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Fertility, Infertility and Female AgeAdvanced
Fertility Center of Chicago Our IVF live birth success rates Our live birth success rates for egg donation 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.
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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:
These figures from the government's 2005 CDC IVF Report show the
impact of advancing female age on IVF success
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 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
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.
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.
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: 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.
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. |
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