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Egg Freezing
Can it Stop Your Biological Clock?




                               FPNC (c) 2012
Agenda

 Update on egg freezing
 The process
 How age impacts fertility
 The success rates
 The pros & cons
 Best options
 Your questions


                              FPNC (c) 2012
Egg Freezing Before

 Considered   experimental treatment
 Not enough data to determine the outcome
  for children born from frozen eggs
 Pregnancy rates after IVF using slow-frozen
  oocytes have traditionally been poor
  –   IR/Egg thawed 4.6% (Boldt, April 2005)
 ASRM says not to be offered for fertility
 preservation
                                               FPNC (c) 2012
Egg Freezing Now

 No longer considered experimental treatment
 Data suggest children born from frozen eggs
  are fine
 Pregnancy rates seem similar to those of IVF
 ASRM: Still not officially recommended for
  “social” fertility preservation, due to limited
  data

                                   FPNC (c) 2012
The Process of Egg Freezing




                              FPNC (c) 2012
Egg Freezing – Gathering the Eggs

   (Egg Freezing A.K.A Oocyte Cryopreservation or
    “OC”)
   Basically the first part of an IVF cycle
   Stimulate multiple egg production with injectable
    hormones
   Measure progress of stimulation with blood
    samples and transvaginal ultrasounds
   Extract eggs from the ovaries (light IV sedation,
    needle extraction through vaginal wall)

                                        FPNC (c) 2012
Egg Freezing – Freezing & Storage

 Freeze  (cryopreservation)
  using Vitrification technique
 Store eggs in computer
  controlled tanks
 Storage estimated to be
  safe for about 10 years;
  perhaps indefinitely


                                  FPNC (c) 2012
Egg Freezing – Fertilizing the Eggs

   Thaw eggs
   Effects of freezing and
    thawing require ICSI for
    fertilization
   Embryology lab monitors
    embryo progress
   Embryo transferred to
    uterus via catheter
   Pregnancy test in 2 weeks   ICSI (Intracytoplasmic
                                   Sperm Injection)

                                       FPNC (c) 2012
Can Egg Freezing Insure Against
Age-Related Infertility?




                           FPNC (c) 2012
Effects of Age on Female Fertility:
Chance of Conceiving Each Month

      22
      20
      18
      16
      14
      12
    % 10
       8
       6
       4
       2
       0
           20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
                                Age         FPNC (c) 2012
Percentage Of Recently Married Couples
   Who Delivered A Living Child By Age Of
   Marriage – Ten Populations 1600-1930

           100
                   94            91         85
            80
                                                       70
 Percent




            60

            40    48                                                  36
                            43         40         35
            20
                                                                 17
             0                                                                 4
                 20-24     25-29      30-34      35-39         40-44        45-49
                                        Age Group

                       Eventually Pregnant       Pregnant The First Year

                                                            FPNC (c) 2012
Adapted using data from Menken J. Science. 1986; 23:1389.
Spontaneous Abortion Following
Documentation Of Fetal Cardiac Activity
  Percent Spontaneous Abortion




                                 30

                                                                   20
                                 20
                                                            15


                                 10
                                              4
                                        0
                                 0
                                      <31   31-35         36-39   >39
                                                    Age
KE Smith. F&S. 1996; 65:35
                                                                  FPNC (c) 2012
Maternal Age And Chromosomal
Abnormalities (Live Births)

                   Age                     Risk
                    20                     1/526
                    25                     1/476
                    30                     1/384
                    35                     1/204
                    40                     1/65
                    45                     1/20
Table adapted from Obstetrics: normal and problem pregnancies, third
edition. Edited by SG Gabbe, JR Niebyl, JL Simpson.
Churchill Livingstone, NY, NY. 1996, data from page 221. (c) 2012
                                                     FPNC
Increased Female Age Contributes to:

 Lower rates of conception
 Higher rates of miscarriage
 Higher rates of chromosomal
  abnormalities




                                FPNC (c) 2012
Success Rates with Frozen Eggs
are Age Dependent

 Success    rates with oocyte
  cryopreservation via either slow-freeze or
  vitrification appear to decline with
  maternal age
 This is consistent with the clinical
  experience with fresh oocytes



                                  FPNC (c) 2012
(BTW, Male Fertility Declines
with Age Too)

  Instudies controlling for female age,
   men older than 50 have pregnancy rates
   23-38% lower than men under age 30.
                Kidd SA. Fert Steril. 2001; 75:237.

  Some  studies suggest a correlation
   between advancing male age and
   increasing miscarriage rates.


