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.
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).
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.
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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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.
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.
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.
Roque M. Freeze-all policy: Is it time for that? J Assist Reprod Genet. 2015;32:171–6.
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.
Barnhart KT. Are we ready to eliminate the transfer of fresh embryos in in vitro fertilization? Fertil Steril. 2014;102:1–2.
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.
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.
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.
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.
Fatemi HM, Popovic-Todorovic B. Implantation in assisted reproduction: a look at endometrial receptivity. Reprod Biomed Online. 2013;27:530–8.
Achache H, Ravel A. Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update. 2006;12:731–46.
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.
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.
Devroey P, Polyzos NP, Blockeel C. An OHSS-Free Clinic by segmentation of IVF treatment. Hum Reprod. 2011;26:2593–7.
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.
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.
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.
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.
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.
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.
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.
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.
Geber S, Sales L, Sampaio MA. Laboratory techniques for human embryos. Reprod Biomed Online. 2002;5:211–8.
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.
Kuwayama M, Vajta G, Kato O, Leibo SP. Highly efficient vitrification method for cryopreservation of human oocytes. Reprod Biomed Online. 2005;11:300–8.
Almodin CG, Minguetti-Camara VC, Paixao CL, Pereira PC. Embryo development and gestation using fresh and vitrified oocytes. Hum Reprod. 2010;25:1192–8.
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.
Polyzos NP, Sunkara SK. Sub-optimal responders following controlled ovarian stimulation: an overlooked group? Hum Reprod. 2015;30:2005–8.
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.
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.
Weinerman R, Mainigi M. Why we should transfer frozen instead of fresh embryos: the translational rationale. Fertil Steril. 2014;102:10–8.
Herrero L, Martínez M, Garcia-Velasco JA. Current status of human oocyte and embryo cryopreservation. Curr Opin Obstet Gynecol. 2011;23:245–50.
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.
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.
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.
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.
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.
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.
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.
Roque M, Valle M, Guimarães F, Sampaio M, Geber S. Cost-effectiveness of the freeze-all policy. JBRA Assist Reprod. 2015;19:125–30.
The English language editing of this manuscript was provided by the Journal Prep.
Conflict of interest
The authors declare that they have no conflict of interest.
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
- Freeze-all policy
- Elective frozen-thawed embryo transfer
- Delayed frozen-thawed embryo transfer
- Embryo cryopreservation