Development of children born from freeze-only versus fresh embryo transfer: follow-up of a randomized controlled trial

Lan Ngoc Vuong*, Trung Thien Ly, Nghia An Nguyen, Loc Minh Tai Nguyen, Xuyen Thi Ha Le, Tien Khac Le, Khanh Tuan Quoc Le, Thanh Van Le, Minh Hoang Nhat Nguyen, Vinh Quang Dang, Robert J. Norman, Ben Willem Mol, Tuong Manh Ho

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Objective: To compare the longer-term development outcomes in children born after freeze-only versus fresh embryo transfer (ET) in women with an ovulatory cycle. Design: Long-term follow-up study (NCT04099784) of babies born alive after the first ET in a randomized controlled trial (RCT) comparing ongoing pregnancy and live birth rates after use of a freeze-only versus fresh ET strategy (NCT02471573). Setting: Private clinic. Patient(s): Of 391 couples randomized to each treatment group in the RCT, 132 (97 singleton/35 twins) and 123 (95 singleton/28 twins) in the freeze-only and fresh ET groups had live birth; 113 parents (86%) from the freeze-only group (147 babies) and 99 (80%) from the fresh ET group (120 babies) returned questionnaires for this follow-up study. Intervention(s): Use of a freeze-only or fresh ET strategy after controlled ovarian hyperstimulation with a follicle-stimulating hormone/gonadotropin-releasing antagonist protocol. Main Outcome Measure(s): Developmental status at ≥2 years after birth, determined using the Developmental Red Flags and Ages & Stages Third Edition (ASQ-3) Questionnaires. Result(s): Mean age of children at the end of follow-up was 37 months. Height (95.0 ± 6.1 vs. 95.7 ± 5.6 cm) and weight (14.9 ± 2.6 vs. 14.8 ± 2.6 kg) were similar in the freeze-only and fresh ET groups (results were similar when singletons and twins were analyzed separately). Overall, ASQ-3 scores for problem solving were significantly better in the freeze-only versus fresh ET group (overall: 53.6 ± 8.4 vs. 51.1 ± 10.2), with no significant between-group difference when singletons (52.3 ± 10.1 vs. 51.0 ± 9.9) and twins (55.0 ± 5.5 vs. 51.4 ± 11.1) were analyzed separately. Fine motor skills scores were numerically higher (with P values approaching statistical significance) in the freeze-only versus fresh ET group in the overall analysis (47.8 ± 11.6 vs. 44.9 ± 12.6) and twins (49.85 ± 8.72 vs. 43.93 ± 12.71), but not singletons (46.0 ± 13.4 vs. 45.4 ± 12.6). The overall proportion of children with abnormal ASQ-3 (6.8% vs. 8.3%) or abnormal Red Flags (5.4% vs. 6.7%) findings in the freeze-only and fresh ET groups was low and did not differ significantly between groups. Conclusion(s): These data provide physicians with additional information on which to base decisions about the relative merits of different approaches to infertility treatment. There do not appear to be any grounds for concern about worse outcomes after use of a freeze-only strategy. However, additional studies comparing childhood development after a freeze-only strategy, fresh ET, and natural cycles are needed before firm conclusions can be drawn.

Original languageEnglish
Pages (from-to)558-566
Number of pages9
JournalFertility and Sterility
Issue number3
Early online date16 Jun 2020
Publication statusPublished - 1 Sept 2020


  • ASQ-3
  • development outcomes
  • frozen embryo transfer
  • In vitro fertilization
  • Red Flag sign


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