Age, Fertility, and Donor Eggs

Unfortunately, there really is such a thing as a biological clock.  A woman's fertility is directly linked to the number and quality of the eggs in her ovaries, which declines as we get older.  Unlike men, who make new sperm all the time, women were born with all the eggs they are ever going to have.   As a matter of fact, a woman starts losing eggs before she is even born.  The ovary starts off with about 6-7 million eggs and is down to 1-2 million by birth.  By puberty, the ovary has 300,000 to 500,000 eggs left.  400-500 of those will ovulate, and the rest will just die off over time.  By the time of menopause, there are very few eggs left.  This loss of eggs has a direct effect on fertility.  It also appears that the best quality eggs ovulate early on in a woman's life, which is another reason why it is so easy to get accidentally pregnant as a teenager and difficult to get purposely pregnant as a 40 year old.

This loss of egg quantity and quality (ovarian reserve) over time starts to affect a woman's fertility in her late 20's.  The decline in fertility is usually pretty gradual until the end of her 30's.  Somewhere around age 40, the dropoff will become significantly faster with the average age at which it becomes impossible to get pregnant being age 42.  Every woman is different, however.  Just as some women going through menopause in their 40's or late 50's instead of their early 50's, the changes in fertility can happen faster or slower in certain women.  I have patients in their 20's who are already having trouble with diminished ovarian reserve and patients in their 40's who are not.  These are the exceptions, however, so most women will follow the time line above.

There are ways to determine a woman's ovarian reserve.  The most common method is with a blood test to look at FSH and estradiol levels on the second, third, or fourth day of your period.  FSH, as I have said in previous blogs, is the hormone your pituitary makes to tell the ovaries to get eggs maturing and ready for ovulation.  At the beginning of a menstrual cycle, which is when this test is done, the ovaries haven't started to do this yet.  So FSH is being produced at a high rate to get the ovaries started.  As the number and quality of eggs left goes down, it takes more and more FSH to get the ovaries going at the beginning of a cycle.  Therefore, the higher the FSH level is at the beginning of a cycle, the poorer the ovarian reserve is.  FSH levels can vary depending on the lab they are measured in, but in general an FSH level under 10 mIU/ml is reassuring.  FSH levels between 10 and 15 mIU/ml are concerning.  It may still be possible to get pregnant with an FSH level in this range, but it is more difficult and often takes more aggressive therapy.  Miscarriage and chromosome abnormalities (such as Downs Syndrome) rates start to go up too.  FSH levels over 15 mIU/ml are associated with sporadic pregnancies, high miscarriage rates,  and higher chromosome abnormality rates too.  Pregnancies occur, but they are fairly rare (about 3 -5% of women with FSH levels over 15 will be able to conceive).  The estradiol level is used as a quality check on the FSH levels.  Estradiol levels should be under 70 pg/ml.  When they are higher, FSH levels will be artificially low and cannot be used to determine ovarian reserve.  When this happens, the test is usually repeated in the next menstrual cycle.

Another test used to look at ovarian reserve is AMH (anti-mullerian hormone).  This is a substance that is made by the eggs in the ovaries.  Therefore, the more AMH there is in the bloodstream, the more eggs there are in the ovaries.  Levels over 1.5 ng/ml are desirable.  Below that, the quantity of eggs left in the ovaries has started to decline enough that it can affect fertility.  It is still fairly controversial as to whether AMH tells you anything about the quality of the eggs.  You can also count the number of follicles in the ovaries at the beginning of a cycle.  Follicles are the sacs in which the eggs grow.  This is called the Basal Antral Follicle Count (BAFC).  Obviously, the more follicles seen in the ovaries, the better the ovarian reserve is.  A final common test of ovarian reserve is the Clomiphene Citrate Challenge Test.  In this test, the FSH and estradiol levels described above are done on day 2.3, or 4 and then Clomid (a mild fertility medication that is described in a previous blog) is given from day 5 to 9 of the cycle, and then the FSH and estradiol are repeated again after the Clomid (on day 10).  The FSH levels should both stay under 10 mIU/ml, and ideally the day 10 FSH level should be lower than the original FSH level.  The estradiol level should start under 70 pg/ml and go up significantly after the Clomid is taken.  This test will often times pick up more subtle problems with ovarian reserve, and it is also helpful if the estradiol levels at the beginning of the cycle are always too high to interpret the FSH level.

The other factor that needs to be considered when determining a woman's chance of getting pregnant is her age.  Age is an important factor in a woman's ability to conceive.  A woman over 40 with a completely normal Clomiphene Citrate Challenge Test only has about a 10% chance of getting pregnant, whereas a 25 year old woman would have a least a 70% chance.  We therefore are more optimistic about the chances for younger women with high FSH levels and more pessimistic about older women with normal FSH levels.

