Effect of noninvasive embryo viability testing versus conventional IVF on the live birth rate in IVF/ICSI patients: a study protocol for a double-blind, multicenter, randomized controlled trial.

BACKGROUND: Preimplantation genetic testing for aneuploidy (PGT-A) was demonstrated to be superior to conventional IVF in reducing the incidence of miscarriage and abnormal offspring after the first embryo transfer (ET). PGT-A requires several embryo trophectoderm cells, but its negative impacts on embryo development and long-term influence on the health conditions of conceived children have always been a concern. As an alternative, noninvasive PGT-A (niPGT-A) approaches using spent blastocyst culture medium (SBCM) achieved comparable accuracy with PGT-A in several pilot studies. The main objective of this study is to determine whether noninvasive embryo viability testing (niEVT) results in better clinical outcomes than conventional IVF after the first embryo transfer. Furthermore, we further investigated whether niEVT results in higher the live birth rate between women with advanced maternal age (AMA, > 35 years old) and young women or among patients for whom different fertilization protocols are adopted. METHODS: This study will be a double-blind, multicenter, randomized controlled trial (RCT) studying patients of different ages (20-43 years) undergoing different fertilization protocols (in vitro fertilization [IVF] or intracytoplasmic sperm injection [ICSI]). We will enroll 1140 patients at eight reproductive medical centers over 24 months. Eligible patients should have at least two good-quality blastocysts (better than grade 4 CB). The primary outcome will be the live birth rate of the first embryo transfer (ET). Secondary outcomes will include the clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, cumulative live birth rate, ectopic pregnancy rate, and time to pregnancy. DISCUSSION: In this study, patients who undergo noninvasive embryo viability testing (niEVT) will be compared to women treated by conventional IVF. We will determine the effects on the pregnancy rate, miscarriage rate, and live birth rate and adverse events. We will also investigate whether there is any difference in clinical outcomes among patients with different ages and fertilization protocols (IVF/ICSI). This trial will provide clinical evidence of the effect of noninvasive embryo viability testing on the clinical outcomes of the first embryo transfer. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) Identifier: ChiCTR2100051408. 9 September 2021.

Optimal Follow-Up Duration for Assessment of Birth Defects After In Vitro Fertilization-Embryo Transfer: A Multicenter 5-Year Cohort Study in China.

Objective: To investigate the impact of a 5-year follow-up on the incidence of identified birth defects in children conceived using assisted reproductive technologies (ART). Methods: A 5-year cohort study was performed in three ART centers from January 2013 to October 2018. 1,543 women with 1,985 infants who delivered successfully or underwent termination of pregnancy due to malformations were recruited in this study. Follow-up was conducted by phone interview, 7 days, 1 year, 3 years, and 5 years after birth. Collected data included whether one or more birth defects were diagnosed, the category of birth defects, and when the malformation was diagnosed. Cumulative incidence of birth defects and the loss to follow-up rate of each follow-up was compared. Results: According to the diagnostic criterion of birth defects, 111 cases of one or more birth defects were recorded, with a total of 117 birth defects after the 5-year follow-up. 0.2% (4/1,985) of birth defects were diagnosed before delivery; 2.7% (54/1,985) at 7 days; 5.0% (100/1,985) after 1 year; 5.5% (109/1,985) after 3 years; and 5.6% (111/1,985) after 5 years. 3.4% (4/117) of defects were diagnosed prenatally, 45.3% (53/117) of defects diagnosed within the first 7 days after delivery, 40.2% (47/117) diagnosed during 7 days to 1 year, and 9.4% (11/117) of defects diagnosed in 1-3 years after birth. The remaining 1.7% (2/117) of defects were diagnosed between the ages of 3 and 5 years. Among the 1,543 patients, 99.9% patients (1,542/1,543) responded to the telephone interview at 7 days after delivery; the response rate was 89.0% (1,373/1,543) at 1 year, 81% (1,250/1,543) at 3 years, and 64.5% (995/1,543) after 5 years. Conclusion: We suggest that in ART, 1-year follow-up should be the minimum requirement and 3-year follow up the optimal length of follow-up that balances resource requirements with ascertainment completeness.