Artificial Reproductive Technology (ART)

  • Kurt Benirschke
  • Graham J. Burton
  • Rebecca N. Baergen


As this chapter is being written, Louise Brown celebrates her 30th birthday and had recently delivered a son, the first “second generation” offspring coming from this new technology. Louise Brown was the first child to be born by ART, that is to say, she was born after in vitro fertilization (Steptoe and Edwards 1978) even though Rock and Menkin were the first investigators to have achieved in vitro fertilization of a human egg (1944). The in vitro fertilization aspect that is part of the ART procedure, performed before the birth of Louise Brown, was undertaken because of obstructed fallopian tubes; numerous earlier attempts had failed. It must also be appreciated that the conception and birth occurred in the midst of considerable social and religious controversy which still prevail. While some of these concerns have somewhat abated, much new controversy has come to light even though millions of conceptions and births have since occurred through the various techniques that are employed by ART physicians. The practice of artificial reproductive technology has since become a recognized specialty in reproductive medicine, specialty journals were created, and the Nobel Prize in Medicine was given to Robert Edwards for this achievement in 2010 (since Steptoe had died in 1988). Interestingly, the practice has yet to be regulated, and only an informal international committee seeks to gather information on the results and problems of ART (Zegers-Hochschild et al. 2006). Since only guidelines, but no regulation exists in the USA, it is worthwhile to read the report on “IFFS Surveillance 07,” edited by Jones et al. (2007). It reports on the laws prevailing in other countries and provides the results from many centers. The Center for Disease Control (CDC) has also issued the clinical results of a large cohort (Wright et al. 2007). The CDC publishes annual reports. In Belgium, the “East Flanders Prospective Twin Study (EFPTS)” was initiated in 1964 and seeks to provide additional data (e.g., Derom et al. 2006). A detailed description of the various types of ART, the success rates of different methods employed, prenatal genetic diagnosis (PGD), and other aspects may be seen at: and in a review by Allen and Wilson (2006). Moreover, a national workshop was held in 2005 whose publication summarizes the then available data (Reddy et al. 2007). It is emphatic about the necessity for counseling the family, the risk of prematurity, the apparent risk of increased frequency of placenta previa, and it also gives directions for future research. The currently increasingly frequent practice of PGD has been examined by Mastenbroek et al. (2007); its success rate for viable gestations was found to be considerably lower than that for other ART procedures.


Placenta Previa Single Embryo Transfer Extravillous Trophoblast Assisted Hatching Monochorionic Twin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Alikani H (2005) Epithelial cadherin distribution in abnormal human pre-implantation embryos. Hum Reprod 20:3369–3375PubMedCrossRefGoogle Scholar
  2. Alikani M, Willadsen SM (2002) Human blastocysts from aggregated mononucleated cells of two or more non-viable zygote-derived embryos. Reprod Biomed Online 5:56–58PubMedCrossRefGoogle Scholar
  3. Alikani M, Cekleniak NA, Walters E, Cohen J (2003) Monozygotic twinning following assisted conception: an analysis of 81 consecutive cases. Hum Reprod 18:1937–1943PubMedCrossRefGoogle Scholar
