Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies
http://www.100md.com
《英国医生杂志》
1 Department of Obstetrics, Gynaecology and Reproductive Medicine, Leiden University Medical Center, NL 2300 Leiden, Netherlands, 2 Department of Obstetrics, Gynaecology and Reproductive Medicine, Flinders University and Flinders Medical Centre, Adelaide, South Australia
Correspondence to: F M Helmerhorst f.m.helmerhorst@lumc.nl
Abstract
Twenty five years of assisted reproductive technology have not freed it from being a focus of medical, social, and political debate. Throughout this, reproductive technology has stood its ground, predominantly by offering parenthood to people who might not otherwise achieve it. However, issues that followed in its wake, such as surrogacy and pre-implantation diagnosis, have kept the momentum going on what many see as a loaded issue. It may be impossible to forecast where this will lead, but it should be possible to assess objectively whether babies born after assisted conception fare better or worse than those born after natural conception.
This question seems to be answered already by the widespread belief that pregnancy outcome is substantially worse after assisted conception.1-3 The difference, however, relates predominantly to the higher frequency of multiple pregnancies.3 The first indication that assisted singleton pregnancies may also have poorer outcomes appeared in 1985,2 but it was not clear how much related to assisted reproduction or to confounders, such as maternal age and parity. Several matched cohort studies have since confirmed these findings.1 4-8 Some studies found an opposite trend,9 10 while most reported differences that were compatible with chance. Moreover, for twin pregnancies the general consensus, with few exceptions,11-13 seems to be that assisted twin pregnancies have outcomes that are either similar to or slightly better than those conceived naturally.1 9 14-17
We identified all published studies on birth outcomes after assisted conception that distinguished singleton from multiple pregnancies and that incorporated an appropriate control group from the same population. We examined whether there are genuine differences in outcome between assisted and natural conceptions and whether they apply to both singleton and twin pregnancies.
Methods
Included studies are listed in tables A and B on www.bmj.com. Seventeen (14 matched and three non-matched) dealt with singleton pregnancies and 17 (10 matched and seven non-matched) with twin pregnancies. The tables show country and years covered by the study, types of assisted conception, number of cases, and type of controls.
Table 1 summarises relative risks of the outcomes in singleton and twin pregnancies after assisted and natural conception. Analyses for preterm birth and perinatal mortality are presented in tables 2, 3, 4, with more details and results for other outcomes in web tables C-I (see www.bmj.com). The website also lists the excluded studies with reasons for exclusion.
Table 1 Summary of risk of various outcomes in singleton and twin pregnancies after assisted conception compared with those conceived naturally. Figures are relative risk (95% confidence intervals)
Table 2 Preterm birth in singleton pregnancies after assisted conception compared with matched controls (natural conception)
Table 3 Preterm birth in twin pregnancies after assisted conception compared with matched controls (natural conception)
Table 4 Perinatal mortality in singleton and twin pregnancies after assisted conception compared with natural conception
Preterm birth
Very preterm singletons (< 32 weeks) were reported in only three studies with a prevalence of 1.3-2.1% in assisted conceptions and 0.3-2.9% in natural conceptions, a relative risk of 3.27 (95% confidence interval 2.03 to 5.28) (table 2).1 9 19 Mildly preterm singletons (32-36 weeks) accounted for 6.5-9.2% and 3.8-7.6%, respectively, (2.05, 1.71 to 2.47) (see web table C).1 9 19 Preterm singletons (< 37 weeks) accounted for 5.8-15% and 1.4-10.5%, respectively (table 2). The relative risk in both the 12 matched1 4-10 12 19 21 22 and two non-matched23 25 studies showed a doubling of the risk of preterm birth after assisted conception.
