Abstract
Purpose
The aim of this analysis was to study whether monozygotic twinning (MZT) events occur in clusters after IVF and, if so, to explore possible explanations for this clustering.
Methods
This is a retrospective cohort study carried out in a single, large university-affiliated reproductive medicine practice. Medical records of all patients who had undergone fresh IVF cycles, resulting in a viable clinical pregnancy, from Jan 2002 to Dec 2013 were reviewed. The incidence of MZT in 6-month intervals and the association with independent risk factors such as maternal age, extended embryo culture, PGD/intracytoplasmic sperm injection (ICSI)/assisted hatching performed were analyzed.
Results
Over the 12-year study period, 25,502 fresh IVF cycles were performed, resulting in 8598 clinical pregnancies. Ninety-five cycles (1.1 %) resulted in MZ twins. The percentage of MZT was >2 standard deviations (SD) higher than the overall percentage of MZT in 4 of the 24 6-month intervals. PGD, extended embryo culture (≥4 days), and more recent cycles (2005 or later) were independent risk factors for MZT. The use of multivariable logistic regression modeling to control for risk factors for MZT did not correct for this clustering effect, with both high-risk interval (clustering) and extended embryo culture remaining significant.
Conclusion
This study supports our hypothesis that MZT occurs in clusters and that this clustering effect could not be explained by demographics and cycle characteristics alone. Although we are unable to explain the clustering phenomenon, this study is important as it highlights high-risk intervals for MZT and opens the door to performing a more detailed investigation, to identify the mechanisms responsible for the spikes of MZT incidence.
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Ms. Ruthazer’s institution (Tufts Clinical and Translational Science Institute, Tufts University) was reimbursed for statistical support. Dr Penzias is a paid consultant for OvaScience and receives payment for lectures including service on speaker bureaus for Ferring Pharmaceuticals.
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Capsule This study supports our hypothesis that MZT occurs in clusters and that this clustering effect could not be explained by demographics and cycle characteristics alone.
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Supplemental figure 1
Bar chart denoting MZT events based on interval (days) between events. 68% of MZT events had an interval <46.2 days apart, which would be the expected interval if MZT events were uniformly distributed and 50% should have occurred. The “p value” for the z-test against a null of 50% is 0.0003. (GIF 77 kb)
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Vaughan, D.A., Ruthazer, R., Penzias, A.S. et al. Clustering of monozygotic twinning in IVF. J Assist Reprod Genet 33, 19–26 (2016). https://doi.org/10.1007/s10815-015-0616-x
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DOI: https://doi.org/10.1007/s10815-015-0616-x