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In Vitro Fertilization IVF 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. 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. Who should be treated with in vitro fertilization? 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 38 5. Reduced ovarian reserve, which means lower quantity (and sometimes quantity) of eggs. 6. Severe endometriosis IVF- 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 stimulation Puregon (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 endometrium Profasi, Pregnyl(human chorionic gonadotropin (hCG)) Prometrium (Progesterone) Estradot patch, Estrace (Estradiol) IVF- Laboratory Processes Eggs retrieved Eggs stripped and cleaned Sperm collection Wash sample Egg equilibration Fertilization- IVF or ICSI Wash/remove excess sperm Assess fertilization Incubate Assess sperm quality and count Egg Retrival ICSI Embryo Development in the Lab Day 1 Day 2 Day 3 Day 4 Day 6 Day 5 Safety Endpoints • Ovarian hyperstimulation syndrome – Monitor using blood test • Miscarriage rate – PGD – Progesterone supplement • Multiple pregnancy rate – 5 day blastocyst transfer • Ectopic pregnancy rate Blood test in monitoring IVF 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. 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 Preimplantation Genetic Diagnosis (PGD) 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 PGD Can Improve Implantation Rate Identification of chromosomes X,Y,13,18,21,15,16,22 PGD Controls Implantation Rate 24.2% 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 48 Births/patient 4% 15% 31% Ferraretti, et al World Congress IVF, 2002 Two blastocysts transferred Two frozen-thawed embryos transferred A single embryo transferred