5 Fertilization

5.2 Why fertilization may not happen

It is estimated by most practitioners that more than 50% of all conceptions are genetically abnormal, and it has been suggested that this results in part from the fertilizing of old eggs. Of course, good maternal health and adequate nutrition are also important for the production of good eggs. To maximize the chance of healthy offspring, perhaps intercourse should be timed so that sperm are present as soon as the egg is ovulated. But, as you have seen for practitioners of natural methods of contraception, timing ovulation may be more easily said than done, and even when it can be pinpointed, it may be socially inconvenient to have intercourse at that time. Many abnormal embryos are in fact aborted naturally, and persistent abortion of this sort may be one cause of infertility.

Q Can you suggest other biological reasons for infertility?

A There are a vast number of points at which the fertilization process might go wrong. But broad categories are failure of sperm production, failure of egg production, and failure of the interactions between them.

It is sometimes impossible for structural reasons for egg and sperm to meet. This may be because sperm are not ejaculated properly, or because there is some kind of anatomical blockage in the woman's reproductive tract. In these cases in vitro fertilization (IVF) may help. This involves removing eggs from the woman's ovaries just before they would normally ovulate, and mixing them with sperm that has either been ejaculated or, if ejaculation is not possible, with sperm removed from the vas deferens. The woman can be treated with hormones so that several eggs ripen at the same time; the sperm can be concentrated if necessary. Either eggs or sperm (or both) can be taken from a donor, rather than from the couple themselves. The gametes are mixed in a dish (in vitro means ‘in a glass’) and observed under a microscope. Enzymes necessary for the whole process, such as hyaluronidase, can be added. Once fertilization has occurred, and the embryos appear to be progressing normally (see Section 6), they can be placed in the woman's uterus, where they may implant and grow normally. Although several embryos may be produced by this method, usually only two or three are given the opportunity to implant (the rest are frozen for future use). This is to reduce the risk of multiple pregnancies, which are not desirable for the welfare of the mother or the babies. A variation of this is GIFT, gamete intra-Fallopian transfer, where the gametes (sperm and eggs), taken from whatever source, are mixed together, then immediately placed in the Fallopian tubes. This ensures that the conditions for fertilization are as ‘natural’ as possible. In both cases, it is important that the woman should be at the correct point in her cycle so that her uterus is able to receive an implanting embryo. This may require her to have hormone treatment.

IVF and GIFT are valuable techniques for overcoming blockages, and their use has made many couples happy, although in general success rates are low: of the order of 10% per menstrual cycle, varying to some extent depending on the practitioner involved. But sometimes couples are infertile for no obvious physical reason: both produce healthy gametes, and have no physical abnormalities. It turns out that some women unwittingly produce antibodies that interfere with their partner's sperm, and prevent their survival.

Antibodies are very large protein molecules, they play an important part in the immune system, the body's machinery to fight infectious disease. As with most proteins, the key to an antibody's functions lies in its shape.

Q Why is the shape of a protein important?

A It allows that protein to interact with (bind to) other specific molecules.

Antibodies have the ability to distinguish between molecules that ‘belong’ in the body, that is, are ‘self’, and other, non-self, molecules. Antibodies patrol the whole body, being carried around in the blood and lymph, but also penetrating the tissues to maintain maximum surveillance. Their response to meeting a non-self molecule is to attach to it, and form an insoluble complex which can be removed by other parts of the immune system. Usually this response is limited to invading microbes, but occasionally antibodies are produced against inappropriate targets – in this case, components of the sperm's membrane. The bodies of women in whom this happens recognize the sperm as non-self, and the immune system responds by making antibodies against them. When the antibodies attach to the sperm's membrane, they prevent it from fertilizing an egg, and infertility results. This type of infertility is not the result of a disease but of an over-enthusiastic defence mechanism. The important point to note from this is that even a normal body mechanism, if deployed inappropriately, can result in abnormal functioning – dis-ease. The treatment for this kind of infertility is to ‘de-sensitize’ the woman, that is, inject her with very low levels of the offending sperm membranes, in an attempt to fool her body into thinking that these are just another few self molecules. Perhaps surprisingly, this treatment often works remarkably well.