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

Natural Fertility and Age 100 90 80 % Achieving Live Birth 70 Birth within 4 years Birth Within 1 Year 60 50 40 30 Age = 30 Age = 35 Age = 40 Leridon, H. Human Reproduction Vol.19, No.7 pp. 1548-1553, 2004

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 Fertility and 60 Age: IVF 50 40 Percent 30 20 10 0 <24 24 26 28 30 32 34 36 38 40 42 44 >44 Age (years) Pregnancies Live births S ingle-infant live births * For consistency, all percentages are based on cycles started.

Percentages of Transfers Using Fresh Embryos from Donor or Nondonor E ggs That Resulted in Live Births, by Age of Woman, 2013 Primacy of 100 90 the Egg 80 70 60 Percent 50 40 30 20 10 0 <30 30 32 34 36 38 40 42 44 46 >47 Age (years) Donor eggs Nondonor eggs

Miscarriages and Age 40 37 35 30 % Risk Miscarriage 27 25 20 20 16 15 13.5 12.2 11.8 10 5 0 Age = 15-20 Age = 21-25 Age = 26-30 Age = 31-35 Age = 36-40 Age = 41-45 Age = 46-50 Leridon, H. Human Reproduction Vol.19, No.7 pp. 1548-1553, 2004

Down Syndrome and Age 140 120 Down Syndrome per 10,000 Births 100 80 60 40 20 0 Age <20 Age 20-24 Age 25-29 Age 30-34 Age 35-39 Age 40+ CDC National Data 2013

What is Female Reproductive Aging? Down Fertility Miscarriage Syndrome

What is Reproductive Aging? Fertility Aging Down Mis- Syndrome carriage

Unifying Concept: Eggs as Gumballs Age

Eggs as Gumballs Young ◦ Quantity: Lots of gumballs (high ovarian reserve) ◦ Quality: Mostly blue ones (genetically normal) Older ◦ Quantity: Few gumballs (low ovarian reserve) ◦ Quality: Mostly green ones (genetically abnormal)

Unifying Concept: Eggs as Gumballs ฀

“Egg Quantity” Eggs: Quality “Egg Quality” & Quantity

AMH and Age Quantity: 12 Ovarian Reserve 10 Testing 8 AMH (ng/mL)  Blood Tests 6 10th Percentile  Anti-Mullerian 50th Percentile Hormone (AMH) 90th Percentile 4  Follicle-Stimulating Hormone (FSH) and 2 Estradiol on Day 2-3 of Menstrual Cycle 0  Ultrasound Imaging 25 30 35 40 >43 Age (years)  Antral Follicle Count Shebl et al. Fertility and Sterility 2011;95: 832 – 4

“Egg Quantity” Eggs: Quality “Egg Quality” & 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) Photo Courtesy Leslie Ramirez PhD • ASRM: 2-12% success per egg • Example: 33-year-old who freezes 10 eggs x 6% per egg might have 60% chance of having a baby from that group of frozen eggs

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 older 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