Why and how should multiple pregnancies be prevented in assisted reproduction treatment programmes?

Although most professional societies have issued guidelines to diminish the number of embryos to be transferred during assisted reproductive techniques, the incidence of multiple pregnancies remains unacceptably high. The burden of morbidity and mortality seems to increase substantially with each fetus in a multiple gestation. As a result, there has been growing debate on the need to prevent multiple pregnancies. The infertility specialists who can solve the infertility problem are usually shielded from the complications of multiple pregnancies. If they were involved in the delivery and, more particularly in the care of multiple pregnancies (both financially and socially), their attitude would probably change. IVF centres should gradually reduce the mean number of embryos per transfer in terms of the cost:benefit ratio. A further reduction to one single embryo per transfer in good cases would be similarly acceptable. Laboratory expertise is of vital importance, especially in terms of embryo culture, embryo selection, and freezing and thawing techniques in embryo transfer programmes for reducing the number of transferred embryos.

[1]  A. Rosano,et al.  Congenital malformations in twins: an international study. , 1999, American journal of medical genetics.

[2]  J. Land,et al.  Risks and complications in assisted reproduction techniques: Report of an ESHRE consensus meeting. , 2003, Human reproduction.

[3]  P. Sutter,et al.  Embryos cultured in vitro with multinucleated blastomeres have poor implantation potential in human in-vitro fertilization and intracytoplasmic sperm injection. , 1998, Human reproduction.

[4]  O. Ozturk,et al.  Avoiding multiple pregnancies in ART: evaluation and implementation of new strategies. , 2001, Human reproduction.

[5]  R. Berkowitz,et al.  A single center experience with 1000 consecutive cases of multifetal pregnancy reduction. , 2001, American journal of obstetrics and gynecology.

[6]  P. Härkki,et al.  Elective single embryo transfer: the value of cryopreservation. , 2001, Human reproduction.

[7]  A. Templeton,et al.  Reducing the risk of multiple births by transfer of two embryos after in vitro fertilization. , 1998, The New England journal of medicine.

[8]  I. Gur,et al.  The outcome of twin pregnancies after IVF. , 1998, Human reproduction.

[9]  M Williams,et al.  Speech and language development in preschool twins. , 1987, Acta geneticae medicae et gemellologiae.

[10]  C. Christiansen,et al.  The economic impact of multiple-gestation pregnancies and the contribution of assisted-reproduction techniques to their incidence. , 1994, The New England journal of medicine.

[11]  D. De Neubourg,et al.  Prevention of twin pregnancy after in-vitro fertilization or intracytoplasmic sperm injection based on strict embryo criteria: a prospective randomized clinical trial. , 1999, Human Reproduction.

[12]  R. Goldenberg,et al.  The Origin and Outcome of Preterm Twin Pregnancies , 1995, Obstetrics and gynecology.

[13]  J. Stone,et al.  Invasive procedures in multiple gestations , 2003, Current opinion in obstetrics & gynecology.

[14]  R. Dickey,et al.  Spontaneous reduction of multiple pregnancy: incidence and effect on outcome. , 2002, American journal of obstetrics and gynecology.

[15]  M. Gissler,et al.  Neonatal outcome and congenital malformations in children born after in-vitro fertilization. , 2002, Human reproduction.

[16]  M Afnan,et al.  Assessment of early cleaving in vitro fertilized human embryos at the 2-cell stage before transfer improves embryo selection. , 2001, Fertility and sterility.

[17]  R. Dickey,et al.  What is the most relevant standard of success in assisted reproduction?: no single outcome measure is satisfactory when evaluating success in assisted reproduction; both twin births and singleton births should be counted as successes. , 2004, Human reproduction.

[18]  C. Matthews,et al.  The obstetric outcome of singleton pregnancies following in-vitro fertilization/gamete intra-fallopian transfer. , 1994, Human reproduction.

[19]  R. Edwards,et al.  Perinatal outcome and congenital malformations in in-vitro fertilization babies from the Bourn-Hallam group. , 1991, Human reproduction.

[20]  N. Gleicher,et al.  The desire for multiple births in couples with infertility problems contradicts present practice patterns. , 1995, Human reproduction.

