Is the tendency to have twins hereditary? It indeed seems so, at least when it comes to fraternal twins

The television show “Friends” ended with a double episode with multiple plot lines, in which Monica and Chandler become parents. Since Monica is unable to conceive, they decide to adopt - and in this episode they accompany Erica, the biological mother, to the delivery room. The episode is nearing its climax as the baby comes out, healthy and perfect, and the audience gives out a sigh of relief. But it is not over yet: it turns out there is another baby. To the surprise of the intended parents, they discover that Erica has been carrying twins, but did not really understand this fact when told so by her doctors. Now that she is aware of this, she remarks: “Come to think of it, we have a lot of twins in our family”. “Interesting!” replies Chandler in shock.

Are twins really a hereditary matter that ‘runs in the family’? The answer is yes - as long as they are fraternal twins.  

Identical twins share the same genetic material, since both of them developed from a single fertilized egg cell. Once an egg cell is fertilized by a sperm cell, the formed cell begins to divide over and over again. Sometimes, at the initial division stages, the embryo splits into two parts, each of which develops into a separate fetus. That is how identical twins are formed. 

In contrast, fraternal (non-identical) twins are formed from separate sets of egg and sperm cells. A woman of childbearing age undergoes ovulation every month, a process in which an egg cell (oocyte) matures and leaves the ovary heading for the uterus. Usually only a single oocyte undergoes this process each month, but sometimes two oocytes can undergo this process simultaneously. If fertilization occurs, a different sperm cell fertilizes each egg cell, and thus each of the fertilized eggs develops into a separate embryo. This occurs naturally in 4% of pregnancies, with no assisted reproductive technology (ART), and this is how fraternal twins are formed. They still share some of their genetic material, as they have the same mother and father - but they are not genetically closer than siblings born as a result of separate pregnancies. 

The probability of having identical twins, as far as we know, does not depend on heredity. In contrast, maturation of two egg cells in a single ovulation cycle, which may lead to the formation of fraternal twins, is dependent upon the mother’s genes and is inherited. That is why fraternal twins are more common in some families. In recent years, researchers were able to identify the genes responsible for this trait.

The twins’ birth sequence from the television show “Friends”:

Two Genes for Two Embryos

A study published in 2016, in which researchers examined the genes of 1,980 mothers of fraternal twins from the Netherlands, Australia and the state of Minnesota in the U.S., comparing them to nearly 13,000 women who never had twins or who had identical twins. They found a few genetic markers, changes in the genetic sequence, that correlated with the occurrence of fraternal twin births. These markers were compared to genes of a different population of mothers of fraternal twins, this time from Iceland, and thus, the researchers were able to identify two highly significant genetic variants, or mutations, which correlated with the chance of giving birth to twins. A single copy of these two mutations renders the woman’s chances of having fraternal twins 29% higher compared to the general population.

What are these genes? One is involved in the production of the Follicle-Stimulating Hormone (FSH). This hormone is required for the maturation of egg cells, and its levels in the bloodstream change during the menstrual cycle. In case its levels remain high for an extended period of time, the probability of maturation of multiple eggs in a single monthly cycle increases. It is easy to envision how such a difference in the activity pattern of this gene could lead to more cases of simultaneous maturation of two eggs, and thus result in the formation of fraternal twins, upon fertilization. 

The second gene found by the researchers was surprising. It is called SMAD3 and is related to the transmission of information within cells - if a cell is exposed to a particular hormone, the protein produced according to this gene assists the hormone in modifying the cell’s activity. It is possible that the product of the SMAD3 gene affects the manner by which ovaries respond to FSH, however its specific role in ovulation and pregnancy is still unknown. 

Researchers are aiming at understanding how this gene affects conception, and hope that in the future, this research may help women who have difficulties conveying or who undergo ART, by potentially enabling both accurate diagnosis of the problem and design of appropriate treatments.


Twins and Assisted Reproductive Technology

While we are on the subject, Assisted Reproductive Technology (ART) has led to a sharp rise in cases of fraternal twins in recent decades, regardless of genetics. Some fertility treatments entail in-vitro fertilization: fertilization of egg cells by sperm cells in a laboratory dish, with the formed embryo being implanted in the woman’s uterus. There is no guarantee that the embryo will be accepted in the uterus and will continue to develop, and thus, to increase the chances of pregnancy, multiple embryos are implanted in the uterus simultaneously. In cases when two or three embryos are accepted, the mother will give birth to twins or triplets - as depicted in an earlier episode of the show “Friends”, with Phoebe's character. 

Even without in-vitro fertilization, fertility treatments may result in the birth of twins. Some of the treatments include drugs that encourage ovulation, which slightly increases the probability of simultaneous maturation of multiple eggs. Other treatments include injections of the FSH hormone, which, as previously described, is also liable to increase those probabilities. Thus, today we see increasing numbers of cases of fraternal twin births that are unrelated to the mother’s genes, but are related from the treatments she may have undergone in order to conceive.

What about Erica, the biological mother of the twins from the TV show “Friends”? Her pregnancy was supposedly unplanned and it is thus quite clear that she received no fertility treatments. She gave birth to fraternal twins - a boy and a girl - and considering her remark regarding the multiplicity of twins in her family, it is very likely that she carries at least one of the aforementioned gene variants.  

And what about you? Do you have a twin, or are there fraternal twins in your family? Were they born following ART? And are there any other twin pairs in your extended family?