European Clinics in Obstetrics and Gynaecology

, Volume 1, Issue 3, pp 177–183 | Cite as

Prevention of multiple pregnancies in assisted reproduction

Clinical Review


The incidence of multiple births has increased parallel with the success of assisted reproduction treatments (ART) mainly because of the multiple embryo transfer. As a response to the increased multiple birth rate, the number of embryos transferred was reduced in 1992–1994 from three or more to two in many European countries. After that, a dramatic drop in the number of triplet and higher-order pregnancies was seen, but the twin rate still remained high. According to the European registers by ESHRE, in 2001 still 34.4% of children conceived with ART originated from multiple pregnancies, of which 94% were twin pregnancies. Obstetric and perinatal complications affect twins more often than singletons, contributing to increased health risk of the mother of twins and the children born as twins. In addition to the medical complications, twin families are at a greater risk for psychosocial burden. From the health-economic point of view, cost impact for twins is threefold to that of singletons. Recently, the standards of success of infertility treatment have been widely debated in journals of reproductive medicine. The general conclusion from this debate is that both the delivery rate per treatment and the final outcome of the pregnancy should be considered when the success of ART is reported. The high iatrogenic twin rate resulting from ART still offers the infertility treatment providers a challenge to strive for minimizing the number of ART-related twins. The most efficient way to reduce twin rate in ART is single embryo transfer (SET). However, the worry about impairment of delivery rate if only one embryo is transferred has hampered the acceptance of SET. The four randomised controlled trials and some retrospective cohort studies published until now have confirmed the effectiveness of elective single embryo transfer (eSET) in reducing the twin rate below 10%. In addition, highly acceptable delivery rate is achieved with eSET. The final results of eSET are most obviously further improved by transfer of frozen-thawed embryos. The experience of eSET until now encourages mowing towards an individualised embryo transfer policy, where eSET is performed in good prognosis patients at high risk for a twin pregnancy when two embryos would be transferred. The aim of this article is to review studies about eSET as a method to prevent ART-related twin pregnancies and the ways used in nationwide implementation of eSET in Finland, Belgium and Sweden.


Assisted reproduction Frozen embryo transfer Multiple pregnancy Pregnancy rate Single embryo transfer Twin rate 


