Skip to main navigation menu Skip to main content Skip to site footer

Original article

Vol. 151 No. 1516 (2021)

Single embryo transfer in all infertile couples treated with assisted reproduction produces excellent results and avoids multiple births

  • Christian De Geyter
DOI
https://doi.org/10.4414/smw.2021.20499
Cite this as:
Swiss Med Wkly. 2021;151:w20499
Published
15.04.2021

Summary

Assisted reproductive technology (ART) is an efficacious and frequently used treatment of infertility. Multiple births resulting from the widespread practice of transfer of more than one embryo per treatment trial have reached epidemic proportions. Since the revision of the Swiss law on ART in September 2017, up to 12 embryos per couple may now be developed in vitro and cryopreserved in Switzerland. This potentially allows for the selection and transfer of only one embryo to avoid multiple birth with ART. We decided to offer transfer of one embryo to all infertile patients undergoing ART in our institution. In this retrospective cohort study the cumulative pregnancy and live-birth rates after universal transfer of one embryo from January 2018 to December 2019 were analysed. The cumulative pregnancy rate per oocyte collection and up to five transfer cycles was as high as 48.9%, whereas the cumulative live-birth rate reached 33.4% and none were multiple births. These results were age-dependent, with best outcome in patients aged 37 years or younger. When still remaining cryopreserved embryos were taken into account, the cumulative birth-rates could exceed 60% per oocyte collection in all age groups. The consequent adoption of a single embryo transfer significantly reduced the incidence of multiple births in the department of obstetrics and the number of prematurely born infants resulting from multiple pregnancies in the department of neonatology. Universal elective single embryo transfer is feasible in Switzerland, benefits infertile couples treated with ART and reduces the number of multiple births in obstetrics and of newborn children hospitalised into neonatal care.

