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The risk of birth defects among children born after vitrified blastocyst transfers and those born after fresh and vitrified cleavage-stage embryo transfers

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

To explore the risk of birth defects among children born after vitrified blastocyst transfers and those born after fresh and vitrified cleavage-stage embryo transfers.

Methods

A retrospective cohort study was conducted including infants born after fresh and vitrified day 3 embryo transfers and those born after vitrified day 5 or 6 blastocyst transfers from January 2005 through December 2016. The outcome measures included any birth defect, multiple birth defects and 13 individual categories of birth defects.

Results

Any birth defect occurred in 1.15% of infants born after fresh day 3 embryo transfers, 1.75% of infants born after vitrified day 3 embryo transfers, 1.60% of infants born after vitrified day 5 blastocyst transfers and 1.10% of infants born after vitrified day 6 blastocyst transfers. There was no difference in the risk of birth defects between vitrified blastocyst-stage transfers and vitrified cleavage-stage transfers (including day 5 vs. day 3 and day 6 vs. day 3) among all births or in only singletons or twins. For infants born after cleavage-stage embryo transfers at day 3, there was no difference in the risk of birth defects between fresh embryo transfers and vitrified embryo transfers among all births or in only singletons or twins.

Conclusions

Transfer of vitrified day 5 or 6 blastocysts does not increase the risk of birth defects compared with vitrified day 3 embryos. However, randomized control trials and follow-up studies of the long-term outcome of children born after blastocyst-stage transfers are needed to confirm the clinical safety of extending embryo culture to the blastocyst stage.

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References

  1. Hardarson T, Van Landuyt L, Jones G (2012) The blastocyst. Hum Reprod 27(suppl 1):i72–i91. https://doi.org/10.1093/humrep/des230

    Article  PubMed  Google Scholar 

  2. Dar S, Lazer T, Shah PS, Librach CL (2014) Neonatal outcomes among singleton births after blastocyst vs. cleavage stage embryo transfer: a systematic review and meta-analysis. Hum Reprod Update 20(3):439–448. https://doi.org/10.1093/humupd/dmu001

    Article  CAS  PubMed  Google Scholar 

  3. Chambers GM, Chughtai AA, Farquhar CM, Wang YA (2015) Risk of preterm birth after blastocyst embryo transfer: a large population study using contemporary registry data from Australia and New Zealand. Fertil Steril 104(4):997–1003. https://doi.org/10.1016/j.fertnstert.2015.07.1130

    Article  PubMed  Google Scholar 

  4. Osamu I, Ryuichiro A, Akira K, Atsuo I, Hidekazu S, David AG (2014) Impact of frozen-thawed single-blastocyst transfer on maternal and neonatal outcome: an analysis of 277,042 single-embryo transfer cycles from 2008 to 2010 in Japan. Fertil Steril 101(1):128–133. https://doi.org/10.1016/j.fertnstert.2013.09.025

    Article  Google Scholar 

  5. Bengt KL, Orvar FM, Anna L, Emma N, Karl-G Sta N, Petra Otterbla O (2010) Blastocyst vs. cleavage stage transfer in in vitro fertilization: differences in neonatal outcome?. Fertil Steril 94(5):1680–1683. https://doi.org/10.1016/j.fertnstert.2009.12.027

    Article  Google Scholar 

  6. Dar S, Librach C, Gunby J, Bissonnette F, Cowan L (2013) Increased risk of preterm birth in singleton pregnancies after blastocyst vs. day 3 embryo transfer: canadian ART Register (CARTR) analysis. Hum Reprod 28(4):924–928

    Article  CAS  PubMed  Google Scholar 

  7. Chen H, Wang Y, Lyu Q, Ai A, Fu Y, Tian H, Cai R, Hong Q, Chen Q, Shoham Z, Kuang Y (2015) Comparison of live-birth defects after luteal-phase ovarian stimulation vs. conventional ovarian stimulation for in vitro fertilization and vitrified embryo transfer cycles. Fertil Steril 103(5):1194–1201. https://doi.org/10.1016/j.fertnstert.2015.02.020

    Article  CAS  PubMed  Google Scholar 

  8. Davies MJ, Rumbold AR, Marino JL, Willson K, Giles LC, Whitrow MJ, Scheil W, Moran LJ, Thompson JG, Lane M, Moore VM (2017) Maternal factors and the risk of birth defects after IVF and ICSI: a whole of population cohort study. BJOG 124(10):1537–1544

    Article  CAS  PubMed  Google Scholar 

  9. Boulet SL, Kirby RS, Reefhuis J, Zhang Y, Sunderam S, Cohen B, Bernson D, Copeland G, Bailey MA, Jamieson MA, Jamieson DJ, Kissin DM (2016) Assisted reproductive technology and birth defects among liveborn infants in Florida, Massachusetts, and Michigan, 2000–2010. JAMA Pediatr 170(6):e154934

