2/21/11 Infertility, In Vitro Fertilization (IVF) and Genetic Testing Susan Sarajari, M.D., Ph.D. History of Infertility n  First written document dealing with infertility may be found in the Kahoun papyrus (oldest Egyptian medical text), dated to 2200-1950 BC n  The early attribution of infertility to women persisted for centuries and was often considered divine punishment n  The only solution to infertility was prayer – to Egyptian Isis, Phoenician Astarte, Greek Aphrodite, or Roman Venus n  The role of the human male in reproduction was not understood in past civilizations and is still veiled in mystery for many of the primitive tribes 1 2/21/11 Overview of Infertility n  Definition: 1 year of well-timed, unprotected intercourse without a pregnancy n  10-15% of population is infertile n  15-20 % of couples have unexplained infertility (work-up is negative) Causes of Infertility 2 2/21/11 Female Reproductive Organs Physiology FSH E2 (+) (-) Developing follicle FSH=Follicle Stimulating Hormone E2=Estradiol 3 2/21/11 Ovary - Female Age n  Women are born with their lifetime egg supply n 4 million at 20 weeks gestation n 400,000 at birth n  100,000 eggs left at time of puberty n  Fertility initially declines at age 27 n  Significant decline at age 37-38 n  Rare pregnancies after age 44 Causes of Female Infertility n  Ovary n  Tubes n  Uterus n  Cervix n  Hormones n  Chromosomes 4 2/21/11 Causes of Female Infertility - Ovary n Age n Problems with ovulation n Premature ovarian failure Percentage of Married Women Who are Infertile From 3 national U.S. surveys Age (years) Infertile 20-24 7.0 25-29 8.9 30-34 14.6 35-39 21.9 40-44 28.7 Menken et al, Science 1989;23:1389 5 2/21/11 Fertility and age: natural populations Marital fertility rates in natural populations (no contraception) as a function of age of wife Science 1986;23:1389 Effects of Aging on the Ovary FSH E2 (+) (-) FSH=Follicle Stimulating Hormone E2=Estradiol 6 2/21/11 Why does fertility decline with increasing maternal age? n  Decline in the number of eggs n Every month there is loss of a group of eggs n  Decline in the quality of eggs n As the egg ages, errors in the dividing embryo increase n These errors may result in aneuploidy (an incorrect number of chromosomes) Prevalence of genetically abnormal oocytes in infertile women 100 90 %) 80 al ( 6700 m % Abnormoral 50 n 40 b A 30 20 10 0 <30 35 40 42 45 Age (years) 7 2/21/11 Ovary - Causes of Anovulation n  Hormone imbalance n  Obesity n  Anorexia n  Significant stress n  Patients display: n Irregular menstrual cycles n Skipped cycles n Minimal or absent premenstrual symptoms Ovary – Premature Ovarian Failure n  Menopause prior to age 40 n  Decreased Estrogen n  Increased FSH n  Causes n Autoimmune n Genetic n Idiopathic n  1-2% pregnancy rate 8 2/21/11 Causes of Female Infertility – Fallopian Tubes n Infection (chlamydia) n Endometriosis n Tubal ligation (female sterilization) Open Tubes 9 2/21/11 Blocked Tubes Female Infertility - Uterus § Uterus § Fibroids § Polyps 10