Fresh vs. frozen embryo transfer: evidence from registry data vs. randomized trials

We welcome the article by Weiss et al. ( 1 Weiss M.S. Luo C. Zhang Y. Chen Y. Kissin D.M. Satten G.A. et al. Fresh vs. frozen embryo transfer: new approach to minimize the limitations of using national surveillance data for clinical research. Fertil Steril. 2023; 119: 186-194 Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar ), who compared fresh vs. frozen single embryo transfer using national surveillance data. They compared the results of their study with those of our randomized trial ( 2 Wei D. Liu J.Y. Sun Y. Shi Y. Zhang B. Liu J.Q. et al. Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial. Lancet. 2019; 393: 1310-1318 Abstract Full Text Full Text PDF PubMed Scopus (236) Google Scholar ) by applying “similar” eligibility criteria. However, there were differences in the included patients between the 2 studies. We screened patients on day 3 of embryo culture, and those with 4 or more cleavage-stage embryos were randomly assigned to minimize the risk of failure of blastocyst formation. However, the patients in their study were those with 4 or more blastocysts, reflecting a better ovarian response and prognosis than those of our patients, as evidenced by more oocytes (averaged at 22 and 17 in their patients vs. 14 in our patients), more embryos created (averaged at 8 and 7 blastocysts in their patients and 7 cleavage-stage embryos in our patients), and a larger percentage of infertility due to male factor (approximately 40% in their patients vs. 20% in our patients). Furthermore, although the reason for “freeze all” was absent, it is likely that a significant proportion of patients in their frozen embryo transfer (FET) group were not elective “freeze all,” but rather were forced by an elevated risk of ovarian hyperstimulation syndrome (OHSS), as evidenced by the 4 times higher risk of moderate or severe OHSS in the FET group than in the fresh transfer group (2.8% vs. 0.7%), whereas the risk of OHSS in our FET group was half of that in the fresh transfer group (0.5% vs. 1.1%). Reply of the Authors: Fresh vs. frozen embryo transfer: new approach to minimize the limitations of using national surveillance data for clinical researchFertility and SterilityVol. 119Issue 6PreviewWe thank Dr. Wei, Dr. Shapiro, and their colleagues for their letters to the Editor regarding our article published in Fertility and Sterility (1). We all agree that randomized controlled trials (RCTs) remain the gold standard for studying the effectiveness of interventions because they ensure that both known and unknown confounders are balanced between treatment groups. Recognizing that we will need to rely on retrospective surveillance data to answer many current and future questions pertaining to assisted reproductive technology, it is imperative that we determine the most accurate way to perform these analyses. Full-Text PDF