  4. Alikani M, Schimmel T, Willadsen SM (2005) Cytoplasmic fragmentation in activated eggs occurs in the cytokinetic phase of the cell cycle, in lieu of normal cytokinesis, and in response to cytoskeletal disorder. Mol Hum Reprod 11:335–344PubMedCrossRefGoogle Scholar
  5. Allen VM, Wilson RD (2006) Pregnancy outcomes after assisted reproductive technology. J Obstet Gynaecol Can 173:220–233Google Scholar
  6. Anand D, Platt MJ, Pharoah PO (2007a) Comparative development of surviving co-twins of vanishing twin conceptions, twins and singletons. Twin Res Hum Genet 10:210–215PubMedCrossRefGoogle Scholar
  7. Anand D, Platt MJ, Pharoah PO (2007b) Vanishing twin: a possible cause of cerebral impairment. Twin Res Hum Genet 10:202–209PubMedCrossRefGoogle Scholar
  8. Assaf SA, Randolph LM, Benirschke K, Wu S, Samadi R, Chmait RH (2010) Discordant blood chimerism in dizygotic monochorionic laser-treated twin-twin transfusion syndrome. Obstet Gynecol 116:483–485PubMedCrossRefGoogle Scholar
  9. Aston KI, Peterson CM, Carrell DT (2008) Monozygotic twinning associated with assisted reproductive technologies: a review. Reproduction 136:377–386PubMedCrossRefGoogle Scholar
  10. Basatemur E, Sutcliffe A (2008) Follow-up of children after ART. Placenta 29(Supplement B):S135–S140CrossRefGoogle Scholar
  11. Behr B, Fisch JD, Racowsky C, Miller K, Pool TB, Milki AA (2000) Blastocyst-ET and monozygotic twinning. J Assist Reprod Genet 17:349–351PubMedCrossRefGoogle Scholar
  12. Bielfeld P, Krüssel J-S (1998) Einfluss der assistierten Reproduktion auf die Inzidenz von Mehrlingsschwangerschaften. Gynakologe 31:203–208CrossRefGoogle Scholar
  13. Blickstein I (2005) Estimating of iatrogenic monozygotic twinning rate following assisted reproduction: pitfalls and caveats. Am J Obstet Gynecol 192:365–368PubMedCrossRefGoogle Scholar
  14. Blickstein I, Keith LG (2007) On the possible cause of monozygotic twinning: lessons from the 9-banded armadillo and from assisted reproduction. Twin Res Hum Genet 10:394–399PubMedCrossRefGoogle Scholar
  15. Bogdanova N, Siebers U, Kelsch R, Markoff A, Röpke A, Exeler R, Tsokas J, Wieacker P (2010) Blood chimerism in a girl with Down syndrome and possible freemartin effect leading to aplasia of the Müllerian derivatives. Hum Reprod 25:1339–1343PubMedCrossRefGoogle Scholar
  16. Cavagna M, Contart P, Petersen CG, Mauri AL, Martins AM, Baruffi RL, Oliveira JB, Franco JG Jr (2006) Implantation sites after embryo transfer into the central area of the uterine cavity. Reprod Biomed Online 13:541–546PubMedCrossRefGoogle Scholar
  17. Cha KY, Han SY, Chung HM, Choi DH, Lim WS, Lo JJ, Yoon TK (2000) Pregnancies and deliveries after in vitro maturation culture followed by in vitro fertilization and embryo transfer without stimulation in women with polycystic ovary syndrome. Fertil Steril 73:978–983PubMedCrossRefGoogle Scholar
  18. Chan OTM, Mannino FL, Benirschke K (2007) A retrospective analysis of placentas from twin pregnancies derived from assisted reproductive technology. Twin Res Hum Genet 10:385–393PubMedCrossRefGoogle Scholar
  19. Chasen T, Luo G, Perni SC, Kalish RB (2006) Are in vitro fertilization pregnancies with early spontaneous reduction high risk? Am J Obstet Gynecol 195:814–817PubMedCrossRefGoogle Scholar
  20. Chung HM, Hong SW, Lim JM, Lee SH, Cha WT, Ko JJ, Han SY, Choi DH, Cha KY (2000) In vitro blastocyst formation of human oocytes obtained from unstimulated and stimulated cycles after vitrification at various maturational stages. Fertil Steril 73:545–551PubMedCrossRefGoogle Scholar
