In Vitro Fertilization: the basics….

Molina B. Dayal, MD

Medical Director

Sher Institute for Reproductive Medicine, St. Louis

All Couples1 in 8 Couples

Age 30-341 in 6 Couples

Age 35-391 in 4 Couples

Age 40-441 in 2 Couples

Inability to conceive after one year’s worth of regular unprotected intercourse:

Can this be applied to everyone?

Age.

Ovulatory status.

Known tubal or male issues.

Infertility --- Basic Statistics

20-25% couples conceive/month in 1st year

85% of couples will have conceived in one year

Those 15% who did not conceive will have a monthly chance of conception of 2-3%/month

2-3%/month is achieved after just 6 months if the woman is 35 years old or older

Causes of infertility

• Ovulatory Factor

• Egg Factor

• Tubal Factor

• Uterine Factor

Sperm Quality

50%

10%

40%

Unknown

Immunologic

Assessment of ovulation

Ovarian reserve screening

Assessment of pelvic anatomy

(Hysterosalpingogram (HSG))

Semen Analysis

Immunologic

What should be done with the information?

Cause of Infertility

• Ovulatory Factor

• Decreased Ovarian Reserve

• Tubal Blockage Or Abnormality

Treatment

• Ovulation Induction• Clomid, etc

• IVF• ?Egg donor

• IVF• Surgery very unlikely to be

successful

Cause of Infertility

• Mild Male Factor

• Moderate to Severe Male Factor

• Uterine Factor

Treatment

• Fertility Meds + IUI

• IVF (ICSI)

• Surgery

Cause of Infertility

• Unexplained

• Immunologic

Treatment

•Fertility Meds + IUI

•IVF

A few words about Intrauterine Insemination (IUI)

Overall IUI Success Rates

15% for women under the age of 30, 12% for women ages 30 to 35, 7% to 8% for women ages 35 to 39< 2% for women over the age of 40.

Clomid with IUI

Success rate dependent on age of female and sperm quality of male

<35 years old ---- 10%

35-40 years old ---- 5%

>40 years old ---- <2%

Unfortunately, Clomid can have a negative impact on uterine lining (therefore approx ½ chance of success compared to overall chance with IUI)

Unexplained Infertility: Intrauterine Insemination

Study Likelihood of Pregnancy per Month

IUI vs. No treatment 4% vs. 3%

Clomid alone vs. No treatment 3% vs. 3%

Clomid + IUI vs. No treatment 8% vs. 3%

FSH inj + IUI vs No treatment 12% vs. 3%

Intrauterine Insemination (IUI)

IVF is oftentimes thought of as a ‘last resort’ but it shouldn’t be….

IVF should be considered as the FIRST line treatment if….

Male factor (abnormal semen analysis)

Tubal factor (blocked or diseased fallopian tubes)

Advanced maternal age

Pre-implantation genetic diagnosis/cGH testing

IVF should be considered as the FIRST line treatment if….

Pre-implantation genetic diagnosis (single gene disorders/disease carrier states)

Protracted infertility

Immunologic Implantation Dysfunction

Need for gestational carrier

Fertility Preservation

What is IVF?

It is the fertilization of eggs with sperm/generation of embryos outside the body

Multi-step process

Medications (“protocols”) for patients are individualized to optimize outcome

IVF: Manipulation of Normal Physiology

FSH

E2

Deprogramming

Birth control pill

Lupron

Ganirelix

De-programs hypothalamic/pituitary axis.

Prevents ovulatory/LH surge.

Stimulation of Follicles

Using FSH (follicle stimulating hormone) to stimulate follicles

Ultrasound Guided Oocyte Retrieval

The Fertilization Procedure

Intracytoplasmic Sperm Injection(ICSI)

Fertilization Check

Embryos at the Blastocyst Stage

Embryo transfer

Solving the Embryo Selection Dilemma

Blastocyst transfer

cGH testing

Embryo Selection Dilemma

Issues related to the transfer of early cleavage stage (day 3) embryos

- Which is normal?

Morphology scoring:Cleavage rate.

Blastomere symmetry.Degree of fragmentation.

Embryo Aneuploidy

40/normal appearance 67%

40/abnormal appearance 70%

Munne et al, Fertil Steril. 1995.

Chromosomal abnormality rates in embryos increase with maternal age even if the embryos appear normal

Age/Embryo Type (on day 3):Rate of Chromosome

Abnormalities:

Why a blastocyst transfer?

Depending on maternal age, the majority of blastocysts are chromosomally normal.

More efficient (less risk of high order multiple pregnancies).

More physiologic.

Why cGH?

While the majority of blastocysts are normal in younger women, this does not hold entirely true in older women.

Able to screen embryos, with high accuracy, for chromosomal abnormalities (Down Syndrome, etc) before an embryo transfer is performed.

Testing for Aneuploidy/Single Gene Disorders:The Embryo Biopsy

Following Embryo Biopsy

Report generated indicating findings from genetic analysis.

Patient and physician decide how many and which embryos to transfer.

Normal embryos are transferred/stored for later use while abnormal ones are disposed.

Additional Advantages of IVF

Assessment of ovarian reserve.

Assessment of fertilization.

Control number of embryos placed in uterus.

Ability to freeze/store embryos for later use.

Take Away Points

Seek evaluation from a fertility specialist after one year of infertility (or sooner if the woman >35 years old, has irregular cycles or there is a known male factor)

Consider fertility medications + IUI in cases of unexplained infertility, limiting treatment to no more than 3 attempts

Consider IVF as first line treatment when ovarian reserve is of concern, tubal disease/blockage and male factor are present, multiple IUI’s have failed, if an immunologic implantation issue is discovered, or you are interested in cGH testing.

Thank you!