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Ovarian Reserve Revisited-Do You Have Enough Good Eggs?

Ovarian Reserve Revisited-Do You Have Enough Good Eggs?

Trying to conceive over age 35 is generally not easy

I know because I tried for years to have a baby without success.  While there are many factors which impact conception, one of the first concerns for women over 35 is if they have enough healthy eggs to get pregnant.  Research has shown that women carry a reserve of eggs throughout their lives and that reserve diminishes over time.  There are several tests which help to determine ovarian reserve including antral follicle testing, the clomid challenge and the AMH test which is relatively new.

The antral follicle test

Uses vaginal ultrasound to count and measure the small follicles, antral follicles, on the ovary.  The higher the number of antral follicles, the better ovarian reserve and better odds for conception.

The AMH Test

Anti-mullerian hormone test, measures the levels of AMH in a woman’s blood.  Since this hormone remains relatively constant over the menstrual cycle, it can be tested at any point in the month.  Women with higher AMH levels tend to have a better ovarian reserve and a better chance at conception.

When I decided to try to conceive one last time at age 44

My reproductive endocrinologist began by ordering the Clomid Challenge Test.  For the test, I took clomid, a fertility drug used to induce ovulation, for 5 days.  Generally speaking, the procedure works like this:

  • On Day 3 of your menstrual cycle, a blood test is given to measure your FSH, LH, and estradiol levels.
  • On Day 5 of your cycle, you begin to take a 5-day supply of clomiphene citrate, 100 mg of clomiphene each day for five days.
  • On Day 10, you will have another blood draw to check FSH, LH, and estradiol levels again.

Normal results include low FSH values on both Day 3 and Day 10, and low estradiol values on Day 3.  Results are abnormal if your FSH values are elevated.  Your doctor may decide to re-test if your results are abnormal.

My results were normal but that is a fraction of the total conception story and half of the ovarian reserve story.  Ovarian reserve consists not only of the quantity of eggs but also the quality of eggs.     Research tells us that while tests like the clomid challenge check for the quantity of eggs, the quality of eggs is generally determined better by age.  This is an unfortunate fact for those of us over 35.

According to Dr. James Toner in his paper “Ovarian Reserve, Female Age and the Chance for Successful Pregnancy”, once women reach their mid thirties, specifically 37, their egg quantity begins to diminish at a faster rate.   Tonor also reports that even if egg quantity is good, chances of a viable pregnancy drop due to the diminishing quality of eggs as women age.

Based on the research, it is clear that the averages do not look promising for women over age 35 trying to have a baby.  There is, however, other information to consider.  Let’s take a look at the bell curve.  Basically, about 2/3 of the cases for a given situation fall in the fat part of the curve meaning that averages generally apply to most people.  However, there are still one third of the people who fall outside of the fat part of the bell curve and averages do not generally apply to them.  As you look at your individual situation, it is your lab work, anatomy and physiology that matter.   I am a classic example of defying the odds.  My ovarian reserve quantity was good but that wasn’t what was preventing me from conceiving a child.  It took many more tests to determine that a badly placed uterine tumor was most likely preventing implantation.  At age 44, the research showed that an average woman in my situation had only a 3% chance of having a healthy baby.  Yet, I was able to conceive in two of 4 IUI treatments and gave birth to a healthy little girl 9 months ago at the age of 45.

There are many components to conceiving a child

Ovarian reserve is one of them.  There are also many medical interventions to boost the odds of conception.  Medical research provides us with excellent information about infertility and age including work on ovarian reserve.  While the research tells us that the odds of getting pregnant in late 30’s and 40’s  diminishes, one needs to remember that each woman is unique and she needs to work with her doctor to explore all options in her quest for pregnancy.

Deborah LynnAbout the Author:  Deborah Lynn is the creator/owner of Over 35 New Moms and a former corporate vice president.   She holds degrees in Education, Kinesiology and pursued doctoral study in Physiology.  She spent over 17 years working in the corporate environment and now focuses her time on raising her daughter and helping other women over 35 in their journey to have a baby.  For more information, visit The Resource Guide for Pregnancy over 40 at http://www.selfgrowth.com

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Egg Reserve and Infertility

Egg Reserve and Infertility

Egg reserve means the number and quality of eggs remaining in the ovaries at a given age. It reflects the fertility potential of a woman irrespective of the cause of infertility, even male factor.

