pregnancies and perinatal health in Finland 1991-1993. Hum Reprod 1995;10:1856-61. (no control group)

    Hack M, Brish M, Serr DM, Insler V, Salomy M, Lunenfeld B. Outcome of pregnancy after induced ovulation. Follow-up of pregnancies and children born after clomiphene therapy. JAMA 1972;220:1329-33. (no assisted procreation and no control group)

    Jonas HA, Lumley J. Triplets and quadruplets born in Victoria between 1982 and 1990. The impact of IVF and GIFT on rising birthrates. Med J Aust 1993;158:659-63. (no separate data for singletons and twins)

    Lancaster PA. Obstetric outcome. Clin Obstet Gynaecol 1985;12:847-64. (no specific obstetric data and overlap with Australian In-Vitro Fertilization Collaborative Group, 1985)

    Levene MI, Wild J, Steer P. Higher multiple births and the modern management of infertility in Britain. The British Association of Perinatal Medicine. Br J Obstet Gynaecol 1992;99:607-13. (no separate data for singletons and twins and no control group)

    Li TC, MacLeod I, Singhal V, Duncan SL. The obstetric and neonatal outcome of pregnancy in women with a previous history of infertility: a prospective study. Br J Obstet Gynaecol 1991;98:1087-92. (data not related to the aim of our study)

    McFaul PB, Patel N, Mills J. An audit of the obstetric outcome of 148 consecutive pregnancies from assisted conception: implications for neonatal services. Br J Obstet Gynaecol 1993;100:820-5. (no specific obstetric data and no control group)

    Minakami H, Sayama M, Honma Y, Matsubara S, Koike T, Sato I et al. Lower risks of adverse outcome in twins conceived by artificial reproductive techniques compared with spontaneously conceived twins. Hum Reprod 1998;13:2005-8. (no specific obstetric data)

    Rizk B, Doyle P, Tan SL, Rainsbury P, Betts J, Brinsden P et al. Perinatal outcome and congenital malformations in in-vitro fertilization babies from the Bourn-Hallam group. Hum Reprod 1991;6:1259-64. (part of MRC Working Party 1990 and no control group)

    Rufat P, Olivennes F, de Mouzon J, Dehan M, Frydman R. Task force report on the outcome of pregnancies and children conceived by in vitro fertilization (France: 1987 to 1989). Fertil Steril 1994;61:324-30. (overlap with FIVNAT and no control group)

    Sassoon DA, Castro LC, Davis JL, Hobel CJ. Perinatal outcome in triplet versus twin gestations. Obstet Gynecol 1990;75:817-20. (no control group)

    Saunders DM,.Lancaster P. The wider perinatal significance of the Australian in vitro fertilization data collection program. Am J Perinatol 1989;6:252-7. (no control group)

    Seoud MA, Toner JP, Kruithoff C, Muasher SJ. Outcome of twin, triplet, and quadruplet in vitro fertilization pregnancies: the Norfolk experience. Fertil Steril 1992;57:825-34. (no specific obstetric data

    Schieve LA.,Meikle SF, Ferre C, Peterson HB, Jeng G, Wilcox LS. Low and very low birth weight in infants conceived with use of assisted reproductive technology. New Engl J Med 2002;346:731-7.(no numerical outcome data for control group; based on birth notifications)

    Spellacy WN, Handler A, Ferre CD. A case-control study of 1253 twin pregnancies from a 1982-1987 perinatal data base. Obstet Gynecol 1990;75:168-71. (no assisted procreation and no control group)

    Steptoe PC, Edwards RG, Walters DE. Observations on 767 clinical pregnancies and 500 births after human in-vitro fertilization. Hum Reprod 1986;1:89-94. (no control group)

    Tan SL, Maconochie N, Doyle P, Campbell S, Balen A, Bekir J et al. Cumulative conception and live-birth rates after in vitro fertilization with and without the use of long, short, and ultrashort regimens of the gonadotropin-releasing hormone agonist buserelin. Am J Obstet Gynecol 1994;171:513-20. (no specific obstetric data and no control group)

    Tanbo T,.Abyholm T. Obstetric and perinatal outcome in pregnancies after assisted reproduction. Curr Opin Obstet Gynecol 1996;8:193-8. (no control group)

    Tuck SM, Yudkin PL, Turnbull AC. Pregnancy outcome in elderly primigravidae with and without a history of infertility. Br J Obstet Gynaecol 1988;95:230-7. (no assisted procreation)

    Venn A,.Lumley J. Clomiphene citrate and pregnancy outcome. Aust N Z J Obstet Gynaecol 1994;34:56-66. (no assisted procreation)

    Wang JX, Clark AM, Kirby CA, Philipson G, Petrucco O, Anderson G et al. The obstetric outcome of singleton pregnancies following in-vitro fertilization/gamete intra-fallopian transfer. Hum Reprod 1994;9:141-6. (no specific obstetric data)

    Wennerholm UB, Janson PO, Wennergren M, Kjellmer I. Pregnancy complications and short-term follow-up of infants born after in vitro fertilization and embryo transfer (IVF/ET). Acta Obstet Gynecol Scand 1991;70:565-573. (no control group)

    Westergaard T, Wohlfahrt J, Aaby P, Melbye M. Population based study of rates of multiple pregnancies in Denmark, 1980-94. BMJ 1997;314:775-9. (no assisted procreation)

    Williams MA, Goldman MB, Mittendorf R, Monson RR. Subfertility and the risk of low birth weight. Fertil Steril 1991;56:668-71. (no separate data on singletons and twins and no control group)

    Wisanto A, Magnus M, Bonduelle M, Liu J, Camus M, Tournaye H et al. Obstetric outcome of 424 pregnancies after intracytoplasmic sperm injection. Hum Reprod 1995;10:2713-8. (no specific obstetric data and no control group)

    Yeh J, Leipzig S, Friedman EA, Seibel MM. Results of in vitro fertilization pregnancies: experience at Boston’s Beth Israel Hospital. Int J Fertil 1990;35:116-9. (overlap with Friedler et al. and no control group)
     

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