title: Clustering of monozygotic twinning in IVF.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Tufts Medical Center, 800 Washington St, Boston, MA, 02111, USA. DVaughan1@tuftsmedicalcenter.org.
authors.forename: Denis A
authors.initials: DA
authors.lastname: Vaughan
authors.affiliation: Research Design Center/ Biostatistics Research Center, Tufts Clinical and Translational Science Institute, Boston MA and Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University, 35 Kneeland St, 7th-11th Floors, Boston, MA, 02111, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Ruthazer
authors.affiliation: Boston IVF, 130 Second Avenue, Waltham, MA, 02451, USA.|Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215, USA.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Penzias
authors.affiliation: Department of Obstetrics and Gynecology, Tufts Medical Center, 800 Washington St, Boston, MA, 02111, USA.
authors.forename: Errol R
authors.initials: ER
authors.lastname: Norwitz
authors.affiliation: Boston IVF, 130 Second Avenue, Waltham, MA, 02451, USA.
authors.forename: Denny
authors.initials: D
authors.lastname: Sakkas
mesh_terms: D000328:Adult; D004624:Embryo Transfer; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D008423:Maternal Age; D008499:Medical Records; D011247:Pregnancy; D020554:Sperm Injections, Intracytoplasmic; D038522:Twinning, Monozygotic
keywords: In vitro fertilization; Monozygotic twins; Risk factors; Trends