Fertility, Infertility and Female Age

The age of the male partner does not appear to matter nearly as much. This is related to the fact that all of a woman's eggs are present at birth. They can not divide or be "resupplied", whereas sperm are produced constantly after puberty in men. Eggs age over time, while new sperm are constantly coming off the production line. Sperm from older men does not usually have a substantially reduced fertilizing potential as compared to sperm from younger men. However, older men often have less interest in frequent intercourse, which can be a factor in chances for conception.

Many people are not aware of the decline in fertility as the age of the female partner increases:

There is a slow decline in pregnancy rates in the early 30's. This decline is more substantial in the late 30's and early 40's. Few women over 45 are still fertile.

Miscarriage rates also increase substantially as the mother ages (more on miscarriage below).

One important caveat is that the above numbers apply to populations, not individuals. A given woman can have rapid decline in egg quantity and quality at an early age - even in her teens or twenties in rare cases.

A study published in 1957 examined the relationship between the age of the female partner and fertility. This study found that:

By age 30, 7% of couples were infertile

By age 35, 11% of couples were infertile

By age 40, 33% of couples were infertile

At age 45, 87% of couples were infertile

Reference: Tietze C: Reproductive span and rate of conception among Hutterite women. Fertility and Sterility 1957;8:89-97.

For several reasons, infertility rates are even higher in the general population in the U.S. today than for the population studied by Tietze in the 1950s.

The graphs below are from the 2005 ART Success Rates report published by the CDC, Centers for Disease Control and Prevention, a US government agency. 

This report was generated from national data from hundreds of clinics and many thousands of IVF cycles. It is not data from our center (although we are included in it). It shows the rate of live births per embryo transfer procedure by the age of the recipient of the embryos. In the graph on the left side, the green line shows data using the infertile woman's own eggs for IVF, while the blue line shows IVF data from couples using donor eggs.

This chart illustrates the decline in live birth success rates by female age beginning at about age 32. Infertility is increased with age. This curve becomes steeper (egg quantity and egg quality is decreasing at a faster rate) starting at about age 36. At age 44 and above there are almost never babies born from IVF using the female partner's eggs - the live birth success rate using eggs over age 43 is 2% per cycle (per attempt). All IVF clinics have an age limit for in vitro fertilization. However, IVF age limits are not the same at every program. Most IVF centers are willing to attempt IVF using the female partner's eggs until about age 43-45, after which the couple would be offered egg donation as the only realistic and appropriate fertility treatment.

It is very important to remember that each data point on the curve below represents an average live birth rate from many cases. Every couple is unique and could be more fertile, or less fertile as compared to the average for their age. Another point illustrated here is that there is no decline in live birth rates by age of recipient when donor egg IVF is being utilized. The age of the eggs is very important, but the age of the uterus is not.

The graph on the right side is the same one, but we drew some lines drawn on it to make several points:

• There is little or no decline in fertility (using own eggs) until about age 32 (on the average) - shown by the red line (graph on right)
• There is a slow annual decline in fertility with aging from about age 32 until about age 36 - purple line
• After age 36 the decline becomes more rapid (steeper curve) - orange line
• There does not really seem to be a drop as the wife's age increases if she uses a (young) donor egg - pink line does not drop as the female donor egg recipient age increases.

These figures from the government's 2005 CDC IVF Report show the impact of advancing female age on IVF success
Although this data is specifically about IVF and age, there is also a similar loss in fertility potential with age in the general "normal" population

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In vitro fertilization and advanced maternal age over 40

This graph shows national average IVF statistics from the 2005 CDC report for women of advanced age (40 and over, using their own eggs)
The IVF live birth rate at each age is shown in the light blue bar for each age (above the red dots)
The national success rate per cycle was 16% at age 40, 8% at age 42 and less than 3% per cycle at age 44

The CDC ART IVF Reports for 2005 was used as a source for the above graphs

The national summary (as well as clinic specific results) of IVF success rates for cycles done in years 1995 through 2005 are posted on the CDC's website

See our IVF success rates

What to do if the first IVF cycle fails

Tests to determine whether age is a significant fertility factor in an individual couple trying to get pregnant

"Age" is one issue, but the real fertility issue is egg quality and quantity and not the number in a woman's age.