Once a woman starts showing signs of diminished ovarian reserve, there is no way to reverse the process.  So time is of the essence.  Fertility medication, inseminations, and sometimes even IVF are recommended for younger women with FSH levels under 15 mIU/ml.  For older women with FSH levels over 10 mIU/ml or any woman with an FSH over 15 mIU/ml, donor eggs may be recommended.  This is a process where IVF (in vitro fertilization, see previous blog on the subject) is performed using a young woman's (usually in her 20's or very early 30's) eggs.  The egg donor is given injectable fertility medication to produce more eggs than the one that is usually produced in a menstrual cycle.  The eggs are then removed from the donor's ovaries, mixed with the patient's partner's sperm (or donor sperm) in the lab, and then 1 or 2 of the resulting embryos are placed back into the uterus of the woman with the diminished ovarian reserve (recipient).

While the donor is taking the fertility medications, the recipient is usually given a medication to shut down her own menstrual cycle so that it can be tracked with the donor's cycle.  Lupron (see previous blog on IVF) is usually the medication used for this.  It is given by injection.  Lupron does not usually cause any side effects in this scenario; but for the few days that it is given without estrogen, it can cause hot flashes, night sweats, and headaches.  The recipient is also given estrogen to build up the lining inside the uterus to make it a good place for an embryo to grow.  Estrogen can make you a little nauseous, give you a stretchy mucus discharge from the vagina, and sometimes is associated with a sense of well being and energy.  The estrogen can be given by pill, patch, or injection.  Once the eggs are removed from the donor, the recipient is started on progesterone too.  This is the hormone the ovaries make after ovulation, and it tells the uterus to get ready for an embryo to implant.  Progesterone can be given by injection or with a suppository or cream that goes into the vagina.  There will also soon be a ring that goes into the vagina and secretes progesterone.   Progesterone can make you a little constipated and tired.

After a few days on the progesterone, the embryo(s) are placed in the uterus.  This procedure feels something like a PAP smear.  A speculum (that metal or plastic instrument that is used during a PAP smear) is placed into the vagina, and the cervix is cleaned off.  A small tube with the embryo(s) is then threaded through the canal in the cervix and up to the top of the uterus.  The embryos are placed at the top of the uterus, and the tube is removed.  Ultrasound is commonly used to watch the tube and make sure it is in the right place before the embryos are deposited.  Your doctor will probably ask you to have a full bladder for this part.  Now there is nothing left to do but continue the estrogen and progesterone and wait.  The chances of conceiving with donor eggs will vary center to center, but they are usually very high.  Donors also tend to make a good number of eggs, so there are usually extra embryos to freeze as well.  The chances of miscarriage or chromosome abnormalities is low as well.   Donated embryos can also be used.  The process is the same for the recipient, except that Lupron is not usually necessary.  Frozen embryos donated by another patient are used instead of donated eggs.  This is usually less expensive than donor egg cycles, but donated embryos are harder to find and most clinics have a waiting list for them.

Beware of therapies that say they will lower your FSH levels too.  It's not the FSH level itself that is the problem, it's what it says about the eggs.  As I described above, estrogen will lower FSH levels.  Many herbal remedies have mild estrogens in them, and so your FSH levels will look better.  However, they cannot give your more or better quality eggs.  DHEAS is another controversial treatment recommended for diminished ovarian reserve.  Although there is some promising data, most of the data is much more pessimistic.  I tell my patients that it may be worth a try so that you feel like you have done absolutely everything you can before moving on, but I am not at all convinced that it will help.

I think this is one of the most confusing and distressing issues for couples struggling with infertility.  It's highly technical, and you may feel lost in all the numbers and statistics.  The internet and your friends  are also full of stories of women who do conceive at older ages and with higher FSH levels.  Remember, I said that pregnancy is still possible even with high FSH levels or in women over 40.  It's just unusual.   The reason these women are posting on the internet or telling your friends their stories is because they are the exception to the rule.  For every woman who beats the odds, there are close to one hundred women who cannot.  Try to be realistic (yes, I know that's not easy).  There is a chance you will be able to get pregnant, but you need to acknowledge the fact that it may not happen.  I believe in miracles (I have 2 myself (see my first few blogs for the full story)), but I also prepared myself to live without kids or to try donor egg.  Dealing with diminished ovarian reserve is awful, and I am sorry if it is happening to you.  You have every right to feel angry, frustrated, depressed, and desperate.  Remember that you are not alone.  Talk to your friends or your doctor, if you can.  There are actually some pretty funny infertility humor sites on the internet that may make you feel a little better too.  Try to make a plan on how long you want to try and where you will draw the line.  Consider all the options, even adoption, and give yourself time.  At first, you may rule out an option like donor egg.  Reconsider all the options after about 6 months or even a year.  Your mind will have had time to process what is going on and you may find that options you considered out of the question now seem more reasonable.  Above all, hang in there!!!  You are still a wonderful person with a lot going for you, even if it doesn't feel like it right now.