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another critical period for getting the embryo’s genetic imprints right. In ART, it happens that embryos are usually still in vitro during this second, vital window, making them vulnerable once again.

Further, infertility is often linked to genetics, and these genetic problems may be inherited by a child produced through ART. This raises the provocative question of whether generations of babies created with IVF or ICSI might ‘naturally’ pass along genetic defects that will lead to a significantly more infertile population. In December 2006, Louise Joy Brown, our first test-tube baby, gave birth to a healthy son; seven years earlier, Louise’s little sister Natalie, who herself was the fortieth child born by IVF, became the first child of ART to have a baby of her own. Neither of the Brown sisters had required fertility treatment. Of course, Lesley and John Brown had turned to IVF because of a blockage in Lesley’s Fallopian tubes, a condition that can often be corrected with surgery. If it had been John whose fertility had been the main issue, and if Louise and Natalie had been a Louis and a Nathan instead, then the next generation might have been more complicated to conceive.

This is especially true for patients of ICSI, which is used when sperm is abnormal. Although ICSI takes longer and is more invasive than artificial insemination using donor sperm, couples trying to conceive still tend to prefer using their own abnormal sperm; a child who is genetically ‘their own’ outweighs all other considerations. Chromosome anomalies are seen in about seven percent of men who fail to produce sufficient sperm – and among this seven percent, more than ninety-nine percent of whatever sperm they do make will exhibit abnormalities.

There are concerns about the effect of using abnormal sperm for ICSI, because abnormal sperm are associated with increased chromosome defects in the babies produced. The chance of having a baby with major malformations through ICSI is twice as high as in the general population – nine percent, versus three to four percent. This may be because abnormal sperm also tend to carry the wrong number of chromosomes. In men with very low sperm counts, seventy percent or more of their sperm will carry too many or too few chromosomes. Moreover, the most commonly recognized genetic cause of infertility in men is the appearance of Y chromosomes with corrupt or missing genes. The genes on the Y chromosome are essential for sperm production – this is, after all, the chromosome that makes males male. But these missing genes could hint that there are abnormalities on other chromosomes too. Indeed, there is evidence that ICSI children have an increased number of abnormalities, mostly inherited from the father’s side, and that ICSI sons are more likely to be affected than daughters.

The missing genetic material could make many of these sons infertile. Already, adult men whose mothers received fertility treatment are reported to have lower sperm concentration and count, more abnormal spermatozoa, smaller testes, and lower testosterone levels. Boys conceived by ICSI sometimes have reduced levels of testosterone. And ART has been associated with hypospadias and another condition, cryptorchidism, where one or both testicles fail to move down into the scrotum before birth. Most of these cases do resolve on their own, but sometimes surgery is required. Unfortunately, as incidents of hypospadias and cryptorchidism increase, poor semen quality and the rate of testicular cancer rise too. So boys diagnosed with hypospadias or cryptorchidism will need to be monitored for testicular cancer throughout life. IVF and ICSI also increase the chance of pre-term birth, low birth weight, and multiple births. And in premature boys, an undescended testicle is more common.

Studies also suggest that Y chromosomes with DNA deleted in particular regions may cause babies to be born with two X chromosomes in some cells of their bodies, but with only one X chromosome in others. While this only impacts the sex chromosomes – the X and the Y – and does not, it should be said, create the situation seen in baby FD or in Jane from Boston, it does result in baby girls who have sexual ambiguities or Turner’s syndrome, which creates females without female sexual characteristics. People with Turner’s syndrome are noted for their short stature, and for a likelihood of other health problems, including difficulties with hearing, sight, thyroid and kidney function, high blood pressure, diabetes, and learning. Their ovaries also don’t work – so these children are nearly always, like their fathers before them, infertile. (They may also, like post-menopausal women, suffer from osteoporosis because of their failed ovaries.)

The bottom line is that, when making babies through ICSI, you are often working with screwed-up sperm. The more screwed up the sperm are, the more abnormalities you will see in them, and the more likely they are to carry damaged DNA. And because the Y chromosome is only ever passed from father to son, if a man is infertile because parts of his Y chromosome are missing, his ICSI son, by definition, will inherit that corrupted Y chromosome and his infertility too.

On the other hand, IVF and other forms of ART also now make it possible to diagnose genetic abnormalities very early – by the time the embryo is three days old – something that is not possible in natural pregnancies. As our techniques improve, screening an embryo to identify an abnormality before it is implanted in the mother’s womb could be utilized to reduce further and further the chances of the diseases that are made more likely by ART.

Today, there are two ways of approaching the process of screening. One, called pre-implantation genetic diagnosis, or PGD, looks for specific genetic disorders that a couple is known to be carrying, and which therefore they have a high risk of transmitting to their children. PGD takes three to four