References

  1. Zegers-Hochschild F Adamson GD de Mouzon J Ishihara O Mansour R Nygren K International Committee for Monitoring Assisted Reproductive Technology World Health Organization. The International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) Revised Glossary on ART Terminology, 2009. Hum Reprod. 2009;24(11):2683–7. doi:.https://doi.org/10.1093/humrep/dep343
  2. Zegers-Hochschild F Adamson GD de Mouzon J Ishihara O Mansour R Nygren K International Committee for Monitoring Assisted Reproductive Technology World Health Organization. International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology, 2009. Fertil Steril. 2009;92(5):1520–4. doi:.https://doi.org/10.1016/j.fertnstert.2009.09.009
  3. Pinborg A Loft A Rasmussen S Nyboe Andersen A. Hospital care utilization of IVF/ICSI twins followed until 2-7 years of age: a controlled Danish national cohort study. Hum Reprod. 2004;19(11):2529–36. doi:.https://doi.org/10.1093/humrep/deh474
  4. Levin S Sheiner E Wainstock T Walfisch A Segal I Landau D Infertility Treatments and Long-Term Neurologic Morbidity of the Offspring. Am J Perinatol. 2019;36(9):949–54. doi:.https://doi.org/10.1055/s-0038-1675159
  5. Rodriguez-Wallberg KA Lundberg FE Ekberg S Johansson ALV Ludvigsson JF Almqvist C Mortality from infancy to adolescence in singleton children conceived from assisted reproductive techniques versus naturally conceived singletons in Sweden. Fertil Steril. 2020;113(3):524–32. doi:.https://doi.org/10.1016/j.fertnstert.2019.10.018
  6. Toftager M Bogstad J Bryndorf T Løssl K Roskær J Holland T Risk of severe ovarian hyperstimulation syndrome in GnRH antagonist versus GnRH agonist protocol: RCT including 1050 first IVF/ICSI cycles. Hum Reprod. 2016;31(6):1253–64. doi:.https://doi.org/10.1093/humrep/dew051
  7. Malchau SS Henningsen AA Forman J Loft A Nyboe Andersen A Pinborg A. Cumulative live birth rate prognosis based on the number of aspirated oocytes in previous ART cycles. Hum Reprod. 2019;34(1):171–80. doi:.https://doi.org/10.1093/humrep/dey341
  8. Pfeifer S Butts S Dumesic D Fossum G Gracia C La Barbera A Practice Committee of the American Society for Reproductive Medicine. Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. Fertil Steril. 2016;106(7):1634–47. doi:.https://doi.org/10.1016/j.fertnstert.2016.08.048
  9. Humaidan P Polyzos NP Alsbjerg B Erb K Mikkelsen AL Elbaek HO GnRHa trigger and individualized luteal phase hCG support according to ovarian response to stimulation: two prospective randomized controlled multi-centre studies in IVF patients. Hum Reprod. 2013;28(9):2511–21. doi:.https://doi.org/10.1093/humrep/det249
  10. Stormlund S Sopa N Zedeler A Bogstad J Prætorius L Nielsen HS Freeze-all versus fresh blastocyst transfer strategy during in vitro fertilisation in women with regular menstrual cycles: multicentre randomised controlled trial. BMJ. 2020;370:m2519. doi:.https://doi.org/10.1136/bmj.m2519
  11. Tiitinen A Halttunen M Härkki P Vuoristo P Hyden-Granskog C. Elective single embryo transfer: the value of cryopreservation. Hum Reprod. 2001;16(6):1140–4. doi:.https://doi.org/10.1093/humrep/16.6.1140
  12. Gerris J De Neubourg D Mangelschots K Van Royen E Vercruyssen M Barudy-Vasquez J Elective single day 3 embryo transfer halves the twinning rate without decrease in the ongoing pregnancy rate of an IVF/ICSI programme. Hum Reprod. 2002;17(10):2626–31. doi:.https://doi.org/10.1093/humrep/17.10.2626
  13. Karlström PO Bergh C. Reducing the number of embryos transferred in Sweden-impact on delivery and multiple birth rates. Hum Reprod. 2007;22(8):2202–7. doi:.https://doi.org/10.1093/humrep/dem120
  14. Tiitinen A Unkila-Kallio L Halttunen M Hyden-Granskog C. Impact of elective single embryo transfer on the twin pregnancy rate. Hum Reprod. 2003;18(7):1449–53. doi:.https://doi.org/10.1093/humrep/deg301
  15. De Geyter Ch Wyns C Calhaz-Jorge C de Mouzon J Ferraretti AP Kupka M 20 years of the European IVF monitoring (EIM) registry: what have we learned? A comparison with registries from two other regions. Hum Reprod. 2020;35(12):2832–49. doi:.https://doi.org/10.1093/humrep/deaa250
  16. Van den Bergh M Hohl MK De Geyter Ch Stalberg AM Limoni C. Ten years of Swiss National IVF Register FIVNAT-CH. Are we making progress? Reprod Biomed Online. 2005;11(5):632–40. doi:.https://doi.org/10.1016/S1472-6483(10)61173-X
  17. Fehr P Nygren KG De Geyter C. Effekt unterschiedlicher Strategien beim Embryotransfer auf die Ergebnisse der assistierten Reproduktion [Effect of different embryo transfer strategies on the outcome of assisted reproduction]. Ther Umsch. 2009;66(12):825–9. doi:.https://doi.org/10.1024/0040-5930.66.12.825
  18. De Geyter C Fehr P Moffat R Gruber IM von Wolff M. Twenty years’ experience with the Swiss data registry for assisted reproductive medicine: outcomes, key trends and recommendations for improved practice. Swiss Med Wkly. 2015;145:w14087.
  19. Bundesgesetz über die medizinisch unterstützte Fortpflanzung (Fortpflanzungsmedizingesetz, FMedG).
  20. Santos-Ribeiro S Siffain J Polyzos NP van de Vijver A van Landuyt L Stoop D To delay or not to delay a frozen embryo transfer after a failed fresh embryo transfer attempt? Fertil Steril. 2016;105(5):1202–1207.e1. doi:.https://doi.org/10.1016/j.fertnstert.2015.12.140
  21. Cooper TG Noonan E von Eckardstein S Auger J Baker HW Behre HM World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16(3):231–45. doi:.https://doi.org/10.1093/humupd/dmp048
  22. Malizia BA Hacker MR Penzias AS. Cumulative live-birth rates after in vitro fertilization. N Engl J Med. 2009;360(3):236–43. doi:.https://doi.org/10.1056/NEJMoa0803072