  1. 1.
    Devine PC, Malone FD, Athanassiou A, Harvey-Wilkes K, D´Alton ME (2001) Maternal and neonatal outcome of 100 consecutive triplet pregnancies. Am J Perinatol 18:225–235PubMedCrossRefGoogle Scholar
  2. 2.
    Elliot JP, Radin TG (1992) Quadruplet pregnancy: contemporary management and outcome. Obstet Gynecol 80:421–424PubMedGoogle Scholar
  3. 3.
    Martin JA, Hamilton BE, Ventura SJ, Menacker F, Park MM, Suton PD (2005) Births: final data for 2001. Natl Vital Stat Rep 51:1–102Google Scholar
  4. 4.
    Klemetti R, Gissler M, Hemminki E (2002) Comparison of perinatal health of children born from IVF in Finland in the early and late 1990s. Hum Reprod 17:2192–2198CrossRefPubMedGoogle Scholar
  5. 5.
    Gardner MO, Goldenberg RL, Cliver SP, Tucker JM, Nelson KG, Copper RL (1995) The origin and outcome of preterm twin pregnancies. Obstet Gynecol 85:553–557PubMedCrossRefGoogle Scholar
  6. 6.
    Koivurova S, Hartikainen A-L, Gissler M, Hemminki E, Sovio U, Järvelin M-R (2002). Neonatal outcome and congenital malformations in children born after in-vitro fertilization. Hum Reprod 17:1391–1398PubMedCrossRefGoogle Scholar
  7. 7.
    Callahan TL, Hall JE, Ettner SL, Christiansen CL, Greene MF, Crowley WF Jr (1994) The economic impact of multiple-gestation pregnancies and the contribution of assisted-reproduction techniques to their incidence. N Engl J Med 331:244–249CrossRefPubMedGoogle Scholar
  8. 8.
    Gissler M, Malin Silverio M, Hemminki E (1995) In-vitro fertilization pregnancies and perinatal health in Finland 1991–1993. Hum Reprod 10:1856–1861PubMedGoogle Scholar
  9. 9.
    Hansen M, Kurinczuk JJ, Bower C, Webb S (2002) The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N Engl J Med 346:725–730CrossRefPubMedGoogle Scholar
  10. 10.
    Hansen M, Bower C, Milne E, de Klerk N, Kurinczuk JJ (2005) Assisted reproductive technologies and the risk of birth defects—a systematic review. Hum Reprod 20:328–338CrossRefPubMedGoogle Scholar
  11. 11.
    Bergh T, Ericson A, Hillensjö T, Nygren KG, Wennerholm UB (1999) Deliveries and children born after in-vitro fertilisation in Sweden 1982–1995: a retrospective cohort study. Lancet 354:1579–1585CrossRefPubMedGoogle Scholar
  12. 12.
    Luke B, Keith LG (1992) The contribution of singletons, twins and triplets to low birth weight, infant mortality and handicap in the United States. J Reprod Med 37:661–666PubMedGoogle Scholar
  13. 13.
    Petterson B, Nelson K, Watson L, Stanley F (1993) Twins, triplets and cerebral palsy in births in Western Australia in the 1980s. Br Med J 307:1239–1243CrossRefGoogle Scholar
  14. 14.
    Pharaoh POD, Cooke T (1996) Cerebral palsy and multiple births. Arch Dis Child 75:F174–F177PubMedGoogle Scholar
  15. 15.
    Strömberg B, Dahlquist G, Ericson A, Finnström O, Koster M, Stjernquist K (2002) Neurological sequelae in children born after in-vitro fertilization: a population based study. Lancet 359:461–465CrossRefPubMedGoogle Scholar
  16. 16.
    Yokoyama Y, Shimizu T, Hayakawa K (1995) Prevalence of cerebral palsy in twins, triplets and quadruplets. Int J Epidemiol 24:943–948PubMedCrossRefGoogle Scholar
  17. 17.
    Olivennes F, Kadhel P, Rufat P, Fanchin R, Fernandez H, Frydman R (1996) Perinatal outcome of twin pregnancies obtained after in vitro fertilization: comparison with twin pregnancies obtained spontaneously or after ovarian stimulation. Fertil Steril 66:105–109PubMedGoogle Scholar
  18. 18.
