Risk factors for monozygotic twinning after in vitro fertilization: a systematic review and meta-analysis

Abstract

Objectives: To establish the risk factors for monozygotic twin (MZT) and monochorionic twin (MCT) pregnancies after in vitro fertilization (IVF). Design: Systematic review and meta-analysis. Setting: Not applicable. Patient(s): Women who achieved MZT and non-MZT pregnancies through IVF. Intervention(s): Systematic search of Medline from January 1995 to October 2018 with cross-checking of references from relevant articles in English. Main Outcome Measure(s): Possible risk factors for MZT or MCT pregnancies after IVF, comprising extended embryo culture, insemination method (conventional IVF and intracytoplasmic sperm injection [ICSI]), embryo biopsy for preimplantation genetic testing for aneuploidies or for monogenic/single-gene defects (PGT-A or PGT-M) programs, assisted hatching (AH), oocytes donation, female age, and embryo cryopreservation. Result(s): A total of 40 studies were included. Blastocyst transfer compared with cleavage-stage embryo transfer, and female age <35 years were associated with a statistically significant increase in the

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

“…There has been consistent evidence of a higher risk of monozygotic twinning following ART compared with natural conception, 1.4% following ART versus 0.4% following natural conception; the high incidence with ART is in agreement with current study findings . This increased risk has been attributed to various underlying factors and processes involved in ART, such as ICSI, assisted hatching, embryo biopsy for pre‐implantation genetic testing for aneuploidies (PGT‐A), monogenic disorders (PGT‐M) and structural chromosomal rearrangements (PGT‐SR), extended embryo culture and embryo cryopreservation . Studies have shown a consistent association between extended embryo culture and embryo splitting .…”

“…The possible reasons for contradictory finding could be differences in embryo biopsy techniques, embryo biopsy at cleavage stage, inclusion of only blastocyst transfers, and limited sample size in the Belgian study . A systematic review reported no increased risk of monozygotic twinning following PGT compared with IVF without PGT after pooling results from four studies (55/2144 versus 336/20 320; OR 1.52, 95% CI 0.76–3.02) . After combining our current study results with the previous meta‐analysis, we found a trend towards increased monozygotic twinning following PGT versus IVF without PGT(94/3749 versus 1263/82 274; OR 1.56, 95% CI 0.99–2.46), but the difference was not statistically significant.…”

“…There is sparse literature on the risk of monozygotic splitting associated with pre‐implantation genetic testing (PGT), which involves embryo biopsy . A recent systematic review and meta‐analysis did not demonstrate an increased risk of monozygotic twinning with PGT than with IVF cycles without PGT . However, the total number of pooled events (monozygotic twins) in this review was 55 in the PGT group.…”

“…Studies have suggested that certain ART procedures are associated with increased risk of monozygotic twinning . Extended embryo culture and blastocyst stage transfers have been reported to be associated with increased incidence of monozygotic twinning .…”

“…Extended embryo culture and blastocyst stage transfers have been reported to be associated with increased incidence of monozygotic twinning . Other ART related techniques such as ovarian stimulation, intracytoplasmic sperm injection (ICSI), assisted hatching and cryopreservation of embryos have also been implicated to carry a risk of monozygotic twinning, although literature has been inconclusive . There is sparse literature on the risk of monozygotic splitting associated with pre‐implantation genetic testing (PGT), which involves embryo biopsy .…”