Abstract
Objective
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.
Design
Retrospective case series and literature review.
Materials and methods
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.
Result(s)
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.
Conclusion(s)
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.
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References
Shibuya Y, Kyono K. A successful birth of healthy monozygotic dichorionic diamniotic (DD) twins of the same gender following a single vitrified-warmed blastocyst transfer. J Assist Reprod Genet. 2012;29(3):255–7. https://doi.org/10.1007/s10815-011-9707-5.
Corner GW. The observed embryology of human single-ovum twins and other multiple births. Am J Obstet Gynecol. 1955;70(5):933–51. https://doi.org/10.1016/0002-9378(55)90001-6.
Herranz G. The timing of monozygotic twinning: a criticism of the common model. Zygote. 2015;23(1):27–40. https://doi.org/10.1017/S0967199413000257.
Coutinho Nunes F, Domingues AP, Vide Tavares M, Belo A, Ferreira C, Fonseca E, et al. Monochorionic versus dichorionic twins: are obstetric outcomes always different? J Obstet Gynaecol J Inst Obstet Gynaecol. 2016;36(5):598–601. https://doi.org/10.3109/01443615.2015.1116501.
Tal R, Fridman D, Grazi RV. Monozygotic triplets and dizygotic twins following transfer of three poor-quality cleavage stage embryos. Case Rep Obstet Gynecol. 2012;2012:1–4. https://doi.org/10.1155/2012/763057.
Vitthala S, Gelbaya TA, Brison DR, Fitzgerald CT, Nardo LG. The risk of monozygotic twins after assisted reproductive technology: a systematic review and meta-analysis. Hum Reprod Update. 2009;15(1):45–55. https://doi.org/10.1093/humupd/dmn045.
Blickstein I, Verhoeven HC, Keith LG. Zygotic splitting after assisted reproduction. N Engl J Med. 1999;340(9):738–9. https://doi.org/10.1056/NEJM199903043400916.
Blickstein I, Jones C, Keith LG. Zygotic-splitting rates after single-embryo transfers in in vitro fertilization. N Engl J Med. 2003;348(23):2366–7. https://doi.org/10.1056/NEJMc026724.
Mateizel I, Santos-Ribeiro S, Done E, van Landuyt L, van de Velde H, Tournaye H, et al. Do ARTs affect the incidence of monozygotic twinning? Hum Reprod. 2016;31(11):2435–41. https://doi.org/10.1093/humrep/dew216.
Maheshwari A, Hamilton M, Bhattacharya S. Should we be promoting embryo transfer at blastocyst stage? Reprod BioMed Online. 2016;32(2):142–6. https://doi.org/10.1016/j.rbmo.2015.09.016.
Tarlatzis BC, Qublan HS, Sanopoulou T, Zepiridis L, Grimbizis G, Bontis J. Increase in the monozygotic twinning rate after intracytoplasmic sperm injection and blastocyst stage embryo transfer. Fertil Steril. 2002;77(1):196–8. https://doi.org/10.1016/S0015-0282(01)02958-2.
Jain JK, Boostanfar R, Slater CC, Francis MM, Paulson RJ. Monozygotic twins and triplets in association with blastocyst transfer. J Assist Reprod Genet. 2004;21(4):103–7. https://doi.org/10.1023/B:JARG.0000029493.54929.be.
Knopman JM, Krey LC, Oh C, Lee J, McCaffrey C, Noyes N. What makes them split? Identifying risk factors that lead to monozygotic twins after in vitro fertilization. Fertil Steril. 2014;102(1):82–9. https://doi.org/10.1016/j.fertnstert.2014.03.039.
Kanter JR, Boulet SL, Kawwass JF, Jamieson DJ, Kissin DM. Trends and correlates of monozygotic twinning after single embryo transfer. Obstet Gynecol. 2015;125(1):111–7. https://doi.org/10.1097/AOG.0000000000000579.
Tocino A, Blasco V, Prados N, Vargas MJ, Requena A, Pellicer A, et al. Monozygotic twinning after assisted reproductive technologies: a case report of asymmetric development and incidence during 19 years in an international group of in vitro fertilization clinics. Fertil Steril. 2015;103(5):1185–9. https://doi.org/10.1016/j.fertnstert.2015.01.033.
Ferreira M, Bos-Mikich A, Höher M, Frantz N. Dichorionic twins and monochorionic triplets after the transfer of two blastocysts. J Assist Reprod Genet. 2010;27(9–10):545–8. https://doi.org/10.1007/s10815-010-9446-z.
Kyono K. The precise timing of embryo splitting for monozygotic dichorionic diamniotic twins: when does embryo splitting for monozygotic dichorionic diamniotic twins occur? Evidence for splitting at the morula/blastocyst stage from studies of in vitro fertilization. Twin Res Hum Genet. 2013;16(4):827–32. https://doi.org/10.1017/thg.2013.32.
