Rehan Salim MD MRCOG
Consultant Gynaecologist & Subspecialist in Reproductive Medicine
Wolfson Fertility Centre - Hammersmith Hospital
Does age affects fertility in women?
Age is the most important factor in women's fertility. As a woman gets older, conditions that could possibly affect her fertility increase. Here is why you shouldn’t wait until you are in your 40s to fulfill your dream of having a family.
A woman’s fertility peaks in her 20’s and starts to declines from around the age of 30, dropping down more steeply from the age of 35. A healthy 30-year-old has about a 20% chance each month of getting pregnant, while a healthy 40-year-old has about a 5% chance each month.
Women do not remain fertile until menopause. The average age for menopause is 51, but sometime most women are unable to have a successful pregnancy in their mid-40s. These percentages are true for natural conception as well as conception using fertility treatment, including in vitro fertilization (IVF).
How does fertility change with age?
The age-related loss of female fertility happens because both, the quality and the quantity of eggs, gradually decline.
1. Egg Quantity (Ovarian Reserve): The number of eggs in women, gradually declines with age. This decrease of egg-containing follicles in the ovaries, is called "loss of ovarian reserve..”
At the time of birth the ovaries of a girl contain around one million eggs; by puberty the number has gone down to approximately 100,000 and this pool of follicles is gradually used up. As this ovarian reserve get used up over time , the follicles become less and less sensitive to hormonal stimulation. So, at a later age they require more stimulation to mature and ovulate.
In the beginning of puberty , periods may come closer together resulting in short cycles that are 21 to 25 days apart. Eventually, the follicles don’t respond well enough to consistently ovulate, resulting in short, irregular cycles. Usually, the decrease in ovarian reserve is related to increasing age, but it is strongly linked to smoking, family history of premature menopause, genetic abnormalities, previous ovarian surgery and parental consanguinity, endometriosis and Vitamin D deficiency.
If a woman has a low ovarian reserve, the chance of becoming pregnant decreases, hence the chance for pregnancy is still directly related to the age of the patient: e.g. a 28 year old patient with a reduced ovarian reserve still has a better chance of conceiving and having a healthy child, compared to a patients in her 40s with the same ovarian reserve. There are medical tests for ovarian reserve, but none have been proven to predict the possibility of becoming pregnant reliably. These tests do not determine whether or not a woman can become pregnant, but they can determine that age-related changes of the ovaries have begun.
Women with poor ovarian reserve have a lower chance of becoming pregnant, than women with normal ovarian reserve in their same age group. No single test nor any combination of tests is 100% accurate.
To test for ovarian reserve, FSH , Follicle Stimulating Hormone is sampled from blood on day-3, and estrogen levels in blood are tested on days 2, 3 and 4 of the menstrual cycle.
High levels of FSH in combination with low levels ofestrogen indicate that ovarian reserve is low. However, FSH increase, is a very late indicator of low ovarian reseve, and many women with diminished ovarian reserve will have normal or slightly elevated FSH levels on day 3. Abnormal day-3 FSH levels, especially confirmed when repeated, showreduced ovarian reserve. Today, the most reliable test of ovarian reserve is the ultrasound assessment of follicle numbers in the beginning of the cycle, called the Antral Follicle Count or AFC.
A more accurate test can be done to measure the ovarian reserve, it’s called AMH test. It measures a hormone called Anti-Müllerian Hormone which is a substance produced by granulosa cells in ovarian follicles.
AMH levels slightly vary throughout the menstrual cycle. Therefore, this hormone can be tested any time of a woman’s cycle.
AMH levels decrease with age. The higher the AMH, the higher the quantity of eggs remaining in a woman’s ovaries. However, it’s important to mention that very high AMH values can sometimes be an indicator of Polycystic Ovarian Syndrome (PCOS).
In general, higher AMH values are associated with higher response to ovarian stimulation as hence more eggs at the time of pick-up during IVF.
