AGE AND FERTILITY

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AGE AND FERTILITY

• AGE AND PREGNANCY
• Kathleen M. Gotzmann, MD
• Department Chair Ob/Gyn
• Upper Chesapeake Medical Center

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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
• 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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TRENDS

• 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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BIOLOGICAL CLOCK

• 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 Womans Age

• Womans Age (y) Conceiving
• in
  12 Mo
  
  
• 20-24 86
• 25-29 78
• 30-34 63
• 35-39 52
  
• Adapted from Hendershot GE, et.al., Infertility
  and age an unresolved issue. Family Planning
  Perspectives. Vol,145 (Sept./Oct 1982), p. 288 ?
  The Alan Guttmacher Institute.

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Is Infertility Affected by Age?

• YES!!

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

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FERTILITY ADVANCES

• 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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HOW OLD?

• 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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HISTORY

• The percentage of pregnancies in women over 35
  yrs old in the US
• 14 before WWII
• 5 in 1970s
• 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 gt16yrs 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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AGE-RACE-CLASS

• 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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FECUNDITY

• 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
  womenlt35 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

• 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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IVF

• Rates are lower for women in late 30s and early
  40s 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
  recipients 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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Miscarriages

• 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

• lt30 yrs old 12
• 30-34 yrs 15
• 35-39 yrs 25
• 40-44 yrs 51
• gt45 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
• lt30 yrs old 5
• 31- 34 yrs 8
• 35- 39 yrs 13
• gt 40 yrs 22

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Ectopic Pregnancy

• Major source of maternal mortality and morbidity
• Studies have shown that gt35 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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Anomalies

• Increased risk of congenital anomalies seen in
  the following studies
• a) gt100,000 abs, stillbirths, live births-
• cardiac defects 4x more common in
• women gt40 yrs old.
• b) over 1 million singleton infants born
• gt20wks 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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HYPERTENSION

• 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 gt40

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DIABETES

• Prevalence increases with maternal age
• Rates of pre-existing DM and gestational
• DM increase 3-6 fold in women gt40.
• 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 gt40 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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Smoking

• 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 gt40yrs

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Dysfunctional Labor And Cesarean Section

• Women age gt35 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
• complications
• b) induction of labor
• c) malposition of baby
• d) maternal request for C-section

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MATERNAL MORTALITY

• 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
  womens 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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SUMMARY

• 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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QUESTIONS??