We all know that fertility is very closely related to age. Puberty is when males and females achieve the ability to reproduce. In today’s society, age related infertility is on the rise due to women postponing child bearing to after 30 years. Though women today are healthier, ovarian aging is an ongoing process which cannot be stopped or reversed. The decline in the number of eggs may occur sooner than most women expect.
The ovaries and the menstrual cycle
Every woman has two ovaries which contain eggs. Eggs are microscopic and cannot be seen but grow within fluid filled sacs called follicles which can be seen on scan. At birth, a female child will have about 2 million eggs in both ovaries. Unfortunately, the egg numbers naturally diminish and by the time of puberty only 300,000 to 500,000 follicles remain. At puberty, the brain sends out hormones to produce growth of the follicles. A group of about 10 follicles begin to grow at the onset of each period. But only one follicle grows bigger and matures to release the egg (ovulation). All other follicles perish naturally – this process being referred to as ‘atresia’. Pregnancy results if the released egg is fertilized by the sperm and the embryo implants in the uterine lining (endometrium). If pregnancy does not occur, a period begins. In a woman’s lifetime only 500 follicles mature and ovulate, while the remainder undergo atresia. Therefore by the age of menopause – eggs are absent.
Hence, it is natural that a woman aged 30 years will not have as many eggs as she had when she was 20years old. A woman’s best reproductive years are in her 20s. Fertility gradually declines in the 30s, particularly after age 35. Each month that she tries, a healthy, fertile 25-year-old woman has a 20% chance of getting pregnant. That means that for every 100 fertile 25-year-old women trying to get pregnant in 1 cycle, 20 will be successful and the other 80 will have to try again. By age 40, a woman’s chance is less than 5% per cycle, so fewer than 5 out of every 100 women are expected to be successful each month.
The important fact is that it is not just egg numbers which decline but also the quality of eggs. This applies equally to a woman who is trying naturally and also a woman who has IVF treatment. The success of IVF treatment will also be lower than it is in a younger woman.
The eggs remaining in both ovaries is called the ‘ovarian reserve’. The ovarian reserve diminishes with increasing age. Often this is manifested in a change in the menstrual cycles which first become shorter and therefore more frequent. With further loss of eggs, cycles become irregular and infrequent and finally stop altogether.
Egg quantity usually diminishes naturally after the age of 40 but can also be seen in younger women when it is called ‘premature ovarian failure’, in smokers and in women who have had ovarian surgery.
How do we estimate the ovarian reserve?
The most reliable test done is the AMH level estimation. AMH stands for anti mullerian hormone. Besides this test, we also count the number of follicles in both ovaries by doing a scan. This is called the ‘antral follicle count’ and should normally be 10 -11.
As the egg number reduces, the remaining follicles become more resistant to stimulation by FSH (a hormone released from the brain). Therefore the brain works harder to increase FSH secretion. A high level of FSH on cycle day 2 is another factor which tells us that the egg numbers are reduced.
As a woman gets to her mid to late thirties, together with the reduction in egg numbers comes another problem (ie) diminishing egg quality. A normal egg has 23 chromosomes and when it is fertilized by a sperm with 23 chromosomes – a normal embryo with 46 chromosomes results. But aging causes faulty division and some eggs may contain more and others less numbers of chromosomes. These are called ‘aneuploidic’ eggs and can give rise to faulty embryos. Faulty embryos may not implant, may result in miscarriage or give rise to an abnormal baby. An example of this is ‘Down’s syndrome’ where the baby has an abnormal number of chromosomes. This is commoner in women who are older than 35 years.
Fertility in males
Though not as abrupt or noticeable as the changes in women, changes in fertility and sexual functioning do occur in men as they grow older. Despite these changes, there is no maximum age at which a man cannot father a child, as evidenced by men in their 60s and 70s conceiving with younger partners.
Sperm numbers do not alter much as a man ages but the appearance of sperms (morphology) changes with more abnormal forms being present. There is also a decrease in motility of sperms. The testes may become softer and smaller in size and older men may complain of a reduced sex drive. Men who maintain good health however may have no problems.
When should a couple seek help?
When the female partner is 35 years or older and has not conceived within 6 months of trying, consultation with a fertility specialist is advised. Treatment will depend on the factor identified. However, no problem may be identified in either partner and this is called ‘unexplained infertility’.
With unexplained infertility, or when traditional treatments have failed, advanced infertility therapies such as superovulation with timed intrauterine insemination (SO/IUI) or in vitro fertilization (IVF) may be suggested. In an SO/IUI cycle, fertility medications are administered to start the growth of multiple eggs in the ovaries. When these eggs are ready to ovulate, the partner’s washed sperm is placed directly into a woman’s uterus. This procedure is called intrauterine insemination (IUI) and causes minimal discomfort. IVF involves removing the eggs and fertilizing them with the male partner’s sperm in the laboratory and then transferring the resulting embryos to the uterus.
In women over 40, the success rate of SO/IUI is generally less than 5% per cycle. This compares to success rates around 10% for women ages 35 to 40. IVF is more effective but also has relatively low success rates in women 40 and older, generally less than 20% per cycle.
This is an option for women who have a diminished ovarian reserve and who have a reduced likelihood of getting pregnant. Women who may need egg donation are those above the age of 40yrs, women with premature ovarian failure, and women who have had ovarian surgery with loss of eggs.
The woman who donates the eggs is called the ‘donor’ and the person receiving the eggs is called the ‘recipient’. Here eggs from a young donor who is between 20 and 30 years of age are fertilized with the sperms from the recipient’s husband. Since the donor is very young the success with egg donation is very high.
Donor-egg IVF offers a woman an opportunity to experience pregnancy, birth, and motherhood. The child, however, will not be genetically related to her but will be genetically related to the father (her husband) and the egg donor. Because success depends heavily upon the quality of eggs that are donated, women in their 20s with proven fertility (who have children of their own) are ideal donors.
Women who wish to delay childbearing until their late 30s or early 40s may consider methods of fertility preservation such as freezing of embryos after IVF or retrieving and freezing eggs for later use. The success of embryo freezing (cryopreservation) is well established, but it requires that the woman have a male partner or use donor sperm. Egg freezing for preservation of fertility is a new technology that shows promise for success.
Age remains a problem faced by women interested in using elective egg freezing. As the age of women undergoing egg freezing increases, the outcomes of assisted reproductive technology cycles utilizing their frozen eggs become less favourable.