Monozygotic Twins

The joy of a positive pregnancy test is immense; imagine how it multiplies and adds thrilling excitement when a multiple pregnancy is diagnosed.

Multiple pregnancies, especially those involving twins, offer a unique experience and require special attention due to higher obstetric risks for both the expectant mother and the fetuses during gestation and in the early months after birth. Carrying two or more fetuses is considered complicated; therefore, reproductive clinics adhere to a strategy of transferring a single embryo into the uterine cavity. However, even with selective embryo transfer, one embryo can split into two or three, leading to the development of a multiple pregnancy. The potential for an embryo to divide is significant, making the phenomenon of monozygotic twins possible!

Monozygotic multiple pregnancies occur when a single egg is fertilized by a single sperm, forming one blastocyst that splits during the cleavage stage into two (or more) parts—resulting in genetic copies (natural cloning)—monozygotic twins (those originating from a single egg).

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Structure of a Blastocyst (Embryo)

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Diagram of blastocyst division, resulting in the formation of Monozygotic Twins

Monozygotic twins can be:

• Monochorionic: Sharing a single placenta between two fetuses.
• Dichorionic: Each fetus has its own separate placenta.

Depending on the number of amniotic cavities filled with amniotic fluid, monozygotic twins can be:

• Monoamniotic: Sharing one common amniotic cavity for all fetuses.
• Diamniotic: Each fetus has its own separate cavity, separated by fetal membranes.

The occurrence of triplets is rare, constituting less than 0.1%.

The embryonic stage at which the embryo splits determines the placental architecture:

• If the embryo divides very early, before differentiation, the resulting fetuses will be dichorionic-diamniotic.
• If the division occurs before blastocyst implantation, the twins will be monochorionic-diamniotic.
• If after blastocyst implantation—monochorionic-monoamniotic.

Dichorionic twins are always diamniotic; monochorionic twins can be either diamniotic (in the vast majority of cases) or monoamniotic.

Dichorionic-diamniotic pregnancies occur in 30%, monochorionic-diamniotic in 70%, and monochorionic-monoamniotic constitute no more than 1% of all monozygotic multiple pregnancies.

Twins have a high genetic similarity and are often referred to as “identical”; however, there are phenotypic discrepancies between them, such as differences in disease susceptibility and certain anthropomorphic features (e.g., fingerprints). These phenotypic variations have a genetic basis. Post-fertilization events, such as chromosomal mosaicism, skewed X-inactivation, imprinting mechanisms, and other epigenetic modifications (e.g., DNA methylation influenced by methafolin), caused by endogenous (internal) and exogenous (external) environmental factors, account for the observed differences between twins.

1. Alterations in the Zona Pellucida (ZP):

•   In early development stages, the ZP acts as a crucial barrier preventing multiple sperm entry and embryo splitting.
•   Disruptions in the ZP, such as atypical holes or cracks at the 1-cell stage, can lead to the development of twin blastocysts during in vitro cultivation.
•   After successful fertilization and the first cleavage to the 2-cell stage, time-lapse imaging has shown that one cell may be expelled through a ZP fissure while the other remains inside.
•  The ZP then serves as a barrier, allowing the two cells to develop into separate blastocysts, one inside and one outside the ZP.

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The membrane around – Zona Pellucida

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2. Internal Cell Mass Division through Expansion:

•   A blastocyst is a 5-7 day old embryo with implantation potential, containing a fluid-filled cavity called the blastocoel and an inner cell mass (ICM) – a group of pluripotent cells capable of developing into any cell type in the human body.
•   Typically, ICM cells cluster together.
•   Time-lapse imaging has shown that natural cavitation in the blastocyst leads to cycles of collapse and re-expansion in the blastocoel.
•   If ICM cells are loosely connected during cavitation, they may split into multiple ICM groups, potentially forming more than one embryo.

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The cavity inside – Blastocoel

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3. Hatching – Embryo “Emergence”:

•  After blastocyst formation, the embryo undergoes hatching, emerging from the ZP to implant into the uterus.
•  During hatching through a small fissure, the blastocyst cavity may constrict into an 8-shaped structure.
•  Time-lapse imaging of hatching has captured that the ICM can split into multiple groups if one group of cells is near the exit fissure and another remains inside the ZP, potentially leading to twin formation:

1. If only the ICM separates without the trophectoderm (outer layer), it may result in monochorionic twins (sharing one placenta).
2. If the trophectoderm splits along with the ICM, it may lead to dichorionic twins.

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Hatching

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“8”-shaped hatching

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4. Conjoined Twins:

• Understanding the mechanisms behind conjoined twin formation is more complex due to their extremely low natural occurrence.
• One theory suggests that conjoined twins result from late splitting of the ICM: either after hatching or even post-implantation.
• However, this theory remains hypothetical, as real-time visualization of embryo development leading to conjoined twins has not been documented.
• The first time-lapse recording of conjoined twins showed that one cell at the 2-cell stage fragmented during further development, while the other non-fragmented cell developed into a small blastocyst, resulting in conjoined twins after uterine transfer.

It’s important to note that such cases are rare and can occur in natural conception as well.

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Two-cell stage of division

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Maternal Factors Influencing Twin Births:

• Maternal Age: Women over 30-35 years are more likely to give birth to twins.
• Family History: Having close relatives with twin births increases the chances.
• Ethnicity: Certain ethnic groups, such as Africans and African Americans, have a higher frequency of twin pregnancies.

While multiple pregnancies bring great joy, they often present unique challenges and potential complications:

1. Non-Specific, Preventable Complications:

•  One of the most significant risks is cervical shortening and preterm labor, with about 60% of twins being born prematurely.
•  Premature infants face increased health risks and may require specialized care in neonatal intensive care units.
•  Maternal strain is significantly higher, increasing the risk of gestational diabetes, preeclampsia, and nutrient deficiencies.
•  These conditions require careful monitoring and medical support to ensure the well-being of both mother and babies.
•  Mothers carrying twins may experience early anemia and excessive weight gain, potentially affecting their overall health.

2. Specific Complications (Less Common and Not Preventable):

• Twin-to-Twin Transfusion Syndrome (TTTS): A condition where blood flow is unevenly distributed between twins sharing a placenta.
•  Selective Intrauterine Growth Restriction (sIUGR): One twin grows at a slower rate than the other.
•  Twin Reversed Arterial Perfusion (TRAP) Sequence: A rare condition involving abnormal blood vessel connections.
•  Twin Anemia-Polycythemia Sequence (TAPS): A condition characterized by significant differences in blood counts between twins.
•  Vanishing Twin Syndrome: One twin disappears in the uterus during pregnancy as a result of miscarriage.

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If you are expecting monozygotic twins, it’s essential to seek high-quality prenatal care.

Developing a comprehensive pregnancy and delivery plan that considers the complexities of multiple pregnancies can help alleviate anxiety, provide emotional stability, and reduce the likelihood of complications during gestation.