Very preterm twins were reported in three matched studies1 9 19 (detailed in table 3) and two non-matched17 26 studies. After we excluded one study that reported live infants only,19 the frequency range was 7.0-10.5% in assisted conceptions and 4.9-10.7% in natural conceptions and was not statistically different (see web table D). Mildly preterm twins accounted for 41.7-45.2% of cases and 33.0-40.5% of controls in the matched studies (1.07, 1.00 to 1.14).1 9 19 Preterm twins differed widely in frequency from 18.8-60.0% and 20.0-52.4%, respectively. The relative risk was 1.07 (1.02 to 1.13) in the nine matched studies1 4 9-13 19 22 (table 3) and 0.99 (0.80 to 1.23) in the two non-matched studies (see web table D).17 23
Birth weight
Singletons weighing < 1500 g were reported for six matched studies1 5 6 9 10 19 and one non-matched study.25 Frequencies in the matched studies were 1.5-3.9% for assisted conceptions and 0.3-2.7% for natural conceptions with a relative risk of 3.00 (2.07 to 4.36) (see web table E). Singletons weighing < 2500 g were more common among cases than among controls in both matched (n = 12)1 4-10 12 19 21 22 and non-matched (n = 2)23 25 studies. Percentages of low birth weight were 2.9-15.7% in cases, 0-11.5% in matched controls, and 3.6-4.8% in non-matched controls (see web table E).
Twins < 1500 g accounted for 5.0-25.0% of cases and 3.8-10.4% of controls (omitting one study reporting live infants only).19 The relative risk was 0.89 (0.74 to 1.07) for the five matched1 9-11 19 and 1.46 (1.01 to 2.11) for the two non-matched studies (see web table F).17 27 Twins < 2500 g accounted for 37.5-70.6% and 50.0-98.6% of cases versus 38.1-58.8% and 52.5-94.5% of controls, with relative risks of 1.03 (0.99 to 1.08) and 1.12 (1.06 to 1.19), respectively, in the eight matched studies1 4 9-13 19 22 and the four non-matched studies.17 23 26 27
Small for gestational age
The 12 studies that reported on infants who were small for gestational age applied various reference charts. The frequency in singleton cases and controls was 1.6-16.3% versus 1.6-13.1% with a relative risk of 1.40 and 1.46, respectively, for the six matched4 6-8 12 20 and two non-matched studies (see web table G).23 25 The four matched4 11-13 and three non-matched17 23 26 twin studies showed no significant difference between assisted and natural conceptions.
Caesarean section
Rates of caesarean section were significantly higher after assisted than after natural conception (see web table H). The effect was more marked for singleton than for twin pregnancies in both matched1 4-8 10 11 13 18 20 21 and non-matched studies.14 17 24-27
NICU admissions
Admissions to neonatal intensive care were more common after assisted conception in both matched and non-matched studies, and the difference was larger for singletons1 5-7 9 10 19 21 23 than for twins (see web table I).1 9-11 14 19 23 26 27
Perinatal mortality
Perinatal mortality differed widely among studies (table 4). In singleton pregnancies it was significantly higher after assisted than after natural conception in both matched and non-matched studies. All of the difference in the matched studies was accounted for by the study of Dhont et al in 1999, which contributed 67% of the cases.1 Without this study mortality was 10.4 per 1000 for both cases and controls.
Matched twin studies were also dominated by the same study, which contributed 78% of the cases,1 and by another with an extraordinarily high mortality among controls.16 However, most twin studies showed a lower mortality after assisted than after natural conception, with a relative risk of 0.58 (0.44 to 0.77) for matched and 0.84 (0.53 to 1.32) for non-matched studies (table 4).
Discussion
Dhont M, De Sutter P, Ruyssinck G, Martens G, Bekaert A. Perinatal outcome of pregnancies after assisted reproduction: a case-control study. Am J Obstet Gynecol 1999;181: 688-95.
Australian In Vitro Fertilisation Collaborative Group. High incidence of preterm births and early losses in pregnancy after in vitro fertilisation. BMJ 1985;291: 1160-3.
Keirse MJNC, Helmerhorst FM. The impact of assisted reproduction on perinatal health care. Soz Pr?ventiv Med 1995;40: 343-51.
Tan SL, Doyle P, Campbell S, Beral V, Rizk B, Brinsden P, et al. Obstetric outcome of in vitro fertilization pregnancies compared with normally conceived pregnancies. Am J Obstet Gynecol 1992;167: 778-84.
