Zygotic splitting following embryo biopsy: a cohort study of 207 697 single‐embryo transfers following IVF treatment

Abstract

Objective To evaluate the risk of monozygotic splitting with embryo biopsy during in vitro fertilisation (IVF). Design A cohort study. Setting Anonymised assisted reproductive technology national data from the Human Fertilisation and Embryology Authority, UK. Population Women undergoing single‐embryo transfer (SET) following either pre‐implantation genetic testing (PGT) involving embryo biopsy or IVF without PGT. Methods Data on women undergoing SET either following PGT and non‐PGT IVF treatment in 2000–2016 were analysed to compare the risk of zygotic splitting and monozygotic twining. Logistic regression analysis was performed adjusting for potential confounders. Main outcomes Monozygotic spitting, monozygotic twin birth. Results Data comprising a total of 207 697 SET cycles (4544 following PGT and 203 153 following non‐PGT IVF) were analysed. The live birth rate per embryo transfer was 31.9% (95% confidence interval [CI] 30.5–33.2%) following PGT and 26.9% (95% CI 26.7–27.1%) following non‐PGT IVF. The incidence of zygotic splitting following PGT was 2.4% (95% CI 1.7–3.3%) versus 1.5% (95% CI 1.4–1.6%) following non‐PGT IVF. There was a significantly higher risk of zygotic splitting with PGT versus non‐PGT IVF cycles (odds ratio [OR] 1.64, 95% CI 1.19–2.27). The higher risk of zygotic splitting with PGT cycles remained significant after adjusting for potential confounders (adjusted OR 1.51, 95% CI 1.06–2.15). Conclusions The present study demonstrated an increased risk of monozygotic splitting with embryo biopsy. Given the current sparse literature, it is important to accumulate further evidence to validate the findings. Tweetable abstract A likely increased risk of monozygotic splitting following embryo biopsy.

Cloning in action: can embryo splitting, induced pluripotency and somatic cell nuclear transfer contribute to endangered species conservation?

“…While the common practice of transferring multiple embryos to increase pregnancy chances is widely known to increase the incidence of dizygotic twins in ART pregnancies, a definitive mechanism to explain the association between ART and MZ twinning remains elusive. Several associations have been drawn in attempts to tease out the cause of MZ twinning in ARTs; prolonged in vitro culture (Liu et al ., 2018a) and embryo biopsy (Kamath, Antonisamy & Sunkara, 2020; Sellers et al ., 2020), as well as maternal age (Liu & Shi, 2021), have been put forward as risk factors. Curiously, MZ twinning appears to be more likely when transferring blastocysts versus cleavage‐stage embryos (MacKenna et al ., 2020).…”

Uterine Transplantation: Review of Livebirths and Reproductive Implications

“…89 Moreover, risk increases after embryo biopsy, in which a recent study identified an increase from 1.5% in non-PGT-A cycles to 2.4% after PGT-A cycles. 90 Optimizing pregnancy rates may not only have psychological and economic benefits, 91 but it could also reduce graft longevity and therefore cumulative immunosuppression exposure. Published reproductive outcomes following UTx remain limited, with most studies awaiting pregnancy or livebirth before reporting.…”

Preimplantation Genetic Testing: Where We Are Today

“…In addition, also a systematic review, pooling results from four studies, reported no increased risk of monozygotic twinning after PGT as compared with IVF without PGT [144]. However, Kamath et al [145] evaluated data from 207,697 SET cycles being performed mainly in women aged <35 years with no infertility diagnosis; many of the cycles were performed as part of a PGT-M or PGT-SR program. There was a significantly higher risk of zygotic splitting with PGT versus non PGT IVF cycles (2.4% vs. 1.5%), even after adjustment for potential confounders.…”