Cumulative live birth rate in freeze-all cycles is comparable to that of a conventional embryo transfer policy at the cleavage stage but superior at the blastocyst stage

In a heterogeneous cohort of patients, the overall cumulative live birth rate of a freeze-all approach seems to prevail if embryo cryopreservation is carried out at the blastocyst stage.

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Volume 110, Issue 4, Pages 703–709


Carlotta Zacà, B.Sc., Antonia Bazzocchi, M.D., Francesca Pennetta, B.Sc., Maria Antonietta Bonu, B.Sc., Giovanni Coticchio, Ph.D., Andrea Borini, M.D.



To determine whether the freeze-all policy ensures a higher efficacy in terms of cumulative live birth rate (CLBR) in comparison with a conventional fresh/frozen embryo transfer (ET) approach in patients with normal ovarian response.


Retrospective, matched, multicenter cohort study.


Private IVF centers.


This study analyzed 564 completed IVF cycles in which an average of 12–18 oocytes were retrieved. In 435 cycles the conventional strategy was applied, with initial ET followed by frozen embryo replacements, whereas in 129 cycles the freeze-all policy was performed, with elective cryopreservation and deferred use of all viable embryos.



Main Outcome Measure(s)

The primary endpoint was CLBR. The secondary endpoint was cumulative clinical pregnancy rate.


Overall, statistically comparable CLBRs were achieved in the fresh/frozen and freeze-all groups (45.5% vs. 53.5%). Stratification of data for age and number of retrieved oocytes confirmed the absence of differences between the two groups. In a subanalysis in which the day of ET and cryopreservation were taken into account, a similar outcome was achieved in cleavage-stage groups (45.6% vs. 46.4%), whereas when ET was performed at the blastocyst stage the CLBR was significantly higher in the freeze-all group (45.3% vs. 66.7%).


Our CLBR analysis indicates that clinical performance of the freeze-all policy is equivalent to that of the conventional strategy when ET is carried out at the cleavage stage. However, it seems to be superior if associated with cryopreservation and transfer at the blastocyst stage.

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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. 


Go to the profile of Hazout Andre
over 3 years ago

We can only agree with the conclusions of the authors not only in terms of results but also in terms of economy of the major IVF centers. Indeed in all cases, and in our experience, in women over 35 years, embryo culture untill blastocyst stage has a diagnostic and prognostic value and becomes a way to conclude after many failures. The embryonic culture up to the blastocyst stage should definitely be the must. Nevertheless, the opacity in the composition of the culture media and the famous precautionary principle do not commit to substantial progress. We believe that biologists should only use media of known composition and / or, as needed, some substances may be added.

Go to the profile of Iavor K Vladimirov
over 3 years ago

Congratulations for this nice work. The big question is why ET is performed at the blastocyst stage the CLBR is significantly higher in the freeze-all groups?  I would try to give explanation for this phenomena. After embryo thawing, a rapid recovery and increase in mitochondrial activity in the trophectodermal cells (1) is observed, which resembles the physiological mechanism in cells prior to implantation of the embryo (2). The embryo freezing and thawing processes cause activation of various physiological processes in the cells, which have a "treatment" effect on the embryo and increase its implantation potential (3).

Iavor K. Vladimirov MD, PhD


1.  Yamanaka M, Hashimoto S, Amo A et al. Developmental assessment of human vitrified-warmed blastocysts based on oxygen consumption. Hum Reprod. 2011; 26:3366-3371.

2. St John JC, Facucho-Oliveira J, Jiang Y et al. Mitochondrial DNA transmission, replication and inheritance: a journey from the gamete through the embryo and into offspring and embryonic stem cells. Hum Reprod Update. 2010; 16: 488–509.

3. Vladimirov IK, Tacheva D, Diez A. Theory about the Embryo Cryo-Treatment. Reprod Med Biol. 2017 Apr 5; 16 (2):118-125.