Blastocyst transfer is not associated with increased rates of monozygotic twins when controlling for embryo cohort quality

The association between blastocyst transfer and monozygotic twinning may be related to the high quality nature of the embryo cohort rather than the extended culture.

Jason M. Franasiak, M.D., Yelena Dondik, M.D., Thomas A. Molinaro, M.D., Kathleen H. Hong, M.D., Eric J. Forman, M.D., Marie D. Werner, M.D., Kathleen M. Upham, B.S., Richard T. Scott Jr., M.D.

Volume 103, Issue 1, Pages 95-100


To compare monozygotic twinning (MZT) rates in patients undergoing blastocyst or cleavage-stage ET.

Retrospective cohort.

Academic research center.

Autologous, fresh IVF cycles resulting in a clinical pregnancy from 1999 to 2014.


Main Outcome Measure(s):
Monozygotic twin pregnancy in blastocyst-stage transfer vs. cleavage-stage transfer when controlling for patient prognosis and embryo cohort quality factors.

There were a total of 9,969 fresh transfer cycles resulting in a pregnancy during the study period. Of these pregnancies, 234 monozygotic twin pregnancies were identified (2.4%). Of all transfers, 5,191 were cleavage-stage and 4,778 were blastocyst-stage transfers. There were a total of 99 MZT identified in the cleavage-stage group (1.9%) and 135 MZT in the blastocyst ET group (2.4%), which was significant. Multivariable logistic regression revealed that increasing age was associated with a significant reduction in MZT, regardless of transfer order. Embryo cohort quality factors, including the number and proportion of six- to eight-cell embryos and availability of supernumerary embryos, were also significant. When controlling for patient age, time period during which the cycle took place, the number and proportion of six- to eight-cell embryos, and availability of supernumerary embryos, there was no longer a difference in MZT rate between blastocyst and cleavage transfer.

Patient prognosis and embryo cohort quality seem to be major factors in MZT rate in women undergoing blastocyst transfer. Although technology-based effects cannot be excluded, patient and embryo characteristics play an important role.

  • Jason Franasiak

    Thank you for the comment Micah. We looked at embryo cohort quality by evaluating both the absolute number of embryos on day 3 in regards to the 6-8 cell status as well as the percentage of the overall cohort that met this criteria. As another marker of cohort quality, we looked at presence or absence of supranumerary embryos. Given that we were comparing cleavage and blast transfer we did not factor in scoring of the blastocyst ICM or TE, although this would be of interest. In terms of the conclusion of transfer order, this was in reference to Table 3 which details MZT rate for eSET vs DET when embryos remained. In patient that have a embryo cohort that has many embryos, suggestive of high cohort quality, an eSET was not associated with increased rates of MZT as compared to SET with no remaining embryos. When DET was performed with embryos remaining from cryopreservation (high quality cohort) vs DET when no embryos remain, there was a increased rate of MZT in that group. The biology is certainly not clear, but perhaps two high quality blastocysts have some sort of paracrine signaling which increases the chances of MZT? This assuredly requires more work to parse out.

    • Micah Hill

      Thank you for the information Jason, very fascinating! Ill be curious to see what parses out from this.

  • Micah Hill

    Jason, congratulations on the study and the results, which I found surprising! Can you clarify for me your results showing higher MZT with higher quality blastocysts? Are you saying higher quality embryos were more likely to have MZT? And was there a specific blastocyst morphologic feature associated with MZT (ie TE grade or ICM or expansion or hatching)? Or was it only day 3 features that were associated? Can you expand on what you mean in the conclusions “thus provides a mechanism by which clinicians can limitMZT risk by reducing transfer order”.

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