No More a Coin Toss

“Is it a boy or a girl?“

This question, which has every parent on their toes since the conception of their offspring, owes its existence to the randomness of fertilization – nature has made the determination of a future child’s sex essentially a coin toss. Recent technological advancements, however, have changed the game — humans now have the ability to bypass this randomness entirely, using new techniques for sex selection that allow couples to choose their future offspring’s sex.

In humans and many other animal species, females are characterized by two X chromosomes  in their body cells, whereas males are characterized by one X chromosome and one Y chromosome in theirs. However, sperm cells and egg cells (collectively called germ cells) are different from the rest of the body cells in this regard as they only have one type of chromosome – an egg cell always has one X chromosome whereas a sperm cell can have either an X or a Y chromosome but not both. A sperm cell with a Y chromosome will lead to a male child (XY) if it fertilizes an egg whereas an X chromosome sperm will lead to a female (XX) on fertilization. This means that the father determines the child’s sex. Normally, males produce an equal mixture of both types of sperm cells, hence leading to the approximate 50% chance of getting a child of particular sex during conception (this chance is slightly biased towards male offspring).

One method of carrying out sex selection is to prepare a sample containing either X or Y chromosome sperm cells only, rather than a random mixture, to fertilize the eggs from the mother. To produce such a sample, the two sperm types have to be separated, in a process known as sperm sorting, using special techniques so that the sample contains only the desired type of sperm cell. That sample can then be used for impregnation through artificial insemination, resulting in a pregnancy with a child of the desired sex.

Normally, X and Y sperm cells cannot be distinguished from each other under a microscope. An older technique for sex selection, called flow cytometry, exploits the fact that the X chromosome is much larger than the Y chromosome because it has more DNA (which is what chromosomes are made of). The technique begins by staining the sperm cells in a sample with a particular dye that binds to DNA inside cells and shines under an ultraviolet (UV) laser light. Since the X chromosome is larger, it can “soak up” more of the dye than the Y chromosome. Hence, X sperm cells can be distinguished from Y cells because they shine brighter due to having more dye inside them (the dye alone is not enough, because even though it makes the DNA inside each sperm cell more visible, individual chromosomes still cannot be seen or differentiated from each other, so there is no way to see if a particular cell has an X or a Y chromosome).

The process of separation and selection of specific sperm cells requires expensive technology and the sorted sample does not give a 100% chance of getting a child of the desired sex, as the technology cannot perfectly separate the sperm cells, so even the sorted sample has a mixture of X and Y sperm cells. According to Microsoft’s clinical trials to sort human sperm, samples selected for X sperm cells produced a pregnancy with a girl in 92% of cases, whereas Y sperm cell samples produced a boy in 83.6% of cases. The technique is considered experimental in humans yet.

Recently, scientists have found a much cheaper chemical method of sperm sorting. Female sperm cells have certain proteins that male sperm cells do not, and these proteins can be targeted by a chemical that allows X sperm cells to be automatically separated from the Y sperm cells in a tube, from which a sorted sample can be taken and used for fertilization. In a tube, sperm cells have a tendency to swim upwards. As the chemical makes X sperm cells swim slower than the Y cells, the Y cells end up higher in the tube while the X cells are left at the bottom. This technique has already been used successfully in mice. Although it does not have a 100% success rate either and has not yet been used in humans, it would be a cheaper alternative due to its relative simplicity.

These techniques can be used not only in humans but in other species of animals as well. Hence, they hold relevance not only to reproductive medicine but also to animal industries and many other fields. For example, female calves and chicks are preferred over males in poultry and cattle industries due to their higher economic value, so sex selection via flow cytometry is used to bias the sex ratio of the population towards females. Conservation programs for endangered species could also make use of such technologies, for example, in captive breeding where there might be a requirement for animals of certain sex to be born to compensate for population deficiencies.

An alternative to sperm sorting and a more direct approach is to fertilize eggs from the mother in a petri dish (in-vitro fertilization – IVF) using a non-sorted sample of sperm cells. This will result in a mixture of male and female embryos as usual. From here, any particular embryo can be selected at random and genetically tested (pre-implantation genetic diagnosis – PGD) to determine its sex. As an added bonus, the embryo can also be checked for the presence of genetic diseases. If it is of the desired sex, the embryo can be taken for pregnancy, thus guaranteeing a child of the desired sex. PGD, however, has its own disadvantages. For example, embryos can be lost during the testing procedures and the diagnosis can give false results (for instance, indicating the presence of a disease when in actuality there is none or vice versa). IVF and PGD are also quite expensive and couples often have to try these procedures multiple times, resulting in financial strain.

People who are against parents’ preference for children of one sex over another might view the practice of sex selection in humans negatively, associating it with problems such as sexism and imbalances in population sex ratios. However, it can have important medical applications. For example, there is a class of genetic diseases known as ‘sex-linked disorders’. One well-known example of such a disorder is hemophilia – in which the sufferer’s blood does not clot properly after injury, making even the slightest injuries dangerous due to the risk of severe blood loss. The essential difference between these and other hereditary disorders is that they involve the child’s sex in the inheritance of disease as well.

Basically, depending on the parents’ genes, it may be possible for a child of one sex to be able to avoid, or be less likely to have, the disease while the other sex is guaranteed, or more likely to suffer from it (e.g. for a certain couple, future sons would always suffer from the disease while daughters would not). Here, sex selection provides an obvious advantage. Couples who know beforehand that at least one of them is a carrier of the disorder could choose to have a child of the sex that is at a lower risk of inheriting the disorder.

Legality in most parts of the world tends to go against sex selection when done for non-medical purposes but is generally in favor of sex selection for couples who are at high risk of passing on sex-linked disorders to their future children. In most of the European countries, PGD tends to be restricted to such medical uses only, due to ethical reservations about parents selecting embryos for reasons deemed medically unnecessary, e.g. against relatively minor defects or variations. In the USA, PGD is not strictly regulated and non-medical sex selection is legal, so the country sees medical tourism from parts of the world where sex selection is restricted. IVF clinics in Pakistan offer PGD, and sex selection for non-medical reasons is legal. Many couples who approach these clinics do so to select a male child, a practice which they do not explicitly encourage, advertising PGD for the aforementioned purpose of detecting disorders. While ethical reservations behind such practices will continue to restrict them legally in many parts of the world, scientists continue their research to improve existing procedures and discover better methods in hopes of benefiting the people who need them. As reproductive technologies become more advanced, ethical questions will become ever more pressing, and more grey areas are likely to emerge. Legislators around the world will be faced with further challenges of having to figure out how to handle the development and usage of reproductive technologies in a way that’s best for their societies.

Abdullah Khan Niazi Member since 2019-09-29

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When it comes to science, Abdullah Niazi is an all-rounder. He finds the life sciences and the physical sciences, and their various sub-fields, to be equally fascinating, and hopes to carry out research in some of them in the future.