    Koudstaal J, Bruinse HW, Helmerholst FM, Vermeiden JP, Willemsen WN, Visser GH (2000) Obstetric outcome of twin pregnancies after in-vitro fertilization: a matched control study in four Dutch university hospitals. Hum Reprod 15:935–940CrossRefPubMedGoogle Scholar
  19. 19.
    Luke B, Morton BB, Nugent C, Gonzales-Quintero VH, Witter FR, Newman RB (2004) Risk factors for adverse outcomes in spontaneous versus assisted conception twin pregnancies. Fertil Steril 81:315–319CrossRefPubMedGoogle Scholar
  20. 20.
    Pinborg A, Loft A, Rasmussen S, Scmidt L, Langhoff-Roos J, Greisen G, Andersen AN (2004) Neonatal outcome in a Danish national cohort of 3438 IVF/ICSI and 10362 non-IVF/ICSI twins born between 1995–2000. Hum Reprod 19:435–441CrossRefPubMedGoogle Scholar
  21. 21.
    Koudstaal J, Braat DDM, Bruinse HW, Naaktgeboren N, Vermeiden JPW, Visser GHA (2000) Obstetric outcome of singleton pregnancies after IVF: a matched control study in four Dutch university hospitals. Hum Reprod 15:1819–1825CrossRefPubMedGoogle Scholar
  22. 22.
    Schieve LA, Meikle SF, Ferre C, Peterson HB, Jeng G, Wilcox LS (2002) Low and very low birth weight infants conceived with use of assisted reproductive technology. N Engl J Med 346:731–737CrossRefPubMedGoogle Scholar
  23. 23.
    Helmerhorst FM, Perquin DAM, Donker D, Keirse MJNC (2004) Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. BMJ 328:261–265CrossRefPubMedGoogle Scholar
  24. 24.
    Pinborg A, Loft A, Schmidt L, Andersen AN (2003) Morbidity in a Danish National cohort of 472 IVF/ICSI twins, 1132 non-IVF/ICSI twins and 634 IVF/ICSI singletons: health-related and social implications for the children and their families. Hum Reprod 18:1234–1243CrossRefPubMedGoogle Scholar
  25. 25.
    Alin Akerman B (2001) Long-term health and psychosocial outcomes, In: Blickstein I, Keith LG (eds) Iatrogenic multiple pregnancy. Clinical implications. Parthenon, New York, pp 199–209Google Scholar
  26. 26.
    Garel M, Salobir C, Blondel B (1997) Psychological consequences of having triplets: a 4-year follow-up study. Fertil Steril 67:1162–1165CrossRefPubMedGoogle Scholar
  27. 27.
    Thorpe K, Golding J, MacGillivray I, Greenwood R (1991) Comparison of prevalence of depression in mothers of twins and mothers of singletons. Br Med J 302:875–878Google Scholar
  28. 28.
    Colpin H, De Munter A, Nys K, Vandemeulebroecke L (1999) Parenting stress and psychosocial well-being among parents with twins conceived naturally or by reproductive technology. Hum Reprod 14:3133–3137CrossRefPubMedGoogle Scholar
  29. 29.
    Glazebrook C, Sheard C, Cox S, Oates M, Ndukwe G (2004) Parenting stress in first-time mothers of twins and triplets conceived after in vitro fertilization. Fertil Steril 81:505–511CrossRefPubMedGoogle Scholar
  30. 30.
    Baor L, Bar-David J, Blickstein I (2004) Psychosocial resource depletion of parents of twins after assisted versus spontaneous reproduction. Int J Fertil Womens Med 49:13–18PubMedGoogle Scholar
  31. 31.
    Wölner-Hanssen P, Rydström H (1998) Cost-effectiveness analysis of in-vitro fertilization: estimated costs per successful pregnancy after transfer of one or two embryos. Hum Reprod 13:88–94CrossRefPubMedGoogle Scholar
  32. 32.
    De Sutter P, Gerris J, Dhont M (2002) A health-economic decision-analytic model comparing double with single embryo transfer in IVF/ICSI. Hum Reprod 17:2891–2896CrossRefPubMedGoogle Scholar
  33. 33.
