The IVF Twinning Mystery: Why Blastocyst Transfers Can Result in Multi-Chorionic Pregnancies
"Challenging the Conventional Wisdom: A Deep Dive into Monozygotic Multi-Chorionic Pregnancies Following Single Embryo Transfer at the Blastocyst Stage"
For decades, the understanding of how twins form after fertilization has been relatively straightforward: the timing of when a single embryo splits determines the type of twin gestation. Dichorionic-diamniotic (DC-DA) twins, where each fetus has its own placenta and amniotic sac, were thought to arise only from embryos splitting within the first three days after fertilization. After that, the thinking went, only monochorionic twins (sharing a placenta) could develop.
However, in vitro fertilization (IVF) has thrown a wrench into this long-held belief. While IVF is known to increase the overall rate of multiple pregnancies (mostly dizygotic, or fraternal twins, due to transferring multiple embryos), it's also been linked to a higher incidence of monozygotic (identical) twins. Even more intriguing is the emerging evidence that blastocyst transfer, a common IVF practice, can sometimes lead to multi-chorionic pregnancies challenging the existing dogma.
This article delves into the fascinating phenomenon of multi-chorionic pregnancies arising from single blastocyst transfers. It examines a case series and reviews existing literature to shed light on this unexpected outcome, exploring the potential factors involved and what it means for our understanding of twinning and IVF.
U.S. Trends After Single Embryo Transfer
A retrospective cohort study examined 28,596 pregnancies after fresh, nondonor single embryo transfer reported to the U.S. National ART Surveillance System from 2003 to 2012. The researchers evaluated trends in monozygotic twin pregnancies and their association with patient and treatment factors. The study also aimed to assess risk factors by day of transfer, but the supplied source material does not give the resulting rates or specific risk-factor findings.
Single-Embryo Transfer and Twinning Risks
Single-embryo transfer is encouraged in IVF because it lowers multiple-pregnancy rates, but monozygotic twinning can still occur after transfer. A review’s meta-analysis found a statistically significant increased risk of monozygotic monochorionic twinning after extended embryo culture. One case-report source gives broad reported ranges: monozygotic twinning is approximately 0.4% in natural pregnancies and 0.2%–12% after IVF, while monozygotic dichorionic-diamniotic multifetal gestation after IVF is reported at 0.04%–5.5%. These ranges describe different outcomes and should not be treated as a single estimate.
Confirming Twin Zygosity
A 2015 report described twins whose pregnancy ultrasound suggested a possible dizygotic origin, but DNA analysis after birth established that they were monozygotic. The report concludes that genetic analysis is the only valid tool to confirm whether like-sex dichorionic twins are monozygotic or dizygotic. This highlights a limitation of relying on ultrasound appearance alone to determine zygosity.
Unraveling the Blastocyst Twinning Enigma: Challenging the Day 3 Split Theory
The conventional wisdom, initially presented by Corner in 1955, dictates that DC-DA twins can only form if the embryo divides within the first three days post-fertilization. Monochorionic-diamniotic (MC-DA) twins were believed to result from division between days 4 and 8, and monochorionic-monoamniotic (MC-MA) twins from division between days 9 and 12. Conjoined twins were considered possible only after day 13.
- Micromanipulation Techniques: Procedures like intracytoplasmic sperm injection (ICSI), assisted hatching, and preimplantation genetic screening (PGS) involve manipulating the zona pellucida (the outer shell of the embryo), which some studies suggest could increase the risk of monozygotic twinning. The mechanism is thought to be either a weakening of the zona, leading to easier splitting, or changes in cell-to-cell adhesion within the embryo.
- Extended Culture: Growing embryos in the lab for longer periods (to the blastocyst stage) might also contribute. Some propose that the culture media can harden the zona pellucida, causing the inner cell mass to pinch off and split during hatching.
- Atypical Hatching: In rare cases, the blastocyst might not hatch normally through a large slit in the zona. Instead, it could herniate through a small hole, leading to division into two halves, each with its own trophoectoderm (outer layer) and inner cell mass.
Dichorionic Twins After Single Blastocyst Transfer
A review of cellular mechanisms of monozygotic twinning notes reports of dichorionic twin pregnancies following single blastocyst transfers. The cited cases include reports by Klein (2005), Kyono (2013), Sundaram (2018), Konno, Li, and Neumann (2020), Dirican and Olgan (2021), Brouillet (2022), and Semrl (2023). The supplied material establishes that these cases have been reported, but does not specify a single mechanism that explains them.
Risk Factors Remain Unclear
A 2020 multicenter study notes that IVF is associated with a higher incidence of monozygotic twin pregnancies, which carry higher risks of major obstetric complications. It states that the reasons behind this association remain unclear and investigates risk factors in pregnancies achieved by IVF. A 2024 conference abstract likewise describes an investigation of risk factors for monozygotic twinning after IVF and embryo transfer, but the supplied abstract snippet provides no results.
ART and Spontaneous Monochorionic Twins
A 2022 systematic review and meta-analysis compared outcomes of monochorionic twin pregnancies conceived through assisted reproductive technology with those conceived spontaneously. The supplied source material does not report the review’s outcome estimates, so it does not support a conclusion about which group had better outcomes. A separate supplied overview distinguishes dizygotic twins, formed from two eggs fertilized by different sperm, from monozygotic twins, formed from one fertilized egg.
Re-evaluating Twinning Theories in the Age of IVF
The cases of multi-chorionic pregnancies arising from single blastocyst transfers challenge the long-held Corner's theory of embryonic division. While micromanipulation of the zona pellucida, extended culture, and rare occurrences of atypical hatching may all play a role, there is still much to learn about the precise mechanisms at play.
Studying Twins After Blastocyst Transfer
A 2024 study abstract reports examining monozygotic twins among 8,063 clinical pregnancies resulting from single blastocyst transfers performed from 2016 to 2023. It considered fresh and frozen blastocysts, with or without biopsy for preimplantation genetic testing and/or blastocyst collapse. The study tracked clinical pregnancy, embryo implantation including twin implantation, and outcomes such as live birth and ongoing pregnancy. The supplied material describes the study design but does not give its findings.
Continued scientific discussion and investigation are crucial to refine our understanding of monozygotic DC-DA twinning, particularly in the context of IVF. Advanced research may reduce the increased risk of monozygotic multiplets linked with IVF technologies. By carefully analyzing and considering these new realities, medical professionals can improve IVF outcomes, potentially reducing the occurrence of monozygotic multiples.
It's time to re-evaluate the traditional framework of twinning and accept that our understanding is evolving, due in large part to the advanced techniques used in modern fertility treatments.