Embryo Transfer Decisions & Genetic Screening Said Daneshmand, MD, FACOG The Fertility Center Las Vegas, Los Angeles, New York University of Nevada School of Medicine

Our Clinic • Established in 1988. • Offices in Las Vegas, Los Angeles & New York. • We help intended parents all over the world – from more than 35 countries in the last year alone. • World renowned for groundbreaking research and publications. • Special Team dedicated to Third Party IVF (Egg Donor & Surrogacy).

2 Offices in Nevada

Office in California

Office in New York

In Vitro Fertilization (IVF) • A woman’s ovaries are stimulated to produce many eggs. • Eggs are collected from the ovaries. • Eggs are fertilized using ICSI (sperm injection into egg). • The best resulting embryo is transferred to the uterus to achieve pregnancy..

Embryo Transfer

Embryo Selection • Embryos are typically selected for transfer based on appearance alone. • Most human embryos are non-viable. • Most do not implant in the uterine lining.

Embryo Quality • Embryos can be graded on their appearance. • Embryos with the best grade are more likely to implant than those with lesser grades. • Many critical features of an embryo cannot be seen and are therefore not considered when grading the embryo. • Among the invisible features are the chromosomes.

Chromosomes

Number of Chromosomes • Normal human cells each have 46 chromosomes • Two copies of chromosome 1, two copies of chromosome 2, etc. • Many human embryos form with abnormal numbers of chromosomes. • Examples: – Only one copy of chromosome 1 – Three copies of chromosome 21

Number of Chromosomes • Almost all embryos with abnormal numbers of chromosomes will stop developing. • A small proportion of embryos with abnormal numbers of chromosomes can achieve live birth, usually with significant birth defects. • We cannot count the chromosomes in our microscopes. Determining the number of chromosomes requires a special test.

Genes

There are about 25,000 genes on all 46 human chromosomes, combined.

Genes • Some patients have a family history of genetic diseases. – Example: A brother with cystic fibrosis.

• May want to ensure those genes are not carried on in their children, grandchildren, etc. • We can test for about 250 diseases carried on individual genes.

Early Embryo Development Day 1

Day 3

Day 4

Day 5

When to transfer an embryo • • • •

Most common transfers are day 3 and day 5. Day 3 transfer slightly reduces lab work and cost. Day 5 transfer allows better embryo selection. The uterus is not the natural environment for an embryo until day 5.

Day 3 Biopsy

Classic day 3 embryo biopsy • On day 3 of embryo culture, 1-2 cells are extracted for genetic analysis. • Fluorescence in situ hybridization (FISH) analysis is used to check for aneuploidy in about 10 chromosomes.

Blastocysts

Blastocyst Biopsy

Blastocyst Biopsy • On day 5 of embryo culture, several cells are removed from the trophectoderm of a blastocyst. • These cells are analyzed for all 46 chromosomes.

Blastocyst Biopsy

Array CGH

Normal CGH Result

Abnormal CGH Results

Complex Abnormal CGH Result

NGS (left) v aCGH (right)

Who can benefit from Genetic Screening? • Family history of genetic disease. • Embryo selection to increase IVF success rates. – 40-50% of embryos from women 30-34 years old have abnormal number of chromosomes. – Rate increases with female age.

• Family balancing (gender selection).

Limitations of Genetic Screening • Sometimes the collected cells do not represent the entire embryo (“mosaicism”). • No tests available yet for some genetic diseases. • Potential harm to embryo. • Delay to await results. May require embryo freezing. However, success rates with thawed embryos are similar to fresh transfers at many centers.

Limitations of Genetic Screening • Little or no improvement in success rates with genetic screening when there is low aneuploidy risk: • Young egg source (Age