  21. Daniel Y, Schreiber L, Geva E, Amit A, Puasner D, Kupferminc MJ, Lessing JB (1999) Do placentae of term singleton pregnancies obtained by assisted reproductive technologies differ from those of spontaneously conceived pregnancies? Hum Reprod 14:1107–1110PubMedCrossRefGoogle Scholar
  22. Daniel Y, Schreiber L, Geva E, Lessing JB, Bar-Am A, Amit A (2001) Morphologic and histopathologic characteristics of placentas from twin pregnancies spontaneously conceived and from reduced and nonreduced assisted reproductive technologies. J Reprod Med 46:735–742PubMedGoogle Scholar
  23. Delbaere I, Goetgeluk S, Derom C, De Bacquer D, De Sutter P, Temmerman M (2007) Umbilical cord anomalies are more frequent in twins after assisted reproduction. Hum Reprod 22:2763–2767PubMedCrossRefGoogle Scholar
  24. Derom C, Vlietinck R, Derom R, van den Berghe H, Thiery M (1987) Increased monozygotic twinning rate after ovulation induction. Lancet i:1236–1238, and ii:170, 1987CrossRefGoogle Scholar
  25. Derom C, Leroy F, Vlietinck R, Fryns J-P, Derom R (2006) High frequency of iatrogenic monozygotic twins with administration of clomiphene citrate and a change in chorionicity. Fertil Steril 85:755–757PubMedCrossRefGoogle Scholar
  26. Dimitriou G, Pharoah PO, Nicolaides KH, Greenough A (2004) Cerebral palsy in triplet pregnancies with and without iatrogenic reduction. Eur J Pediatr 163:449–451PubMedCrossRefGoogle Scholar
  27. Dodson WC, Hughes CL Jr, Haney AF (1988) Multiple pregnancies conceived with intrauterine insemination during superovulation: an evaluation of clinical characteristics and monitored parameters of conception cycles. Am J Obstet Gynecol 159:382–385PubMedGoogle Scholar
  28. Ecker DJ, Stein P, Xu Z, Williams CJ, Kopf GS, Bilker WB, Abel T, Schultz RM (2004) Long-term effects of culture of preimplantation mouse embryos on behavior. Proc Natl Acad Sci USA 101:1595–1600PubMedCrossRefGoogle Scholar
  29. Edwards R, Mettler L, Walters D (1986) Identical twins and in vitro fertilization. J In Vitro Fert Embryo Transf 3:114–117PubMedCrossRefGoogle Scholar
  30. Ekelund CK, Skibsted L, Søgaard K, Main KM, Dziegiel MH, Schwartz M, Moeller N, Roos L, Tabor A (2008) Dizygotic monochorionic twin pregnancy conceived following intracytoplasmic sperm injection treatment and complicated by twin-twin transfusion syndrome and blood chimerism. Ultrasound Obstet Gynecol 32:832–834PubMedCrossRefGoogle Scholar
  31. El-Toukhy T, Khalaf Y, Braude P (2006) IVF results: optimize not maximize. Am J Obstet Gynecol 194:322–331PubMedCrossRefGoogle Scholar
  32. Englert Y, Imbert MC, van Rosendael E, Belaisch J, Segal L, Feichtinger W, Wilkin P, Frydman R, Leroy F (1987) Morphological anomalies in the placentae of IVF pregnancies: preliminary report of a multicentric study. Hum Reprod 2:155–157PubMedGoogle Scholar
  33. Fauser BCJM, Devroey P, Macklon NS (2005) Multiple birth resulting from ovarian stimulation for subfertility treatment. Lancet 365:1807–1816PubMedCrossRefGoogle Scholar
  34. Gavriil P, Jauniaux E, Leroy F (1993) Pathologic examination of placentas from singleton and twin pregnancies obtained after in vitro fertilization and embryo transfer. Pediatr Pathol 13:453–462PubMedCrossRefGoogle Scholar
  35. Gelbaya TA, Tsoumpou I, Nardo LG (2010) The likelihood of live birth and multiple birth after single versus double embryo transfer at the cleavage stage: a systematic review and meta-analysis. Fertil Steril 94:936–945PubMedCrossRefGoogle Scholar
