Freeze all policy fresh vs frozen thawed embryo transfer

Capsule:
Even in patients that undergo fresh embryo transfer without progesterone elevation, endometrial receptivity may be impaired by controlled ovarian stimulation, and outcomes may be improved by using the freeze-all policy.

Authors:
Matheus Roque, M.D., Marcello Valle, M.D., Fernando Guimarães, B.S., Marcos Sampaio, M.D., Ph.D., Selmo Geber, M.D., Ph.D.

Volume 103, Issue 5, Pages 1190-1193

Abstract:

Objective:
To compare in vitro fertilization (IVF) outcomes between fresh embryo transfer (ET) and frozen-thawed ET (the “freeze-all” policy), with fresh ET performed only in cases without progesterone (P) elevation.

Design:
Prospective, observational, cohort study.

Setting:
Private IVF center.

Patient(s):
A total of 530 patients submitted to controlled ovarian stimulation (COS) with a gonadotropin-releasing hormone–antagonist protocol, and cleavage-stage, day-3 ET.

Intervention(s):
None.

Main Outcome Measure(s):
Ongoing pregnancy rates.

Result(s):
A total of 530 cycles were included in the analysis: 351 in the fresh ET group (when P levels were ≤1.5 ng/mL on the trigger day); and 179 cycles in the freeze-all group (ET performed after endometrial priming with estradiol valerate, at 6 mg/d, taken orally). For the fresh ET group vs. the freeze-all group, respectively, the implantation rate was 19.9% and 26.5%; clinical pregnancy rate was 35.9% and 46.4%; and ongoing pregnancy rate was 31.1% and 39.7%.

Conclusion(s):
The IVF outcomes were significantly better in the group using the freeze-all policy, compared with the group using fresh ET. These results suggest that even in a select group of patients that underwent fresh ET (P levels ≤1.5 ng/mL), endometrial receptivity may have been impaired by COS, and outcomes may be improved by using the freeze-all policy.

  • Micah Hill

    An interesting article comparing results of fresh transfer when P 1.5. It is encouraging to see ongoing pregnancy rates of 40% in the FET group where P was elevated in the retrieval cycle.
    Unfortunately, I don’t think this study has appropriate comparison groups to be able to draw significant clinical conclusions from. Several studies demonstrate that patients with elevated P differ significantly from those with normal P in baseline and stimulation characteristics, and table 1 of this paper shows the same thing. So this study is comparing 2 different treatment strategies in 2 different patient populations. This makes it very difficult to draw clinical conclusions from. The comparisons of interest really are fresh versus FET in patients with elevated P and fresh versus FET in the general population. Unfortunately, we don’t have good prospective controlled data to answer either of these questions definitively yet.
    So while this study is interesting and the results in the FET cohort encouraging, this study can’t demonstrate either that freeze all is superior to fresh transfer in P >1.5 cycles or that freeze all is superior to fresh transfer in normal P cycles.
    Any thoughts from the authors on the concerns would be appreciated.

    • Shvetha Zarek

      The paper states that (frozen-thawed embryo transfer) FET cycles were cancelled if P was > 1.5 ng/ml. Specifically, in the section on “Frozen-Thawed Cycles”, “If the endometrium was 1.5 ng/mL after endometrial priming, the ET was canceled.” Thus, the two (fresh and frozen) cohorts had P1.5 in the RETRIEVAL cycle, however, most would say that it is the effects of P on the endometrium during the transfer cycle that is of primary relevance. Thus, this study demonstrates a valid comparison. If the authors could kindly clarify, that would be helpful.

      • Micah Hill

        Thanks for the comment Shvetha. Author clarification would be appreciated. My understanding was that P>1.5 resulted in cancelled fresh cycles and were sent to the FET cohort. “Fresh ET was performed only if P was1.5 ng/mL on the
        trigger day.”

  • Jane Doe

    I understand the science behind this, but I truly believe that “freeze all policies” are not in the best interest of the patients. Treatment should be individually based, not by wrote. I have never had an embryo make it to freeze. I have two children from IVF from day 3 transfers, one where I transferred 3 embryos because that was all we had left. The other, we had 5 remaining embryos, but it was determined that they would not survive cryo.

    Where does a policy like this leave a patient like me? Nowhere.

    • Shvetha Zarek

      Thank you for contributing with a valid point from your personal experience. Adopting a freeze all policy seems premature at this point. In addition, it suggests a “one size fits all” practice of medicine when we should be striving to personalize treatment and care. Thank you for your comments.

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