Research

Anti-oestrogens (Clomid)


Benefits of single embryo transfer (SET)

  • One Child at a Time, Report of the Expert Group on Multiple Births after IVF, October 2006, p34, para 11.2.1. PDF. Download the report (PDF).
  • Thurin et al. Elective single-embryo-transfer versus double embryo transfer in IVF New England Journal of Medicine 2004; 351: 2392–2402. Download the abstract
  • Khalaf Y, El-Toukhy T, Coomarasamy A, Kamal A, Bolton V, Braude P (2008). Selective single blastocyst transfer reduces the multiple pregnancy rate and increases pregnancy rates: a pre- and postintervention study BJOG: An International Journal of Obstetrics and Gynaecology 115 (3), 385–390 doi:10.1111/j.1471–0528.2007.01584.x. Read the study

Bringing up twins

  • Bryan, E. The impact of multiple preterm births on the family BJOG 2003; 110: 24–28. Download the abstract.  
  • Colpin, H et al. Parenting stress and psychosocial well-being among parents with twins conceived naturally or by reproductive technology Human Reproduction 1999; 14: 3133–3137. Read the article.
  • Ellison, M and Hall J. Social stigma and compounded losses: quality of life issues for multiple birth families Fertility and Sterility 2003; 80: 405–414. Download the abstract
  • Ellison, M et al. Psychosocial risks associated with multiple births resulting from assisted reproduction Fertility and Sterility 2005; 83: 1422–1428. Download the abstract.  
  • ESHRE Task Force on Ethics and Law. Ethical issues related to multiple pregnancies in medically assisted procreation Human Reproduction 2003; 18: 1976–1979. Read the article
  • Glazebrook, C et al. Parenting stress in first-time mothers of twins and triplets conceived after in vitro fertilisation Fertility and Sterility 2004; 81: 505–511. Download the abstract
  • Groothuis, J et al. Increased Child Abuse in Families with Twins Pediatrics 1982; 70: 769–773. Download the abstract (PDF). 
  • Klock, SC. Psychosocial adjustment to twins after infertility Best Practice and Research Clinical Obstetrics and Gynaecology 2004; 18: 645–656. Download the abstract.
  • Nelson HB and Martin CA. Increased child abuse in twins Child Abuse and Neglect 1985; 9: 501–505. Download the abstract.
  • Olivienne F et al. Behavioural and cognitive development as well as family functioning of twins conceived by assisted reproduction: findings from a large population study. Fertility and Sterility 2005: 84: 725–33.
  • One Child at a Time, Report of the Expert Group on Multiple Births after IVF, October 2006, p27, para 7.1, 7.2, 7.3 and 7.4. Download the report (PDF).
  • Ostfeld, BM et al. Maternal behaviour toward premature twins: implications for development Twin Research 2000; 3: 234–241. Read the article.
  • Pinborg, A. IVF/ICSI twin pregnancies: risks and prevention Human Reproduction Update 2005; 11: 575–593. Read the article.
  • Tamba website. What help can I get?
  • The Best Possible Start to Life: a consultation document on multiple births after IVF; HFEA; April 2007, p09, para 6.3. Download the consultation document (PDF).
  • Yokoyama Y. Comparison of child-rearing problems between mothers with multiple children who conceived after infertility treatment and mothers with multiple children who conceived spontaneously. Twin Research 2003: 6: 89–96. Download the article.

 

Chances of success with single embryo transfer (SET)

  • Khalaf Y, El-Toukhy T, Coomarasamy A, Kamal A, Bolton V, Braude P (2008). Selective single blastocyst transfer reduces the multiple pregnancy rate and increases pregnancy rates: a pre- and postintervention study BJOG: An International Journal of Obstetrics and Gynaecology 115 (3), 385–390 doi:10.1111/j.1471–0528.2007.01584.x. Download the study.
  • Bergh C, Olivius C, Thurin-Kjellberg A. Cumulative Live-Birth Rates in a Trial of Single-Embryo or Double-Embryo Transfer The New England Journal of Medicine, volume 361:1812-1813 read the article.
  • Tarek A. Gelbaya M.D.a, Ioanna Tsoumpou M.D.b and Luciano G. Nardo M.D.a The likelihood of live birth and multiple birth after single versus double embryo transfer at the cleavage stage: a systematic review and meta-analysis, American Society for Reproductive Medicine (2009). Read the abstract
  • Kader A, Choi A, Orief Y, Agarwal A, Factors affecting the outcome of human blastocyst vitrification, Reproductive Biology and Endocrinology 2009, 7:99doi:10.1186/1477-7827-7-99. Read the abstract