A woman can be 43 with exceptionally good quality eggs and still be fertile (which is rare at that age), or, she can be 25 with very poor quality eggs and be infertile. These are extreme examples, but the point is that egg quantity and quality tends to decline significantly in the late 30s and faster in the early 40s, but egg quantity and quality in an individual woman can be average for her age, better than average, or worse than average.

It would be nice to have a reliable test to determine how good the eggs are in an individual woman at a point in time. We do have some screening tests for ovarian reserve, however, they are far from perfect. Day 3 FSH testing and antral follicle counts are tests used by infertility specialists to help predict ovarian reserve. These tests are very helpful, but they predict quantity of eggs remaining rather than the quality of those eggs.

Many infertility doctors recommend that women over about 38 that are infertile should have aggressive treatment and proceed to in vitro fertilization relatively quickly - before all fertility potential is lost.

A dark, low quality egg with an irregular shape from a 41 year old
The egg is the ovoid structure in the center surrounded by hundreds of ovarian cumulus cells

Pictures of high quality eggs

Miscarriage and female age

Numerous studies have documented the increased risk for miscarriage as women get older. The following table is a summary of information from several studies:

Miscarriage rates for women with a history of infertility tend to be higher than for fertile women. Most of the increased risk for miscarriage in "older" women is due to the increase in chromosomal abnormalities (karyotype) in their eggs. This is also a great part of the reason for the decline in overall fertility with female aging.

This graph shows national data on miscarriage rates after IVF from the 2004 CDC report (using own eggs)
The CDC data only includes pregnancy losses after a fetal heart is seen on ultrasound - the miscarriage rate would be higher if earlier miscarriages were included
The miscarriage rate after fetal heart activity is seen on ultrasound was 11% at age 30, 20% at age 38, and 41% at 42 years old

Chromosomal problems in aging eggs

We do not know exactly why there is an increase in chromosomal abnormalities in the eggs of women as they age. However, research studies have clarified some of the issues involved.

The meiotic spindle is a critical component of eggs that is involved in organizing the chromosome pairs so that a proper division of the pairs can occur as the egg is developing. An abnormal spindle can predispose to development of chromosomally abnormal eggs.

A study published in the medical journal "Human Reproduction" in October of 1996 investigated the influence of maternal age on meiotic spindle assembly in human eggs:
D.E. Battaglia, et al:  Influence of maternal age on meiotic spindle assembly in oocytes from naturally cycling women. Human Reproduction October, 1996; (Vol. 11): Pages 2217-2222.

In this research project, 17% of the eggs studied from women 20-25 years old were found to have an abnormal spindle appearance and at least one chromosome displaced from proper alignment.

In contrast, 79% of the eggs studied from women 40-45 years old were found to have an abnormal spindle appearance and at least one chromosome displaced from proper alignment.

This study illustrates how chromosomally abnormal eggs (and therefore, embryos) are produced more often in older women. When the chromosomes line up properly in a straight line on the spindle apparatus in the egg, the division process would be expected to proceed normally so that the egg would end up with its proper complement of 23 chromosomes. However, with a disordered arrangement on an abnormal spindle, the division could easily be uneven - resulting in an unbalanced chromosomal situation in the egg.

This is illustrated in the pictures below, which are taken from the journal article. These photos taken with confocal fluorescence microscopy of eggs stained with special dyes to show the spindles and chromosomes. The orange spots are pairs of chromosomes in the eggs. The green area is the spindle apparatus. In the picture on the left, the egg is from a woman in her 20's and the chromosomes are in a straight line. The photo on the right shows an egg from a woman in her early 40's - the chromosomes are not arranged in a straight line - and this makes a mishap at the time of chromosome separation much more likely. The excellent article (referenced above) has a thorough discussion of this topic.

Normal Chromosomes line up straight on spindle	Abnormal Chromosomes line up erratically

The bottom line of all of this is that as women get older the incidence of chromosomally abnormal eggs increases dramatically. This results in lower chances for getting pregnant, as well as increased risk for miscarriage. When moms are 35 or older, amniocentesis is recommended to test the baby's chromosomes because of the increased risk of a chromosomally abnormal child (e.g. Down  Syndrome).

Discussion regarding PGD - preimplantation genetic diagnosis (also referred to as PGS - preimplantation genetic screening) to test the chromosomal status of IVF embryos.