  36. Gicquel C, Gaston V, Mandelbaum J, Siffroi J-P, Flahault A, Le Bouc Y (2003) In vitro fertilization may increase the risk of Beckwith-Wiedemann syndrome related to the abnormal imprinting of the KCNQ1OT gene. Am J Hum Genet 72:1338–1341PubMedCrossRefGoogle Scholar
  37. Ginsberg NA, Ginsberg S, Rechitsky S, Verlinsky Y (2005) Fusion as the etiology of chimerism in monochorionic dizygotic twins. Fetal Diagn Ther 20:20–22PubMedCrossRefGoogle Scholar
  38. Hack M, Brish M, Serr DM, Insler V, Lunenfeld B (1970) Outcome of pregnancy after induced ovulation. Follow-up of pregnancies and children born after gonadotropin therapy. JAMA 211:791–797PubMedCrossRefGoogle Scholar
  39. Hall JG (2005) Pediatricians beware: the age of ARTS is upon us. J Pediatr 146:450–452PubMedCrossRefGoogle Scholar
  40. 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 346:725–730PubMedCrossRefGoogle Scholar
  41. Heijnen EMEW, Eijkemans MJC, De Clerk C, Polinder S, Beckers NGM, Klinkert ER, Broekmans FJ, Passchier J, Te Velde ER, Macklon NS, Fauser BCJM (2007) A mild treatment strategy for in-vitro fertilization: a randomized non- inferiority trial. Lancet 369:743–749PubMedCrossRefGoogle Scholar
  42. Hvidtjørn D, Grove J, Schendel DE, Vaeth M, Ernst E, Nielsen LF, Thorsen P (2006) Cerebral palsy among children born after in vitro fertilization: the role of preterm delivery – a population-based, cohort study. Pediatrics 118:475–482PubMedCrossRefGoogle Scholar
  43. Jackson RA, Gibson KA, Wu YW, Croughan MS (2004) Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstet Gynecol 103:551–563PubMedCrossRefGoogle Scholar
  44. Jacod BC, Lichtenbelt KD, Schuring-Blom GH, Laven JS, van Opstal D, Eijkemans MJ, Macklon NS (2008) IVF-CPM study group: does confined placental mosaicism account for adverse perinatal outcomes of IVF pregnancies? Hum Reprod 23:1107–1112PubMedCrossRefGoogle Scholar
  45. Jain JK, Boostaufar R, Slater CC, Francis MM, Paulson RJ (2004) Monozygotic twins and triplets in association with blastocyst transfer. J Assist Reprod Genet 21:103–107PubMedCrossRefGoogle Scholar
  46. Jauniaux E, Englert Y, Vanesse M, Hiden M, Wilkin P (1990) Pathologic features of placentas from singleton pregnancies obtained by in vitro fertilization and embryo transfer. Obstet Gynecol 76:61–64PubMedGoogle Scholar
  47. Jones HW, Cohen J, Cooke I, Kempers R (2007) IFFS surveillance 07. Fertil Steril 87(suppl 1):S1–S67PubMedGoogle Scholar
  48. Kansal KS, Ratcliffe SJ, Milman L, Gracia CR, Coutifaris C, Barnhart KT (2011) Perinatal morbidity after in vitro fertilization is lower with frozen embryo transfer. Fertil Steril 95:548–553CrossRefGoogle Scholar
  49. Katari S, Turan N, Bibikova M, Erinle O, Chalian R, Foster M, Gaughan JP, Coutifaris C, Sapienza C (2009) DNA methylation and gene expression differences in children conceived in vitro or in vivo. Hum Mol Genet 18:3769–3778PubMedCrossRefGoogle Scholar
  50. Klonoff-Conen HS, Natarajan L (2004) The effect of advancing paternal age on pregnancy and live birth rates in couples undergoing in vitro fertilization or gamete intrafallopian transfer. Am J Obstet Gynecol 191:507–514CrossRefGoogle Scholar
  51. Kohl B (2007) Embryo culture. Making babies in the twenty-first century, Sarah Crichton books. Farrar, Straus and Giroux, New YorkGoogle Scholar
  52. Kraay GJ, Menard DP, Bedoya M (1983) Monozygous cattle twins as a result of transfer of a single embryo. Can Vet J 24:281–283PubMedGoogle Scholar
  53. Lancaster PAL (2004) Monozygotic twins and triplets after assisted conception. Twin Res 7:361 (abstract)Google Scholar