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Embryo grading

  • Criteria from One Child at a Time, Report of the Expert Group on Multiple Births after IVF, October 2006, p 39, para 11.5.3. Download the report (PDF).
  • Jan Holte et al, Uppsala University. Papers have been presented at ESHRE 2003 and 04, a paper has also recently been accepted for publication in Human Reproduction.

Embryo transfer: 2–3 day (cleavage stage)

  • Chitayat D and Hall JG. Genetic aspects of twinning in: Multiple Pregnancy Kilby M et al (eds), RCOG 2006.
  • HFEA statistics for year 2005 collected from the HFEA Register 2005: Because definitive information on the developmental stage of transferred embryos has only recently started being collected, all relevant information has been inferred based on the number of days incubation.
  • Khalaf Y, El-Toukhy T, Coomarasamy A, Kamal A, Bolton V, Braude P (2008). Selective single blastocyst transfer reduces the multiple pregnancy rate and increases pregnancy rates: a pre- and postintervention study BJOG: An International Journal of Obstetrics and Gynaecology 115 (3), 385–390 doi:10.1111/j.1471–0528.2007.01584.x. Download the study.
  • Kurinczuk, J. Epidemiology of multiple pregnancy: changing effects of assisted conception in: Multiple Pregnancy Kilby M et al (eds) RCOG 2006.
  • HFEA register data (2005) based on 38,264 cycles given to 29,688 women between 1 April 2003 and 31 March 2004, leading to 8,251 births and 10,242 children born.

 

Embryo transfer: 5–6 day (blastocyst stage)

  • Blake DA et al. The merits of blastocyst versus cleavage stage embryo transfer: a Cochrane review Human Reproduction 2004; 19: 795–807. Download the abstract and errata.
  • Blake DA, Farquhar CM, Johnson N, Proctor M. Cleavage stage versus blastocyst stage embryo transfer in assisted conception. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD002118. DOI: 10.1002/14651858.CD002118.pub3. Read the review.
  • Criniti, A et al. Elective single blastocyst transfer reduces twin rates without compromising pregnancy rates Fertility and Sterility 2005; 84: 1613–1619. Download the abstract
  • Henman, M et al. Elective transfer of single fresh blastocysts and alter transfer of cryostored blastocysts reduces the twin pregnancy rate and can improve in vitro fertilisation live birth rate in younger women. Fertility and Sterility 2005; 84: 1620–1627. Download the abstract.  
  • Khalaf Y, El-Toukhy T, Coomarasamy A, Kamal A, Bolton V, Braude P (2008). Selective single blastocyst transfer reduces the multiple pregnancy rate and increases pregnancy rates: a pre- and postintervention study BJOG: An International Journal of Obstetrics and Gynaecology 115 (3), 385–390 doi:10.1111/j.1471–0528.2007.01584.x. Read the study

