It has been widely proposed that the chance of success in IVF fertility treatment can be best predicted by a measurement of 'ovarian reserve'. How can that best be done - and why are experts getting excited about a hormone known as AMH?
Age is not the only predictor of successful fertility treatment
The huge databases of the UK and American authorities leave no doubt that the chance of live birth in IVF declines markedly with age. For example, data collected by the UK's fertility watchdog, the Human Fertilisation & Embryology Authority (HFEA), between 1992 and 2004 show that pregnancy rates in IVF begin their gradual but steady decline at around the age of 33 years. In the USA, age-related pregnancy rates in IVF begin to fall below 40% once a woman reaches 34 years. By the age of 40, pregnancy rates have declined to 23%.
However, while age provides the greatest statistical prediction of success or failure in IVF, it does not give any true and precise indication in each individual patient. This depends more on the quantity and quality of follicles stored within the ovary and how they will develop to become eggs ready for release at ovulation; this ability of the ovaries to generate viable eggs from these tiny follicles has now become known as 'ovarian reserve' - and, for some fertility researchers, ovarian reserve is now the most predictive marker of success or failure in IVF.
Measuring ovarian reserve
While it is well known that overall measures of ovarian reserve also decline with time and age, the rate of this decline varies considerably from one woman to another. Thus, two women at the age of 35 may have quite different measures of ovarian reserve, even though their chronological age is the same. That's why experts have proposed that a precise measurement of ovarian reserve would be an important step in our ability to predict IVF outcome, especially in women over the age of 35, when their chances of success begin to decline.
A measurement of the earliest 'primordial' follicles within the ovary is simply not possible, but studies have shown that counting the later developing 'antral' follicles in the ovary provide a reliable alternative. Unlike primordial follicles in the ovary, antral follicles can be seen by an ultrasound scanner, and their number counted.
A high number of antral follicles would suggest an adequate ovarian reserve - and thus a good chance of pregnancy in IVF. Indeed, some studies have even shown that antral follicle count has better predictive value for IVF success or failure than body mass index (BMI) or age. Now, however, even antral follicle count may be superseded by a more sensitive and predictive measure of ovarian reserve, which is exciting fertility clinics throughout the world.
Anti-Mullerian hormone (AMH) as a measure
In 2008, a review of several studies showed that the measurement of just a single hormone - anti-Mullerian hormone - was just as reliable as antral follicle count in predicting a poor response to IVF.
Anti-Mullerian hormone (or AMH), which can be measured from a simple blood test, is produced by cells from the outer layer of the follicle. And the highest concentrations of AMH are found in the cells of pre-antral and small antral follicles - and are thus thought to correlate with the number of antral follicles within the ovary. In recent years, therefore, AMH has emerged as a possible predictor of ovarian response to drug stimulation in IVF, and thus as a measure of ovarian reserve likely to predict success or failure.
A recent study from Scotland has proposed that women with very low AMH concentration are at risk of either cycle cancellation or poor response to ovarian stimulation; those with medium levels have a good chance of a normal response, and those with very high levels may be at risk of ovarian hyperstimulation.
AMH and the diagnoses of premature menopause
Measurement of AMH has also been used to help confirm a diagnosis of premature menopause, a distressing condition which can affect young women even in their twenties. While the cause is thought to be mainly genetic, a premature menopause means that the ovarian reserve of those affected is simply exhausted and that, even at their young ages, the supply of follicles with which they were born has gone for ever. Ovulation and natural conception are not possible, and pregnancy can only be achieved by egg donation.
The accuracy of using the Anti-Mullerian hormone as a predictor of successful fertility treatment
As yet, the accuracy of AMH in predicting the outcome of IVF and ICSI treatment has been confined to studies assessing response to ovarian stimulation - whether a poor, normal or excessive response. Correlation of AMH levels with live birth rates - which are what matter to patients - are so far less conclusive, though occasional studies suggest that measures of AMH can help determine the most appropriate treatment approach for each individual patient.
However, AMH, say investigators, like antral follicle count, only represents the number of follicles present in the ovaries, and the chance of pregnancy after IVF depends on much more than just follicle number; embryo quality, the transfer technique, and whether the embryo implants within the uterus are all key factors in the progress of a pregnancy.
Nevertheless, studies so far lend much weight to the role of AMH in predicting response to ovarian stimulation before IVF, and that may yet provide a guide to the most appropriate treatment for each individual patient.