[21]  D. Sherer,et al.  Adverse Perinatal Outcome of Twin Pregnancies According to Chorionicity: Review of the Literature , 2001, American journal of perinatology.

[22]  L. Veeck,et al.  Embryo quality and pregnancy rates in patients attempting pregnancy through in vitro fertilization. , 1991, Fertility and sterility.

[23]  O. Hovatta,et al.  Elective transfer of one embryo results in an acceptable pregnancy rate and eliminates the risk of multiple birth , 1999 .

[24]  H. Leese,et al.  Non-invasive amino acid turnover predicts human embryo developmental capacity. , 2002, Human reproduction.

[25]  P. C. Steptoe,et al.  Factors influencing the success of in vitro fertilization for alleviating human infertility , 1984, Journal of in Vitro Fertilization and Embryo Transfer.

[26]  C. Bergh,et al.  Obstetric outcome and follow-up of children born after in vitro fertilization (IVF) , 2000, Human fertility.

[27]  H. Hepp,et al.  Multifetal Gestation – Maternal and Perinatal Outcome of 112 Pregnancies , 2002, Fetal Diagnosis and Therapy.

[28]  K Petersen,et al.  Embryo morphology or cleavage stage: how to select the best embryos for transfer after in-vitro fertilization. , 1997, Human reproduction.

[29]  D. Trichopoulos,et al.  Risk Factors for Cerebral Palsy , 1996, Scandinavian journal of social medicine.

[30]  V. Beral,et al.  Obstetric outcome of in vitro fertilization pregnancies compared with normally conceived pregnancies. , 1992, American journal of obstetrics and gynecology.

[31]  R. Mcduffie,et al.  Assisted Reproductive Interventions and Multiple Birth , 2001, Obstetrics and gynecology.

[32]  P. Devroey,et al.  The relationship between embryo quality and the occurrence of multiple pregnancies , 1992, Fertility and sterility.

[33]  D. De Neubourg,et al.  Calculating the implantation potential of day 3 embryos in women younger than 38 years of age: a new model. , 2001, Human reproduction.

[34]  M Orava,et al.  One versus two embryo transfer after IVF and ICSI: a randomized study. , 2001, Human reproduction.

[35]  P. Devroey,et al.  Avoidance of triplet pregnancies by elective transfer of two good quality embryos. , 1993, Human reproduction.

[36]  B. Vohr,et al.  Maternal and neonatal morbidity associated with in vitro fertilization. , 1995, The Journal of pediatrics.

[37]  R. Mueller Twinning and Twins , 1989 .

[38]  C. Giorgetti,et al.  Embryo score is a better predictor of pregnancy than the number of transferred embryos or female age. , 2001, Fertility and sterility.

[39]  P. Doyle,et al.  The outcome of multiple pregnancy. , 1996, Human reproduction.

[40]  L. Engmann,et al.  Trends in the incidence of births and multiple births and the factors that determine the probability of multiple birth after IVF treatment. , 2001, Human reproduction.

[41]  J. Lessing,et al.  Analysis of 104 twin pregnancies conceived with assisted reproductive technologies and 193 spontaneously conceived twin pregnancies. , 2000, Fertility and sterility.

[42]  K. Nygren,et al.  Assisted reproductive technology in Europe, 1999. Results generated from European registers by ESHRE. , 2002, Human reproduction.

[43]  J. Tesarik,et al.  The probability of abnormal preimplantation development can be predicted by a single static observation on pronuclear stage morphology. , 1999, Human reproduction.

[44]  D. Mattison,et al.  The Changing Epidemiology of Multiple Births in the United States , 2003, Obstetrics and gynecology.

[45]  R. Frydman,et al.  Infertility therapy-associated multiple pregnancies (births): an ongoing epidemic. , 2003, Reproductive biomedicine online.

[46]  R. Fanchin,et al.  Perinatal outcome of twin pregnancies obtained after in vitro fertilization: comparison with twin pregnancies obtained spontaneously or after ovarian stimulation. , 1996, Fertility and sterility.

[47]  A. Campana,et al.  Early cleavage of human embryos to the two-cell stage after intracytoplasmic sperm injection as an indicator of embryo viability. , 1998, Human reproduction.

