An Randomized Double Blind Controlled Trial of niPGT-A in Women With RPL

Objectives: To compare the efficacy in embryo selection based on morphology alone compared to morphology and non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) in women with recurrent pregnancy loss (RPL) undergoing in vitro fertilization (IVF).Hypothesis to be tested: The embryo selection based on morphology and niPGT-A results in a lower miscarriage rate and a higher live birth rate in IVF as compared with that based on morphology alone.Design and subjects: Randomized double-blind randomized controlled trial. Women with RPL undergoing IVF will be enrolled.Interventions: Spent culture medium (SCM) of each blastocyst will be frozen individually. They will be randomly allocated into two groups: (1) the intervention group based on morphology and niPGT-A and (2) the control group based on morphology alone.In the control group, blastocysts with the best quality morphology will be replaced first. In the intervention group, blastocysts with the best morphology and euploid result of SCM will be replaced first.Main outcome measures: The primary outcome is the miscarriage rate per the first embryo transfer.Data analysis: Comparison of quantitative variables will be performed using Student's t, while categorical variables will be compared using a Chi-square analysis. All statistical analyses will be performed with the intention to treat and per protocol, and a p-value <0.05 will be considered statistically significant.Expected outcome results: The embryo selection based on morphology and niPGT-A results in a lower miscarriage rate and a higher live birth rate in IVF as compared with the control group based on morphology alone.

Inclusion Criteria:Women aged less than 40 years at the time of ovarian stimulation and>=two spontaneous miscarriages in the first trimesterUnexplained recurrent pregnancy loss after standard investigationAt least one blastocyst available on day 5 or 6 after the retrieval.Exclusion Criteria:Women undergoing PGT for monogenic diseases or structural rearrangement of chromosomes;Use of donor oocytes;Hydrosalpinx shown on pelvic scanning and not surgically treatedUterine anomalies distorting the uterine cavity in three dimensional ultrasoundNo usable blastocysts on day 5 or 6 after the retrieval