Multi-chorionic pregnancies following single embryo transfer at the blastocyst stage: a case series and review of the literature

To report cases of in vitro fertilization-frozen embryo transfer (IVF-FET) with single blastocyst transfer resulting in di- or tri-chorionic pregnancies, and to review the literature on monozygotic, multi-chorionic pregnancies originating at the blastocyst stage.

Retrospective case series and literature review.

All in vitro fertilization cycles (fresh, frozen, autologous, and donor oocyte) performed between June 2012 and June 2017 at the University of California, San Francisco Center for Reproductive Health, were reviewed retrospectively. Cycles with cleavage-stage embryos or transfer of more than one blastocyst were excluded. Cycles were analyzed to determine if clinical pregnancy occurred with the presence of two or more gestational sacs noted on initial ultrasound. An in-depth chart review was performed with further exclusions applied that would lend credence to dizygosity rather than monozygosity such as fetal/neonatal sex discordance, fresh embryo transfer, and natural cycle FET (in which concomitant spontaneous pregnancy could have occurred). Demographic, clinical and IVF-FET cycle characteristics of the resulting patients were collected. Additionally, a review of the English language literature was performed (PUBMED, PMC) using the search words monozygotic twins, dichorionic diamniotic, in vitro fertilization, and single embryo transfer in order to identify cases of DC-DA monozygotic twinning from 1978 to 2017. Resulting articles were reviewed to eliminate all cases of dizygosity and day 3 embryo transfers. We obtained the following data from the literature search: basic patient demographics, type of fertilization, type and day of embryo transferred, number of embryos transferred, gestational ultrasound details, presence of any genetic testing if performed after delivery, and number of live births.

Two thousand four hundred thirty-four women underwent fresh or frozen single embryo transfer between June 2012 and June 2017 at the University of California, San Francisco Center for Reproductive Health. Of these, 11 women underwent a single blastocyst transfer with subsequent clinical pregnancies identified as multi-chorionic gestations. Four were in downregulated controlled FET cycles, in which concomitant spontaneous pregnancy could not have been possible. We then reviewed all cases of monozygotic dichorionic-diamniotic (DC-DA) splitting in IVF patients reported in the literature from 1978 to 2017. These eight cases demonstrate monozygotic splitting after the blastocyst stage, which challenges the existing dogma that only monochorionic twins can develop after day 3 post-fertilization.

The accepted theory of monozygotic twinning resulting from the splitting of an embryo per a strict post-fertilization timing protocol must be re-examined with the advent of observed multi-chorionic pregnancies resulting from single blastocyst transfer in the context of IVF.