  54. Lasloševic D, Tabš D, Krnojelac D, Vejnovic T, Radunovic N (2003) Histological characteristics of placentas from assisted reproduction programs. Med Pregl 56:521–527CrossRefGoogle Scholar
  55. Lee KA, Oh KJ, Lee SM, Kim A, Jun JK (2010) The frequency and clinical significance of twin gestations according to\zygosity and chorionicity. Twin Res Hum Genet 13:609–619PubMedCrossRefGoogle Scholar
  56. Loos R, Derom C, Vlietinck R, Derom R (1998) The east Flanders prospective twin survey (Belgium): a population-based register. Twin Res 1:167–175PubMedGoogle Scholar
  57. Ma S, Tang SS, Yen BH, Bruyere H, Peñaherrera M, Robinson WP (2003) Cytogenetic and molecular study of a premature male infant with 46. XX derived from ICSI: a case report. Hum Reprod 18:2298–2301PubMedCrossRefGoogle Scholar
  58. Machin GA, Bamforth F (1996) Zygosity and placental anatomy in 15 consecutive sets of spontaneously conceived triplets. Am J Med Genet 61:247–252PubMedCrossRefGoogle Scholar
  59. Maher ER, Brueton LA, Bowdin SC, Luharia A, Cooper W, Cole TR, Macdonald F, Sampson JR, Barratt CL, Reik W, Hawkins MM (2003) J Med Genet 40:62–64PubMedCrossRefGoogle Scholar
  60. Malizia BA, Hacker MR, Penzias AS (2009) Cumulative live-birth rates after in vitro fertilization. N Engl J Med 360:236–243PubMedCrossRefGoogle Scholar
  61. Markens S (2008) Surrogate motherhood and the politics of reproduction. University of California Press, BerkeleyGoogle Scholar
  62. Mastenbroek S, Twisk M, van Echten-Arends J, Sikkema-Raddatz B, Korevaar JC, Verhoeve HR, Vogel NEA, Arts EGJM, de Vries JWA, Bossuyt PM, Buys CHCM, Heineman MJ, Repping S, van der Veen F (2007) In vitro fertilization with preimplantation genetic diagnosis. N Engl J Med 357:9–17 (see also the editorial of Collins that follows: pp 61–63, and those by Munné and others pp. 1769–1771)PubMedCrossRefGoogle Scholar
  63. McLernon DJ, Harrild K, Bergh C, Davies MJ, DeNeuberg D, Dumoulin CM, Gerris J, Kremer JAM, Martikainen H, Mol BW, Norman RJ, Thurin-Kjellberg A, Tiltinen A, VanMontfoort APA, Van Perpstraten AM, Van Royen E, Bhattacharya S (2010) Clinical effectiveness of elective single versus double embryo transfer: meta-analysis of individual patient data from randomized trials. BMJ 341:1–13 (c6945doi:10.1136/bmj.c6945)CrossRefGoogle Scholar
  64. Milki AA, Jun SH, Hinckley MD, Behr B, Giudice LC, Westphal LM (2003) Incidence of monozygotic twinning with blastocyst transfer compared to cleavage-stage transfer. Fertil Steril 79:503–506PubMedCrossRefGoogle Scholar
  65. Minor A, Harmer K, Peters N, Yuen BH, Ma S (2006) Investigation of confined placental mosaicism (CPM) at multiple sites in post-delivery placentas derived through intracytoplasmic sperm injection (ICSI). Am J Med Genet A 140:24–30PubMedGoogle Scholar
  66. Mio Y, Maeda K (2008) Time-lapse cinematography of dynamic changes occurring during in vitro development of human embryos. Am J Obstet Gynecol 199:660.e1–660.e5CrossRefGoogle Scholar
  67. Miura K, Niikawa N (2005) Do monochorionic dizygotic twins increase after pregnancy by assisted reproductive technology? J Hum Genet 50:1–6PubMedCrossRefGoogle Scholar
  68. Mottla GL, Adelman MR, Hall JL, Gindoff PR, Stillman RJ, Johnson KE (1995) Lineage tracing demonstrates that blastomeres of early cleavage-stage human pre-embryos contribute to both trophectoderm and inner cell mass. Hum Reprod 10:384–391PubMedGoogle Scholar
  69. Moyaert I, Bouters R, Bouquet Y (1982) Birth of a monozygotic cattle twin following non surgical transfer of a single 7 day old embryo. Theriogenology 18:127–132PubMedCrossRefGoogle Scholar
