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Extending the culture of cleavage-stage embryos to the blastocyst stage after warming increases the chance of live birth: does it have a regenerative effect?

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

Abstract

Purpose

We aimed to evaluate the effect of extending the culture of cleavage-stage embryos to the blastocyst stage in vitrified–warmed cycles on pregnancy outcomes.

Methods

This is a retrospectively designed pilot study of a single center. All patients who applied for freeze-all cycle procedures during in vitro fertilization treatment were included in the study. Patients were classified into three subgroups. The embryos obtained were frozen at the cleavage or blastocyst stage. After a warming process, the cleavage-stage embryos were divided into two subgroups: the first group of embryos was transferred (vitrification day 3–embryo transfer (ET) day 3 (D3T3)) on the warming day; for the second group, the embryo culture was extended to the blastocyst stage (vitrification day 3–ET day 5 (after the extension of the embryo culture to the blastocyst stage), (D3T5)). Frozen blastocyst-stage embryos were transferred after warming (vitrification day 5–ET day 5 (D5T5)). Hormone replacement treatment was the only endometrial preparation regimen given during the embryo transfer cycle. The main outcome of the study was live birth rates. The clinical pregnancy rate and positive pregnancy test rate were determined as the secondary outcomes of the study.

Results

The study included a total of 194 patients. The positive pregnancy test rates (PPR) and clinical pregnancy rates (CPR) of the D3T3, D3T5, and D5T5 groups were 14.0% and 59.2%; 43.8% and 9.3%; and 56.3% and 39.6%, respectively (p < 0.001 and p < 0.001). The live birth rates (LBR) of patients in the D3T3, D3T5, and D5T5 groups were 7.0%, 44.7%, and 27.1%, respectively (p < 0.001). In subgroup analysis of patients with a poor number of 2PN embryos (defined as having <  = 4 2PN embryos), the D3T5 group had significantly higher PPR (10.7%, 60.6%, 42.4%; p < 0.001), CPR (7.1%, 57.6%, 39.4%; p < 0.001), and LBR (3.6%, 39.4%, 21.2%; p: 0.001).

Conclusion

Extending the culture after warming to the blastocyst stage may be a better alternative than a cleavage-stage embryo transfer.

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Data availability

Upon request authors are ready to share relevant documentation or data in order to verify the validity of the results presented. This could be in the form of raw data, samples, records, etc. Sensitive information in the form of confidential or proprietary data is excluded.

References

  1. Gardner DK, Schoolcraft WB, Wagley L, Schlenker T, Stevens J, Hesla J (1998) A prospective randomized trial of blastocyst culture and transfer in in-vitro fertilization. Hum Reprod 13(12):3434–3440

    Article  CAS  PubMed  Google Scholar 

  2. Wong KM, van Wely M, Mol F, Repping S, Mastenbroek S (2017) Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev 3(3):CD011184

    PubMed  Google Scholar 

  3. Rienzi L, Gracia C, Maggiulli R, LaBarbera AR, Kaser DJ, Ubaldi FM et al (2017) Oocyte, embryo and blastocyst cryopreservation in ART: systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for the development of global guidance. Hum Reprod Update 23(2):139–155

    CAS  PubMed  Google Scholar 

  4. Glujovsky D, Farquhar C, Quinteiro Retamar AM, Alvarez Sedo CR, Blake D (2016) Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database Syst Rev 2016(6):CD002118

    Google Scholar 

  5. Van Landuyt L, Polyzos NP, De Munck N, Blockeel C, Van de Velde H, Verheyen G (2015) A prospective randomized controlled trial investigating the effect of artificial shrinkage (collapse) on the implantation potential of vitrified blastocysts. Hum Reprod 30(11):2509–2518

    Article  PubMed  Google Scholar 

  6. Vladimirov IK, Tacheva D, Diez A (2017) Theory about the embryo cryo-treatment. Reprod Med Biol 16(2):118–125

    Article  PubMed  PubMed Central  Google Scholar 

  7. Alpha Scientists in Reproductive M, Embryology ESIGo. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod 2011;26(6):1270–83.