  23. de Mouzon J Chambers GM Zegers-Hochschild F Mansour R Ishihara O Banker M International Committee for Monitoring Assisted Reproductive Technologies world report: assisted reproductive technology 2012†. Hum Reprod. 2020;35(8):1900–13. doi:.https://doi.org/10.1093/humrep/deaa090
  24. Wyns C Bergh C Calhaz-Jorge C De Geyter C Kupka MS Motrenko T European IVF-monitoring Consortium (EIM)‡ for the European Society of Human Reproduction and Embryology (ESHRE). ART in Europe, 2016: results generated from European registries by ESHRE. Hum Reprod Open. 2020;2020(3):hoaa032. doi:.https://doi.org/10.1093/hropen/hoaa032
  25. Sunkara SK Rittenberg V Raine-Fenning N Bhattacharya S Zamora J Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod. 2011;26(7):1768–74. doi:.https://doi.org/10.1093/humrep/der106
  26. Arlettaz Mieth R Ersfeld S Douchet N Wellmann S Bucher HU. Higher multiple births in Switzerland: neonatal outcome and evolution over the last 20 years. Swiss Med Wkly. 2011;141:w13308. doi:.https://doi.org/10.4414/smw.2011.13308
  27. Källén B. Maternal morbidity and mortality in in-vitro fertilization. Best Pract Res Clin Obstet Gynaecol. 2008;22(3):549–58. doi:.https://doi.org/10.1016/j.bpobgyn.2008.02.001
  28. Magnusson Å Wennerholm UB Källén K Petzold M Thurin-Kjellberg A Bergh C. The association between the number of oocytes retrieved for IVF, perinatal outcome and obstetric complications. Hum Reprod. 2018;33(10):1939–47. doi:.https://doi.org/10.1093/humrep/dey266
  29. Veleva Z Vilska S Hydén-Granskog C Tiitinen A Tapanainen JS Martikainen H. Elective single embryo transfer in women aged 36-39 years. Hum Reprod. 2006;21(8):2098–102. doi:.https://doi.org/10.1093/humrep/del137
  30. Niinimäki M Suikkari AM Mäkinen S Söderström-Anttila V Martikainen H. Elective single-embryo transfer in women aged 40-44 years. Hum Reprod. 2013;28(2):331–5. doi:.https://doi.org/10.1093/humrep/des399
  31. Stormlund S Sopa N Zedeler A Bogstad J Prætorius L Nielsen HS Freeze-all versus fresh blastocyst transfer strategy during in vitro fertilisation in women with regular menstrual cycles: multicentre randomised controlled trial. BMJ. 2020;370:m2519. doi:.https://doi.org/10.1136/bmj.m2519
  32. Zhu Q Chen Q Wang L Lu X Lyu Q Wang Y Live birth rates in the first complete IVF cycle among 20 687 women using a freeze-all strategy. Hum Reprod. 2018;33(5):924–9. doi:.https://doi.org/10.1093/humrep/dey044
  33. Leijdekkers JA Eijkemans MJC van Tilborg TC Oudshoorn SC McLernon DJ Bhattacharya S OPTIMIST group. Predicting the cumulative chance of live birth over multiple complete cycles of in vitro fertilization: an external validation study. Hum Reprod. 2018;33(9):1684–95. doi:.https://doi.org/10.1093/humrep/dey263
  34. Sunkara SK Khalaf Y Maheshwari A Seed P Coomarasamy A. Association between response to ovarian stimulation and miscarriage following IVF: an analysis of 124 351 IVF pregnancies. Hum Reprod. 2014;29(6):1218–24. doi:.https://doi.org/10.1093/humrep/deu053
  35. Scott RT Jr Upham KM Forman EJ Hong KH Scott KL Taylor D Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial. Fertil Steril. 2013;100(3):697–703. doi:.https://doi.org/10.1016/j.fertnstert.2013.04.035
  36. Tiegs AW Tao X Zhan Y Whitehead C Kim J Hanson B A multicenter, prospective, blinded, nonselection study evaluating the predictive value of an aneuploid diagnosis using a targeted next-generation sequencing-based preimplantation genetic testing for aneuploidy assay and impact of biopsy. Fertil Steril. 2021;115(3):627–37. doi:.https://doi.org/10.1016/j.fertnstert.2020.07.052
  37. Munné S Kaplan B Frattarelli JL Child T Nakhuda G Shamma FN STAR Study Group. Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial. Fertil Steril. 2019;112(6):1071–1079.e7. doi:.https://doi.org/10.1016/j.fertnstert.2019.07.1346
  38. Calhaz-Jorge C De Geyter CH Kupka MS Wyns C Mocanu E Motrenko T Survey on ART and IUI: legislation, regulation, funding and registries in European countries: The European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). Hum Reprod Open. 2020;2020(1):hoz044. doi:.https://doi.org/10.1093/hropen/hoz044
  39. Fiddelers AA van Montfoort AP Dirksen CD Dumoulin JC Land JA Dunselman GA Single versus double embryo transfer: cost-effectiveness analysis alongside a randomized clinical trial. Hum Reprod. 2006;21(8):2090–7. doi:.https://doi.org/10.1093/humrep/del112
  40. Dixon S Faghih Nasiri F Ledger WL Lenton EA Duenas A Sutcliffe P Cost-effectiveness analysis of different embryo transfer strategies in England. BJOG. 2008;115(6):758–66. doi:.https://doi.org/10.1111/j.1471-0528.2008.01667.x
  41. Connolly MP Ledger W Postma MJ. Economics of assisted reproduction: access to fertility treatments and valuing live births in economic terms. Hum Fertil (Camb). 2010;13(1):13–8. doi:.https://doi.org/10.3109/14647270903401747
  42. van Heesch MM van Asselt AD Evers JL van der Hoeven MA Dumoulin JC van Beijsterveldt CE Cost-effectiveness of embryo transfer strategies: a decision analytic model using long-term costs and consequences of singletons and multiples born as a consequence of IVF. Hum Reprod. 2016;31(11):2527–40. doi:.https://doi.org/10.1093/humrep/dew229
  43. Hunault CC Habbema JD Eijkemans MJ Collins JA Evers JL te Velde ER. Two new prediction rules for spontaneous pregnancy leading to live birth among subfertile couples, based on the synthesis of three previous models. Hum Reprod. 2004;19(9):2019–26. doi:.https://doi.org/10.1093/humrep/deh365
  44. Bensdorp AJ van der Steeg JW Steures P Habbema JDF Hompes PGA Bossuyt PMM CECERM study group. A revised prediction model for natural conception. Reprod Biomed Online. 2017;34(6):619–26. doi:.https://doi.org/10.1016/j.rbmo.2017.03.014