In vitro fertilization (IVF) involves fertilizing an egg outside the body and transferring the resulting embryo into the uterus. A Single Embryo Transfer (SET) places only one viable embryo into the uterus, unlike the multiple transfers common in earlier IVF days. The primary goal of SET is to achieve a healthy, singleton pregnancy while eliminating the significant health risks associated with multiple gestations. Despite transferring only one embryo, it is still possible for the patient to become pregnant with twins. This unexpected outcome occurs when the single transferred embryo spontaneously divides, resulting in identical or monozygotic twins.
The Primary Goal of Single Embryo Transfer
SET was widely adopted to reduce the high-risk complications associated with multiple pregnancies. Dizygotic (fraternal) twins occur when two separate embryos implant, a risk virtually eliminated by transferring only one embryo. Historically, transferring multiple embryos frequently led to twin pregnancies, which carry substantial risks for both the mother and the developing fetuses.
Carrying twins significantly increases the risk of maternal complications such as preeclampsia and gestational diabetes. For the fetuses, the primary concerns are preterm birth and low birth weight, both linked to long-term health and developmental problems. By limiting the transfer to a single, high-quality embryo, reproductive medicine aims to mitigate these risks and maximize the chance of a successful, full-term, singleton birth. SET is widely recommended for patients with a good prognosis to ensure the healthiest outcome for mother and child.
The Mechanism of Identical Twinning After IVF
Twins emerging after a Single Embryo Transfer result from monozygotic splitting, which leads to identical twins. This occurs when the single embryo, after successful transfer and implantation, spontaneously divides into two genetically identical entities. Monozygotic twinning is rare in natural conception (about 0.4% of pregnancies), but the rate is significantly higher following IVF, ranging from about 1.2% to 8.9% in some studies.
The timing of this split dictates the type of placenta and amniotic sac structure the twins will develop, which is a key factor in managing the pregnancy. If the embryo splits within the first three days post-fertilization, the twins will typically be dichorionic-diamniotic, meaning they each have their own placenta and amniotic sac. A split occurring between four and eight days after fertilization results in monochorionic-diamniotic twins, where they share one placenta but have separate amniotic sacs. The most complex and highest-risk scenario is a split after eight days, leading to monochorionic-monoamniotic twins who share both a placenta and a single amniotic sac.
Procedural Factors That May Increase Splitting Risk
The increased rate of monozygotic twinning in IVF compared to natural conception suggests that specific laboratory procedures may influence the embryo’s tendency to split. One factor is the extended culture of the embryo to the blastocyst stage (Day 5 or Day 6) before transfer. Transferring a blastocyst, which is more developed, has a higher incidence of monozygotic twinning compared to transferring a less developed Day 2 or Day 3 cleavage-stage embryo.
Another procedural factor is the manipulation of the zona pellucida, the outer shell of the embryo. Techniques such as Assisted Hatching, where a small opening is created in the shell to aid implantation, have been associated with a greater risk of splitting, particularly with Day 2-3 transfers. The process of cryopreservation (freezing and thawing the embryo) may also increase the risk of splitting. While the specific mechanisms are not fully understood, these procedural steps are thought to introduce mechanical or environmental stresses that can prompt the embryo’s inner cell mass to divide.
Managing Pregnancies Resulting from Monozygotic Twinning
When a single embryo transfer results in identical twins, the pregnancy requires specialized and close monitoring due to the potential for unique complications. The primary risk is linked to the shared placenta, which occurs in the majority of monozygotic twin pregnancies. The presence of shared blood vessels between the fetuses can lead to conditions not seen in dichorionic (fraternal) twins.
One of the most serious complications is Twin-to-Twin Transfusion Syndrome (TTTS), where blood is unequally distributed between the two fetuses through the shared placenta. Another condition is Selective Fetal Growth Restriction (sFGR), where one twin receives a disproportionately small share of the placenta, hindering its growth. Management of these monochorionic pregnancies involves frequent ultrasound surveillance, often every two weeks starting in the mid-trimester, to detect these complications early. Patients are typically referred to a maternal-fetal medicine specialist for intensive monitoring and for potential in-utero treatments, such as laser surgery for severe TTTS.