    Gerris J, De Sutter P, De Neubourg D, Van Royen E, Vander Elst J, Mangelschots K, Vercruyssen M, Kok P, Elseviers M, Annemans L, Pauwels P, Dhont M (2004) A real-life prospective health economic study of elective single embryo transfer versus two-embryo transfer in first IVF/ICSI cycles. Hum Reprod 19:917–923CrossRefPubMedGoogle Scholar
  34. 34.
    Lukassen MHG, Schönbeck Y, Adang EMM, Braat DDM, Zielhuis GA, Kremer JAM (2004) Cost analysis of singleton versus twin pregnancies after in vitro fertilization. Fertil Steril 81:1240–1245CrossRefPubMedGoogle Scholar
  35. 35.
    Koivurova S, Hartikainen AL, Gissler M, Hemminki E, Klemetti R, Järvelin MR (2004) Health care costs resulting from IVF: prenatal and neonatal periods. Hum Reprod 19:2798–2805CrossRefPubMedGoogle Scholar
  36. 36.
    Staessen C, Nagy ZP, Liu J, Janssenswillen C, Camus M, Devroey P, Van Steirteghem AC (1995) One year’s experience with elective transfer of two good quality embryos in the human in-vitro fertilization and intracytoplasmic sperm injection programmes. Hum Reprod 10:3305–3312PubMedGoogle Scholar
  37. 37.
    STAKES (2005) Finnish IVF Statistics 2003 and preliminary data for 2004. National Research and Development Centre for Welfare and Health, accessible at
  38. 38.
    Bergh C (2005) Single embryo transfer: mini-review. Hum Reprod 20:323–3Google Scholar
  39. 39.
    Andersen AN, Gianaroli L, Felderbaum R, de Mouzon J, Nygren KG (2005) Assisted reproductive technology in Europe, 2001. Results generated from European registers by ESHRE. Hum Reprod 20:1158–1176CrossRefPubMedGoogle Scholar
  40. 40.
    Vayena E, Rowe PJ, Griffin PD (eds) (2001) Current practices and controversies in assisted reproduction: report of a meeting on “Medical, Ethical and Social Aspects of Assisted Reproduction” held at WHO Headquarters in Geneva, Switzerland, 17–21 September 2001Google Scholar
  41. 41.
    Edwards RG, Steptoe PC (1983) Current status of in-vitro fertilization and implantation of human embryos. Lancet 1:537–540PubMedGoogle Scholar
  42. 42.
    Tan SL, Royston P, Campbell S, Jacobs HS, Betts J, Mason B, Edwards RG (1992) Cumulative conception and livebirth rates after in-vitro fertilisation. Lancet 339:1390–1394CrossRefPubMedGoogle Scholar
  43. 43.
    Templeton A, Morris JK, Parslow W (1996) Factors that affect outcome of in-vitro fertilization treatment. Lancet 348:1402–1406CrossRefPubMedGoogle Scholar
  44. 44.
    Elsner CW, Tucker MJ, Sweitzer CL, Brockman WDW, Morton PC, Wright G, Toledo AA (1997) Multiple pregnancy rate and embryo number transferred during in vitro fertilization. Am J Obstet Gynecol 177:350–357CrossRefPubMedGoogle Scholar
  45. 45.
    Bollen N, Camus M, Staessen C, Tournaye H, Devroey P, Van Steirteghem AC (1991) The incidence of multiple pregnancy after in vitro fertilization and embryo transfer. Gamete or zygote intrafallopian transfer. Fertil Steril 55:314–318PubMedGoogle Scholar
  46. 46.
    Schieve LA, Peterson HB, Meikle SF, Jeng G, Danel I, Burnett NM, Wilcox LS (1999) Live-birth rates and multiple-birth risk using in vitro fertilization. JAMA 282:1832–1838CrossRefPubMedGoogle Scholar
  47. 47.
    Coetsier T, Dhont M (1998) Avoiding multiple pregnancies in in-vitro fertilization: who’s afraid of single embryo transfer? Hum Reprod 13:2663–2670PubMedGoogle Scholar
  48. 48.
    Strandell A, Bergh C, Lundin K (2000) Selection of patients suitable for one-embryo transfer may reduce the rate of multiple births by half without impairment of overall birth rates. Hum Reprod 15:2520–2525CrossRefPubMedGoogle Scholar