  8. Gardner DK, Schoolcraft WB (1999) Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol 11(3):307–311

    Article  CAS  PubMed  Google Scholar 

  9. Dobson SJA, Lao MT, Michael E, Varghese AC, Jayaprakasan K (2018) Effect of transfer of a poor quality embryo along with a top quality embryo on the outcome during fresh and frozen in vitro fertilization cycles. Fertil Steril 110(4):655–660

    Article  PubMed  Google Scholar 

  10. Li Y, Liu S, Lv Q (2021) Single blastocyst stage versus single cleavage stage embryo transfer following fresh transfer: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 267:11–17

    Article  PubMed  Google Scholar 

  11. Guerin P, El Mouatassim S, Menezo Y (2001) Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum Reprod Update 7(2):175–189

    Article  CAS  PubMed  Google Scholar 

  12. Tanaka A, Nagayoshi M, Takemoto Y, Tanaka I, Kusunoki H, Watanabe S et al (2015) Fourteen babies born after round spermatid injection into human oocytes. Proc Natl Acad Sci U S A 112(47):14629–14634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Eftekhar M, Aflatoonian A, Mohammadian F, Tabibnejad N (2012) Transfer of blastocysts derived from frozen-thawed cleavage stage embryos improved ongoing pregnancy. Arch Gynecol Obstet 286(2):511–516

    Article  PubMed  Google Scholar 

  14. Rahav-Koren R, Inbar S, Miller N, Wiser A, Yagur Y, Berkowitz C et al (2021) Thawing day 3 embryos and culturing to day 5 may be a better method for frozen embryo transfer. J Assist Reprod Genet 38(11):2941–2946

    Article  PubMed  PubMed Central  Google Scholar 

  15. De Croo I, Colman R, De Sutter P, Stoop D, Tilleman K (2022) No difference in cumulative live birth rates between cleavage versus blastocyst transfer in patients with four or fewer zygotes: results from a retrospective study. Hum Reprod Open 2022(3):hoac031

    Article  PubMed  PubMed Central  Google Scholar 

  16. Xiong F, Li G, Sun Q, Wang S, Wan C, Chen P et al (2019) Clinical outcomes after transfer of blastocysts derived from frozen-thawed cleavage embryos: a retrospective propensity-matched cohort study. Arch Gynecol Obstet 300(3):751–761

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Başkent University School of Medicine, Şehit Temel Kuğuoğlu Cd. No: 34 Bahçelievler, Ankara, Turkey

    Göğşen Önalan, Mehmet Tunç, Aytaç Tohma, Emre Günakan, Tahir Eryılmaz & Hulusi B. Zeyneloğlu

Authors
  1. Göğşen Önalan
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  2. Mehmet Tunç
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  3. Aytaç Tohma
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  4. Emre Günakan
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  5. Tahir Eryılmaz
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  6. Hulusi B. Zeyneloğlu
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Contributions

All authors contributed to the study. GÖ: supervision, project administration, review, and editing. MT: data curation, formal analysis, investigation, project administration, writing—original draft, and corresponding author. AT: data curation, methodology, and review and editing. EG: data curation, conceptualization, methodology, review and editing, and project administration. TE: data curation. HBZ: review and editing, and supervision. The corresponding author accepts full responsibility for the finished work and/or the conduct of the study.

Corresponding author

Correspondence to Mehmet Tunç.

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All authors have contributed to the manuscript and the authors declare that there are no conflicts of interest—financial or otherwise—related to the material presented herein.

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Önalan, G., Tunç, M., Tohma, A. et al. Extending the culture of cleavage-stage embryos to the blastocyst stage after warming increases the chance of live birth: does it have a regenerative effect?. Arch Gynecol Obstet 307, 1969–1974 (2023). https://doi.org/10.1007/s00404-023-07031-7

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  • DOI: https://doi.org/10.1007/s00404-023-07031-7

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