Tanbo T, Dale PO, Lunde O, Moe N, Abyholm T. Obstetric outcome in singleton pregnancies after assisted reproduction. Obstet Gynecol 1995;86: 188-92.
Verlaenen H, Cammu H, Derde MP, Amy JJ. Singleton pregnancy after in vitro fertilization: expectations and outcome. Obstet Gynecol 1995;86: 906-10.
Reubinoff BE, Samueloff A, Ben Haim M, Friedler S, Schenker JG, Lewin A. Is the obstetric outcome of in vitro fertilized singleton gestations different from natural ones? A controlled study. Fertil Steril 1997;67: 1077-83.
Koudstaal J, Braat DD, Bruinse HW, Naaktgeboren N, Vermeiden JP, Visser GH. Obstetric outcome of singleton pregnancies after IVF: a matched control study in four Dutch university hospitals. Hum Reprod 2000;15: 1819-25.
Dhont M, De Neubourg F, Van der Elst J, De Sutter P. Perinatal outcome of pregnancies after assisted reproduction: a case-control study. J Assist Reprod Genet 1997;14: 575-80.
Isaksson R, Gissler M, Tiitinen A. Obstetric outcome among women with unexplained infertility after IVF: a matched case-control study. Hum Reprod 2002;17: 1755-61.
Moise J, Laor A, Armon Y, Gur I, Gale R. The outcome of twin pregnancies after IVF. Hum Reprod 1998;13: 1702-5.
Tallo CP, Vohr B, Oh W, Rubin LP, Seifer DB, Haning RV Jr. Maternal and neonatal morbidity associated with in vitro fertilization. J Pediatr 1995;127: 794-800.
Koudstaal J, Bruinse HW, Helmerhorst FM, Vermeiden JP, Willemsen WN, Visser GH. Obstetric outcome of twin pregnancies after in-vitro fertilization: a matched control study in four Dutch university hospitals. Hum Reprod 2000;15: 935-40.
Agustsson T, Geirsson RT, Mires G. Obstetric outcome of natural and assisted conception twin pregnancies is similar. Acta Obstet Gynecol Scand 1997;76: 45-9.
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.
Fitzsimmons BP, Bebbington MW, Fluker MR. Perinatal and neonatal outcomes in multiple gestations: assisted reproduction versus spontaneous conception. Am J Obstet Gynecol 1998;179: 1162-7.
Olivennes F, Kadhel P, Rufat P, Fanchin R, Fernandez H, Frydman R. Perinatal outcome of twin pregnancies obtained after in vitro fertilization: comparison with twin pregnancies obtained spontaneously or after ovarian stimulation. Fertil Steril 1996;66: 105-9.
D'Souza SW, Rivlin E, Cadman J, Richards B, Buck P, Lieberman BA. Children conceived by in vitro fertilisation after fresh embryo transfer. Arch Dis Child Fetal Neonatal Ed 1997;76: F70-4.
Koivurova S, Hartikainen AL, Gissler M, Hemminki E, Sovio U, Jarvelin MR. Neonatal outcome and congenital malformations in children born after in-vitro fertilization. Hum Reprod 2002;17: 1391-8.
Maman E, Lunenfeld E, Levy A, Vardi H, Potashnik G. Obstetric outcome of singleton pregnancies conceived by in vitro fertilization and ovulation induction compared with those conceived spontaneously. Fertil Steril 1998;70: 240-5.
Nuojua-Huttunen S, Gissler M, Martikainen H, Tuomivaara L. Obstetric and perinatal outcome of pregnancies after intrauterine insemination. Hum Reprod 1999;14: 2110-5.
Petersen K, Hornnes PJ, Ellingsen S, Jensen F, Brocks V, Starup J, et al. Perinatal outcome after in vitro fertilisation. Acta Obstet Gynecol Scand 1995;74: 129-31.
Addor V, Santos-Eggimann B, Fawer CL, Paccaud F, Calame A. Impact of infertility treatments on the health of newborns. Fertil Steril 1998;69: 210-5.