Benefits of Testing for Egg Reserve

Testing for egg reserve results should be interpreted with caution. Abnormal values should not be a cause for denying fertility treatment because the predictive power for pregnancy with own eggs is modest. For women, ovarian reserve tests give women insight into the chance of pregnancy with there own eggs. It also may indicate the need to promptly avoid delay in seeking fertility treatment.  For reproductive endocrinologists, the tests have value in designing fertility treatment and selecting the most appropriate fertility treatment protocol. They predict response to fertility medications and allow infertility specialists to select treatment protocol and gonadotropin dose. Egg reserve also predicts the number of eggs retrieved for IVF or egg freezing.

Egg Reserve: Egg Number

Although the number of eggs in the ovaries decrease with age there is significant individual variation in initial number endowed in the ovaries and the rate of decrease. Some young women has low egg number and older with large number of eggs. Ovarian reserve tests are used to estimate this number.

Egge reserve: the number of eggs in the ovaries drops with age

Egge reserve: the number of eggs in the ovaries drops with age

History

Medical history may indicate low egg reserve in women with prior excision of ovarian cysts, endometriosis of the ovaries,  women who smoke and with family history of early menopause

Antral follicle count

The number of antral follicles in the ovaries (the structures that contain the eggs) can be seen and counted using vaginal ultrasound. Performed by an experienced reproductive endocrinologist, it can accurately estimate ovarian reserve. Low count e.g <10 in both ovaries points to low reserve.

Day 3 FSH, Estradiol

FSH is produced by the master gland in the base of the brain. Estradiol is made by the follicles themselves. Measured in the second or third day of menstrual cycle, high FSH (>12) of high estradiol (>75) points to low egg reserve.

Antimullerian Hormone (AMH)

AMH is produced by the cells surrounding the eggs in small follicles and is a more direct measure of egg reserve than FSH. It can be accurately measured any day in the cycle with  little variations in between cycles. Levels <1.5 ng/dL generally indicates low egg reserve. It correlates well with antral follicle count.

Genetic Screening

Low egg reserve in few women is due to a genetic cause. Fragile X syndrome is a genetic disease that causes low egg reserve and mental deficiency in newborn males. Chromosomal abnormalities e.g Turner syndrome, translocations are also associated with low egg reserve. Genetic screening is performed using a simple blood test before starting fertility treatment.

Egg Reserve: Egg Quality

What does egg quality means ?

Good quality eggs are chromosomaly normal (has 23 chromosomes). The most important factor that prevents the achievement of pregnancy or leads to early miscarriage is an abnormal egg (has extra or missing chromosome or piece of a chromosome). Many eggs at any age in any woman are abnormal and the normal eggs are the ones that are successful in being fertilized with sperm, implant and achieve a pregnancy. These errors takes place when the original cell that produce the eggs divide to reduce the number of chromosomes to half. The division (meiosis) is many times unequal leading to an egg with an extra or missing chromosome.

Age and egg quality

The ovary releases better quality age earlier in life and lower quality age later, for unknown reason. Female age is the most important indicator for egg quality, chance for spontaneous pregnancy and after fertility treatment. Older women need to try longer to achieve pregnancy and at an increased risk for miscarriage, ectopic pregnancy and delivering a baby with chromosomal abnormalities e.g Down Syndrome. This effect of age become clinically evident at age 30 or even earlier. Age is more important than the number of eggs in the ovaries. Young women with few eggs in the ovary are more successful in getting pregnant than older women with many eggs in the ovary.

Meiosis

Meiosis

Testing for egg quality: PGD

Age is the only available noninvasive method to estimate egg quality. Healthy eggs cannot be identified using any non invasive method. It is possible to identify chromosomal errors in the egg during IVF fertility treatment after biopsy of the first polar body of unfertilized egg or after removing one cell from an embryo after the egg is fertilized then test this material for chromosomal abnormality. This process is called PGD or preimplantation genetic diagnosis. It is important to remember that PGD is not proven so far as method of enhancing fertility potential. It simply detects if the egg or embryo is chromosomaly normal or not but will not make an unhealthy egg healthy.

Read more about ovarian reserve and low response to ovarian stimulation in my review here.

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Egg Quality and Fertility Treatment Success

Egg Quality and Fertility Treatment Success

What does egg quality means?

