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ACOG COMMITTEE OPINION Number 413 ·…
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ACOG COMMITTEE OPINION
Number 413 · August 2008
Age-Related Fertility Decline
Committee on ABSTRACT: Age is a significant factor influencing a woman's ability to conceive.
Gynecologic Social trends have led to deferred childbearing, and an increasing number of women are
Practice experiencing age-related infertility and pregnancy loss. Women older than 35 years
This document reflects should receive expedited evaluation and treatment after 6 months of failed attempts to
emerging clinical and sci-
entific advances as of the
conceive, or earlier if clinically indicated.
date issued and is subject
to change. The informa-
tion should not be con-
strued as dictating an The number of oocytes in the ovaries years (5). A similar trend has been observed
exclusive course of treat- declines naturally and progressively through in analyses of data derived from in vitro fer-
ment or procedure to be
followed.
the process of atresia. The maximum com- tilization (IVF) embryo transfer programs in
plement of oocytes is 67 million and exists the United States. For the year 2006, the per-
at 20 weeks of gestation in the female fetus. centage of embryo transfers resulting in live
The number of oocytes decreases to approx- births decreased progressively from 44.9% in
imately 12 million oocytes at birth; women younger than 35 years to 37.3% for
300,000500,000 at puberty; 25,000 at age women aged 3537 years, 26.6% for women
37 years; and 1,000 at age 51 years, the aver- aged 3840 years, 15.2% for women aged 41
age age of menopause in the United States 42 years, and 6.7% for women aged 4344
(13). Fecundity declines gradually but sig- years (6). By contrast, in cycles using eggs
nificantly beginning approximately at age 32 obtained from healthy, young donors, 54% of
years, and decreases more rapidly after age 37 transfers resulted in a live birth, regardless of
years, reflecting primarily a decrease in egg the age of the recipient (6). As age increases,
quality in association with a gradual increase the risks of other disorders that may adversely
in the circulating level of follicle-stimulating affect fertility, such as fibroids, tubal disease,
hormone (3). The mechanisms involved are and endometriosis, also increase. Women
poorly understood, but appear to include with a history of prior ovarian surgery,
multiple factors encoded by genes on both chemotherapy, radiation therapy, severe
the X chromosome and the autosomes (4). endometriosis, smoking, pelvic infection, or
Age alone has an impact on fertility. a strong family history of early menopause
Historical data suggest that among popula- may be at increased risk for having a prema-
tions that do not use contraception, fertility ture decline in the size of their follicular pool
American Society for rates decrease with increasing age of women and their fertility.
Reproductive (Fig. 1). Because sexual activity also declines The age-related decline in fertility is
Medicine with age, it is difficult to separate out the accompanied by a significant increase in the
effects of sexual behavior from age. However, rates of aneuploidy and spontaneous abor-
a classic French study was able to separate tion (7). Autosomal trisomy is the most fre-
behavioral and age effects by studying nor- quent finding and is related, at least in part,
mal women with azoospermic husbands to changes in the meiotic spindle (8) that
undergoing donor insemination. The study predispose to nondisjunction (9). Even for
found that pregnancy rates decreased pro- morphologically normal embryos selected
gressively with increasing age of the recipient for transfer in IVF cycles, the prevalence of
The American College female (5). The cumulative pregnancy rate aneuploidy is high in women of advanced
of Obstetricians observed across up to 12 insemination cycles maternal age (10). The fetal loss rate also is
and Gynecologists was 74% for women younger than 31 years significantly higher, even after fetal heart rate
Women's Health Care and decreased to 62% for women aged 3135 motion is detected by transvaginal ultra-
Physicians years and to 54% for women older than 35 sonography (11). Whereas 9.9% of women
600
500
400
Rate per 1,000 wives
300
200
100
0
20 25 30 35 40 45 50
Age of wife
Fig.1. Marital fertility rates by 5-year age groups. The ten populations (in descending order at
age 2024 years) are Hutterites, marriages from 192130 (); Geneva bourgeoisie, husbands
born in 160049 (); Canada, marriages 170030 (); Normandy, marriages 176090 ( );
Hutterites, marriages before 1921 ( ); Tunis, marriages of Europeans 184059 ( );
Normandy, marriages 16741742 (); Norway, marriages 187476 ( ); Iran, village mar-
riages, 194050 (); Geneva bourgeoisie, husbands born before 1600 ( ). From Menken J,
Trussel J, Larsen U. Age and infertility. Science 1986;233:138994. Reprinted with permission
from AAAS.
younger than 33 years who conceive during IVF with a References
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fetal heart activity is observed, the rate of miscarriage in human ovaries. Proc R Soc Lond B Biol Sci 1963;158:
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years, 13.7% for women aged 3537 years, 19.8% for 2. Block E. Quantitative morphological investigations of the
women aged 3840 years, 29.9% for women aged 4142 follicular system in women; variations at different ages. Acta
years, and 36.6% for women older than age 42 years (11). Anat (Basel) 1952;14:10823.
Therefore, given the anticipated age-related decline in fer- 3. Faddy MJ, Gosden RG, Gougeon A, Richardson SJ, Nelson
tility, the increased incidence of disorders that impair fer- JF. Accelerated disappearance of ovarian follicles in mid-
tility, and the higher risk of pregnancy loss, women older life: implications for forecasting menopause. Hum Reprod
than 35 years should receive expedited evaluation and 1992;7:13426.
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In conclusion, fertility in women is closely related to Menopause: biology and pathobiology. San Diego (CA):
Academic Press; 2000. p. 7794.
reproductive age and becomes significantly compromised
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desires pregnancy. Women older than 35 years should
6. Society for Assisted Reproductive Technology. Clinic sum-
receive expedited evaluation and treatment after 6 mary report: all SART member clinics. Birmingham (AL):
months of failed attempts to conceive, or earlier if clini- SART; 2007. Available at: https://www.sartcorsonline.com/
cally indicated. rptCSR_PublicMultYear.aspx?ClinicPKID=0. Retrieved
March 18, 2008.
2 ACOG Committee Opinion No. 413
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reproduced, stored in a retrieval system, posted on the Internet, or
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of maternal age on meiotic spindle assembly in oocytes photocopying, recording, or otherwise, without prior written permis-
from naturally cycling women. Hum Reprod 1996;11: sion from the publisher. Requests for authorization to make photo-
221722. copies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
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Maternal aging and chromosomal abnormalities: new data Age-related fertility decline. ACOG Committee Opinion No. 413.
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morphology, developmental rates, and maternal age are
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