Biological Clock

A female has the maximum number of eggs she will ever have as a fetus in utero at 20 weeks gestation, approximately 20 million.  During the last 20 weeks of in utero development, over 90% of the eggs will be lost, forming scars in the ovary.  At the time of birth, there are about a million eggs.  At puberty, when the brain-ovarian axis matures and ovulation begins, a few hundred thousand eggs remain.  The process of egg loss is known as atresia, and will continue until the last egg is released – menopause.

Each month when the menstrual cycle begins, a number of eggs start to develop – this group of eggs can vary in size from one to as many as thirty or forty eggs, depending on the number of eggs an individual is born with and her age.  With each reproductive cycle the entire group of eggs starts to develop; one egg out of this group develops to maturity and is released, i.e. ovulates, but the entire cohort of eggs is lost.  On rare occasions, more than one egg may ovulate, bringing about the opportunity for a multiple pregnancy.  This process of egg loss continues until menopause.  Typically, five to six years before menopause, cycles will become increasingly irregular as the quality of eggs that are released are often poor and may not produce enough estrogen to trigger ovulation.

Some individuals are born with much lower numbers of eggs.  These individuals are at risk for premature menopause – sometimes this occurs as early as the teenage years.  It is unknown why some women are born with fewer eggs, but likely is a function of genetics, i.e. menopause is often closely timed to maternal menopause.  The time of menopause can be influenced by a number of environmental factors, including surgeries, radiation, chemotherapy and smoking.  Starting your period early does not accelerate menopause.  Likewise, being on birth control pills, which prevents ovulation, does not delay menopause.  Again, there is a programmed loss of eggs each month.

Am I at risk for premature menopause?

It is important to identify those individuals that may be at risk for early menopause, not only for fertility concerns, but also for potential hormone replacement needs.  There are three primary means to guesstimate ovarian, i.e. egg, reserve:

Age

Age can be looked at as a rather crude guesstimate of remaining ovarian reserve, as some individuals are born with much greater numbers of eggs than others.  Certainly it is true that on average a 20-year-old is going to have far greater ovarian reserve than a 30-year-old, who would be expected to have far greater ovarian reserve than a 40-year-old.

Again, because of differences in the number of eggs someone is born with and potentially harmful environmental factors, there can be considerable variability in ovarian reserve at any age.  More accurate assessments of ovarian reserve include:

Hormonal Tests

Day 3 FSH/estradiol levels

Inhibin levels

Clomiphene citrate challenge tests

Antimullerian hormone

Ultrasound Assessment of Ovary

Counting the  number of egg/follicle units in the ovary, “antral follicle count” early in the cycle, typically days 2-4.

Combining different ovarian reserve tests is likely to give a more accurate assessment of ovarian reserve. Ovarian reserve can decrease abruptly in some individuals, likely representing an accelerated period of atresia, much like what happens in the second half of intrauterine development.  This is relatively common and can be seen in patients whose mother had an early menopause or who have been exposed to chemotherapeutic drugs, radiation, or destructive ovarian surgeries.  For others there are no obvious causes.  If an individual is at increased risk for accelerated egg loss, it is important to do regular ovarian reserve testing, especially if future fertility is a concern.

Fertility Preservation Options

Oocyte Cryopreservation

Oocyte cryopreservation is a relatively new, exciting technology for those individuals who do not have a male partner or who are uncertain as to whether they will stay with their current partner.  Worldwide, there are approximately 1500 babies born from frozen eggs.  Because of the limited number of babies born and relatively short follow up on these children, this technology should still be considered research and therefore should be carried out under an IRB (Institutional Review Board) protocol.  The institutional review board serves to review results from oocyte cryopreservation both in terms of efficacy and safety.  There are many programs throughout the country advertising egg freezing.  Many of these programs have had little or no success.  It is, therefore, important to ask some key questions when trying to identify a competent institution.  Namely, the number of babies that have been born from that particular embryology lab, not an affiliated lab or program.  Ask the number of eggs that were frozen to achieve these pregnancies, thereby getting an idea of efficacy.  The number of eggs available to an individual less than age 35 years of age or younger, on average, will vary typically between 8 and 16 each month.  For those individuals 36 and above, the cohort size is likely to be reduced, averaging between 5 and 12.  Ovarian reserve testing, again, will give a better estimate of individual egg number.  Depending on the efficiency of the program and an individual’s ovarian reserve, more than one stimulation cycle may be necessary to have a realistic chance for pregnancy.  Programs involved with oocyte cryopreservation should maintain a registry as to any birth defects or any development problems.

Florida Institute for Reproductive Medicine has been involved with oocyte cryopreservation since 1998.  To date, we have had 63 babies born from frozen eggs.  On average, we have required ten mature eggs to produce a healthy ongoing pregnancy in mothers 35 years or less.  For individuals 36-38, we are requiring on average fourteen mature eggs.  We do not offer oocyte cryopreservation for individuals over the age of 38, as the great majority of these individuals will have low ovarian reserve and a very high percentage of poor quality eggs, i.e. they are unlikely to benefit from cryopreservation.

Pre-embryo or embryo fertility preservation

This is an appropriate option for those individuals who are in a stable relationship.  In general, if there is any concern about potentially discarding an embryo, the option of cryopreserving pre-embryos should be considered.  Freezing a pre-embryo is, in essence, freezing male and female nuclear material that are close to each other but have not combined to form an individual.  Pre-embryo and embryo cryopreservation have been available since the mid-1980’s.  There have been hundreds of thousands of babies born from both pre-embryos and embryos.  There is a large body of reassuring health data, on babies born from (pre)embryos.  Fertility rates with (pre)embryos vary tremendously depending on the reproductive medicine program.  Each advanced reproductive medicine program in the United States is required by law to report their data to the CDC; therefore, before considering an individual program, check with the CDC registry (www.cdc.gov/ART/ART2011) on the program’s cryo IVF data.

Costs for oocyte cryopreservation as well as (pre)embryo cryopreservation should mimic those of a typical IVF cycle; the steps are basically the same.  Ongoing storage costs will typically vary from $100 – $400 per year.