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Freeze-all cycle for all normal responders?

  • Assisted Reproduction Technologies
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Abstract

Purpose

The purpose of this study is to evaluate the freeze-all strategy in subgroups of normal responders, to assess whether this strategy is beneficial regardless of ovarian response, and to evaluate the possibility of implementing an individualized embryo transfer (iET) based on ovarian response.

Methods

This was an observational, cohort study performed in a private IVF center. A total of 938 IVF cycles were included in this study. The patients were submitted to controlled ovarian stimulation (COS) with a gonadotropin-releasing hormone (GnRH) antagonist protocol and a cleavage-stage day 3 embryo transfer. We performed a comparison of outcomes between the fresh embryo transfer (n = 523) and the freeze-all cycles (n = 415). The analysis was performed in two subgroups of patients based on the number of retrieved oocytes: Group 1 (4–9 oocytes) and Group 2 (10–15 oocytes).

Result(s)

In Group 1 (4–9 retrieved oocytes), the implantation rates (IR) were 17.9 and 20.5% (P = 0.259) in the fresh and freeze-all group, respectively; the ongoing pregnancy rates (OPR) were 31 and 33% (P = 0.577) in the fresh and freeze-all group, respectively. In Group 2 (10–15 oocytes), the IR were 22.1 and 30.1% (P = 0.028) and the OPR were 34 and 47% (P = 0.021) in the fresh and freeze-all groups, respectively.

Conclusion(s)

Although the freeze-all policy may be related to better in vitro fertilization (IVF) outcomes in normal responders, these potential advantages decrease with worsening ovarian response. Patients with poorer ovarian response do not benefit from the freeze-all strategy.

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References

  1. Cobo A, de los Santos MJ, Castellò D, Gámiz P, Campos P, Remohí J. Outcomes of vitrified early cleavage-stage and blastocyst-stage embryos in a cryopreservation program: evaluation of 3,150 warming cycles. Fertil Steril. 2012;98:1138–46.

    Article  PubMed  Google Scholar 

  2. Wong KM, Mastenbroek S, Repping S. Cryopreservation of human embryos and its contribution to in vitro fertilization success rates. Fertil Steril. 2014;102:19–26.

    Article  CAS  PubMed  Google Scholar 

  3. Albertini DF. Phasing in and out of the FREEZE-ALL mentality: Was Mother Neture right after all? J Assist Reprod Genet. 2015;32:169–70.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Roque M. Freeze-all policy: Is it time for that? J Assist Reprod Genet. 2015;32:171–6.

    Article  PubMed  Google Scholar 

  5. Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. High ongoing pregnancy rates after deferred transfer through bipronuclear oocyte cryopreservation and post-thaw extended culture. Fertil Steril. 2009;92:1594–9.

    Article  PubMed  Google Scholar 

  6. Barnhart KT. Are we ready to eliminate the transfer of fresh embryos in in vitro fertilization? Fertil Steril. 2014;102:1–2.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Siristatidis C, Sergentanis TN, Kanavidis P, Trivella M, Mavromatis I, Psaltopoulou T, et al. Controlled ovarian hyperstimulation for IVF: impact on ovarian, endometrial and cervical cancer—a systematic review and meta-analysis. Hum Reprod Update. 2013;19:105–23.

    Article  CAS  PubMed  Google Scholar 

  8. Nikas G, Develioglu OH, Toner JP, Jones Jr HW. Endometrial pinopodes indicate a shift in the window of receptivity in IVF cycles. Hum Reprod. 1999;14:787–92.

    Article  CAS  PubMed  Google Scholar 

  9. Richter KS, Shipley SK, McVearry I, Tucker MJ, Widra EA. Cryopreserved embryo transfers suggest that endometrial receptivity may contribute to reduced success rates of later developing embryos. Fertil Steril. 2006;86:862–6.

    Article  PubMed  Google Scholar 

  10. Horcajadas JA, Riesewijk A, Polman J, van Os R, Pellicer A, Mosselman S, et al. Effect of controlled ovarian hyperstimulation in IVF on endometrial gene expression profiles. Mol Hum Reprod. 2005;11:195–205.