Good quality eggs are mature eggs that are able to fertilize, develop into normal embryos that are able to implant and progress to a healthy baby. Good quality eggs have normal chromosomes. A normal egg contains 23 chromosomes and when fertilized with a sperm produce a zygote that has 46 chromosomes.

How is egg quality tested?

Two methods

  1. Non invasive: asking a woman about her age. Age is the most important determinant of fertility. All women have abnormal eggs and well as normal ones. With advance in age the proportion of normal eggs decrease because the ovary ovulates the healthier eggs earlier in life. Older women have less eggs and more abnormal eggs. Apart from age and ovarian reserve testing there are no other noninvasive methods to test for egg quality. Couples may present with unexplained infertility, minor abnormalities or repeated unsuccessful fertility treatment. Other indicators of lower egg quality are recurrent early first trimester pregnancy loss (biochemical pregnancy), pregnancy loss in the first trimester when chromosome analysis of products of conception is abnormal. Ectopic pregnancies are more common with chromosomally abnormal embryos.
  2. Invasive method: the eggs can be retrieved and DNA analyzed via PGD, before or after fertilization to detect the number and structure of chromosomes. This is usually done during actual fertility treatment.
Advance in maternal age is associated with lower chance for conception due to lower number of eggs with normal chromosomes

Advance in maternal age is associated with lower chance for conception due to lower number of eggs with normal chromosomes

 

How can we improve egg quality during fertility treatment?

Strategies employed to improve egg quality during fertility treatment include

  1. Random increase in the number of eggs produced: Ovarian stimulation can increase the number of eggs produced increasing the odds that one or more of those eggs have normal chromosomes. This random increase in the number of eggs is employed in IUI and IVF cycles. We do not know if any of the eggs are normal but generally the more eggs you make the higher the likelihood that one or more are normal.
    Human eggs retrieved after ovarian stimulation

    Human eggs retrieved after ovarian stimulation

  2. Tweaking of ovarian stimulation protocol: Many changes to the stimulation protocol can improve response and egg quality including, choosing an agonist or antagonist based protocol, the addition of an oral agents like clomid or letrozole, reducing the dose of gonadotropins, changing the timing for the trigger shot hCG.
  3. Embryo selection using morphology: Healthy embryos divide and double the number of cells every 24 hours or less (8 to 10 cells on day 3). Healthy embryos have equal cells and each has a single nucleus. Healthy embryos are not fragmented (due to cell breakdown). These embryos are identified under the microscope. The problem with morphology is that many unhealthy embryos are good looking. the prediction ability of morphology in detecting chromosomally normal embryos is probably 60% or less. Morphology, however is non invasive and cheep. Extended vulture is used to push embryos to day 5 to observe which embryo will reach the blastocyst stage and select it for transfer. Blstocysts have generally higher implantation rates than day 3 embryos because of the ability to select the better embryos. Extended culture is employed when many embryos are available on day 3 (usually five or more).
  4. Genetic analysis of eggs or embryos: The most important point to know about genetic analysis of eggs and embryos is that PGD does not create a new potential or improve the overall success for fertility treatment for a given stimulation cycle. It just detects fairly accurately (not 100% accurate) the chromosome makeup of eggs or embryos. The potential advantage of PGD is to directly select the embryo, out of available cohort, that is most likely to implant instead of selecting based on morphology. Thus it maybe helpful for women with large number of embryos available on day 3 and day 5. In other words if you have two embryos available on day 3 and you are transferring two embryos, there is no point in testing them. On the other hand if you have eight embryos on day 3 and you will only transfer 1-2 embryos, then PGD may makes sense to go directly to the embryos most likely to work.

The potential disadvantages of PGD are the need for embryo biopsy that potentially may harm the embryo. PGD assumes that the cell obtained represents the whole embryo while sometimes that cell chromosomes maybe different than the embryo. The method for analysis used is not 100% accurate. In other words the method may misdiagnose a healthy embryo as abnormal or vice versa or on occasions fail to diagnose the embryo at all. PGD is expensive requiring embryo biopsy and embryo genetic analysis.

So far no large scientific studies are available and reproduced by many centers indicating increase in fertility potential of IVF. Because of all these factors, PGD is selectively applied to select patients and not a universal step in all IVF cycles.

Other methods suggested as supplements as well experimental methods as mitochondrial transfer still lack scientific evidence that they work.

 

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