Frydman R, Belaisch-Allart J, Fries N, Hazout A, Glissant A, Testart J. An obstetric assessment of the first 100 births from the in vitro fertilization program at Clamart, France. Am J Obstet Gynecol 1986;154: 550-5.
Olivennes F, Rufat P, Andre B, Pourade A, Quiros MC, Frydman R. The increased risk of complication observed in singleton pregnancies resulting from in-vitro fertilization (IVF) does not seem to be related to the IVF method itself. Hum Reprod 1993;8: 1297-300.
Bernasko J, Lynch L, Lapinski R, Berkowitz RL. Twin pregnancies conceived by assisted reproductive techniques: maternal and neonatal outcomes. Obstet Gynecol 1997;89: 368-72.
Daniel Y, Ochshorn Y, Fait G, Geva E, Bar-Am A, Lessing JB. Analysis of 104 twin pregnancies conceived with assisted reproductive technologies and 193 spontaneously conceived twin pregnancies. Fertil Steril 2000;74: 683-9.
Lambalk CB, van Hooff M. Natural versus induced twinning and pregnancy outcome: a Dutch nationwide survey of primiparous dizygotic twin deliveries. Fertil Steril 2001;75: 731-6.
Pandian Z, Bhattacharya S, Templeton A. Review of unexplained infertility and obstetric outcome: a 10 year review. Hum Reprod 2001;16: 2593-7.
Keirse MJNC, Rush RW, Anderson ABM, Turnbull AC. Risk of pre-term delivery in patients with previous pre-term delivery and/or abortion. Br J Obstet Gynaecol 1978;85: 81-5.
Keirse MJNC. International variations in intrauterine growth. Eur J Obstet Gynecol Reprod Biol 2000;92: 21-8.
Nygren KG, Anderson AN. Assisted reproductive technology in Europe 1998. Results generated from European registers by ESHRE. Hum Reprod 2001;16: 384-91.
Chow JS, Benson CB, Racowsky C, Doubilet PM, Ginsburg E. Frequency of a monochorionic pair in multiple gestations: relationship to mode of conception. J Ultrasound Med 2001;20: 757-60.(Frans M Helmerhorst, asso)
Correspondence to: F M Helmerhorst f.m.helmerhorst@lumc.nl
Abstract
Twenty five years of assisted reproductive technology have not freed it from being a focus of medical, social, and political debate. Throughout this, reproductive technology has stood its ground, predominantly by offering parenthood to people who might not otherwise achieve it. However, issues that followed in its wake, such as surrogacy and pre-implantation diagnosis, have kept the momentum going on what many see as a loaded issue. It may be impossible to forecast where this will lead, but it should be possible to assess objectively whether babies born after assisted conception fare better or worse than those born after natural conception.
This question seems to be answered already by the widespread belief that pregnancy outcome is substantially worse after assisted conception.1-3 The difference, however, relates predominantly to the higher frequency of multiple pregnancies.3 The first indication that assisted singleton pregnancies may also have poorer outcomes appeared in 1985,2 but it was not clear how much related to assisted reproduction or to confounders, such as maternal age and parity. Several matched cohort studies have since confirmed these findings.1 4-8 Some studies found an opposite trend,9 10 while most reported differences that were compatible with chance. Moreover, for twin pregnancies the general consensus, with few exceptions,11-13 seems to be that assisted twin pregnancies have outcomes that are either similar to or slightly better than those conceived naturally.1 9 14-17
We identified all published studies on birth outcomes after assisted conception that distinguished singleton from multiple pregnancies and that incorporated an appropriate control group from the same population. We examined whether there are genuine differences in outcome between assisted and natural conceptions and whether they apply to both singleton and twin pregnancies.
Methods
Included studies are listed in tables A and B on www.bmj.com. Seventeen (14 matched and three non-matched) dealt with singleton pregnancies and 17 (10 matched and seven non-matched) with twin pregnancies. The tables show country and years covered by the study, types of assisted conception, number of cases, and type of controls.