    Article  CAS  PubMed  Google Scholar 

  11. Fatemi HM, Popovic-Todorovic B. Implantation in assisted reproduction: a look at endometrial receptivity. Reprod Biomed Online. 2013;27:530–8.

    Article  CAS  PubMed  Google Scholar 

  12. Achache H, Ravel A. Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update. 2006;12:731–46.

    Article  PubMed  Google Scholar 

  13. Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozen-thawed embryo transfer in normal responders. Fertil Steril. 2011;96:344–8.

    Article  PubMed  Google Scholar 

  14. Roque M, Lattes K, Serra S, Solà I, Geber S, Carreras R, et al. Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis. Fertil Steril. 2013;99:156–62.

    Article  PubMed  Google Scholar 

  15. Devroey P, Polyzos NP, Blockeel C. An OHSS-Free Clinic by segmentation of IVF treatment. Hum Reprod. 2011;26:2593–7.

    Article  PubMed  Google Scholar 

  16. Blockeel C, Drakopoulos P, Santos-Ribeiro S, Polyzos NP, Tournaye H. A fresh look at the freeze-all protocol: a SWOT analysis. Hum Reprod. 2016;31:491–7.

    Article  PubMed  Google Scholar 

  17. Aflatoonian A, Oskouian H, Ahmadi S, Oskouian L. Can fresh embryo transfers be replaced by cryopreserved-thawed embryo trasnfers in assisted reproductive cycles? A randomized controlled trial. J Assist Reprod Genet. 2010;27:357–63.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozen-thawed embryo transfer in high responders. Fertil Steril. 2011;96:516–8.

    Article  PubMed  Google Scholar 

  19. Rodriguez-Purata J, Lee J, Whitehouse M, Duke M, Grunfeld L, Sandler B, et al. Reproductive outcome is optimized by genomic embryo screening, vitrification, and subsequent transfer into a prepared synchronous endometrium. J Assist Reprod Genet. 2016;33:401–12.

    Article  PubMed  Google Scholar 

  20. Chen ZJ, Shi Y, Sun Y, Zhang B, Liang X, Cao Y, et al. Fresh versus frozen embryos for infertility in the polycystic ovary syndrome. N Engl J Med. 2016;375:523–33.

    Article  PubMed  Google Scholar 

  21. Roque M, Valle M, Guimarães F, Sampaio M, Geber S. Freeze-all policy: fresh vs. frozen-thawed embryo transfer. Fertil Steril. 2015;103:1190–3.

    Article  PubMed  Google Scholar 

  22. Braga DP, Setti AS, Sávio Figueira RC, Azevedo MC, Iaconelli A Jr, Lo Turco EG, Borges E Jr. Freeze-all, oocyte vitrification, or fresh embryo transfer? Lessons from an egg-sharing donation program. Fertil Steril 2016.

  23. Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L, et al. ESHRE consensus on the definition of “poor response” to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011;26:1616–24.

    Article  CAS  PubMed  Google Scholar 

  24. Geber S, Sales L, Sampaio MA. Laboratory techniques for human embryos. Reprod Biomed Online. 2002;5:211–8.

    Article  PubMed  Google Scholar 

  25. Geber S, Moreira AC, de Paula SO, Sampio M. Comparison between two forms of vaginally administered progesterone for luteal phase support in assisted reproduction cycles. Reprod Biomed Online. 2007;14:155–8.

    Article  CAS  PubMed  Google Scholar 

  26. Kuwayama M, Vajta G, Kato O, Leibo SP. Highly efficient vitrification method for cryopreservation of human oocytes. Reprod Biomed Online. 2005;11:300–8.

    Article  PubMed  Google Scholar 

  27. Almodin CG, Minguetti-Camara VC, Paixao CL, Pereira PC. Embryo development and gestation using fresh and vitrified oocytes. Hum Reprod. 2010;25:1192–8.

    Article  PubMed  Google Scholar 

  28. Clarke JF, van Rumste MME, Farquhar CM, Johnson NP, Mol BWJ, Herbison P. Measuring outcomes in infertility trials: can we rely on clinical pregnancy rates? Fertil Steril. 2010;94:1647–51.

    Article  PubMed  Google Scholar 

  29. Polyzos NP, Sunkara SK. Sub-optimal responders following controlled ovarian stimulation: an overlooked group? Hum Reprod. 2015;30:2005–8.

