In my fertility practice, there have been occasions when men in their late 60s or even early 70s have come for consultation, keen to father a child. I have prescribed the semen analysis expecting low sperm numbers (oligozoospermia) or poorly swimming sperm (asthenozoospermia), only to see the patient a few weeks later in my clinic with normal semen results and be confronted with the question, ‘What next?’ In males, the creation of sperm is a continuous process which is maintained until late in life. Collection of the male gametes is generally easy.
By contrast, the situation in females is very different. Women ovulate only during the reproductive phase of their life. Nature predetermines a fixed number of oocytes while a woman is still unborn in her mother’s uterus and no new follicles are created during adult life. At birth she will have approximately 200,000 oocytes and will begin her reproductive cycles at puberty ovulating approximately 400 times during her reproductive years until menopause. Only a very small proportion of the oocytes ever make it to maturity, the vast majority do not make the grade or abandon their development along the way. Each month a small cohort of ovarian follicles, each containing an oocyte, begins to develop before a single dominant follicle takes over and becomes the one destined for ovulation in that cycle. The remaining follicles develop no further.
The term ‘ovarian reserve’ is used to describe the size of the pool of potentially functional follicles remaining in the ovary. This is related to the number of times ovulation will occur in the future and also to the quality of the eggs that will develop. When explaining the idea of ‘reproductive age’ to medical students, I stress the important of ovarian reserve by expanding the reproductive life of a woman to 100 reproductive years; where she is one year old at the age of 15 and 100 years old at the age of 45. So if a woman decides to start a family at the age of 39 she is really closer to 90 years old in her reproductive lifetime.
A large proportion of women seeking help about their fertility are above 37 years of age. The biggest factor affecting IVF success rates is age. Ovarian reserve starts to decline after approximately 37 years old and is typically extremely low over the age of around 43. The lower the ovarian reserve, the less the ovarian response to fertility treatments, and the lower the quality of the eggs obtained. This is why IVF success rates are low in women over 41, despite the best of treatment methods.
Ovarian reserve assessment is generally advised for women seeking fertility treatment. It helps to understand an individual woman’s status with regard to her reproductive age. This is important when we wish to choose between mild therapies such as ovulation induction, or more involved treatments like IVF. While wishing to do the minimum to be effective, we are also conscious that unnecessary delay due to following inappropriate treatments may lead to further decrease in ovarian reserve. Furthermore, an appreciation of ovarian reserve is important in deciding the strength and dose of any fertility drugs that may be prescribed, enough to elicit a good response, but not too much so as to risk ovarian hyperstimulation.
It is not always easy to know the ovarian reserve exactly, every woman is different, but there are two tests that are commonly used either together or in isolation. The first of these is antral follicle count (AFC). Antral follicles represent a fraction of the ovarian reserve that has matured enough to be recruited for further development. AFC is best performed with a transvaginal scan in the first days of the menstrual cycle where small follicles measuring 2-6mm are counted in each ovary. A count of more than 12 antral follicles suggests the possibility of polycystic ovaries and a count of 2 or fewer follicles indicates very low ovarian reserve. The second is a blood test to measure Anti-Mullerian Hormone (AMH). AMH levels peak around the age of 25 and after a mild reduction remain stable until the late 30s, followed by a steep decline. I would generally recommend a combination of a blood test for AMH and transvaginal scan for AFC to assess ovarian reserve.
Over the last decade IVF success rates have gradually increased, mainly as a result improved techniques for handling embryos in-vitro and ever more advanced diagnostic procedures. It has become routine to freeze sperm or embryos and store them almost indefinitely. The science of egg freezing has traditionally lagged behind, but developments over the last few years now make this a reality. Younger women are being given the option of freezing the high quality eggs obtained when they have a good ovarian reserve, for use later in their life.
Whether it is selecting the right fertility treatment, balancing ovarian stimulation requirements or freezing eggs to use later, an appreciation of ovarian reserve and ageing is informing and empowering women, enabling them to take control and make the right decisions regarding their fertility.
Mr Kamal Ojha MD, MRCOG. Clinical Director, Concept Fertility Clinic. firstname.lastname@example.org