How Age Affects Fertility
The Impact of Age on Female Fertility
What is the Biologic Clock?
The "Biologic Clock" is a collective term that refers to the incessant winding down of the reproductive organs along with the physiologic wear and tear occurring throughout the normal aging process.
Few topics related to infertility arouse so much anxiety and confusion as the effect of aging on fertility and ultimately pregnancy. It is a source of internal stress that can be overwhelming as a woman worries about her "biologic clock", which can sometimes lead to additional medical problems like anxiety and depression. During this time it can be helpful to become well informed in order to best understand how the physiologic process of aging affects fertility.
What Happens to Reproduction as Women Age?
Although it is not frequently discussed, reproduction in humans is very inefficient at best. Even during peak human fertility in the teen years and the 20's, the chance of pregnancy is about 20% per month, assuming a woman has regular ovulation, with open Fallopian tubes and a partner with normal sperm production. Dysfunction in any of these factors can lead to infertility or may prolong the time needed to become pregnant.
Additional gynecologic problems such as endometriosis, pelvic scarring and uterine fibroid tumors can occur at any time and may interfere with the normal process of egg entry into the Fallopian tubes or failed implantation of the embryo.
How does Aging Affect Human Eggs (Oocytes)?
One of life's greatest ironies is that just at the right time when a woman is prepared emotionally and personally to begin her family, she may be confronted by the obstacles associated with infertility (Life is just not fair!)
Note that the terms "eggs" and "oocytes " will be used interchangeably in this discussion. At birth, most women (but not all) are born with about 2 million oocytes (eggs) that are stored in their ovaries. Each egg is a microscopic, fluid filled cell lying in a protective capsule called a follicle, which in turn is located within the ovaries.
Each oocyte is formed with a pre-determined lifespan that cannot be altered and may be as brief as a few days or up to many years. From the time of birth until menopause, there is a natural, unrelenting loss or attrition of the oocyte number as they are eliminated from the resting pool.
The magnitude of egg loss is truly staggering, such that by adolescence, 90% of the eggs available for ovulation has been lost, leaving about 100,000 from the original 2 million at birth (see graph 1). Unlike ongoing fresh sperm production in men, there is no new formation of fresh, healthy eggs in women. (Again, life is not fair).
Age Related Changes in the Internal Structure of Human Eggs
The cytoplasmic fluid within the egg contains many tiny organelles along with microtubules collectively known as the cytoskeleton which control critical internal motion and alignment. Certain organelles, like the mitochondria, are the energy powerhouses of the oocyte and are essential for normal egg function. Disturbances within the structure of microtubules and aging of the maternal mitochondria can interfere with normal fertilization and growth. This may lead to the development of sub optimal embryos that fail to develop normally, leading to implantation failure or loss of the pregnancy (miscarriage) during the first few weeks.
Chromosomal and Genetic Abnormalities Associated with Aging
Among the most common types of errors related to aging is ANEUPLOIDY, a term given to numerical abnormalities in the number of chromosomes Physiologic aging can disturb the function of a delicate barrel shaped internal organelle called the SPINDLE resulting in uneven distribution of chromosomes as the embryo begins to grow. This can lead to the loss or abnormal duplication of entire chromosomes. This will lead to failed implantation of the embryo or may result in multiple miscarriages. The most well known of these types of chromosomal errors is Down Syndrome where one extra chromosome is seen in the 21st pair of chromosomes (Trisomy21).
Chromosomes contain thousands of gene sequences that form the "genetic blueprint" controlling every aspect of human life. Spontaneous errors or genetically linked diseases can be transmitted in some families where the parents are "carriers" of the genetic mutation. This may lead to a birth defect or an early pregnancy loss because vital DNA information necessary for the development of a normal child is abnormal. An example of a genetic mutation is the disease called Cystic Fibrosis.
These types of abnormalities can be diagnosed with In-Vitro Fertilization using a specialized technique called Pre-Implantation Genetic Screening (PGS).
THE NATURAL PROCESS OF EGG SELECTION
Only the Strongest Egg Survives
Each month, at the start of a new menstrual cycle, the ovaries initiate recruitment of 40 to 50 eggs from the resting oocyte pool. An elimination process begins such that by ovulation time 14 days later, only the most favorable oocyte is released each month.
Even with this rigorous selection, an oocyte can still have undetectable abnormalities, which can slip by nature's protective screening mechanisms. These checks and balances help minimize abnormal pregnancies, insuring that only the healthiest embryos can implant.
Unsuitable eggs may fail to become fertilized or not divide properly leading to failed implantation or abortion. Unfortunately, the changes discussed above cannot be reversed and with advancing age, even IVF may not overcome the egg abnormalities. In these cases the physician may recommend the use of donor eggs to bring about a healthy pregnancy and a happy family.