                                          FPNC (c) 2012
The Pros and Cons of Egg
Freezing




                           FPNC (c) 2012
Egg Freezing – Considered Safe
   Considered very safe with proper monitoring by
    specialist (reproductive endocrinologist)
   Possibly some discomfort, bloating during
    stimulation
   Mild to Moderate ovarian hyperstimulation
    –   ~8.5% (ASRM 2008), monitoring helps avoid this
   Less than 1% experience any serious
    complications, such as:
    –   Severe ovarian hyperstimulation
    –   Intraperitoneal bleeding
    –   Ovarian torsion
    –   Ruptured ovarian cyst
    –   Infection
                                                 FPNC (c) 2012
Egg Freezing – Considered Safe

A study of 200 infants born from 165 vitrified
 oocyte pregnancies revealed no difference
 in birth weight or congenital anomalies
 among those born from vitrified oocytes
 compared to children conceived after fresh
 IVF.



                                 FPNC (c) 2012
Egg Freezing – Considered Safe

   A recent review of over 900 live births derived
    from cryopreserved oocytes, principally using
    slow-freeze, suggests there is no increased risk
    of congenital anomalies compared to the general
    US population.
   Only about 1500 babies born worldwide from
    frozen eggs – development of children must be
    studied further to determine true outcomes



                                        FPNC (c) 2012
Egg Freezing – Challenges

 Not   all eggs survive the freezing or thawing
  –   Eggs have high water content
  –   Freezing can damage the cell membrane
  –   Vitrification (rapid freezing) has reduced this
      problem
  –   Requires high concentrations of cryoprotectant
 Not all eggs will be likely to fertilize
 Not all transplanted embryos will continue to
  develop
                                       FPNC (c) 2012
Egg Freezing – Challenges

 Delayed     pregnancy (40s)
   –   Patients in their 40s have a higher chance of
       complications
 More  difficult for frozen eggs to fertilize;
  ICSI required
 ICSI may not deter transmission of
  genetic abnormalities from sperm
 Not enough data about storing frozen
  eggs

                                         FPNC (c) 2012
Egg Freezing – Cost Efficient?

 Costs   are similar to IVF:
  –   $9,850 for medical care and lab services
  –   Another $2,000-$6,000 for medication
  –   Long term cryopreservation about $600/year
 Eggfreezing for “social” reasons is not
 covered by insurance



                                      FPNC (c) 2012
Drawbacks to Egg Freezing

 No guarantee that fertility is safeguarded
 May require several cycles to obtain
  enough eggs for best chances
 Short and long-term costs
 Estimated that most women will never use
  their frozen eggs
 May increase the number of much older
  parents

                                 FPNC (c) 2012
In Support of Egg Freezing

 Offers some control over reproductive
  destiny
 Can provide women ‘a backup plan’
 Younger eggs have lower rates of
  abnormalities
 Considered as safe as IVF
 Estimated success rates similar to IVF


                                 FPNC (c) 2012
Success Rates for Egg Freezing




                           FPNC (c) 2012
ART Pregnancy Rates Using Fresh Eggs
           70


           60


           50
 Percent




           40


           30


           20


           10


            0
              5




                                                                                    7
                  26




                            30


                                 32


                                      34


                                            36




                                                                42


                                                                      44


                                                                            46
                       28




                                                   38


                                                         40
           <2




                                                                                 >4
                                           Patient Age
Art Cycles Live Births                                                 National Data
                                      Own Eggs     Donor Eggs        FPNC (c) 2012
     Per Transfer                                                        CDC 2006
Egg Freezing – Success Rates

   Slow freezing – 2-10% per embryo transferred
   Vitrification – data suggest that:
    –   85% will survive thawing
    –   Success rates similar to IVF
          45% pregnancy rate if eggs frozen before age 36
          More data needed to determine with certainty

   “There is good evidence that fertilization and
    pregnancy rates are similar to IVF/ICSI with fresh
    oocytes when vitrified/warmed oocytes are used
    as part of IVF/ICSI in young infertility patients
    and oocyte donors.” (ASRM 2012)
                                                    FPNC (c) 2012
FPNC 2010 Ongoing Pregnancy per
Embryo Transfer Procedure
                                               PER PROCEDURE
2010 Ongoing Pregnancy per                <35       35-37 38-40 41-42
Embryo Transfer Procedure                Years       Years     Years       Years
Fresh IVF with Own Eggs
(n=323)                                  44%         34%       34%         28%

Frozen Embryo Transfer (FET)
with Own Eggs (n=148)                    41%         37%       36%         2/11