FAQs–patients

  • ESHRE Task Force on Ethics and Laws, Ethical Issues related to multiple pregnancies in medically assisted reproduction. 2003; 18(9): 1976–1979. Read the article.
  • Gardner D, Surrey E, Minjarez D, Leitz A, Stevens J, Schoolcraft W. Single blastocyst transfer: a prospective randomised trial. Fertil Steril 2004;81:551–5. Download the abstract
  • Khalaf Y, El-Toukhy T, Coomarasamy A, Kamal A, Bolton V, Braude P (2008). Selective single blastocyst transfer reduces the multiple pregnancy rate and increases pregnancy rates: a pre- and postintervention study BJOG: An International Journal of Obstetrics and Gynaecology 115 (3), 385–390 doi:10.1111/j.1471–0528.2007.01584.x. Read the study
  • Z, Bhattacharya S, Ozturk O, Serour GI, Templeton A. Number of embryos for transfer following in-vitro fertilisation or intra-cytoplasmic sperm injection. Cochrane Database Syst Rev 2004:CD003416. Read the article
  • Papanikolaou EG, Camus M, Kolibianakis EM, Van Landuyt L, Van Steirteghem A, Devroey P. In vitro fertilization with single blastocyst-stage versus single cleavage-stage embryos. N Engl J Med 2006;354:1139–46. Read the article
  • Topp et al. Acta Obstetrics and Gynecology Scandinavia 2004; 83: 548–553.

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FAQs–professionals

  • Jan Holte et al, Uppsala University. Papers have been presented at ESHRE 2003 and 04, a paper has also recently been accepted for publication in Human Reproduction.
  • One Child at a Time, Report of the Expert Group on Multiple Births after IVF, October 2006, para 11.5.2. Download the report (PDF).
  • Pandian, Z et al. Number of embryos for transfer after IVF and ICSI: A Cochrane review Human Reproduction 2005; 20: 2681–2687. Read the article
  • Tiitinen, A et al. Elective single embryo transfer: the value of cryopreservation Human Reproduction 2001; 16: 1140–1144. Read the article

 

Gamete intra-fallopian transfer (GIFT)

  • HFEA register for the years 1993–2006 gives a multiple birth rate of 26.2% for all GIFT births. Data from UK clinics, collected in 2007, gives multiple birth rates ranging from 8.7% to 45.5%. Figures from Australia showed a similar discrepancy, with the multiple birth rate ranging from 9.4% to 24.3%.
  • HFEA Code of Practice for clinics, guidance note 7: Limits on egg and embryo transfer. Read the Code.

 

Hormone treatment

  • Farquhar C, Brown J, Marjoribanks J. Laparoscopic drilling by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev. 2012 Jun 13;6. Read the review.
  • Fauser et al. A mild treatment strategy for in-vitro fertilisation: a randomised non-inferiority trial. The Lancet 2007; 369:743–749. Download the abstract.
  • Price, F. Too much of a good thing. New Scientist.  Issue: 1730, 18 August 1990. Read the article
  • Mono-ovulatory cycles: a key goal in profertility programmes, Human Reproduction Update, Volume 9, Number 3, June 2003 , pp. 263–274(12). Download the article (PDF). 

 

In vitro fertilisation (IVF)

  • Chitayat D and Hall JG. Genetic aspects of twinning in: Multiple Pregnancy Kilby M et al (eds), RCOG 2006. HFEA 2005 statistics.
  • HFEA Code of Practice for clinics, para 8.5.1, Risks: number of eggs or embryos to transfer. Read the Code.
  • Kurinczuk, J. Epidemiology of multiple pregnancy: changing effects of assisted conception in: Multiple Pregnancy Kilby M et al (eds) RCOG 2006.
  • HFEA register data (2005) based on 38,264 cycles given to 29,688 women between 1 April 2003 and 31 March 2004, leading to 8,251 births and 10,242 children born.
  • Office of National Statistics figures for total IVF births and multiple births following IVF (with added equivalent figures for Scotland and N Ireland), year 2005.
  • One Child at a Time, Report of the Expert Group on Multiple Births after IVF, October 2006, p8. Download the report (PDF).
  • The Best Possible Start to Life: a consultation document on multiple births after IVF; HFEA; April 2007, p10, para 7.4. See for example Neonatal Perinatal Epidemiology Unit (2005), p06. Download the consultation document (PDF).
  • Olga B. A. van den Akker: Reproductive Health Psychology, ISBN: 978-0-470-68337-8, March 2012, Wiley-Blackwell.