  49. 49.
    Barri P (2005) Multiple pregnancies: a plea for informed caution. Hum Reprod Update 11:1–2CrossRefPubMedGoogle Scholar
  50. 50.
    Thurin A, Hardarson T, Hausken J, Jablonowska B, Lundin K, Pinborg A, Bergh C (2005) Predictors of ongoing implantation in IVF in a good prognosis group of patients. Hum Reprod 20:1876–1880CrossRefPubMedGoogle Scholar
  51. 51.
    Staessen C, Camus M, Bollen N, Devroey P, Van Steirteghem A (1992) The relationship between embryo quality and the occurrence of multiple pregnancies. Fertil Steril 57:626–630PubMedGoogle Scholar
  52. 52.
    Giorgetti C, Terriou P, Auquier P, Hans E, Spach J, Salzmann J Roulier R (1995) Embryo score to predict implantation after in vitro fertilization: based on 957 single embryo transfers. Hum Reprod 10:2427–2431PubMedGoogle Scholar
  53. 53.
    Van Royen E, Mangelschots K, De Neubourg D, Valkenburg M, Van de Meerssche M, Ryckaert G, Eestermans W, Gerris J (1999) Characterization of a top quality embryo, a step towards single-embryo transfer. Hum Reprod 14:2345–2349CrossRefPubMedGoogle Scholar
  54. 54.
    Gerris J, Neubourg D, Mangelschots K, Van Royen E, Van de Meerssche M, Valkenburg M (1999) Prevention of twin pregnancy after in-vitro fertilization or intracytoplasmic sperm injection based on strict embryo criteria: a prospective randomized clinical trial. Hum Reprod 14:2581–2587CrossRefPubMedGoogle Scholar
  55. 55.
    Vilska S, Tiitinen A, Hydén-Granskog C, Hovatta O (1999) Elective transfer of one embryo results in an acceptable pregnancy rate and eliminates the risk of multiple birth. Hum Reprod 14:2392–2395CrossRefPubMedGoogle Scholar
  56. 56.
    Martikainen H, Tiitinen A, Tomás C, Tapanainen J, Orava M, Tuomivaara L, Vilska S, Hydén-Granskog C, Hovatta O, Finnish ET Study Group (2001) One versus two embryo transfer after IVF and ICSI: a randomized study. Hum Reprod 16:1900–1903CrossRefPubMedGoogle Scholar
  57. 57.
    Thurin A, Hausken J, Hillensjö T, Jablanowska B, Pinborg A, Strandell A, Bergh C (2004) Elective single-embryo transfer versus double embryo transfer in in-vitro fertilization. N Engl J Med 351:2392–2402CrossRefPubMedGoogle Scholar
  58. 58.
    Gardner DK, Phil D, Surrey E, Minjarez D, Leitz A, Stevens J, Schoolcraft W (2004) Single blastocyst transfer: a prospective randomised trial. Fertil Steril 81:551–555CrossRefPubMedGoogle Scholar
  59. 59.
    Gerris J, De Neubourg D, Mangelschots K, Van Royen E, Vercruyssen M, Barudy-Vasquez J, Valkenburg M, Ryckaert G (2002) Elective single day 3 embryo transfer halves the twinning rate without decrease in the ongoing pregnancy rate of an IVF/ICSI programme. Hum Reprod 17:2626–2631CrossRefPubMedGoogle Scholar
  60. 60.
    De Sutter P, Van der Elst J, Coetsier T, Dhont M (2003) Single embryo transfer and multiple pregnancy rate reduction in IVF/ICSI: a 5-year appraisal. Reprod Biomed Online 6:464–469PubMedCrossRefGoogle Scholar
  61. 61.
    Tiitinen A, Unkila-Kallio L, Halttunen M, Hydén-Granskog C (2003) Impact of elective single embryo transfer on the twin pregnancy rate. Hum Reprod 18:1449–1453CrossRefPubMedGoogle Scholar
  62. 62.
    Gerris J, Van Royen E (2000) Avoiding multiple pregnancies in ART: a plea for single embryo transfer. Hum Reprod 15:1884–1888CrossRefPubMedGoogle Scholar
  63. 63.
    Menken J, Trussell J, Larsen U (1986) Age and infertility. Science 233:1389–1394PubMedCrossRefGoogle Scholar
  64. 64.