  70. Narine LH, Vezmar M, Sutija VG, Shah B, Sidhu S, Schwarz RH, Gudavalli M (2003) Mode of conception, placental morphology and perinatal outcome of twin gestations. J Perinat Med 31:99–104PubMedCrossRefGoogle Scholar
  71. Navarro J, Risco R, Toschi M, Schattman G (2008) Gene therapy and intracytoplasmic sperm injection (ICSI) – a review. Placenta 29(Supplement B):S193–S199CrossRefGoogle Scholar
  72. Nunley WC Jr (2004) The slippery slopes of advanced reproductive technologies. Presidential address. Am J Obstet Gynecol 191:588–592PubMedCrossRefGoogle Scholar
  73. Paffoni A, Brevini TAL, Gandolfi F, Ragni G (2008) Parthenogenetic activation: biology and applications in the ART University of Cambridge Centre for Trophoblast Research. Placenta 29(Supplement B):S121–S125Google Scholar
  74. Papanikolaou EG, Camus M, Kolibianakis EM, van Landuyt E, van Steirteghem A, Devroey P (2006) In vitro fertilization with single blastocysts-stage versus single cleavage-stage embryos. N Engl J Med 354:1139–1146PubMedCrossRefGoogle Scholar
  75. Patrizio P, Sakkas D (2009) From oocytes to baby: a clinical evaluation of the biological efficiency of in vitro fertilization. Fertil Steril 91(4):1061–1066PubMedCrossRefGoogle Scholar
  76. Patrizio P, Fragouli E, Bianchi V, Borini A, Wells D (2007) Molecular methods for selection of the ideal oocytes. Reprod Biomed Online 15:346–353PubMedCrossRefGoogle Scholar
  77. Paulson RJ, Lobo RA, Stein A, Toker R, Moegle A, Macaso T (1988) Gestational triplets after intrauterine implantation of two embryos. N Engl J Med 318:1339–1340PubMedCrossRefGoogle Scholar
  78. Payne D, Fisherty SP, Barry MF, Matthews CD (1997) Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography. Hum Reprod 12:532–541PubMedCrossRefGoogle Scholar
  79. Peramo B, Ricciarelli E, Cuadros-Ferñandez JM, Huguet E, Hernández ER (1999) Blastocyst transfer and monozygotic twinning. Fertil Steril 72:1116–1117PubMedCrossRefGoogle Scholar
  80. Perni SC, Predanik M, Cho JE, Baergen RN (2005) Placental pathology and pregnancy outcomes in donor and non-donor oocytes in vitro fertilization pregnancies. J Perinat Med 33:27–32PubMedCrossRefGoogle Scholar
  81. Platt MJ, Marshall A, Pharoah OD (2001) The effects of assisted reproduction on the trends and zygosity of multiple births in England and Wales 1974–1999. Twin Res 4:417–421PubMedGoogle Scholar
  82. Quintero RA, Mueller OT, Martinez JM, Arroyo J, Gilbert-Barness E, Hilbelink D, Papenhausen P, Sutcliffe M (2003) Twin-twin transfusion syndrome in a dizygotic monochorionic-diamniotic twin pregnancy. J Matern Fetal Neonatal Med 14:279–281PubMedGoogle Scholar
  83. Reddy UM, Wapner RJ, Rebar RW, Tasca RJ (2007) Infertility, assisted reproductive technology, and adverse pregnancy outcomes. Executive summary of a National Institute of Child Health and Human Development Workshop. Obstet Gynecol 109:967–977PubMedCrossRefGoogle Scholar
  84. Rock J, Menkin MF (1944) In vitro fertilization and cleavage of human ovarian eggs. Science 100:105–107PubMedCrossRefGoogle Scholar
  85. Romundstad LB, Romundstad PR, Sunde A, von Düring V, Skjaerven R, Vatten LJ (2006) Increased risk of placenta previa in pregnancies following IVF/ICSI; a comparison of ART and non-ART pregnancies in the same mother. Hum Reprod 21:2353–2358PubMedCrossRefGoogle Scholar
  86. Schachter M, Raziel A, Friedler S, Strassburger D, Bern O, Ron-El R (2001) Monozygotic twinning after assisted reproductive techniques: a phenomenon independent of micromanipulation. Hum Reprod 16:1264–1269PubMedCrossRefGoogle Scholar