Table 1 summarises relative risks of the outcomes in singleton and twin pregnancies after assisted and natural conception. Analyses for preterm birth and perinatal mortality are presented in tables 2, 3, 4, with more details and results for other outcomes in web tables C-I (see www.bmj.com). The website also lists the excluded studies with reasons for exclusion.
Table 1 Summary of risk of various outcomes in singleton and twin pregnancies after assisted conception compared with those conceived naturally. Figures are relative risk (95% confidence intervals)
Table 2 Preterm birth in singleton pregnancies after assisted conception compared with matched controls (natural conception)
Table 3 Preterm birth in twin pregnancies after assisted conception compared with matched controls (natural conception)
Table 4 Perinatal mortality in singleton and twin pregnancies after assisted conception compared with natural conception
Preterm birth
Very preterm singletons (< 32 weeks) were reported in only three studies with a prevalence of 1.3-2.1% in assisted conceptions and 0.3-2.9% in natural conceptions, a relative risk of 3.27 (95% confidence interval 2.03 to 5.28) (table 2).1 9 19 Mildly preterm singletons (32-36 weeks) accounted for 6.5-9.2% and 3.8-7.6%, respectively, (2.05, 1.71 to 2.47) (see web table C).1 9 19 Preterm singletons (< 37 weeks) accounted for 5.8-15% and 1.4-10.5%, respectively (table 2). The relative risk in both the 12 matched1 4-10 12 19 21 22 and two non-matched23 25 studies showed a doubling of the risk of preterm birth after assisted conception.
Very preterm twins were reported in three matched studies1 9 19 (detailed in table 3) and two non-matched17 26 studies. After we excluded one study that reported live infants only,19 the frequency range was 7.0-10.5% in assisted conceptions and 4.9-10.7% in natural conceptions and was not statistically different (see web table D). Mildly preterm twins accounted for 41.7-45.2% of cases and 33.0-40.5% of controls in the matched studies (1.07, 1.00 to 1.14).1 9 19 Preterm twins differed widely in frequency from 18.8-60.0% and 20.0-52.4%, respectively. The relative risk was 1.07 (1.02 to 1.13) in the nine matched studies1 4 9-13 19 22 (table 3) and 0.99 (0.80 to 1.23) in the two non-matched studies (see web table D).17 23
Birth weight
Singletons weighing < 1500 g were reported for six matched studies1 5 6 9 10 19 and one non-matched study.25 Frequencies in the matched studies were 1.5-3.9% for assisted conceptions and 0.3-2.7% for natural conceptions with a relative risk of 3.00 (2.07 to 4.36) (see web table E). Singletons weighing < 2500 g were more common among cases than among controls in both matched (n = 12)1 4-10 12 19 21 22 and non-matched (n = 2)23 25 studies. Percentages of low birth weight were 2.9-15.7% in cases, 0-11.5% in matched controls, and 3.6-4.8% in non-matched controls (see web table E).
Twins < 1500 g accounted for 5.0-25.0% of cases and 3.8-10.4% of controls (omitting one study reporting live infants only).19 The relative risk was 0.89 (0.74 to 1.07) for the five matched1 9-11 19 and 1.46 (1.01 to 2.11) for the two non-matched studies (see web table F).17 27 Twins < 2500 g accounted for 37.5-70.6% and 50.0-98.6% of cases versus 38.1-58.8% and 52.5-94.5% of controls, with relative risks of 1.03 (0.99 to 1.08) and 1.12 (1.06 to 1.19), respectively, in the eight matched studies1 4 9-13 19 22 and the four non-matched studies.17 23 26 27
Small for gestational age
The 12 studies that reported on infants who were small for gestational age applied various reference charts. The frequency in singleton cases and controls was 1.6-16.3% versus 1.6-13.1% with a relative risk of 1.40 and 1.46, respectively, for the six matched4 6-8 12 20 and two non-matched studies (see web table G).23 25 The four matched4 11-13 and three non-matched17 23 26 twin studies showed no significant difference between assisted and natural conceptions.
