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10/28/2016 Disclosure No one involved in the planning or presentation of this activity has any relevant financial relationships with a commercial Fertility After 35 interest to disclose . Center for Reproductive Health Center for Reproductive

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10/28/2016 1

Fertility After 35

Center for Reproductive Health

Evelyn Mok-Lin, MD

Assistant Professor, Obstetrics, Gynecology and Reproductive Sciences Medical Director, UCSF Center for Reproductive Health

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Disclosure

No one involved in the planning or presentation of this activity has any relevant financial relationships with a commercial interest to disclose.

Center for Reproductive Health

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Fertility After 35

  • It is more difficult for women to conceive after

age 35

  • Why?

– Increased rates of medical comorbidities – obesity, HTN, DM – Decreased egg quantity and less frequent

  • vulation

– Decreased egg quality

Center for Reproductive Health

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Decreasing Egg Quantity

Center for Reproductive Health

Wallace and Kelsey, PLoS 2010

  • Finite number of follicles at birth
  • 12% remaining at age 30
  • 3% remaining at age 40
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SLIDE 2

10/28/2016 2

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Decreasing Egg Quality

Center for Reproductive Health

Heffner, NEJM 2004

Abnormal Spindles in Older Eggs

20-25 year old eggs

– 17% of eggs with abnormal spindle assembly

40-45 year old eggs

– 83% of eggs with abnormal spindle assembly

7 Battaglia et al, Human Reproduction 1996

Increasing Rates of Chromosomal Abnormalities

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Aneuploidy Rates in Couples Undergoing IVF

9 Franasiak et al. Fertility and Sterility 2014

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10/28/2016 3 Age at which to start trying to conceive

10 Habbema et al. Human Reproduction 2015 11

What to do in women >35 who desire to conceive

  • Preconception counseling

– Prenatal vitamins – Modifiable lifestyle factors – Timed intercourse: menstrual tracking, use of

  • vulation predictor kits (OPKs)
  • Preconception testing
  • Initiate fertility evaluation in women over 35 if

after trying to conceive for >6 months

– >3 months in women over 40

Center for Reproductive Health

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Treatment Options

  • Superovulation

– Ovulation of >1 egg to overcome the age effect – Oral agents (Clomid, Letrozole) – Injectable FSH/LH (Gonal-F, Follistim, Menopur) – Often used in conjunction with intrauterine insemination (IUI)

Center for Reproductive Health

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Clomiphene Citrate (Clomid)

  • Selective Estrogen

Receptor Modulator (SERM)

  • ER antagonist at

the hypothalamus

  • Inhibits negative

feedback of estrogen

  • Increased GnRH

pulsatility

  • Increased pituitary

FSH and LH secretion

Center for Reproductive Health

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Clomid Instructions

Center for Reproductive Health

Take 50-150mg (1-3 tabs) daily x 5 days Start on cycle day 3 (days 3-7)

Check ovulation kit starting day 10 until + Intercourse or IUI 12-24 hours after +kit Ultrasound on day 10 Intercourse or IUI 24-36 hours after hCG trigger hCG trigger

Based on a 28 day cycle

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Potential Side Effects of Clomid

  • Increased multiple pregnancy rate (7%)
  • Mood swings
  • Hot flushes
  • Headaches
  • Bloating
  • Visual symptoms and light sensitivity
  • Decreased endometrial thickness
  • Decreased cervical mucus

Center for Reproductive Health

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Artificial Insemination (AI) or Intrauterine Insemination (IUI)

Center for Reproductive Health

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Letrozole (Femara)

  • Aromatase inhibitor

(AI)

  • Blocks conversion
  • f androgens into

estrogen

  • Inhibits negative

feedback of estrogen

  • Increased GnRH

pulsatility

  • Increased pituitary

FSH and LH secretion

Center for Reproductive Health

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SLIDE 5

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Letrozole (Femara)

  • 2.5-7.5mg (1-3 tabs) daily x 5 days
  • Not FDA approved for fertility use
  • More expensive
  • Fewer side effects (fatigue and dizziness)
  • Increased success rates in PCOS patients

– Legro et al., NEJM 2014 – 750 infertile women 18-40 years of age – Randomized to Letrozole or Clomid with intercourse for up to 5 cycles – Higher ovulation, pregnancy and live-birth rates in Letrozole group

Center for Reproductive Health

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Center for Reproductive Health

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IVF

Center for Reproductive Health

Veeck, Atlas of Human Gametes and Conceptuses 21

IVF Procedure

Center for Reproductive Health

1 3 5 7 9

FSH+LH

hCG trigger Egg Retrieval

11 13 Days

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IVF Procedure

Center for Reproductive Health

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Intracytoplasmic Sperm Injection (ICSI)

Center for Reproductive Health

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Preimplantation Genetic Screening

  • PGS vs PGD
  • Benefits of PGS for women > 37:

– Decreased risk of early miscarriages – Decreased risk of genetically abnormal pregnancies – Decreased number of embryo transfer attempts – Decreased risk of multiple gestation

Center for Reproductive Health

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Preimplantation Genetic Screening

  • Risks of PGS:

– Increased cost – Increased manipulation of the embryo – Decreased total number of embryos for transfer (possible decrease in cumulative pregnancy rate) – Error rates and mosaicism

Center for Reproductive Health

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Summary

  • Fertility rates decrease and miscarriage rates

increase more steeply >35 years of age

  • Offer preconception counseling and testing
  • Initiate infertility evaluation and refer to REI if a

woman > 35 has been trying to conceive for 3-6 months

  • Treatment options include superovulation / IUI

vs IVF (+/- PGS)

Center for Reproductive Health

Thank you