Fresh IVF with Donor Eggs               All Ages
(n=29)                                   55%
 This data showing ongoing pregnancy rates is not final, and has not yet been
 reported to SART/CDC. Final “Live Birth” rates will be reported when the
 outcomes for all ongoing pregnancies are known.             FPNC (c) 2012
Egg Freezing – Success Rates

 Best   chance of success for one pregnancy:
  –   Women under 35
  –   20 eggs frozen (may require multiple cycles)
  –   Still, NO guarantee of successful thaw,
      fertilization, implantation, or live birth




                                          FPNC (c) 2012
Your Options

 Timelyand natural conception
 Frozen eggs
 IVF
 Frozen embryos
 Donor eggs




                                 FPNC (c) 2012
Can ART Make Up For Babies Lost By
Delaying Attempts to Conceive?


Begins          Pregnant         Not      ART      Total
Attempt         %                Preg              Pregnant
At Age
30              91               9        -        91
35              82               18       4        86
40              57               43       7        64

Assume attempt 4 yr if <35, 3 yr if 35-40, 2 yr if >40;
2 cycles of IVF
                         Leridon. Hum Reprod 2004;19(7):1548-53.
                                                    FPNC (c) 2012
Best Defense Against Infertility:
Follow a Healthy Lifestyle

 Maintain  a healthy diet and weight
 Moderate, regular exercise
 Prenatal vitamins
 Minimize caffeine
 Avoid smoking and alcohol
 Avoid / treat sexually transmitted diseases




                                    FPNC (c) 2012
Key Messages

 Prevent  infertility by appropriate life choices
 Plan your career AND your family
 Don’t wait for perfection—there is never a
  perfect time to start a family
 Test your ovarian reserve
 Seek expert help if any risk factors are
  present
 Know the facts about your reproductive life
                                    FPNC (c) 2012
We appreciate your feedback.
Please use the evaluation form to share
your thoughts with us. Thank you!




             Questions & Answers
                                    FPNC (c) 2012

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Fertility Physicians of Northern California Egg Freezing 20121203

