Hormone tests for women’s fertility seem not to work

Women seeking to defer motherhood are often encouraged to check their fertility. Though fecundity is tied to age, the effect of time’s passage varies. Some 35-year-olds find they cannot get pregnant. Others manage at the first attempt.

The main causes of fertility’s reduction with advancing years are declines in the number and quality of the eggs in a woman’s ovaries. Unlike men, who manufacture sperm throughout their post-pubertal lives, albeit in ever-decreasing quantities, all of a woman’s potential eggs develop while she is still a fetus. A newborn girl has over 1m of them. By puberty, she is left with about 400,000. When the menopause arrives, that has been whittled down below 1,000, which are likely to be duds.

But fertility tests currently on offer neither count the number of eggs remaining nor assess their quality. Rather, they rely on an indirect approach—sampling what are hoped to be relevant hormones. Hormone tests do have some value in estimating the timing of menopause and the success of harvesting eggs for in vitro fertilisation. But forecasting pregnancy? The evidence suggests that they can’t.

One test-sceptic is Anne Steiner of the Duke Fertility Centre, in North Carolina. She suspects hormone tests do indicate how many eggs are left to a woman, but that this is not what matters—rather, it is the eggs’ quality which is crucial.

Between 2008 and 2016 Dr Steiner and her colleagues ran the Time to Conceive study. Its purpose was to determine whether hormone levels could indeed assess a woman’s fertility, independent of her age. The team found then that those levels had no value in predicting pregnancy in the year subsequent to testing. Now, in a follow up to the original investigation, just published in Fertility and Sterility, Dr Steiner has shown that they have no longer-term predictive power, either.

Time to Conceive looked at 750 women aged between 30 and 44 who were living with a male partner not known to be infertile, had no diagnosis of infertility of their own, and had recently started trying to become pregnant. The team took blood and urine samples from these volunteers and measured levels of three hormones often examined by fertility tests. They then followed each volunteer for a year. The upshot, published in 2017, was that hormone levels were uncorrelated with pregnancy within the 12-month window through which the researchers were looking.

But perhaps, Dr Steiner subsequently speculated, that window was too narrow. In 2020 she therefore got back in touch with the original participants for a follow-up. She asked them if they would fill out a questionnaire about how many children they had had, how long it had taken to get pregnant and whether they had been diagnosed with infertility.

Some 336 of them agreed to participate. Among these there had been 239 pregnancies, resulting in 225 live births. More sadly, 73 participants were infertile. But the hormone levels in the tests carried out in the original study did not predict these outcomes. There was no difference, the researchers found, between women with poor results and those with normal ones.

In the case of one substance, for example—anti-Mullerian hormone, which is thought predictive because it is produced by cells in the egg-bearing follicles of the ovaries, and is thus believed to reflect the number of those follicles—79% of those with low levels of it went on to give birth. That was statistically indistinguishable from the 71% of mothers with normal levels. The decline in fertility, says Dr Steiner, is thus clearly not related to the decline in the quantity of eggs, but presumably to their quality. And how to measure that remains unknown. ■

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