Caesarean section
Rates of caesarean section were significantly higher after assisted than after natural conception (see web table H). The effect was more marked for singleton than for twin pregnancies in both matched1 4-8 10 11 13 18 20 21 and non-matched studies.14 17 24-27
NICU admissions
Admissions to neonatal intensive care were more common after assisted conception in both matched and non-matched studies, and the difference was larger for singletons1 5-7 9 10 19 21 23 than for twins (see web table I).1 9-11 14 19 23 26 27
Perinatal mortality
Perinatal mortality differed widely among studies (table 4). In singleton pregnancies it was significantly higher after assisted than after natural conception in both matched and non-matched studies. All of the difference in the matched studies was accounted for by the study of Dhont et al in 1999, which contributed 67% of the cases.1 Without this study mortality was 10.4 per 1000 for both cases and controls.
Matched twin studies were also dominated by the same study, which contributed 78% of the cases,1 and by another with an extraordinarily high mortality among controls.16 However, most twin studies showed a lower mortality after assisted than after natural conception, with a relative risk of 0.58 (0.44 to 0.77) for matched and 0.84 (0.53 to 1.32) for non-matched studies (table 4).
Discussion
Dhont M, De Sutter P, Ruyssinck G, Martens G, Bekaert A. Perinatal outcome of pregnancies after assisted reproduction: a case-control study. Am J Obstet Gynecol 1999;181: 688-95.
Australian In Vitro Fertilisation Collaborative Group. High incidence of preterm births and early losses in pregnancy after in vitro fertilisation. BMJ 1985;291: 1160-3.
Keirse MJNC, Helmerhorst FM. The impact of assisted reproduction on perinatal health care. Soz Pr?ventiv Med 1995;40: 343-51.
Tan SL, Doyle P, Campbell S, Beral V, Rizk B, Brinsden P, et al. Obstetric outcome of in vitro fertilization pregnancies compared with normally conceived pregnancies. Am J Obstet Gynecol 1992;167: 778-84.
Tanbo T, Dale PO, Lunde O, Moe N, Abyholm T. Obstetric outcome in singleton pregnancies after assisted reproduction. Obstet Gynecol 1995;86: 188-92.
Verlaenen H, Cammu H, Derde MP, Amy JJ. Singleton pregnancy after in vitro fertilization: expectations and outcome. Obstet Gynecol 1995;86: 906-10.
Reubinoff BE, Samueloff A, Ben Haim M, Friedler S, Schenker JG, Lewin A. Is the obstetric outcome of in vitro fertilized singleton gestations different from natural ones? A controlled study. Fertil Steril 1997;67: 1077-83.
Koudstaal J, Braat DD, Bruinse HW, Naaktgeboren N, Vermeiden JP, Visser GH. Obstetric outcome of singleton pregnancies after IVF: a matched control study in four Dutch university hospitals. Hum Reprod 2000;15: 1819-25.
Dhont M, De Neubourg F, Van der Elst J, De Sutter P. Perinatal outcome of pregnancies after assisted reproduction: a case-control study. J Assist Reprod Genet 1997;14: 575-80.
Isaksson R, Gissler M, Tiitinen A. Obstetric outcome among women with unexplained infertility after IVF: a matched case-control study. Hum Reprod 2002;17: 1755-61.
Moise J, Laor A, Armon Y, Gur I, Gale R. The outcome of twin pregnancies after IVF. Hum Reprod 1998;13: 1702-5.
Tallo CP, Vohr B, Oh W, Rubin LP, Seifer DB, Haning RV Jr. Maternal and neonatal morbidity associated with in vitro fertilization. J Pediatr 1995;127: 794-800.
Koudstaal J, Bruinse HW, Helmerhorst FM, Vermeiden JP, Willemsen WN, Visser GH. Obstetric outcome of twin pregnancies after in-vitro fertilization: a matched control study in four Dutch university hospitals. Hum Reprod 2000;15: 935-40.
Agustsson T, Geirsson RT, Mires G. Obstetric outcome of natural and assisted conception twin pregnancies is similar. Acta Obstet Gynecol Scand 1997;76: 45-9.