  87. Schachter M, Tovbin Y, Arieli S, Friedler S, Ron-El R, Sherman ZD (2002) In vitro fertilization is a risk factor for vasa previa. Fertil Steril 78:642–643PubMedCrossRefGoogle Scholar
  88. Schieve LA (2006) The promise of single-embryo transfer. N Engl J Med 354:1190–1193PubMedCrossRefGoogle Scholar
  89. Schieve LA, Meikle SF, Ferre C, Peterson HB, Jeng G, Wilcox LS (2002) Low and very low birth weights in infants conceived with use of assisted reproductive technology. N Engl J Med 346:731–737PubMedCrossRefGoogle Scholar
  90. Schinzel A, Baumer A (2003) Imprinting defects following artificial insemination and ICSI. Eur Cytogeneticists Assoc News 12:5–6Google Scholar
  91. Segal NL (2009) The birth of octuplets: a research puzzle. Twin Res Hum Genet 12:328–329PubMedCrossRefGoogle Scholar
  92. Shalev SA, Shalev E, Pras E, Shneor Y, Gazir E, Yaron Y, Lowenthal R (2006) Evidence for blood chimerism in dizygotic spontaneous twin pregnancy discordant for Down syndrome. Prenat Diagn 26:782–784PubMedCrossRefGoogle Scholar
  93. Shevell T, Malone FD, Vidaver J, Porter TF, Luthy DA, Comstock CH, Hankins GD, Eddleman K, Dolan S, Dugoff L, Craigo S, Timor IE, Carr SR, Wolfe HM, Bianchi DW, D’Alton ME, for the FASTER Research Consortium (2005) Assisted reproductive technology and pregnancy outcome. Obstet Gynecol 106:1039–1045PubMedCrossRefGoogle Scholar
  94. Sills ES, Tucker MJ, Palermo GD (2000a) Assisted reproductive technologies and monozygous twins: implications for future study and clinical practice. Twin Res 3:217–223PubMedCrossRefGoogle Scholar
  95. Sills ES, Moomjy M, Zaninovic N, Veeck LL, McGee M, Palermo GD, Rosenvaks Z (2000b) Human zona pellucida micromanipulation and monozygotic twinning frequency after IVF. Hum Reprod 15:890–895PubMedCrossRefGoogle Scholar
  96. Souter VL, Kapur RP, Nyholt DR, Skogerboe K, Myerson D, Ton CC, Opheim KE, Easterling TR, Shields LE, Montgomery GW, Glass IA (2003) A report of dizygous monochorionic twins. N Engl J Med 349:154–158PubMedCrossRefGoogle Scholar
  97. Spar D (2005) Reproductive tourism and the regulatory map. N Engl J Med 352:531–533PubMedCrossRefGoogle Scholar
  98. Spar D (2007) The egg trade – making sense of the market for human oocytes. N Engl J Med 356:1289–1291PubMedCrossRefGoogle Scholar
  99. Steinman G (2003) Mechanism of twinning. VI. Genetics and the etiology of monozygotic twinning in in vitro fertilization. J Reprod Med 48:583–590PubMedGoogle Scholar
  100. Steinman G, Valderrama E (2001) Mechanism of twinning: III. Placentation, calcium reduction, and modified compaction. J Reprod Med 46:995–1002PubMedGoogle Scholar
  101. Steptoe PC, Edwards RG (1978) Birth after the reimplantation of a human embryo. Lancet 2:366PubMedCrossRefGoogle Scholar
  102. Styer AK, Parker HJ, Roberts DJ, Palmer-Toy D, Toth TL, Ecker JL (2003) Placental villitis of unclear etiology during ovum donor in vitro fertilization pregnancy. Am J Obstet Gynecol 189:1184–1186PubMedCrossRefGoogle Scholar
  103. Styer AK, Wright DL, Wolkovich AM, Veiga C, Toth TL (2008) Single-blastocyst transfer decreases twin gestation without affecting pregnancy outcome. Fertil Steril 89:1702–1708PubMedCrossRefGoogle Scholar
  104. Tagawa M, Matoba S, Narita M, Saito N, Nagai T, Imai K (2008) Production of monozygotic twin calves using the blastomere separation technique and Well of the Well culture system. Theriogenology 69:574–582PubMedCrossRefGoogle Scholar
  105. Templeton A (2004) The multiple gestation epidemic: the role of the assisted reproductive technologies. Am J Obstet Gynecol 190:894–898PubMedCrossRefGoogle Scholar
