Retrospective evaluation of first-trimester miscarriage following euploid embryo transfer

This study investigated the possible causes of first-trimester miscarriages after euploid embryo transfer from both genetic and maternal perspectives.

Data were retrospectively collected from seven in-vitro fertilisation centres and two preimplantation genetic testing laboratories in Hong Kong. The study included patients who underwent preimplantation genetic testing for aneuploidy (PGT-A) between 2015 and 2024, followed by frozen-thawed single euploid embryo transfer resulting in confirmed clinical pregnancies that ended in miscarriage before 12 weeks of gestation. Baseline demographic data and, when available, genetic results for the products of gestation (POG) were reviewed.

In total, 1792 PGT-A cycles and 884 embryo transfers were performed. Sixty-five transfers resulted in clinical pregnancies that ended in miscarriage before 12 weeks of gestation. Genetic testing was conducted on 14 POG samples in this study. In one case, the PGT-A and POG results were discordant; mosaic trisomy 8 was detected only in the POG. No consistent pattern in maternal demographic factors was evident.

Preimplantation genetic testing for aneuploidy appears effective; the majority of firsttrimester miscarriages after euploid embryo transfers are unlikely to be explained by discordant PGT-A results. Despite its high accuracy, PGT-A cannot detect all forms of chromosomal mosaicism and therefore cannot completely prevent miscarriage. Reviews of clinical and medical histories, along with cytogenetic testing of POG after a miscarriage following euploid embryo transfer in selected cases, may provide additional insights into possible contributing factors and future management options. The underlying cause may remain unexplained in many cases.