Infertility, In Vitro Fertilization (IVF) and Genetic Testing Michele Evans, M.D. [email protected] you have any friends or family members that have struggled with infertility? a. Yes b. NoDo you think that you are fertile? a. Yes b. NoWhat percentage of the population is subfertile or infertile? a. 2% b. 5% c. 10% d. 15% e. 25%Outline n Infertility n Treatment Options n In Vitro Fertilization n Egg Freezing n Surrogacy n Genetic Testing n Preconception n Preimplantation n Prenatal n ControversiesNormal Fertility 00.20.40.60.811 2 3 4 5 6 7 8 9 10 11 12Months of Follow UpCumulative Pregnancy RatesHull, et al: Br Med J 1985:291;1693Overview of Infertility n Definition: 1 year of well-timed, unprotected intercourse without a pregnancy n 10-15% of population is infertile (subfertile)What factor might cause problems with fertility? a. boxer shorts b. drinking a glass of wine every day c. eating disorder d. hiking for 30 minutes per day e. history of yeast infectionsCauses of InfertilityFemale Reproductive OrgansFSH (+) FSH=Follicle Stimulating Hormone Physiology E2 (-) E2=Estradiol Developing follicleCauses of Female Infertility n Ovary n Tubes n Uterus n Cervix n Hormones n ChromosomesCauses of Female Infertility - Ovary n AGE n Problems with ovulation n Premature ovarian failureDo women continue to produce eggs throughout their life (from puberty until death)? a. Yes b. NoOvary - 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 44Percentage 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;23:1389Prevalence of genetically abnormal oocytes in infertile women 0102030405060708090100Abnormal (%)<30 35 40 42 45Age (years)Abnormal (%)Ovary - OvulationOvary - 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 symptomsOvary – 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 rateWhat factor would not cause a woman's fallopian tubes to be blocked? a. diabetes b. ruptured appendix c. endometriosis d. chlamydia infection e. tubal ligationCauses of Female Infertility – Fallopian Tubes n Infection (chlamydia) n Endometriosis n Tubal ligation (female sterilization)Open TubesBlocked TubesFemale Infertility - Uterus n Uterus n Fibroids n Polyps n Mullerian (congenital) defects n Absent n Bicornuate/SeptumFemale Infertility n Uterine muscle tumor n Benign (>95%) n 25-30% of womenNormal Shape of UterusFibroid UterusFemale Infertility - Uterus n Uterus n Tumors n Fibroids n Polyps n Mullerian defects (congenital) n Absent uterus n Bicornuate/septateMullerian DefectTreatment with HysteroscopyTreatment with LaparoscopyFemale Infertility - Cervix n Cervix n Post-surgical n Stenosis n Mucus changesFemale Infertility - Hormones n Endocrine abnormality (hormones) n Thyroid n Prolactin n Polycystic ovary syndrome (PCOS) n Estrogen, insulin n Hypothalamic hypogonadism n Stress n Exercise (ballet dancer)Other Causes of Female Infertility n Others n Chromosome abnormalities n Turnerʼs syndrome (XO) n Androgen Insensitivity (XY) n Male pseudohermaphrodite n Female phenotype n Blind vaginal canal n Inguinal hernia (50%)Sperm Are Also Required!!Do men continue to produce sperm throughout their life (from puberty until death)? a. Yes b. NoCauses of Male Infertility n Abnormality in sperm production n Abnormality in sperm function n Obstruction in the ductal systemMale Reproductive OrgansSperm: Semen Analysis n Volume: > 2 mL n Concentration: > 20,000,000 per mL n Motility: > 50% n Normal morphology: > 40% normal n Krueger strict criteria: > 14% normal n Best predictor of fertilizing abilityNormal Sperm MorphologyAbnormal MorphologyAbnormal MorphologySperm n How many are needed for fertilization? n Natural conception n 20,000,000 n Intra-uterine insemination n 1,000,000 n In-vitro fertilization (IVF) n 10,000 n Intra-cytoplasmic sperm injection (ICSI) n 1Causes of Male Infertility n Abnormality in sperm production n Abnormality in sperm function n Obstruction in the ductal systemAbnormalities of Sperm Production n Genetic n Y chromosome microdeletions n Damage to testes – anatomical n Cryptorchidism n Varicocele n Infection n Mumps orchitis n GonadotoxinsAbnormalities of Sperm Function n Antisperm antibodies n Genital tract inflammation n prostatitis n Varicocele n Failure of acrosome reaction n Problems with sperm binding/penetrationObstructions in Ductal System n Vasectomy n Congenital bilateral absence of the vas deferens n Epididymis/ejaculatory ducts n Congenital or acquiredWhat percentage of men desire another pregnancy after having a vasectomy? a. 1% b. 5% c. 10% d. 25% e. 100%Male Infertility - Lifestyle n Tobacco n Marijuana n Alcohol n Cocaine n Steroids (can be permanent) n Heat n ExerciseInfertility: Initial Evaluation n Eggs n Ovulation n Egg quality n Sperm n Presence n Quality n Gamete transport/Implantation n HysterosalpingogramUnexplained Infertility n Work-up is negative n 15-20 % of couplesInfertility Treatments n Improve Timing of Intercourse n Intrauterine insemination (IUI) n Clomiphene citrate + IUI n FSH + IUI n In