    Article  PubMed  PubMed Central  Google Scholar 

  10. Simpson JL (2014) Birth defects and assisted reproductive technologies. Semin Fetal Neonatal Med 19(3):177–182

    Article  PubMed  Google Scholar 

  11. Yan J, Huang G, Sun Y, Zhao X, Chen S, Zou S, Hao C, Quan S, Chen ZJ (2011) Birth defects after assisted reproductive tech -nologies in China: analysis of 15,405 ofspring in seven centers (2004–2008). Fertil Steril 95(1):458–460. https://doi.org/10.1016/j.fertnstert.2010.08.024

    Article  PubMed  Google Scholar 

  12. Shi W, Xue X, Zhang S, Zhao W, Liu S, Zhou H, Wang M, Shi J (2012) Perinatal and neonatal outcomes of 494 babies delivered from 972 vitrifed embryo transfers. Fertil Steril 97(6):1338–1342. https://doi.org/10.1016/j.fertnstert.2012.02.051

    Article  PubMed  Google Scholar 

  13. Belva F, Bonduelle M, Roelants M, Verheyen G, Van Landuyt L (2016) Neonatal health including congenital malformation risk of 1072 children born after vitrifed embryo transfer. Hum Reprod 31(7):1610–1620. https://doi.org/10.1093/humrep/dew103

    Article  CAS  PubMed  Google Scholar 

  14. Kato O, Kawasaki N, Bodri D, Kuroda T, Kawachiya S, Kato K, Takehara Y (2012) Neonatal outcome and birth defects in 6623 singletons born following minimal ovarian stimulation and vitrified vs. fresh single embryo transfer. Eur J Obstet Gynecol Reprod Biol 161(1):46–50

    Article  PubMed  Google Scholar 

  15. Glujovsky D, Farquhar C (2016) Cleavage-stage or blastocyst transfer: what are the benefits and harms? Fertil Steril 106(2):244–250. https://doi.org/10.1016/j.fertnstert.2016.06.029

    Article  PubMed  Google Scholar 

  16. PCOT Technology (2013) Blastocyst culture and transfer in clinical-assisted reproduction: a committee opinion. Fertil Steril 99(3):667

    Article  Google Scholar 

  17. Papanikolaou EG, Kolibianakis EM, Tournaye H, Venetis CA, Fatemi H, Tarlatzis B, Devroey P (2008) Live birth rates after transfer of equal number of blastocysts or cleavage-stage embryos in IVF. A systematic review and meta-analysis. Hum Reprod 23(1):91–99. https://doi.org/10.1093/humrep/dem339

    Article  PubMed  Google Scholar 

  18. Papanikolaou EG, Camus M, Kolibianakis EM, Van Landuyt L, Van Steirteghem A, Devroey P (2006) In vitro fertilization with single blastocyst-stage vs. single cleavage-stage embryos. New Engl J Med 354(11):1139–1146. https://doi.org/10.1056/NEJMoa053524

    Article  CAS  PubMed  Google Scholar 

  19. Embryologist DB, Proctor M, Johnson N, Olive D (2002) Cleavage stage vs. blastocyst stage embryo transfer in assisted conception. Cochrane Database Syst Rev 7(2):D2118. https://doi.org/10.1002/14651858.CD002118

    Article  Google Scholar 

  20. Maheshwari A, Hamilton M, Bhattacharya S (2016) Should we be promoting embryo transfer at blastocyst stage? Reprod Biomed Online 32(2):142–146

    Article  PubMed  Google Scholar 

  21. Lonergan P, Rizos D, Gutierrez-Adan A, Fair T, Boland MP (2003) Effect of culture environment on embryo quality and gene expression—experience from animal studies. Reprod Biomed Online 7(6):657–663

    Article  CAS  PubMed  Google Scholar 

  22. Calle A, Fernandez-Gonzalez R, Ramos-Ibeas P, Laguna-Barraza R, Perez-Cerezales S, Bermejo-Alvarez P, Ramirez MA, Gutierrez-Adan A (2012) Long-term and transgenerational effects of in vitro culture on mouse embryos. Theriogenology 77(4):785–793. https://doi.org/10.1016/j.theriogenology.2011.07.016

    Article  PubMed  Google Scholar 

  23. Katsuhiko T, Tetsunori M, Tetsuya G, Chikahiro O (2005) Perinatal outcome of blastocyst transfer with vitrification using cryoloop: a 4-year follow-up study. Fertil Steril 84(1):88–92. https://doi.org/10.1016/j.fertnstert.2004.12.051

