O-291 Clinical Application of Noninvasive PGT for Patients with Recurrent Pregnancy Loss or Repeated Implantation Failure
Authors: Li N , Zhao J , Xi H , Yao Y , Lu S 
Published: June 2023

Abstract

Study question
Has noninvasive PGT been allied with the patients experiencing recurrent pregnancy loss (RIF) and recurrent implantation failure (RPL)? What are the clinical beneficiaries?

Summary answer
Embryo selection through noninvasive PGT can reduce the miscarriage rate in patients experiencing RPL and improve the clinical pregnancy rate in patients experiencing RIF.

What is known already
Chromosomal abnormalities exist in early human embryos, especially in patients with RPL and RIF. Therefore, embryos are usually evaluated through pre-implantation genetic testing for aneuploidy (PGT-A). However, a biopsy is an important concern for undetermined health risks. Meanwhile, the researchers observed genomic DNA contents in the embryo culture medium. Since then, multiple studies have been published using culture medium for analyzing chromosomal ploidy. In 2016, Xu et al. first reported a noninvasive chromosome screening (NICS) assay using a spent blastocyst culture medium. Nevertheless, the clinical application of NICS has not been evaluated in patients experiencing RPL or RIF.

Study design, size, duration
We designed a retrospective cohort study including 303 subjects from July 2018 to May 2021, according to the records of the Reproductive Centre at the Second Affiliated Hospital of Wenzhou Medical University.
Patients experiencing RPL or RIF who received the NICS for aneuploidy were included in the NICS group, while those who underwent conventional morphology embryo transfer during the same period were included in the non-NICS group.

Participants/materials, setting, methods
We included women with a history of RPL (≥2 pregnancies) or RIF (≥3 implantations), exclusion criteria were antiphospholipid syndrome (APS), diabetes, hypothyroidism, or other severe complications.
Routine IVF/ICSI was performed based on sperm quality. The embryos were placed in droplets. Approximately 30 mL of blastocyst medium from each embryo was transferred into cell lysis buffer. Whole-genome amplification was performed using culture media, followed by library preparation using ChromInst (Yikon Genomics; EK100100724 NICS Inst Library Preparation Kit).

Main results and the role of chance
For the patients experiencing RPL, the miscarriage rate per FET was significantly lower in the NICS group than in the non-NICS group (17.9% vs. 42.6%), whereas the ongoing pregnancy rate (40.7% vs. 25.0%) and live birth rate (38.9% vs. 20.6%) were significantly higher in the NICS group compared to the non-NICS group. Nevertheless, no differences were identified in pregnancy rates per patient between the NICS and non-NICS groups (49.6% vs. 44.9%).
For the patients experiencing RIF, the pregnancy rates per FET were significantly higher in the NICS group than in the non- NICS group (46.9% vs. 28.7%), whereas the live birth rate and ongoing pregnancy rate per FET and per patient were no significant difference in the NICS group than in the non-NICS group. Nevertheless, no differences were identified in the miscarriage rate per clinical pregnancy between the NICS and non-NICS groups (23.3% vs. 25.9%).

Limitations, reasons for caution
As a retrospective study, patients in the NICS groups had different clinical prognoses than those in the non-NICS groups, introducing bias in the study results.

Wider implications of the findings
Non-invasive PGT can be used not only for aneuploidy detection but also for a comprehensive evaluation of morphology and DNA concentration, mosaic ratio, resolution, etc. The accumulation of clinical outcomes can also be combined with the clinical data of patients as an index to predict the clinical outcomes of embryos.

Trial registration number
NA