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AGE AND FERTILITY. AGE AND PREGNANCY Kathleen M. Gotzmann, MD Department Chair Ob/Gyn Upper Chesapeake Medical Center. BACKGROUND. Women are born with all the eggs they will ever have, about 1 million Some are ovulated, but several hundred are pre-programmed to die each month

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Kathleen M. Gotzmann, MD

Department Chair Ob/Gyn

Upper Chesapeake Medical Center

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  • Women are born with all the eggs they will ever have, about 1 million

  • Some are ovulated, but several hundred are pre-programmed to die each month

  • Accelerate egg loss--- smoking, ovarian

    surgery, pelvic radiation, chemo agents

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Infertility Facts

  • The average chance of becoming pregnant each cycle is only 20%

  • It takes 5 to 6 months for the average fertile couple to conceive

  • One out of every six couples has trouble conceiving and/or carrying a child to term

  • There are an estimated 2.4 million new infertility cases each year in the U.S. alone

  • Over 1.2 million deliveries worldwide using assisted reproduction

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  • Many women today are attempting pregnancy at older ages, when they are biologically less fertile.

  • Pregnancy rates sharply decline after

    age 35.

  • The exact age at which a women can no longer conceive varies widely.

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The trend in delaying fertility may be due to a greater emphasis on establishing a career, later marriages, and remarkable improvements in the area of contraception.

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Pregnancy Rates Related to A Woman’s Age

Woman’s Age (y) % Conceiving

in 12 Mo

20-24 86

25-29 78

30-34 63

35-39 52

  • Adapted from Hendershot GE,, Infertility and age: an unresolved issue. Family Planning Perspectives. Vol,14;5 (Sept./Oct 1982), p. 288  The Alan Guttmacher Institute.

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Is Infertility Affected by Age?


15 - 20% of all couples will experience difficulties with conception, but this increases up to 50% at age 35 – 40.

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  • The evaluation and treatment of infertility has changed dramatically over the past 3 decades.

  • Louise Brown, the first IVF baby, was born in 1978.

  • Since then, there have been over a million

    deliveries worldwide using assisted reproduction.

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Maternal Age Specific Birth Rates

15-17 yrs old 22/1,000 women

18-19 yrs 70/1,000

20-24 yrs 101.8/1,000

25-29 yrs 115.5/1,000

30-34 yrs 95.5/1,000

35-39 yrs 45.5/1,000

40-44 yrs 9.0/1,000

45-54 yrs 0.6/1,000

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  • Women 50 yrs and older are more likely to

    - conceive with ART

    - have multiple gestations

    - have LBW babies

    Births as old as 66 yrs of age using ART have been reported.

    Oldest women to conceive naturally is 57 yrs old.

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The percentage of pregnancies in women over 35 yrs old in the US:

14% before WWII

5% in 1970’s

since 1980- ~ 14%

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Why are # of births increasing?

A) increased number of women aged 35-45

B) later marriages, second marriages

C) better contraceptive options available

D) more opportunities to further education

and career

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Education of women has been increasing at a greater rate than that of the general population.

1980– 43% of women aged 35-39

had >16yrs of education

1994- 52% of women

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Maternal Education

Is the strongest predictor of:

use of contraception

timing of childbearing

total # of children

College educated women typically have low birth rates in their 20s and higher in their 30s.

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  • Effect of advancing age varies by socioeconomic status and by race.

  • African American women have 2X the risk

    of adverse perinatal outcomes. (Htn, diabetes)

    On average, the prevalence of maternal health problems associated with poor outcome, increase more rapidly in advancing age in African american than in caucasian women.

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  • Conception rate of normal fertile couples

    (~ 20% /month)

    Probability of clinical pregnancy following intercourse on most fertile day of cycle:

    19-26 yrs old 50%

    27-34 yrs 40%

    35-39 yrs 30%

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Reduced Fecundity

  • Poor quality of aging oocytes

  • Chromosomal abnl., morphologic abnl.

  • Decreased ovarian reserve

  • Altered hormonal environment– ovulatory dysfunction

  • More conditions in older women– polyps,endometriosis, fibroids…

  • Sexual factors– decreased coital frequency

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Pelvic Pathology

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Treatment Options

  • Ovarian hyperstimulation with IUI

    - generates more eggs and sperm to be present at the optimal time of conception.

  • IVF (in-vitro fertilization)- vital to older when time is critical , tubal pathology

    (live birth rate drop from 32% in women<35 to 10% in women 41-42 yrs)

  • Oocyte donation- option for older women

    Pregnancy rates are determined by age of donor, but pregnancy complications by age of mother.

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  • ART cannot compensate for all of the natural decline in fertility with advancing age.

  • Disadvantages- multiple birth rate elevated

    • 2003 data- 22% of births in women age 45-54 were multiples vs. 2% in 1990

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ART Pregnancy and Live Birth Rates by Age of Woman

Source: Centers for Disease Control and Prevention 2001.

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Multiple Births

  • Increased risk of fetal, neonatal complications and complete pregnancy loss when compared to singletons

  • Economic/psychosocial impact on families

  • Increase in major congenital anomalies over spontaneously conceived controls

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  • Rates are lower for women in late 30’s and early 40’s than for women under 35yrs old.