2. Egg Quality: No matter how you take care of yourself, you cannot slow down ovarian aging. A woman’s age is the most precise test of egg quality. By the time women reach their 40s, most of their eggs will be of poor quality. Poor quality is directly related to genetic information of the eggs.
Genetically abnormal eggs decrease the chance of a successful pregnancy, and increase the risk of miscarriage and having genetically abnormal (aneuploid) embryos. Generally, a normal egg and sperm should have 23 chromosomes each. After fertilisation the resulting embryo will have46 chromosomes, which is chromosomatically the normal amount. As a woman gets older, more and more of her eggs have either too few or too many chromosomes.
That means that if fertilisation occurs it will result in an aneuploid embryos with too many or too few chromosomes or displaced or missing chromosomes that will prevent a development of a healthy embryo. This helps explain the lower chance of pregnancy and higher chance of miscarriage in older women. In fact, after having genetically normal embryos being transferred in IVF/PGS (genetic screening of embryos) cycles, the chances of a successful pregnancy are the same between a 25 year old and a 45 year old patient.
3. Menopausal period or the end of menstruation marks the end of fertility, causing a woman to no longer be able to become pregnant. Although potential age-related infertility can be expected to end 5 to 10 years before the age of menopause especially the oocytes being released during this life-span will have a higher risk of being genetically abnormal
What is Premature Ovarian Insufficiency (POI)?
Premature or Primary Ovarian Insufficiency, also called premature ovarian failure (POF) occurs when the ovaries normally stop working in women who are younger than 40 years. This condition is characterised by the following:
Infrequent ovulation or complete stop of follicle growth and ovulation
Decrease or stop of production of reproductive hormones
Development of POI often is a slow process, in case it is not caused by treatment with chemotherapy or radiation or extensive ovarian surgery. Some women with POI do not stop menstruating totally, but could experience very irregular or infrequent periods. Hence, the condition does not always mean that pregnancy is impossible. However, it may be very difficult.
POI may affect women at any age, even while they are teenagers.
Premature ovarian insufficiency and premature ovarian failure, are sometimes used synonymously, but failure more exactly refers to permanent infertility and complete reduction of follicles.
What are the causes of POI?
In most cases, the cause of POI is unknown. However, there are several known causes, among them is the genetic cause (example: Turner syndrome and Fragile X syndrome, parental consanguinity). Moreover, the condition may be also associated with autoimmune disease, including those affecting the thyroid and adrenal glands.
Therefore, it is assumed that there might be some hereditary influence, as POI can be found in females of the same family. It may also develop after a pelvic surgery, which causes ovarian tissue damage or exposure to radiation or chemotherapy treatment for cancer.
What are the symptoms of POI?
The typical symptoms are irregular bleeding or amenorrhea (absence of menstruation period) and usual symptoms or signs of estrogen deficiency, like found in perimenopausal women. e.g. hot flushes, sweating at night, mood fluctuations, osteoporosis, vaginal atrophy, and decreased libido.
How is POI diagnosed?
Premature ovarian insufficiency can be diagnosed based on the clinical findings, serum FSH levels and the level of the Anti-Muellerian-Hormone (AMH). These tests might have to be repeated to confirm the diagnosis. Other tests like karyotype may help to find the cause of ovarian insufficiency or failure in women below 35.
If a patient believes that she may be at risk of having or developing POI, she should consult a gynaecologist specialised in reproductive endocrinology. Further information will be discussed by our consultants in the outpatient department during your consultation.
How is POI treated?
Unfortunately for non-reversible causes of POI, no treatments exist to reverse the ovarian failure. Since this condition is related primarily to the depletion of afollicle in the ovaries; there is no medical or surgical treatment to make more eggs once they are gone.
Since POI is related primarily to depletion of follicles in ovaries, once all of them have gone, there is no medical or surgical method that can restore normal function or make more eggs. In cases where the cause of POI is non-reversible, unfortunately, at the momentno treatments exist to reverse the condition.
For medically- induced causes of POI such as radiation and chemotherapy, in some cases part of the ovarian function may return naturally over time. Hormonal therapy can be used to treat the symptoms related to the hormonal deficiency.