In Vitro FertilizationIVF

The first IVF baby in the world was born in July of 1978 in England. Today, many thousands of children are born annually as a result of this technique.

IVF involves taking eggs from the woman, fertilizing them in the laboratory with her partner's sperm and transferring the resulting embryos back to her uterus 2-6 (usually 3 or 5) days later.

It is generally used in couples who have failed to conceive after at least one year of trying who also have one or more of the following:

1. Blocked fallopian tubes or pelvic adhesions with distorted pelvic anatomy. 2. Severe male factor infertility (low sperm count or low motility) 3. Failed 2-6 cycles of ovarian stimulation with intrauterine insemination (IUI). 4. Advanced female age - over 385. Reduced ovarian reserve, which means lower quantity (and sometimes quantity) of eggs.

6. Severe endometriosis

Who should be treated with in vitro fertilization?

IVF- Clinical ProcessesIVF- Clinical Processes

The medications used fall into 3 groups.1.For ovarian suppression. These drugs put the ovaries to sleep and allow us to manipulate the growth of the follicles using medications.

Synarel Suprefact Lupron (gonadotropin-releasing hormone (GnRH) analogues.)

2.For ovarian stimulationPuregon (follitropin beta, synthetic form of follicle stimulating hormone (FSH) from CHO cells via recombinant DNA technology)

Gonal F(follitropin alpha)

Pergonal, Repronex, Bravelle (gonadotropins that include FSH and luteinizing hormone (LH) extracted from the urine of postmenopausal women )

3.For egg maturation and then support of the endometriumProfasi, Pregnyl(human chorionic gonadotropin (hCG))

Prometrium (Progesterone)

Estradot patch, Estrace (Estradiol)

IVF- Laboratory ProcessesIVF- Laboratory Processes

Eggs retrieved

Eggs stripped and cleaned

Assess sperm quality and count

Wash sample

Sperm collection

Egg equilibration

Fertilization- IVF or ICSI

Assess fertilization

Incubate

Wash/removeexcess sperm

Egg Retrival

ICSI

Embryo Development in the LabDay 1

Day 5

Day 4Day 3

Day 2

Day 6

Safety Endpoints

• Ovarian hyperstimulation syndrome– Monitor using blood test

• Miscarriage rate– PGD– Progesterone supplement

• Multiple pregnancy rate– 5 day blastocyst transfer

• Ectopic pregnancy rate

1. To be certain that there is an adequate, but not excessive response to the hormones.

2. To time oocyte (egg) retrieval.

3. To be sure that as many mature oocytes as possible are retrieved.

4. To watch for changes in hormone levels. Particularly those hormones that are thought to indicate, or to cause poor oocyte quality.

One or another of three different hormones:

estradiol ("E2"), luteinizing hormone ("LH"), and progesterone.

Blood test in monitoring IVF

Estradiol ("E2")

Ovary stimulation: development of follicles (e.g. 150 to 500 pg/ml on

day 8, doubles every 48 hrs.)

Ovary suppression <30pg/ml

luteinizing hormone ("LH")

LH surge: ovulation and release of the oocyte has begun.

Progesterone

forms once there has been an LH surge

: problem in development of follicles

Commonly, more than 100 diseases can be detected through testing, including…

• Hemophilia A

• Muscular dystrophy

• Tay-Sachs disease

• Cystic fibrosis

• Down Syndrome

Removal of one cell from day 3 embryo for testing

Preimplantation Genetic Diagnosis (PGD)

PGD Can Improve Implantation Rate

Identification of chromosomes X,Y,13,18,21,15,16,22

Implantation Rate

PGD 24.2%

Controls 12.4% (p<0.001)

PGD Predicts IVF Outcome

• Age >37• > 2 failed cycles of IVF• 216 couples• 3 groups, depending on # normal embryos available after PGD

0 normal 1 normal >1 normal#patients 27 26 55#embryos 114 118 322#transfers 8 14 48Births/patient 4% 15% 31%

Ferraretti, et al World Congress IVF, 2002

Two blastocysts transferred

Two frozen-thawed embryos transferred

A single embryo transferred