    Söderström-Anttila V, Tiitinen A, Foudila T, Hovatta O (1998) Obstetric and perinatal outcome after oocyte donation—comparison with in vitro fertilization pregnancies. Hum Reprod 13:483–490CrossRefPubMedGoogle Scholar
  65. 65.
    Söderström-Anttila V, Vilska S, Mäkinen S, Foudila T, Suikkari A-M (2003) Elective single embryo transfer in recipients of donated oocytes. Hum Reprod 18:1858–1863CrossRefPubMedGoogle Scholar
  66. 66.
    Tiitinen A, Halttunen M, Härkki P, Vuoristo P, Hydén-Granskog C (2001) Elective single embryo transfer: the value of cryopreservation. Hum Reprod 16:1140–1144CrossRefPubMedGoogle Scholar
  67. 67.
    Hydén-Granskog C, Unkila-Kallio L, Halttunen M, Tiitinen A (2005) Single embryo transfer is an option in frozen embryo transfer. Hum Reprod 20:2935–2938CrossRefPubMedGoogle Scholar
  68. 68.
    Land JA, Evers JLH (2003) Risks and complications in assisted reproduction techniques: report of an ESHRE consensus meeting. Hum Reprod 18:455–457CrossRefPubMedGoogle Scholar
  69. 69.
    Gleicher N, Cambell DP, Chan CL, Karande V, Rao R, Balin M, Pratt D (1995) The desire for multiple births in couples with infertility problems contradicts present practice patterns. Hum Reprod 10:1079–1084PubMedGoogle Scholar
  70. 70.
    Murdoch A (1997) Triplets and embryo transfer policy. Hum Reprod 12:88–92PubMedGoogle Scholar
  71. 71.
    Child T, Henderson AM, Tan SL (2004) The desire for multiple pregnancy in male and female infertility patients. Hum Reprod 19:558–561CrossRefPubMedGoogle Scholar
  72. 72.
    Ryan GL, Zhang SH, Dokras A, Syrop CH, Van Voorhis BJ (2004) The desire of infertile patients for multiple births. Fertil Steril 81:500–504CrossRefPubMedGoogle Scholar
  73. 73.
    Grobman WA, Milad MP, Stout J, Klock SC (2001) Patient perceptions of multiple gestations: an assessment of knowledge and risk aversion. Am J Obstet Gynecol 185:920–924CrossRefPubMedGoogle Scholar
  74. 74.
    Kalra SK, Milad MP, Klock SC, Grobman WA (2003) Infertility patients and their partners: differences in the desire for twin gestations. Obstet Gynecol 102:152–155CrossRefPubMedGoogle Scholar
  75. 75.
    Pinborg A, Loft A, Schmidt L, Andersen AN (2003) Attitudes of IVF/ICSI-twin mothers towards twins and single embryo transfer. Hum Reprod 18:621–627CrossRefPubMedGoogle Scholar
  76. 76.
    Blennhorn M, Nilsson S, Hillervik C, Hellberg D (2005) The couple’s decision-making in IVF: one or two embryos at transfer? Hum Reprod 20:1292–1297CrossRefPubMedGoogle Scholar
  77. 77.
    Murray S, Shetty A, Rattray A, Taylor V, Bhattacharya S (2004) A randomised comparison of alternative methods of information provision on the acceptability of elective single embryo transfer. Hum Reprod 19:911–916CrossRefPubMedGoogle Scholar
  78. 78.
    Dhont M (2001) Single-embryo transfer. Semin Reprod Med 19:251–258CrossRefPubMedGoogle Scholar
  79. 79.
    Ombelet W, De Sutter P, Van der Elst J, Martens G (2005) Multiple gestation and infertility treatment: registration, reflection and reaction—the Belgian project. Hum Reprod Update 11:3–14CrossRefPubMedGoogle Scholar
  80. 80.
    Saldeen P, Sundström P (2004) Would legislation imposing single embryo transfer be a feasible way to reduce the rate of multiple pregnancies after IVF treatment? Hum Reprod 20:4–8CrossRefPubMedGoogle Scholar

Copyright information

© European Board and College of Obstetrics and Gynaecology 2005

Authors and Affiliations

  1. 1.Infertility Clinicthe Family Federation of FinlandHelsinkiFinland

Personalised recommendations