Diminished Ovarian Reserve

DIMINISHED Ovarian Reserve

by Brett Davenport, MD

The biological clock. Every woman feels it to some degree.

For some women it is a soft whispering reminder that can be drowned out by life’s boisterous pace. Others may hit the ‘snooze’ button in hopes that the reminder doesn’t resurface too soon. Still for others it is like a deafening smoke alarm that may trigger panic. Regardless, it is a call that should be heard and understood in order for a woman to make a good decision regarding her plans for a family.

WHY IS AGING IMPORTANT TO THE OVARIES? Age is an important factor when talking about fertility because it inversely correlates with a woman’s chances of conception and live birth. Even though the average woman’s reproductive window is quite broad, the overall chances of conceiving begins declining much more rapidly around age 34. In other words, the hill down towards infertility becomes steeper. But it’s important to recognize that it is indeed a hill not a cliff (Figure 1). So, what does that mean?

Most of the declining live birth rates as a woman ages are due to the aging of her eggs. Aging has several effects on the eggs, including a steadily diminishing number of eggs, decreasing egg health, and an overall increase in the number of eggs that are genetically abnormal when ovulated. This all translates into a decreased ability to get pregnant (decreased pregnancy rate), stay pregnant (increased miscarriage rate), and deliver a baby (decreased live birth rate).

EGG QUANTITY It may be a sobering fact that a woman who is of reproductive age loses a group of 15-20 eggs each day on average. In fact, by the time a woman is 30 years old, only 12% of her egg population that she had at birth remains. By the time she is 40, she has only 3% of this population remaining. As a result of declining egg quantity, many women will begin to have more frequent periods as their ovarian reserve begins to deplete. This can sometimes mean that an egg will ovulate prior to it being fully mature. It is also not uncommon to skip ovulation cycles as egg reserve becomes very depleted.

EGG QUALITY Just as the rest of our organs suffer from ‘wear and tear’ as we age, the ovaries are no exception. In an ovary each egg depends on a cluster of cells around it called the cumulus complex for nourishment. These cumulus cells allow the essential nutrients and hormones from a woman’s bloodstream to reach an egg. As a woman ages, this group of nourishing cells begins to become smaller and smaller, causing each remaining egg to be less healthy than in younger eggs.

INCREASED ANEUPLOIDY OF EGGS Just prior to an egg ovulating it undergoes an equal division of chromosomes (the genetic material passed on to your offspring). If an equal division of these chromosomes does not occur, the egg is said to be aneuploid because it will have one too many or one too few chromosomes. An unequal division can occur in women of all ages. However, with age comes an increasing frequency of unequal division and a greater percentage of a woman’s eggs being aneuploid (figure 2). The large majority of aneuploid eggs will not be able to result in a viable pregnancy due to inability to fertilize or implant, or due to miscarriage. For the rare occurrence that an aneuploid egg does result in pregnancy, the child will usually have a syndrome (Down’s syndrome, etc.). Although a woman’s overall chances of having a baby with an aneuploidy increase with age, the absolute risk for a woman who is less than 40 is only 1.5%.

HOW DOES A WOMAN KNOW IF SHE HAS DIMINISED OVARIAN RESERVE? If a woman who is less than 35 years old has regular menstrual cycles, she has no reason to be concerned about her ovarian reserve since it is more than likely adequate. However, around age 35 a woman’s level of concern about diminished ovarian reserve should certainly increase. Even though menstrual cycles may remain normal, ovarian reserve is reaching its limits in these women. Several tests exist that will hint at how many and/or the quality of eggs remaining. Antimullerian hormone is a substance secreted by the cumulus cells around the egg, and is a good indicator about the number and/or quality of eggs. FSH during the first few days of a menstrual cycle is also a good indicator of the degree of egg depletion. Finally, an ultrasound can be performed to check the ‘antral follicle count’. This is a snapshot in time of the follicles that are next in the cue to grow and mature, but also hints at how many eggs remain. No test exists that predicts your specific risk of aneuploidy. Aneuploidy rate must be assumed based on your age alone.

WHAT IF I DO HAVE DIMINISHED OVARIAN RESERVE? If the above tests do indicate that your ovarian reserve is diminished, here are some things to keep in mind:

• You are already on your way to the most important step which is gaining an awareness that time is of the essence. If you are in a life position to have children, do it while you can!

• If you are 35 or over and have been trying to conceive unsuccessfully for 6 months or greater, it is prudent to allow for an infertility specialist to perform a thorough infertility work-up that will detect any other potential fertility issues that might further delay or hinder your ability to conceive or carry a child.

• An infertility specialist can also help you stimulate multiple eggs each cycle, which will act to increase your overall chances to conceive each cycle.

• Because time is of the essence, in vitro fertilization (IVF) may be recommended to you in certain situations or if your DOR is severe. IVF will give you the highest chances for pregnancy in the shortest amount of time. This can also allow you to freeze embryos for future use while you still have eggs left.

• Your infertility specialist may recommend antioxidants, which may slow the aging process and possibly decrease the aneuploidy rate of your eggs.

• Other supplements like DHEA, growth hormone, transdermal testosterone, and vitamin D have to date been shown to be possibly beneficial in certain patients with DOR. These should be discussed with an infertility specialist to see if any are right for you.

CAN I DO ANYTHING TO SLOW OR PREVENT THE AGING OF MY EGGS? In short, ovarian aging cannot be prevented, and the most powerful determinant in ovarian reserve and aging are your genetics. However, as with the rest of our organs in our body, the ovaries age slower when they are subjected to less stress. Healthy eating and exercise are the best place to start. Avoiding stressors like smoking, excessive alcohol, and environmental toxins, and minimizing lifestyle stressors are all good ways to maximize the potential of your ovaries. Antioxidants can also help slow this process and can be found in many dietary sources or supplemented in pill form (e.g. CoQ10).

WHAT IF I’M NOT READY TO HAVE CHILDREN UNTIL IT IS TOO LATE? For women who are planning to have children later in life, it might be wise to consider the freezing of some of her eggs while she is in her 20s or early 30s. Even women in their late 30’s who are not yet desiring children may opt for egg freezing before their ovarian reserve is depleted. Cryopreservation of her eggs allows for better pregnancy that are consistent with the age of when the eggs were frozen rather than a patient’s current age. This process is called elective egg freezing.

CONCLUSION No need to panic, but also don’t wait until it’s too late to listen to your biological clock. Several ways exist to test your ovarian reserve, and several interventions are available that may help if your reserve is diminished. Anticipate when you might plan for a family and consider freezing your eggs or embryos if you think you may be older and still desiring to have kids. Lastly, don’t hesitate to call an infertility specialist to help you assess your situation! We are here to help!

Brett Davenport, M.D., Practice Director Fertility Institute of North Alabama 532 Madison Street, Huntsville, AL 35801 Phone: 256-217-9613 Fax: 256-217-9618