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Risks to the child

  • Blickstein I. Epidemiology of cerebral palsy in multiple pregnancies in: Multiple Pregnancy Kilby M et al (eds), RCOG 2006.
  • Bower C, Colvin L, Hansen M, de Klerk N, Kurinczuk J, Petterson B. Twins born following assisted reproductive technology: perinatal outcomes and admissions to hospital. Human Reproduction. Read the article
  • Bryan, E. The impact of multiple preterm births on the family BJOG 2003; 110: 24–28. Download the abstract
  • Colpin, H et al. Parenting stress and psychosocial well-being among parents with twins conceived naturally or by reproductive technology Human Reproduction 1999; 14: 3133–3137. Read the article.
  • Cook R et al. A preliminary study of parental stress and child behaviour in families with twins conceived by in-vitro fertilisation Human Reproduction 1998; 13: 3244–3246. Read the study (PDF). 
  • Costeloe, K et al. The EPICure study: outcomes to discharge from hospital for infants born at the threshold of viability. Pediatrics 2000; 106: 659–671. Read the study
  • D’Alton, M. Infertility and the desire for multiple births, Fertility and Sterility 2004 81(3) 523–525.
  • Ellison, M et al. Psychosocial risks associated with multiple births resulting from assisted reproduction Fertility and Sterility 2005; 83: 1422–1428. Download the abstract.
  • ESHRE Task Force on Ethics and Laws, Ethical Issues related to multiple pregnancies in medically assisted reproduction. 2003; 18(9): 1976–1979. Read the article.
  • Glazebrook, C et al. Parenting stress in first-time mothers of twins and triplets conceived after in vitro fertilization Fertility and Sterility 2004; 81: 505–511. Download the abstract.
  • Klock, SC. Psychosocial adjustment to twins after infertility Best Practice and Research Clinical Obstetrics and Gynaecology 2004; 18: 645–656. Download the abstract
  • Kurinczuk, JJ. Epidemiology of multiple pregnancy: changing effects of assisted conception in: Multiple pregnancy Kilby, M et al. (eds) RCOG 2006-07-07 and Sebire, NJ Anomalous development in twins (including monozygotic duplication) in: ibid.
  • Marlow, N. Does neonatal and infant neurodevelopment of twins and singletons differ? in: Multiple Pregnancy Kilby M et al (eds) RCOG 2006. According to Marlow, any possible small effect of twinning on developmental progress will be swamped by the serious sequelae of very preterm birth often endured by twins.
  • Moser K, Macfarlane A, Chow YH, Hilder L, Dattani N. Introducing new data on gestation-specific infant mortality among babies born in 2005 in England and Wales. Health Statistics Quarterly, Autumn 2007; 13–27. Download the abstract
  • Oakley, L and Doyle P. Predicting the impact of in vitro fertilisation and other forms of assisted conception on perinatal and infant mortality in England and Wales: examining the role of multiplicity BJOG 2006; 113: 738–741. Download the abstract. Updated to 2003 figures through personal correspondence with the authors.
  • Olivennes, F et al. Behavioural and cognitive development as well as family functioning of twins conceived by assisted reproduction: findings from a large population study. Fertility and Sterility 2005; 84:725–733. Download the abstract.
  • Ombelet et al. Human Reproduction 2006; 21: 1025–1032.
  • Ostfeld, BM et al. Maternal behaviour toward premature twins: implications for development Twin Research 2000; 3: 234–241. Read the article (PDF).
  • Pinborg, A. et al. 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. Human Reproduction 2003; 18(6): 1234–1243. Read the article
  • Pinborg, A. IVF/ICSI twin pregnancies: risks and prevention Human Reproduction Update 2005; 11: 575–593. Read the article.
  • The Practice Committee of the American Society for Reproductive Medicine, Multiple pregnancy associated with infertility therapy, Fertility and Sterility 2004, 82, Suppl 1, S153–157. 
  • Topp et al Acta Obstetrics and Gynaecology Scandinavia 2004; 83: 548–553.
  • Yokoyama Y, Shimizu T and Hayakawa K (1995). Incidence of handicaps in multiple births and associated factors. Acta Genet Med Gemellol (Roma) 44, 81–91. Download the abstract.

