Routine Fresh or Frozen Embryo Transfers?

Two NEJM papers on the question require cautious interpretation

In recent years, a number of colleagues have been pushing the concept of so-called all-freeze IVF cycles. They have been arguing that pregnancy chances are better if embryos are not transferred in fresh cycle, as has been routine IVF practice for over 30 years, but if all embryos are frozen, and then transferred in subsequent cycles. The rationale behind this proposed practice change was the hypothesis that, with use of fertility drugs, stimulated cycles created an unfavorable uterine environment for implantation.

CHR VOICE on a number of previous occasions addressed this question, and we always pointed out in our comments that proponents of all-freeze cycles reported highly biased outcome statistics, and that, therefore, in our opinion evidence in support of such a radical practice change was lacking. We, indeed, concluded that multiple additional arguments favored transfer of fresh embryos:

Box 1: Arguments against routine all-freeze cycles

  • Reported outcome benefits do not hold up to scrutiny
  • Underlying hypothesis of poorer implantation environment in stimulated cycles has never been proven
  • Increased IVF cost to patients
  • Treatment delays
  • Increased difficulties in assessing a program’s IVF outcomes*
  • Recently reported randomized studies**
  • Differences in outcome benefits between specific patient populations

*CHR’s investigators recently demonstrated that a number of surprisingly prominent IVF centers abuse the concept of all-freeze cycle to manipulate their centers’ reported outcomes. These centers push their pregnancy rates upwards by excluding poor prognosis patients from reporting, via the concept of “embryo banking” [Kushnir et al., CDC-reported assisted reproductive technology live-birth rates may mislead the public. Reprod Biomed Online 2017;35(2):161-164]
**The two papers recently published in the New England Journal of Medicine and discussed here.

We do not want to be repetitive here, but two large, recently published prospectively randomized studies from China and Vietnam, respectively, in the prestigious New England Journal of Medicine [Shi et al., N Engl J Med 2018;378(2):126-136 and Vuong et al., New Engl J Med 2018;378(2):137-147] demonstrated conclusively that there was no outcome advantage in live birth rates in transferring frozen embryos in subsequent cycles. Indeed, IVF outcomes were identical.

What, however, neither authors of both studies, nor the lay media reporting on these two studies commented on, was that both studies were performed in only very good prognosis patients with excellent pregnancy and live birth chances. These data, therefore, are not applicable to poorer prognosis patients, with much lower pregnancy and live birth chances.

In poor prognosis patients, considerable data, indeed, suggest that embryo survival after cryopreservation and thawing is much poorer. In such patients, unnecessary freezing of embryos will, therefore, with great likelihood reduce cumulative pregnancy chance.

Box 2: Medical indications for embryo cryopresearvation

  • Threat of Ovarian Hyperstimulation Syndrome (OHSS)
  • Excessive progesterone rises in follicular phase
  • Inadequate endometrial thickness or other endometrial abnormalities
  • Excessive number of embryos
  • Embryo banking to reach adequate embryo numbers*

*We consider this a very questionable indication since women with small embryo numbers usually are poor prognosis patients, and such patients’ cumulative pregnancy chances are usually reduced by freezing of embryos.

CHR, therefore, maintains its position that there is no good reason for elective embryo cryopreservation, though, of course, there are many good medical reasons for cryopreservation (see Box 2), and both of above noted recent studies demonstrate in their excellent IVF outcomes how much progress the field has made in the quality of cryopreservation of embryos.

This is a part of the February 2018 CHR VOICE.

Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned reproductive endocrinologist, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.