Meintjes M, Guerami AR, Rodriguez JA, Crider-Pirkle SS, Madden JD. Prospective identification of an in vitro-assisted monozygotic pregnancy based on a double-inner-cell-mass blastocyst. Fertil Steril. 2001;76(3):S172–3. https://doi.org/10.1016/S0015-0282(01)02509-2.
Langendonckt AV, Wyns C, Godin PA, Toussaint-Demylle D, Donnez J. Atypical hatching of a human blastocyst leading to monozygotic twinning: a case report. Fertil Steril. 2000;74(5):1047–50. https://doi.org/10.1016/S0015-0282(00)01554-5.
Behr B, Milki AA. Visualization of atypical hatching of a human blastocyst in vitro forming two identical embryos. Fertil Steril. 2003;80(6):1502–3.
Knopman J, Krey LC, Lee J, Fino ME, Novetsky AP, Noyes N. Monozygotic twinning: an eight-year experience at a large IVF center. Fertil Steril. 2010;94(2):502–10. https://doi.org/10.1016/j.fertnstert.2009.03.064.
Luke B, Brown MB, Wantman E, Stern JE. Factors associated with monozygosity in assisted reproductive technology (ART) pregnancies and risk of recurrence using linked cycles. Fertil Steril. 2014;101(3):683–9. https://doi.org/10.1016/j.fertnstert.2013.11.034.
Derom C, Vlietinck R, Thiery E, Leroy F, Fryns J-P, Derom R. The East Flanders Prospective Twin Survey (EFPTS). Twin Res Off J Int Soc Twin Stud. 2002;5(5):337–41. https://doi.org/10.1375/136905202320906057.
Osianlis T, Rombauts L, Gabbe M, Motteram C, Vollenhoven V. Incidence and zygosity of twin births following transfers using a single fresh or frozen embryo. Hum Reprod Oxf Engl. 2014;29(7):1438–43. https://doi.org/10.1093/humrep/deu064.
Takehara I, Takahashi T, Hara S, Matsuo K, Igarashi H, Kurachi H. Dizygotic twin pregnancy after single embryo transfer: a case report and review of the literature. J Assist Reprod Genet. 2014;31(4):443–6. https://doi.org/10.1007/s10815-013-0170-3.
Hershlag A, Paine T, Cooper GW, Scholl GM, Rawlinson K, Kvapil G. Monozygotic twinning associated with mechanical assisted hatching. Fertil Steril. 1999;71(1):144–6.
Nakasuji T, Saito H, Araki R, Nakaza A, Nakashima A, Kuwahara A, et al. The incidence of monozygotic twinning in assisted reproductive technology: analysis based on results from the 2010 Japanese ART national registry. J Assist Reprod Genet. 2014;31(7):803–7. https://doi.org/10.1007/s10815-014-0225-0.
Elizur SE, Levron J, Shrim A, Sivan E, Dor J, Shulman A. Monozygotic twinning is not associated with zona pellucida micromanipulation procedures but increases with high-order multiple pregnancies. Fertil Steril. 2004;82(2):500–1. https://doi.org/10.1016/j.fertnstert.2004.02.106.
Alikani M, Noyes N, Cohen J, Rosenwaks Z. Monozygotic twinning in the human is associated with the zona pellucida architecture. Hum Reprod Oxf Engl. 1994;9(7):1318–21.
Kolibianakis EM, Devroey P. Blastocyst culture: facts and fiction. Reprod BioMed Online. 2002;5(3):285–93.
Dessolle L, Allaoua D, Fréour T, le Vaillant C, Philippe HJ, Jean M, et al. Monozygotic triplet pregnancies after single blastocyst transfer: two cases and literature review. Reprod BioMed Online. 2010;21(3):283–9. https://doi.org/10.1016/j.rbmo.2010.04.011.
Behr B, Fisch JD, Racowsky C, Miller K, Pool TB, Milki AA. Blastocyst-ET and monozygotic twinning. J Assist Reprod Genet. 2000;17(6):349–51. https://doi.org/10.1023/A:1009461213139.
Van de Velde H, Cauffman G, Tournaye H, Devroey P, Liebaers I. The four blastomeres of a 4-cell stage human embryo are able to develop individually into blastocysts with inner cell mass and trophectoderm. Hum Reprod. 2008;23(8):1742–7. https://doi.org/10.1093/humrep/den190.
López-Moratalla N, Cerezo M. The self-construction of a living organism. In: Terzis G, Arp R, editors. Information and living systems. Cambridge: The MIT Press; 2011. p. 177–204. https://doi.org/10.7551/mitpress/9780262201742.003.0008.
Redline RW. Nonidentical twins with a single placenta--disproving dogma in perinatal pathology. N Engl J Med. 2003;349(2):111–4. https://doi.org/10.1056/NEJMp030097.
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Sundaram, V., Ribeiro, S. & Noel, M. Multi-chorionic pregnancies following single embryo transfer at the blastocyst stage: a case series and review of the literature. J Assist Reprod Genet 35, 2109–2117 (2018). https://doi.org/10.1007/s10815-018-1329-8
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DOI: https://doi.org/10.1007/s10815-018-1329-8