    Article  Google Scholar 

  24. Wikland M, Hardarson T, Hillensjö T, Westin C, Westlander G, Wood M, Wennerholm UB (2010) Obstetric outcomes after transfer of vitrified blastocysts. Hum Reprod 25(7):1699

    Article  CAS  PubMed  Google Scholar 

  25. Van LL, Stoop D, Verheyen G, Verpoest W, Camus M, Van DVH, Devroey P, Van DAE (2011) Outcome of closed blastocyst vitrification in relation to blastocyst quality: evaluation of 759 warming cycles in a single-embryo transfer policy. Hum Reprod 26(3):527–534

    Article  Google Scholar 

  26. Rama RG, Jaya PG, Murali KK, Madan K (2009) Neonatal outcome after vitrified day 3 embryo transfers: a preliminary study. Fertil Steril 92(1):143–148. https://doi.org/10.1016/j.fertnstert.2008.05.014

    Article  Google Scholar 

  27. Liu SY, Teng B, Fu J, Li X, Zheng Y, Sun XX (2013) Obstetric and neonatal outcomes after transfer of vitrified early cleavage embryos. Hum Reprod 28(8):2093–2100. https://doi.org/10.1093/humrep/det104

    Article  CAS  PubMed  Google Scholar 

  28. Samadirad B, Khamnian Z, Hosseini MB, Dastgiri S (2012) Congenital anomalies and termination of pregnancy in Iran. J Pregnancy 2012:574513. https://doi.org/10.1155/2012/574513

    Article  PubMed  PubMed Central  Google Scholar 

  29. Svensson E, Ehrenstein V, Norgaard M, Bakketeig LS, Rothman KJ, Sorensen HT, Pedersen L (2014) Estimating the proportion of all observed birth defects occurring in pregnancies terminated by a second-trimester abortion. Epidemiology 25(6):866–871. https://doi.org/10.1097/EDE.0000000000000163

    Article  PubMed  Google Scholar 

  30. Hackshaw A, Rodeck C, Boniface S (2011) Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls. Hum Reprod Update 17(5):589–604. https://doi.org/10.1093/humupd/dmr022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Deng C, Yi L, Mu Y, Zhu J, Qin Y, Fan X, Wang Y, Li Q, Dai L (2015) Recent trends in the birth prevalence of down syndrome in China: impact of prenatal diagnosis and subsequent terminations. Prenat Diagn 35(4):311–318. https://doi.org/10.1002/pd.4516

    Article  PubMed  Google Scholar 

  32. Rocheleau CM, Bertke SJ, Lawson CC, Romitti PA, Sanderson WT, Malik S, Lupo PJ, Desrosiers TA, Bell E, Druschel C, Correa A, Reefhuis J (2015) Maternal occupational pesticide exposure and risk of congenital heart defects in the National Birth Defects Prevention Study. Birth Defects Res A Clin Mol Teratol 103(10):823–833. https://doi.org/10.1002/bdra.2335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We gratefully acknowledge the staff of the Department of Assisted Reproduction in the Shanghai Ninth People’s Hospital for their contribution.

Funding

This work was supported by the National Nature Science Foundation of China (Grant nos. 81571397, 31770989), the Shanghai Ninth People’s Hospital Foundation of China (Grant no. JYLJ030), the Nature Science Foundation of Shanghai (Grant no. 16ZR1419500).

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Author notes

  1. Qianqian Zhu and Ningling Wang contributed equally to this paper.

Authors and Affiliations

  1. Department of Assisted Reproduction, Shanghai Ninth People’s Hospital Affiliated to Jiaotong University, School of Medicine, Zhizaoju Road No. 639, Shanghai, China

    Qianqian Zhu, Ningling Wang, Bian Wang, Yun Wang & Yanping Kuang

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  1. Qianqian Zhu
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  2. Ningling Wang
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  3. Bian Wang
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  4. Yun Wang
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  5. Yanping Kuang
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Contributions

QQZ: Manuscript writing, data analysis; NLW: Data analysis; BW: Data collection; YW: Data collection; YPK: Project development.

Corresponding authors

Correspondence to Yun Wang or Yanping Kuang.

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The authors declare that there are no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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All participants gave written informed consent for this research.

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Zhu, Q., Wang, N., Wang, B. et al. The risk of birth defects among children born after vitrified blastocyst transfers and those born after fresh and vitrified cleavage-stage embryo transfers. Arch Gynecol Obstet 298, 833–840 (2018). https://doi.org/10.1007/s00404-018-4870-x

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  • DOI: https://doi.org/10.1007/s00404-018-4870-x

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