[48]  J Cohen,et al.  Human embryo fragmentation in vitro and its implications for pregnancy and implantation. , 1999, Fertility and sterility.

[49]  M. Duyme,et al.  Perinatal mortality in twin pregnancies: a 3-year analysis in Seine Saint-Denis (France). , 1999, European journal of obstetrics, gynecology, and reproductive biology.

[50]  V. Beral,et al.  Congenital malformations in twins in England and Wales. , 1991, Journal of epidemiology and community health.

[51]  L A Scott,et al.  The successful use of pronuclear embryo transfers the day following oocyte retrieval. , 1998, Human reproduction.

[52]  T. Möls,et al.  Influence of oocytes and spermatozoa on early embryonic development. , 2002, Fertility and sterility.

[53]  M. Senat,et al.  How does multiple pregnancy affect maternal mortality and morbidity? , 1998, Clinical obstetrics and gynecology.

[54]  F. Olivennes Avoiding multiple pregnancies in ART. Double trouble: yes a twin pregnancy is an adverse outcome. , 2000, Human reproduction.

[55]  F. Shenfield Ethical Dilemmas in Assisted Reproduction , 1999 .

[56]  J. Martin,et al.  Births : final data for 2006 , 2009 .

[57]  J. Van der Elst,et al.  Perinatal outcome of pregnancies after assisted reproduction: a case-control study. , 1999, Journal of assisted reproduction and genetics.

[58]  Istituto Gregorio Mendel,et al.  Acta geneticae medicae et gemellologiae , 1952 .

[59]  E. Vayena,et al.  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 2001 , 2002 .

[60]  M. Levene,et al.  Higher multiple births and the modern management of infertility in Britain , 1992 .

[61]  J. Balasch,et al.  Risk factors for high-order multiple implantation after ovarian stimulation with gonadotrophins: evidence from a large series of 1878 consecutive pregnancies in a single centre. , 2001, Human reproduction.

[62]  W. Grobman,et al.  Patient perceptions of multiple gestations: an assessment of knowledge and risk aversion. , 2001, American journal of obstetrics and gynecology.

[63]  B. Källén,et al.  Congenital malformations in twins: a population study. , 1986, Acta geneticae medicae et gemellologiae.

[64]  E. Alberman,et al.  Cerebral palsy: effects of twinning, birthweight, and gestational age. , 1996, Archives of disease in childhood. Fetal and neonatal edition.

[65]  Andres Salumets,et al.  Early cleavage predicts the viability of human embryos in elective single embryo transfer procedures. , 2003, Human reproduction.

[66]  J. Ellenberg,et al.  The Risk of Mortality or Cerebral Palsy in Twins: A Collaborative Population-Based Study , 2002, Pediatric Research.

[67]  J. Gerris,et al.  Avoiding multiple pregnancies in ART: a plea for single embryo transfer. , 2000, Human reproduction.

[68]  M. D'Alton,et al.  Prospective risk of fetal death in singleton, twin, and triplet gestations: implications for practice. , 2003, Obstetrics and gynecology.

[69]  B. Luke,et al.  The contribution of singletons, twins and triplets to low birth weight, infant mortality and handicap in the United States. , 1992, The Journal of reproductive medicine.

[70]  J. Lessing,et al.  Transfer of six or more embryos improves success rates in patients with repeated in vitro fertilization failures. , 1995, Fertility and sterility.

[71]  P. Devroey,et al.  The role of the number of replaced embryos on intracytoplasmic sperm injection outcome in women over the age of 40. , 1997, Human reproduction.

[72]  A. Campana,et al.  Early cleavage of in-vitro fertilized human embryos to the 2-cell stage: a novel indicator of embryo quality and viability. , 1997, Human reproduction.

[73]  J. Edwards,et al.  The value of twin surveys in the study of malformations. , 1983, European journal of obstetrics, gynecology, and reproductive biology.

[74]  Eshre Campus Course Report Prevention of twin pregnancies after IVF/ICSI by single embryo transfer. ESHRE Campus Course Report. , 2001, Human reproduction.

[75]  C. Harro Practice Committee Report , 1998 .

[76]  M. Falagario,et al.  Incidence and outcome of multiple pregnancy after in vitro fertilization. , 1995, Acta Europaea fertilitatis.