  • 1. Egg Freezing Can it Stop Your Biological Clock? FPNC (c) 2012
  • 2. Agenda  Update on egg freezing  The process  How age impacts fertility  The success rates  The pros & cons  Best options  Your questions FPNC (c) 2012
  • 3. Egg Freezing Before  Considered experimental treatment  Not enough data to determine the outcome for children born from frozen eggs  Pregnancy rates after IVF using slow-frozen oocytes have traditionally been poor – IR/Egg thawed 4.6% (Boldt, April 2005)  ASRM says not to be offered for fertility preservation FPNC (c) 2012
  • 4. Egg Freezing Now  No longer considered experimental treatment  Data suggest children born from frozen eggs are fine  Pregnancy rates seem similar to those of IVF  ASRM: Still not officially recommended for “social” fertility preservation, due to limited data FPNC (c) 2012
  • 5. The Process of Egg Freezing FPNC (c) 2012
  • 6. Egg Freezing – Gathering the Eggs  (Egg Freezing A.K.A Oocyte Cryopreservation or “OC”)  Basically the first part of an IVF cycle  Stimulate multiple egg production with injectable hormones  Measure progress of stimulation with blood samples and transvaginal ultrasounds  Extract eggs from the ovaries (light IV sedation, needle extraction through vaginal wall) FPNC (c) 2012
  • 7. Egg Freezing – Freezing & Storage  Freeze (cryopreservation) using Vitrification technique  Store eggs in computer controlled tanks  Storage estimated to be safe for about 10 years; perhaps indefinitely FPNC (c) 2012
  • 8. Egg Freezing – Fertilizing the Eggs  Thaw eggs  Effects of freezing and thawing require ICSI for fertilization  Embryology lab monitors embryo progress  Embryo transferred to uterus via catheter  Pregnancy test in 2 weeks ICSI (Intracytoplasmic Sperm Injection) FPNC (c) 2012
  • 9. Can Egg Freezing Insure Against Age-Related Infertility? FPNC (c) 2012
  • 10. Effects of Age on Female Fertility: Chance of Conceiving Each Month 22 20 18 16 14 12 % 10 8 6 4 2 0 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 Age FPNC (c) 2012
  • 11. Percentage Of Recently Married Couples Who Delivered A Living Child By Age Of Marriage – Ten Populations 1600-1930 100 94 91 85 80 70 Percent 60 40 48 36 43 40 35 20 17 0 4 20-24 25-29 30-34 35-39 40-44 45-49 Age Group Eventually Pregnant Pregnant The First Year FPNC (c) 2012 Adapted using data from Menken J. Science. 1986; 23:1389.
  • 12. Spontaneous Abortion Following Documentation Of Fetal Cardiac Activity Percent Spontaneous Abortion 30 20 20 15 10 4 0 0 <31 31-35 36-39 >39 Age KE Smith. F&S. 1996; 65:35 FPNC (c) 2012
  • 13. Maternal Age And Chromosomal Abnormalities (Live Births) Age Risk 20 1/526 25 1/476 30 1/384 35 1/204 40 1/65 45 1/20 Table adapted from Obstetrics: normal and problem pregnancies, third edition. Edited by SG Gabbe, JR Niebyl, JL Simpson. Churchill Livingstone, NY, NY. 1996, data from page 221. (c) 2012 FPNC
  • 14. Increased Female Age Contributes to:  Lower rates of conception  Higher rates of miscarriage  Higher rates of chromosomal abnormalities FPNC (c) 2012
  • 15. Success Rates with Frozen Eggs are Age Dependent  Success rates with oocyte cryopreservation via either slow-freeze or vitrification appear to decline with maternal age  This is consistent with the clinical experience with fresh oocytes FPNC (c) 2012
  • 16. (BTW, Male Fertility Declines with Age Too)  Instudies controlling for female age, men older than 50 have pregnancy rates 23-38% lower than men under age 30. Kidd SA. Fert Steril. 2001; 75:237.  Some studies suggest a correlation between advancing male age and increasing miscarriage rates. FPNC (c) 2012
  • 17. The Pros and Cons of Egg Freezing FPNC (c) 2012
  • 18. Egg Freezing – Considered Safe  Considered very safe with proper monitoring by specialist (reproductive endocrinologist)  Possibly some discomfort, bloating during stimulation  Mild to Moderate ovarian hyperstimulation – ~8.5% (ASRM 2008), monitoring helps avoid this  Less than 1% experience any serious complications, such as: – Severe ovarian hyperstimulation – Intraperitoneal bleeding – Ovarian torsion – Ruptured ovarian cyst – Infection FPNC (c) 2012
  • 19. Egg Freezing – Considered Safe A study of 200 infants born from 165 vitrified oocyte pregnancies revealed no difference in birth weight or congenital anomalies among those born from vitrified oocytes compared to children conceived after fresh IVF. FPNC (c) 2012
  • 20. Egg Freezing – Considered Safe  A recent review of over 900 live births derived from cryopreserved oocytes, principally using slow-freeze, suggests there is no increased risk of congenital anomalies compared to the general US population.  Only about 1500 babies born worldwide from frozen eggs – development of children must be studied further to determine true outcomes FPNC (c) 2012
  • 21. Egg Freezing – Challenges  Not all eggs survive the freezing or thawing – Eggs have high water content – Freezing can damage the cell membrane – Vitrification (rapid freezing) has reduced this problem – Requires high concentrations of cryoprotectant  Not all eggs will be likely to fertilize  Not all transplanted embryos will continue to develop FPNC (c) 2012
  • 22. Egg Freezing – Challenges  Delayed pregnancy (40s) – Patients in their 40s have a higher chance of complications  More difficult for frozen eggs to fertilize; ICSI required  ICSI may not deter transmission of genetic abnormalities from sperm  Not enough data about storing frozen eggs FPNC (c) 2012
  • 23. Egg Freezing – Cost Efficient?  Costs are similar to IVF: – $9,850 for medical care and lab services – Another $2,000-$6,000 for medication – Long term cryopreservation about $600/year  Eggfreezing for “social” reasons is not covered by insurance FPNC (c) 2012
  • 24. Drawbacks to Egg Freezing  No guarantee that fertility is safeguarded  May require several cycles to obtain enough eggs for best chances  Short and long-term costs  Estimated that most women will never use their frozen eggs  May increase the number of much older parents FPNC (c) 2012
  • 25. In Support of Egg Freezing  Offers some control over reproductive destiny  Can provide women ‘a backup plan’  Younger eggs have lower rates of abnormalities  Considered as safe as IVF  Estimated success rates similar to IVF FPNC (c) 2012
  • 26. Success Rates for Egg Freezing FPNC (c) 2012
  • 27. ART Pregnancy Rates Using Fresh Eggs 70 60 50 Percent 40 30 20 10 0 5 7 26 30 32 34 36 42 44 46 28 38 40 <2 >4 Patient Age Art Cycles Live Births National Data Own Eggs Donor Eggs FPNC (c) 2012 Per Transfer CDC 2006
  • 28. Egg Freezing – Success Rates  Slow freezing – 2-10% per embryo transferred  Vitrification – data suggest that: – 85% will survive thawing – Success rates similar to IVF  45% pregnancy rate if eggs frozen before age 36  More data needed to determine with certainty  “There is good evidence that fertilization and pregnancy rates are similar to IVF/ICSI with fresh oocytes when vitrified/warmed oocytes are used as part of IVF/ICSI in young infertility patients and oocyte donors.” (ASRM 2012) FPNC (c) 2012
  • 29. FPNC 2010 Ongoing Pregnancy per Embryo Transfer Procedure PER PROCEDURE 2010 Ongoing Pregnancy per <35 35-37 38-40 41-42 Embryo Transfer Procedure Years Years Years Years Fresh IVF with Own Eggs (n=323) 44% 34% 34% 28% Frozen Embryo Transfer (FET) with Own Eggs (n=148) 41% 37% 36% 2/11 Fresh IVF with Donor Eggs All Ages (n=29) 55% This data showing ongoing pregnancy rates is not final, and has not yet been reported to SART/CDC. Final “Live Birth” rates will be reported when the outcomes for all ongoing pregnancies are known. FPNC (c) 2012
  • 30. Egg Freezing – Success Rates  Best chance of success for one pregnancy: – Women under 35 – 20 eggs frozen (may require multiple cycles) – Still, NO guarantee of successful thaw, fertilization, implantation, or live birth FPNC (c) 2012
  • 31. Your Options  Timelyand natural conception  Frozen eggs  IVF  Frozen embryos  Donor eggs FPNC (c) 2012
  • 32. Can ART Make Up For Babies Lost By Delaying Attempts to Conceive? Begins Pregnant Not ART Total Attempt % Preg Pregnant At Age 30 91 9 - 91 35 82 18 4 86 40 57 43 7 64 Assume attempt 4 yr if <35, 3 yr if 35-40, 2 yr if >40; 2 cycles of IVF Leridon. Hum Reprod 2004;19(7):1548-53. FPNC (c) 2012
  • 33. Best Defense Against Infertility: Follow a Healthy Lifestyle  Maintain a healthy diet and weight  Moderate, regular exercise  Prenatal vitamins  Minimize caffeine  Avoid smoking and alcohol  Avoid / treat sexually transmitted diseases FPNC (c) 2012
  • 34. Key Messages  Prevent infertility by appropriate life choices  Plan your career AND your family  Don’t wait for perfection—there is never a perfect time to start a family  Test your ovarian reserve  Seek expert help if any risk factors are present  Know the facts about your reproductive life FPNC (c) 2012
  • 35. We appreciate your feedback. Please use the evaluation form to share your thoughts with us. Thank you! Questions & Answers FPNC (c) 2012

