Prediction of the age of menopause and hence a woman's reproductive prime

UK researchers have shown a strong direct relationship between ovarian volume and the number of primordial follicles (eggs) remaining in the ovaries of women of reproductive age. The measurement of ovarian volume by transvaginal ultrasound will enable an accurate prediction of the age of menopause and hence a woman's reproductive age.

They say that the possibility of making an accurate assessment of ovarian reserve will revolutionize the care of women seeking assisted conception, those who have had treatment for childhood cancer and women who may want to delay a family for personal or professional reasons.

"In essence, it means we now have the potential to be able to tell a woman how fast her biological clock is ticking and how much time she has before it will run down," said lead author Dr. Hamish Wallace, consultant paediatric oncologist at the Royal Hospital for Sick Children in Edinburgh, Scotland and a senior lecturer at the University of Edinburgh.

The findings are reported today (Thursday 17 June) in Europe's leading reproductive medicine journal Human Reproduction[1].

The human ovary contains a fixed pool of primordial eggs, which form in the fourth month of pregnancy. They peak at several million in the five-month foetus then start to decline. By birth, this number has already fallen significantly and the decline continues relentlessly. When the number reaches around 25,000 (corresponding to an average age of 37 years) the decline accelerates until numbers are down to around 1,000 follicles in a peri-menopausal woman.

Dr. Hamish Wallace and Dr Thomas Kelsey of the School of Computer Sciences at the University of St Andrews, developed their technique for measuring a woman's 'bioclock' by building on other research on follicle decline with age, and the relationship between follicle numbers and ovarian volume. They then applied the latest mathematical and computer models/analysis[2] in such a way that they could describe the follicle population decline for women entering the menopause early or late.

"We already know from published data using transvaginal ultrasound to measure the volume of ovaries, that they shrink as a woman ages," said Dr Wallace. "What we have done is obtain a highly significant correlation between primordial follicle numbers and ovarian volume. We have shown that ovarian volume in women aged from 25 to 51, as measured by tranvaginal ultrasound, may be used to estimate accurately how many follicles (eggs) are left and therefore what is the woman's 'reproductive age'."

Said Dr. Wallace: "The age of menopause varies from woman to woman and there is currently no reliable test of ovarian reserve for an individual woman that will predict accurately her remaining reproductive life-span. What we have done is to come up with a method that may allow us to predict for a woman (aged 25–50 years) what ovarian reserves she has and at what age she is likely to experience the menopause."

He said they had used two inherent assumptions in their calculations – both shown in other research to be reliable – that variation in age at menopause is due to wide variation in the number of follicles present at birth, and that ovarian volume between the ages of 25 and 50 is directly related to the remaining number of follicles.

The researchers are currently involved in clinical studies on young women successfully treated for cancer (where fertility may be impaired or lost through treatment) in the hope of providing them with more accurate fertility advice allowing them to realistically plan having a family.

They are also setting up long-term studies to follow young healthy women with regular assessments of ovarian volume until they reach the menopause.

"The possibility of providing a direct and easily reproducible assessment of ovarian reserve and reproductive age through the transvaginal measurement of ovarian volume for all interested women would be a real advance," said Dr Wallace. "It opens the door to the possibility of screening women for early ovarian ageing. These women may be at increased risk to their general health from the effects of having an early menopause."

[2] A full explanation of the methods used – the Faddy-Gosden model of ovarian follicle decline, the Runge–Kutta numerical method of estimating human oocyte radiosensitivity, and the Maple computer algebra system used to solve the differential equation that expressed the rate of change in the follicle population from birth – is contained in the research paper. Examples of predictions of ovarian volume and reproductive age compared with chronological age are given.