Female Reproductive Aging & Egg Freezing JOSHUA U. KLEIN, MD, - - PowerPoint PPT Presentation

Female Reproductive Aging & Egg Freezing

JOSHUA U. KLEIN, MD, FACOG ASSISTANT CLI NICAL PROFESSOR OF OBSTETRICS, GYNECOLOGY, & REPRODUCTIVE SCI ENCE I CAHN SCHOOL OF MEDICINE AT MOUNT SI NAI

Egg Freezing: Media Darling

What You Need To Know

Female Fertility and Aging Eggs as Gumballs Quantity and Quality Egg Freezing in 2016: A Primer Jewish Considerations

Natural Fertility and Age

30 40 50 60 70 80 90 100 Age = 30 Age = 35 Age = 40 % Achieving Live Birth Birth within 4 years Birth Within 1 Year

Leridon, H. Human Reproduction Vol.19, No.7 pp. 1548-1553, 2004

Fertility and Age: IVF

Percentages of ART C ycles Using Fresh Nondonor Eggs or Embryos That Resulted in Pregnancies, Live Births, and Single-Infant Live Births, by Age of Woman,* 2013

Percent 10 20 30 40 50 60 Age (years) <24 24 26 28 30 32 34 36 38 40 42 44 >44 Pregnancies Live births S ingle-infant live births

Primacy of the Egg

Percentages of Transfers Using Fresh Embryos from Donor or Nondonor E ggs That Resulted in Live Births, by Age of Woman, 2013

Percent 10 20 30 40 50 60 70 80 90 100 Age (years) <30 30 32 34 36 38 40 42 44 46 >47 Donor eggs Nondonor eggs

Miscarriages and Age

11.8 12.2 13.5 16 20 27 37 5 10 15 20 25 30 35 40 Age = 15-20 Age = 21-25 Age = 26-30 Age = 31-35 Age = 36-40 Age = 41-45 Age = 46-50 % Risk Miscarriage

Leridon, H. Human Reproduction Vol.19, No.7 pp. 1548-1553, 2004

Down Syndrome and Age

20 40 60 80 100 120 140 Age <20 Age 20-24 Age 25-29 Age 30-34 Age 35-39 Age 40+ Down Syndrome per 10,000 Births

CDC National Data 2013

What is Female Reproductive Aging?

Fertility Miscarriage Down Syndrome

What is Reproductive Aging?

Aging

Fertility

Mis- carriage

Down Syndrome

Unifying Concept: Eggs as Gumballs

Age

Eggs as Gumballs

Young

• Quantity: Lots of gumballs (high
• varian reserve)
• Quality: Mostly blue ones

(genetically normal)

Older

• Quantity: Few gumballs (low
• varian reserve)
• Quality: Mostly green ones

(genetically abnormal)

Unifying Concept: Eggs as Gumballs

฀

Eggs: Quality & Quantity

“Egg Quality” “Egg Quantity”

Quantity: Ovarian Reserve Testing

2 4 6 8 10 12 25 30 35 40 >43

AMH (ng/mL) Age (years)

AMH and Age

10th Percentile 50th Percentile 90th Percentile

• Blood Tests
• Anti-Mullerian

Hormone (AMH)

• Follicle-Stimulating

Hormone (FSH) and Estradiol on Day 2-3 of Menstrual Cycle

• Ultrasound Imaging
• Antral Follicle Count

Shebl et al. Fertility and Sterility 2011;95: 832–4

Eggs: Quality & Quantity

“Egg Quality” “Egg Quantity”

Quality: Age and Genetic Aneuploidy

• Minimal variation

for a given age

• No effective

diagnostic test for unfertilized eggs

• Genetic testing of

embryos is closest approximation

Franasiak et al. Fertility and Sterility 2014: 101:656-663.e1

Egg Freezing: Managing Reproductive Aging

• Freezing the eggs prevents further

deterioration of those eggs over time

• Quantity: freeze a group of eggs,

not just one

• Quality: freeze eggs at an age

when many are still genetically normal

Brief History of Egg Freezing

• First healthy baby born from a frozen egg in 1986
• Highly inefficient, with little progress in technology in 1980’s and 1990’s
• 2000’s: Development of Vitrification – “flash freezing” (cooled at 20-

40,000 degrees Celsius per minute)

• Reduces ice crystal formation that can be damaging to the eggs
• 2013: American Society for Reproductive Medicine (ASRM) and

American Congress of Obstetricians and Gynecologists (ACOG) remove “experimental” designation for egg freezing

Egg Freezing Process

Consultation and Ovarian Reserve Testing 10 days of daily hormone injections and 5-6 brief visits for sonogram and hormone testing 15 minute outpatient minor surgical procedure to extract the eggs using a needle, done under "twilight" anesthesia

Who Should Consider Freezing Eggs?

• Women with low ovarian reserve
• Women who will be exposed to medications known to damage egg

supply, e.g. chemotherapy

• All healthy women in their late 20’s or older who are not in a position to

have children in the near future, or are concerned about family size

• Who should not freeze their eggs?
• Any woman who is ready to complete their family now

Egg Freezing Outcomes

• Data are evolving as technology is new and significant “lag time”

to using the eggs

• Likelihood of success will be directly correlated with:
• Number of eggs frozen (Quantity)
• Age at freezing (Quality)
• ASRM: 2-12% success per egg
• Example: 33-year-old who freezes 10 eggs x 6% per egg might have 60% chance
• f having a baby from that group of frozen eggs

Photo Courtesy Leslie Ramirez PhD

Egg Freezing: Safety

Short Term:

• Ovarian Hyperstimulation Syndrome (OHSS)
• 30% risk of mild OHSS (bloating, cramping, mood symptoms)
• 0.5-1% risk of severe OHSS (requiring IV hydration, possible hospitalization)
• Procedural and/or anesthesia complication
• 1/1,000 risk

Long Term:

• Baby health
• Data are early but reassuring
• Risks of hormone therapy, e.g. lifetime cancer risk
• Overall data are reassuring

Egg Freezing: Areas for Research

• Success and safety in longer-term studies of larger groups of women
• Egg freezing in “Older” Women
• Duration of storage (currently one reported case >10 years)
• Clarification on optimal age to consider freezing eggs and number of

eggs to target

Egg Freezing: Cost

• Generally not covered by insurance except in patients with cancer
• Currently costs are typically $8,000-$12,000
• Costs likely will be declining over time
• Some large employers (e.g. Facebook, Apple) are now offering egg

freezing benefits as part of their employment package

Egg Freezing in Jewish Community

• Egg freezing may prevent the pain and suffering of infertility and its

treatment later in life

• Egg freezing may help families achieve their desired family size
• Numerous Orthodox Rabbis not only permit egg freezing, but generally

encourage single women who are in their 30’s to consider freezing eggs

Summary

• Female reproductive aging is a function of decreasing quantity and

quality of eggs

• Reproductive aging is responsible for decreased fertility as well as

increased miscarriages and genetic problems like Down Syndrome at

• lder ages
• Freezing a group of eggs stops the process of deterioration for those

eggs and can help women have healthy children at an age when they might not otherwise have that opportunity

• There is a large degree of support in the Jewish community for single

women to consider freezing their eggs

Contact Information

Joshua U. Klein, MD Email address: doctorklein@joshuakleinmd.com