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Fertility, Infertility and Female Age
Background information on aging and fertility
Female age is very important in consideration of probability for getting pregnant. The real issue is egg quantity and quality - which translates over to embryo quality after fertilization. Increased infertility with age is a well documented problem and very apparent in modern society. As women wait longer to have children, a higher percentage of couples have fertility problems because of the quality of the eggs, and other issues that affect fertility and are more common in older women.
Women's liberation has brought many advantages to women. However, as women increasingly delay childbearing, our society has done a very poor job of educating people about the decline in female fertility with increasing age. Too many couples learn about the impact of age when it could already be too late for them. Many couples end up needing advanced treatments such as IVF to help overcome the age related decline in egg quality. If they had tried to have a baby years sooner, good old-fashioned "sex in the bedroom" could have built the family. The American Society for Reproductive Medicine said it well: "As women delay childbearing, there is now an unrealistic expectation that medical science can undo the effects of aging".
We certainly try our best to overcome the effects of increasing female age with advanced fertility treatments such as IVF. Women often ask whether there is an age limit on having in vitro fertilization. All clinics have some upper age limit after which they will not perform in vitro fertilization with the woman's own eggs. The age limit is somewhere between 42 and 45 at most programs in the US. Most IVF clinics allow a woman to be a recipient of donor eggs through about age 50.
Successful pregnancy outcome with treatment is very much related to female age - when using the woman's own eggs. When donor eggs are being used, the age of the egg donor is the important issue. With egg donation, the age of the recipient woman does not seem to affect the chance for success. This means that the age of the egg is very important, but the age of the uterus is not. See the graph below for more on this.
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.Age and Fertility Statistics
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 (see more about 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 of fertility rate by age in women was published in 1957. The study was on a large population that never used birth control. The investigators measured the relationship between the age of the female partner and fertility. This study found:
- 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 higher in the general population in the U.S. today than for the population above studied by Tietze in the 1950s.
The graphs below are from the 2006 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 blue line shows data using the infertile woman's own eggs for IVF, while the black line shows IVF data from using donor eggs.
This chart illustrates the decline in live birth success rates by female age beginning at about age 31. Infertility is increased with age. This curve becomes steeper (egg quantity and egg quality is decreasing at a faster rate) starting at about age 35. At age 45 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 44 is less than 1% per cycle (per try). 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 42-44, 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 little or 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 carrying the embryos is not important.
The second graph below is the same as the first, but with lines drawn to make some points:
- There is little or no decline in fertility (using own eggs) until about age 31 (on the average) - shown by the orange line (lower graph)
- There is a slow annual decline in fertility with aging from about age 31 until about age 35 - purple line
- After age 36 the decline becomes more rapid (steeper curve) - blue line
- There does not really seem to be a drop as the wife's age increases if she uses a (young) donor egg - the yellow line does not drop as the donor egg recipient's age increases.
See details of research done by Dr. Sherbahn on recipient age and egg donation success
The graphs above from the government's 2006 CDC IVF Report show the impact of advancing female age on IVF success. Although these age and fertility statistics are specifically about IVF success, there is a similar loss in fertility potential with aging in the general "normal fertile" population.
In vitro fertilization success statistics and advanced maternal age over 40:
The graph above 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 per cycle (shown in middle bar for each age - at red dot) was 16% per cycle at age 40 and only 2.6% per cycle at age 44.
The national summary (as well as clinic specific results) of IVF success rates for cycles done in years 1995 through 2006 are posted on the CDC's website.
Check your fertility doctor's IVF success rates
See our egg donation 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. Poor egg quality results in poor embryo quality which severely reduces the chances for becoming pregnant and having a successful outcome. A woman can be 43 with exceptionally good quality eggs and still be fertile (which is quite 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 mid to late 30s and declines faster in the late thirties to early 40s. With this in mind, 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, AMH levels and antral follicle counts are tests used by infertility specialists to predict ovarian reserve. These tests are helpful, but they predict the 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
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:
Maternal age |
Pregnancy |
< 30 |
5% |
30-34 |
8% |
35-39 |
16% |
40-41 |
30% |
42-43 |
40% |
44-46 |
60% |
Miscarriage rates for women with a history of infertility tend to be higher than for fertile women. The main reason for the increased risk for miscarriage in "older" women is due to the increase in chromosomal abnormalities (abnormal karyotype) in their eggs. This is also a great part of the reason for the decline in overall fertility with female aging.
The graph above shows national data on miscarriage rates after IVF from the 2004 CDC report (using own eggs). The CDC data only includes pregnancy losses after ultrasound confirmed pregnancy - the miscarriage rate would be higher if very early miscarriages (such as "chemical pregnancies") were included. The miscarriage rate after ultrasound confirmation of pregnancy 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.
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| Normal Chromosomes line up straight on spindle |
Abnormal Chromosomes line up erratically |
The bottom line 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 - such as Down Syndrome.
More information:
Discussion of PGD - preimplantation genetic diagnosis (also called PGS - preimplantation genetic screening) and whether it helps to test the chromosomes of IVF embryos.
Discussion about Egg Donation