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.
Fitzsimmons BP, Bebbington MW, Fluker MR. Perinatal and neonatal outcomes in multiple gestations: assisted reproduction versus spontaneous conception. Am J Obstet Gynecol 1998;179: 1162-7.
Olivennes F, Kadhel P, Rufat P, Fanchin R, Fernandez H, Frydman R. Perinatal outcome of twin pregnancies obtained after in vitro fertilization: comparison with twin pregnancies obtained spontaneously or after ovarian stimulation. Fertil Steril 1996;66: 105-9.
D'Souza SW, Rivlin E, Cadman J, Richards B, Buck P, Lieberman BA. Children conceived by in vitro fertilisation after fresh embryo transfer. Arch Dis Child Fetal Neonatal Ed 1997;76: F70-4.
Koivurova S, Hartikainen AL, Gissler M, Hemminki E, Sovio U, Jarvelin MR. Neonatal outcome and congenital malformations in children born after in-vitro fertilization. Hum Reprod 2002;17: 1391-8.
Maman E, Lunenfeld E, Levy A, Vardi H, Potashnik G. Obstetric outcome of singleton pregnancies conceived by in vitro fertilization and ovulation induction compared with those conceived spontaneously. Fertil Steril 1998;70: 240-5.
Nuojua-Huttunen S, Gissler M, Martikainen H, Tuomivaara L. Obstetric and perinatal outcome of pregnancies after intrauterine insemination. Hum Reprod 1999;14: 2110-5.
Petersen K, Hornnes PJ, Ellingsen S, Jensen F, Brocks V, Starup J, et al. Perinatal outcome after in vitro fertilisation. Acta Obstet Gynecol Scand 1995;74: 129-31.
Addor V, Santos-Eggimann B, Fawer CL, Paccaud F, Calame A. Impact of infertility treatments on the health of newborns. Fertil Steril 1998;69: 210-5.
Frydman R, Belaisch-Allart J, Fries N, Hazout A, Glissant A, Testart J. An obstetric assessment of the first 100 births from the in vitro fertilization program at Clamart, France. Am J Obstet Gynecol 1986;154: 550-5.
Olivennes F, Rufat P, Andre B, Pourade A, Quiros MC, Frydman R. The increased risk of complication observed in singleton pregnancies resulting from in-vitro fertilization (IVF) does not seem to be related to the IVF method itself. Hum Reprod 1993;8: 1297-300.
Bernasko J, Lynch L, Lapinski R, Berkowitz RL. Twin pregnancies conceived by assisted reproductive techniques: maternal and neonatal outcomes. Obstet Gynecol 1997;89: 368-72.
Daniel Y, Ochshorn Y, Fait G, Geva E, Bar-Am A, Lessing JB. Analysis of 104 twin pregnancies conceived with assisted reproductive technologies and 193 spontaneously conceived twin pregnancies. Fertil Steril 2000;74: 683-9.
Lambalk CB, van Hooff M. Natural versus induced twinning and pregnancy outcome: a Dutch nationwide survey of primiparous dizygotic twin deliveries. Fertil Steril 2001;75: 731-6.
Pandian Z, Bhattacharya S, Templeton A. Review of unexplained infertility and obstetric outcome: a 10 year review. Hum Reprod 2001;16: 2593-7.
Keirse MJNC, Rush RW, Anderson ABM, Turnbull AC. Risk of pre-term delivery in patients with previous pre-term delivery and/or abortion. Br J Obstet Gynaecol 1978;85: 81-5.
Keirse MJNC. International variations in intrauterine growth. Eur J Obstet Gynecol Reprod Biol 2000;92: 21-8.
Nygren KG, Anderson AN. Assisted reproductive technology in Europe 1998. Results generated from European registers by ESHRE. Hum Reprod 2001;16: 384-91.
Chow JS, Benson CB, Racowsky C, Doubilet PM, Ginsburg E. Frequency of a monochorionic pair in multiple gestations: relationship to mode of conception. J Ultrasound Med 2001;20: 757-60.(Frans M Helmerhorst, asso)