Risks to the mother

  • A and Neilson JP. Twin clinics: a model for antenatal care in multiple gestations in: Multiple Pregnancy Kilby M et al (eds) RCOG 2006.
  • Carlin et al and Neilson. in: Multiple Pregnancy Kilby et al (eds) RCOG 2006.
  • Colpin H, De Munter A; Nys K.  Psychology. Parenting stress and psychosocial well-being among parents with twins conceived naturally or by reproductive technology. Human Reproduction, Volume 14, Number 12, December 1999 , pp. 3133-3137(5). Read the article.
  • Cook, R., Bradley, S. & Golombok, S. A preliminary study of parental stress and child behaviour in families with twins conceived by in vitro fertilisation. 1998 Human Reproduction, 13, No. 11, 101-103. Read the study (PDF). 
  • El-Thouky, T et al. IVF results: optimize not maximize American Journal of Obstetrics and Gynecology 2006; 194: 322–331.
  • Ellison, M and Hall J. Social stigma and compounded losses: quality of life issues for multiple birth families Fertility and Sterility 2003; 80: 405 – 414. Download the abstract
  • Feldman R, Weller A, Leckman JF, Kuint J and Eidelman AI. The Nature of the Mother’s Tie to Her Infant: Maternal Bonding under Conditions of Proximity, Separation, and Potential Loss The Journal of Child Psychology and Psychiatry and Allied Disciplines 1999, 40: 929–939. Download the abstract.
  • Glazebrook C, Sheard C, Cox S, Oates M, Ndukwe G. Parenting stress in first-time mothers of twins and triplets conceived after in vitro fertilization.  Fertility and Sterility , Volume 81 , Issue 3 , pages 505–511. Download the abstract.
  • Land JA and Evers, JLH. Risks and complications in assisted reproduction techniques: Report of an ESHRE consensus meeting Human Reproduction 2003; 18: 455–457. Read the article.
  • One Child at a Time, Report of the Expert Group on Multiple Births after IVF, October 2006, p8. Download the report (PDF). 
  • Santema et al. Eur J Obstet Gynecol Reprod Biol 1995; 58: 9.
  • Thurin Kjellberg A et al. Randomized single versus double embryo transfer: obstetric and paediatric outcome and a cost-effectiveness analysis Human Reproduction 2006; 21: 210–216; Read the article

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Stimulated intrauterine insemination (IUI)

  • Guzick DS, Carson SA, Coutifaris C, Overstreet JW, Factor-Litvak P, Steinkampf MP, et al. Efficacy of superovulation and intrauterine insemination in the treatment of infertility. National Cooperative Reproductive Medicine Network. N Engl J Med 1999;340:177–83. Read the article
  • NICE (p78 of CG011 Full Guideline): ‘The multiple birth rates for twins, triplets and quadruplets were 22%, 4% and 3%, respectively, in the stimulated IUI group and there were no multiple births in the unstimulated group.’ (US study.) Download the Guidance
  • Nyboe Anderson A et al. Human Reproduction (2007).

 

What other countries are doing

  • ‘Code of Practice for Assisted Reproductive Technology Units’ Fertility Society of Australia Reproductive Technology Accreditation Committee, February 2005. para 7.4. Download the Code
  • Criteria for number of embryos to transfer: a committee opinion’ ASRM Practice Committee.  Fertility and Sterility.  Vol 99, No1, January 2013. Read the article.
  • Källen, B et al. Temporal trends in multiple births after in vitro fertilisation in Sweden, 1982–2001: a register study BMJ 2006; 331: 382. Read the paper.
  • Multiple births and single embryo transfer review: evidence base and policy analysis, HFEA, October 2007. Section B, p12, para 7.3–7.5.
  • One Child at a Time, Report of the Expert Group on Multiple Births after IVF, October 2006, table p18–19. Download the report (PDF).
  • The Best Possible Start to Life: a consultation document on multiple births after IVF; HFEA; April 2007, p12, para 9.2–9.6. Download the consultation document (PDF).
  • Wang YA, Chambers G, Dieng M & Sullivan EA, Assisted reproductive technology in Australia and New Zealand 2007 Australian Institute of Health and Welfare. 24 September 2009; ISSN 1038-7234; ISBN-13 978 1 74024 955 3; AIHW cat. no. PER 47; 66pp. Read the report

 

Which patients are suitable for single embryo transfer (SET)?