  106. Thurin A, Hausken J, Hillensjö T, Jablonska B, Pinborg A, Strandell A, Bergh C (2004) Elective single-embryo transfer versus double-embryo transfer in in vitro fertilization. N Engl J Med 351:2392–2402PubMedCrossRefGoogle Scholar
  107. Tsunoda Y, Tokunaga T, Sugie T, Katsumata M (1985) Production of monozygotic twins following the transfer of bisected embryos in the goat. Theriogenology 24:337–342PubMedCrossRefGoogle Scholar
  108. Turan N, Katari S, Gerson LF, Chalian R, Foster MW, Gaughan JP, Coutifaris C, Sapienza C (2010) Inter- and intra-individual variation in allele-specific DNA methylation and gene expression in children conceived using assisted reproductive technology. PLoS Genet 6:e1001033, PMID 20661447PubMedCrossRefGoogle Scholar
  109. Ubaldi F, Rienzi L (2008) Morphological selection of gametes. Placenta 29(Supplement B):S115–S120CrossRefGoogle Scholar
  110. Unger S, Hoopmann M, Bald R, Foth D, Nawroth F (2004) Monozygotic triplets and monozygotic twins after ICSI and transfer of two blastocysts: case report. Hum Reprod 19:110–113PubMedCrossRefGoogle Scholar
  111. van Voorhis BJ (2007) In vitro fertilization. N Engl J Med 356:379–385PubMedCrossRefGoogle Scholar
  112. Vitthala S, Gelbaya TA, Brison DR, Fitzgerald CT, Nardo LG (2009) The risk of monozygotic twins after assisted reproductive technology: a systematic review and meta-analysis. Hum Reprod Update 15:45–55PubMedCrossRefGoogle Scholar
  113. von Rango U (2008) Fetal tolerance in human pregnancy – a crucial balance between acceptance and limitation of trophoblast invasion. Immunol Lett 115:21–32CrossRefGoogle Scholar
  114. Wells D, Patrizio P (2008) Gene expression profiling of human oocytes at different maturational stages and after in vitro maturation. Am J Obstet Gynecol 198:455.e1–455.e9, and e9–e11CrossRefGoogle Scholar
  115. Wenstrom KD, Syrop C, Hammitt DG, van Voorhis BJ (1993) Increased risk of monochorionic twinning associated with assisted reproduction. Fertil Steril 60:510–514PubMedGoogle Scholar
  116. Williams CA, Wallace MR, Drury KC, Kipersztok S, Edwards RK, Williams RS, Haller MJ, Schatz DA, Silverstein JH, Gray BA, Zori RT (2004) Blood lymphocyte chimerism associated with IVF and monochorionic dizygous twinning: a case report. Hum Reprod 19:2816–2821PubMedCrossRefGoogle Scholar
  117. Wilson EE (2005) Assisted reproductive technologies and multiple gestations. Clin Perinatol 32:315–328PubMedCrossRefGoogle Scholar
  118. Wright VC, Chang J, Jeng G, Chen M, Macaluso M (2007) Assisted reproductive technology surveillance – United States, 2004. MMWR Surveill Summ 56:1–22PubMedGoogle Scholar
  119. Yoon G, Beischel LS, Johnson JP, Jones MC (2005) Dizygotic twin pregnancy conceived with assisted reproductive technology associated with chromosomal anomaly, imprinting disorder, and monochorionic placentation. J Pediatr 146:565–567PubMedCrossRefGoogle Scholar
  120. Zegers-Hochschild F, Nygren KG, Adamson GD, de Mouzon J, Lancaster P, Mansour R, Sullivan E (2006) International committee monitoring assisted reproductive technologies (ICMART) glossary on ART terminology. Fertil Steril 86:16–19PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Kurt Benirschke
    • 1
  • Graham J. Burton
    • 2
  • Rebecca N. Baergen
    • 3
  1. 1.La JollaUSA
  2. 2.Physiological LaboratoryUniversity of Cambridge Centre for Trophoblast ResearchCambridgeUK
  3. 3.Department of Pathology and Laboratory Medicine New York-Presbyterian HospitalWeill Medical College of Cornell UniversityNew YorkUSA

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