Lan Ngoc Vuong1, Trung Thien Ly2, Nghia An Nguyen3, Loc Minh Tai Nguyen4, Xuyen Thi Ha Le2, Tien Khac Le2, Khanh Tuan Quoc Le2, Thanh Van Le2, Minh Hoang Nhat Nguyen4, Vinh Quang Dang5, Robert J Norman6, Ben Willem Mol7, Tuong Manh Ho5. 1. Department of Obstetrics and Gynecology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam; HOPE Research Center, My Duc Hospital, Ho Chi Minh City, Vietnam. Electronic address: lanvuong@ump.edu.vn. 2. IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam. 3. Department of Pediatrics, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam. 4. HOPE Research Center, My Duc Hospital, Ho Chi Minh City, Vietnam. 5. IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam; HOPE Research Center, My Duc Hospital, Ho Chi Minh City, Vietnam. 6. Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia; Fertility SA, Adelaide, South Australia, Australia. 7. Department of Obstetrics and Gynaecology, School of Medicine, Monash University, Melbourne, Victoria, Australia.
Abstract
OBJECTIVE: To compare the longer-term development outcomes in children born afterfreeze-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 strategyafter 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.
RCT Entities:
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.