  • Gerris, J et al. Prevention of twin pregnancy after IVF or ICSI based on strict embryo criteria: a prospective randomised clinical trial Human Reproduction 1999; 14: 2581–2587. Read the article
  • Martikainen, H. One versus two embryo transfer after IVF and ICSI: a randomised study Human Reproduction 2001; 16: 1900–1903. Read the article.
  • The Best Possible Start to Life: a consultation document on multiple births after IVF; HFEA; April 2007, p15, Box 5: Predicted outcome and single embryo transfer. Download the consultation document (PDF).
  • Veleva, Z et al. Elective single-embryo transfer in women aged 36–39 years Hum. Reprod. Advance Access published on June 1, 2006. doi:10.1093/humrep/del137. Read the article
  • Khalaf Y, El-Toukhy T, Coomarasamy A, Kamal A, Bolton V, Braude P (2008). Selective single blastocyst transfer reduces the multiple pregnancy rate and increases pregnancy rates: a pre- and postintervention study BJOG: An International Journal of Obstetrics and Gynaecology 115 (3), 385–390 doi:10.1111/j.1471–0528.2007.01584.x. Read the study.
  • Adriana B, The new IVF gamble: single embryos Canadian Fertility and Andrology Society (originally published in Globe and Mail) October 2009. Read the article 

 

Why should I recommend single embryo transfer (SET)?

  • Bergh, C. Single embryo transfer: a mini review Human Reproduction 2005; 20: 323–327. Read the article.
  • Chambers, G et al.  Hospital Costs of Multiple-Birth and Singleton-Birth Children During the First 5 Years of Life and the Role of Assisted Reproductive Technology.  View information or read abstract.
  • Derom et al in Multiple Pregnancy eds Isaac Blickstein and Louis G Keith, 2005.
  • Gerris, J et al. Prevention of twin pregnancy after IVF or ICSI based on strict embryo criteria: a prospective randomised clinical trial Human Reproduction 1999; 14: 2581–2587. Read the article.
  • Khalaf Y, El-Toukhy T, Coomarasamy A, Kamal A, Bolton V, Braude P (2008). Selective single blastocyst transfer reduces the multiple pregnancy rate and increases pregnancy rates: a pre- and postintervention study BJOG: An International Journal of Obstetrics and Gynaecology 115 (3), 385–390 doi:10.1111/j.1471–0528.2007.01584.x. Read the study.
  • Ledger, WL. BJOG 2006; 113: 21–25.
  • National Perinatal Epidemiology Unit (2005). A survey of current neonatal unit organisation and policy. Download the report (PDF).
  • Office of National Statistics for 2003: around 9000 twin babies born. Births: 1938-2004, Maternities with multiple births. Taken from Table 6.1 published in Birth Statistics - Historical series FM1 Vol No 13, Table 6.3 in Birth Statistics FM1 Vol No's 11 to 16 and Table 6.4 in FM1 Vol No's 17 to 33. View information.
  • HFEA register data: around 3600 twin babies born.
  • Ombelet et al. Human Reproduction 2006; 21: 1025–1032.
  • One Child at a Time, Report of the Expert Group on Multiple Births after IVF, October 2006, p18–20, para 3.1, 3.2 and 3.3. Download the report (PDF).
  • Pandian, Z et al. Number of embryos for transfer after IVF and ICSI: A Cochrane review Human Reproduction 2005; 20: 2681–2687. Read the article.
  • Pinborg A et al. 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 Human Reproduction 2003; 18: 1234–1243. Read the article
  • The Best Possible Start to Life: a consultation document on multiple births after IVF; HFEA; April 2007, p10, para 7.4. Download the consultation document (PDF).
  • Thurin et al. Elective single-embryo-transfer versus double embryo transfer in IVF New England Journal of Medicine 2004; 351: 2392–2402. Download the abstract.

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