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In Vitro Fertilization

In Vivo vs. In Vitro

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Oocyte Donation

  • Only effective option for women over the age of 40 with diminished ovarian function.

  • The risk of chromosomal abnormality correlates to the age of the donor, but the risks of pregnancy complications (DM, HTN) correlate to the recipient’s age.

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Early Pregnancy Issues

  • Risk is higher for some problems:

    • spontaneous abortions

    • ectopic pregnancies

    • chromosomal abnormalities

    • congenital malformations

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  • Older women have an increased number of abortions usually due to decline in oocyte quality.

  • Also, change in uterine/hormonal function

    overall rate of Abs requiring hospitalization is ~ 11%.

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Risk of Pregnancy Loss

<30 yrs old ~12%

30-34 yrs ~15%

35-39 yrs ~25%

40-44 yrs ~51%

>45 yrs ~93%

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Cardiac Activity on Ultrasound

  • The risk of eventual miscarriage in women of advancing age is significant despite the presence of cardiac activity on US:

    study of over 2000 IVF pregnancies lost after seeing cardiac activity:

    <30 yrs old ~ 5%

    31- 34 yrs ~ 8%

    35- 39 yrs ~ 13%

    > 40 yrs ~ 22%

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Ectopic Pregnancy

  • Major source of maternal mortality and morbidity

  • Studies have shown that >35 yrs old associated with a 4-8 fold increase

  • Higher, why? - multiple partners

    - pelvic infections

    - tubal pathology

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Chromosomal Abnormalities

  • Biological basis--- oocytes reach metapase I during fetal period and remain on metaphase plate until oocyte is stimulated to divide (prior to ovulation).

  • Age related errors appear to increase the risk of nondisjunction leading to unequal chromosome products.

  • A steady increase in the risk of aneuploidy as a women ages.

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Congenital Malformations

  • Clubfoot

  • Cardiac malformations

  • Diaphragmatic hernias

    These are all structural abnormalities and not related to aneuploidy, thus not detected by karyotype analysis.

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  • Increased risk of congenital anomalies seen in the following studies:

    a) >100,000 abs, stillbirths, live births-

    cardiac defects 4x more common in

    women >40 yrs old.

    b) over 1 million singleton infants born

    >20wks in Atlanta 1968-2000—

    **** advanced maternal age associated with all cardiac defects ****

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Late Pregnancy Issues

  • Some obstetrical issues in older women

    are related to maternal age.

  • Others are related to higher parity and co-

    existing medical conditions.

    (hypertension, diabetes, placental issues)

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  • The most frequent medical problem in pregnancy.

  • Older women have a two fold higher risk of being diagnosed with HTN.

  • Preeclampsia in general population is

    3 to 4%. 5 to 10% in women >40

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  • Prevalence increases with maternal age

  • Rates of pre-existing DM and gestational

    DM increase 3-6 fold in women >40.

    Incidence of gestational DM in general OB population is 3%.

    ~7-12% in women over age 40

    ~20% in women over age 50

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Placental Problems

  • Abruptio placenta

  • Placenta previa

    nulliparous women >40 have a tenfold increased risk of placenta previa compared to women 20-29 yrs old.

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Perinatal Morbidity

Advanced maternal age is responsible for a substantial proportion of the increase in the rate of LBW babies and preterm delivery in the last several years.

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Clinical Study

Swedish study…. Nulliparous women

173,715 women compared the birth outcome of women 20-24 yrs to 35-40 yrs

Older women had higher risk of LBW

and preterm delivery

Rates were almost doubled in the older women by age 45…..

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  • Has been associated with an increase in perinatal morbidity in all groups

  • Increase especially higher in smokers age 30-39

  • Smoking increases stillbirth rates in all ages

  • Stillbirth rates particularly higher in >40yrs

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Dysfunctional Labor And Cesarean Section

  • Women age >35 yrs are more likely to be delivered by C-section.

  • C-section rates in general population in U.S. are almost 30%

  • Rate is almost 50% in women age 40-45

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Why Higher C/S Rates??

Influencing factors:

a) increased frequency of medical


b) induction of labor

c) malposition of baby

d) maternal request for C-section

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  • Risk of maternal mortality for women age 35-39 yrs old is more than twice that of women age 25-29 yrs old.

    (21 vs. 9/100,000 live births)

    Risk for women over the age of 40 is 5x higher

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Discuss With The Advanced Maternal Age Mother

  • Delaying childbearing may increase infertility and the chance of developing chronic medical conditions.

  • If no pregnancy after 6 months of trying, refer to specialist!! Time is vital for these patients.

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Tests to Quantify Risks

There are multiple tests today to quantify a women’s risk of chromosomal abnormality:

nuchal translucency

first trimester serum screening

quad screen in 2nd trimester

invasive testing– CVS , amniocentesis

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What Patients Need To Know

  • Discuss the risk of adverse outcome:

    • preterm birth

    • growth restriction

    • stillbirths

  • Discuss the risks of HTN, DM, low

    socioeconomic class….all influence outcome.

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    • Advanced maternal age is associated with reduced fertility and increased risk of adverse pregnancy outcomes.

    • Associations are due to poor oocyte quality, age-related changes in uterine/hormonal function.

    • Fortunately, the prospects for couples to conceive are better than ever with advancing age.

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