Notas do Editor

  1. FPNC (c) 2012
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  3. FPNC (c) 2012
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  5. FPNC (c) 2012
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  7. FPNC (c) 2012 Information about natural fertility rates associated with aging is difficult to determine today due to widespread use of contraception and limits on family size. In this compilation of data from 1600-1930 in women who used no form of contraception, a clear age-related decline in fertility was noted. Among women who were aged 40 or older when first married, nearly two-thirds were unable to ever have a child, a percentage much higher than for women who were younger when they married.
  8. FPNC (c) 2012 The rate of pregnancy loss after clinical documentation of pregnancy also increases with age. In this study of 201 infertility patients undergoing ovulation induction (excluding women who had 2 or more miscarriages in the past), 20% of pregnancies miscarried after documentation of cardiac activity in women aged 40 or older, compared with a less than 5% rate of loss for women who are aged 35 or less. This high rate of miscarriage in older women is likely due to a higher incidence of aneuploidy in the embryos.
  9. FPNC (c) 2012 Abnormalities in the oocyte associated with aging are the most likely explanation for the increased rate of chromosomally abnormal livebirths noted with advancing maternal age. The rate of chromosomal abnormalities is even higher at amniocentesis.
  10. FPNC (c) 2012 Modest decreases in pregnancy rate were associated with advancing age of the male partner in this review. Significant changes were seen later for men than have been noted in women. There is no age at which a man cannot father a child. Given all of these findings, it can be concluded that age-related infertility is largely a problem that can be attributed to a decline in female fertility. It is unlikely that increasing age of the male partner explains much of the age-related decrease in fertility noted for women.
  11. FPNC (c) 2012
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  13. FPNC (c) 2012 (c) FPNC 2010 - IVF Seminar
  14. FPNC (c) 2012 (c) FPNC 2010 - IVF Seminar
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  17. FPNC (c) 2012