    Article  CAS  PubMed  Google Scholar 

  30. Drakopoulos P, Blockeel C, Stoop D, Camus M, de Vos M, Tournaye H, et al. Conventional ovarian stimulation and single embryo transfer for IVF/ICSI. How many oocytes do we need to maximize cumulative live birth rates utilization of all fresh and frozen embryos? Hum Reprod. 2016;31:370–6.

    PubMed  Google Scholar 

  31. AbdelHafez FF, Desai N, Abou-Setta AM, Falcone T, Goldfarb J. Slow freezing, vitrification and ultra-rapid freezing of human embryos: a systematic review and meta-analysis. Reprod Biomed Online. 2010;20:209–22.

    Article  PubMed  Google Scholar 

  32. Weinerman R, Mainigi M. Why we should transfer frozen instead of fresh embryos: the translational rationale. Fertil Steril. 2014;102:10–8.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Herrero L, Martínez M, Garcia-Velasco JA. Current status of human oocyte and embryo cryopreservation. Curr Opin Obstet Gynecol. 2011;23:245–50.

    PubMed  Google Scholar 

  34. Pavone ME, Innes J, Hirshfeld-Cytron J, Kazer R, Zhang J. Comparing thaw survival, implantation and live birth rates from cryopreserved zygotes, embryos and blastocysts. J Hum Reprod Sci. 2011;4:23–8.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Edgar DH, Gook DA. A critical appraisal of cryopreservation (slow cooling versus vitrification) of human oocytes and embryos. Hum Reprod Update. 2012;18:536–54.

    Article  PubMed  Google Scholar 

  36. Group P, Alviggi C, Andersen CY, Buehler K, Conforti A, De Placido G, et al. A new more detailed stratification of low responders to ovarian stimulation: from a poor response to a low prognosis concept. Fertil Steril. 2016;105:1452–3.

    Article  Google Scholar 

  37. Ubaldi F, Bourgain C, Tournaye H, Smitz J, Van Steirteghem A, Devroey P. Endometrial evaluation by aspiration biopsy on the day of oocyte retrieval in the embryo transfer cycles in patients with serum progesterone rise during follicular phase. Fertil Steril. 1997;67:521–6.

    Article  CAS  PubMed  Google Scholar 

  38. Kolibianakis E, Bourgain C, Albano C, Osmanagaoglu K, Smitz J, Van Steirteghem A, et al. Effect of ovarian stimulation with recombinant follicle-stimulating hormone, gonadotropin releasing hormone antagonists, and human chorionic gonadotropin on endometrial maturation on the day of oocyte pick-up. Fertil Steril. 2002;78:1025–9.

    Article  PubMed  Google Scholar 

  39. Labarta E, Martínez-Conejero JA, Alamá P, HOrcajadas JA, Pellicer A, Simón C, et al. Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011;26:1813–25.

    Article  CAS  PubMed  Google Scholar 

  40. Ji J, Liu Y, Tong XH, Luo L, Ma J, Chen Z. The optimum number of oocytes in IVF treatment: an analysis of 2455 cycles in China. Hum Reprod. 2013;28:2728–34.

    Article  PubMed  Google Scholar 

  41. Roque M, Valle M, Guimarães F, Sampaio M, Geber S. Cost-effectiveness of the freeze-all policy. JBRA Assist Reprod. 2015;19:125–30.

    Article  PubMed  Google Scholar 

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Acknowledgments

The English language editing of this manuscript was provided by the Journal Prep.

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Correspondence to Matheus Roque.

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The authors declare that they have no conflict of interest.

Additional information

Capsule Although the freeze-all policy may be related to better IVF outcomes in normal responders, these potential advantages decrease with worsening ovarian response. Patients with poorer ovarian response do not benefit from the freeze-all strategy. The implementation of an individualized embryo transfer (iET) would ultimately benefit patients with respect to IVF outcomes.

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Roque, M., Valle, M., Guimarães, F. et al. Freeze-all cycle for all normal responders?. J Assist Reprod Genet 34, 179–185 (2017). https://doi.org/10.1007/s10815-016-0834-x

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  • DOI: https://doi.org/10.1007/s10815-016-0834-x

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