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Infertility Objectives nDefine primary and secondary infertility nDescribe the causes of infertility nDiagnosis and management of infertility Requirements for Conception nProduction of healthy egg and sperm nUnblocked tubes that allow sperm to reach the egg nThe sperms ability to penetrate and fertilize the egg nImplantation of the embryo into the uterus nFinally a healthy pregnancy Infertility nThe inability to conceive following unprotected sexual intercourse u1 year (age 35) uAffects 15% of reproductive couples t6.1 million couples uMen and women equally affected Infertility nReproductive age for women uGenerally 15-44 years of age 20% of women have their first child after age 30 u1/3 of couples over 35 have fertility problems tOvulation decreases tHealth of the egg declines nWith the proper treatment 85% of infertile couples can expect to have a child Infertility nPrimary infertility ua couple that has never conceived nSecondary infertility uinfertility that occurs after previous pregnancy regardless of outcome Psychosocial Issues nExpectations nStress on Relationships nStress on Finances nAlternatives- Adoption or Childless nCounseling, Support Groups Etiologies nMale Factor40% nTubal Factor40% nOvulation Problem10% nUnexplained10% Start with History. . . What Clues Can You Find on History? nMale Factor nTubal Factor nOvulation T LH FSH GnRH T = Testosterone LH = Leuteinizing Hormone (regulates T secretion) FSH = Follicle Stimulating Hormone (regulates seminiferous tubule function) GnRH = Gonadotropin Releasing Hormone (regulates LH & FSH secretion) INHIBIN from Sertoli cells feedsback on the pituitary to regulate FSH secretion PITUITARY/TESTIS FEEDBACK SYSTEM TIME CONCENTRATION INHIBIN HYPOTHALAMUS GnRH (Gonadotropin releasing hormone) PITUITARY LH (Luteinizing hormone) FSH (Follicle stinulating hormone) TESTIS Leydig cells (produce Testosterone) Sertoli cells (produce Inhibin) Male Reproduction: Anatomy & Physiology 1. Sperm Production 2. Sperm Transport Etiology of Male Infertility Multi-factorial Prevalence n Varicocele 35% n Idiopathic 25% n Infection genito-urinary tract 10% n Genetic 10% n Endocrine 1 - 5% n Immunologic 1 - 5% n Obstruction 1 - 5% n Developmental 1 - 5% n Lifestyle: smoking, diet, heat ?% Etiology of Male Infertility Multi-factorial n Varicocele n Idiopathic n Infection n Genetic n Endocrine n Immunologic n Obstruction n Developmental n Lifestyle: smoking, diet, heat Dilated testicular veins Mechanisms of Injury: Increased Heat Venous Stasis Causes of Male Subfertility nThe most common identifiable cause of male subfertility is a varicocele, a condition of palpably distended veins of the pampiniform plexus of the spermatic cord. Etiology of Male Infertility Multi-factorial Prevalence n Varicocele 35% n Idiopathic 25% n Infection genito-urinary tract 10% n Genetic 10% n Endocrine 1 - 5% n Immunologic 1 - 5% n Obstruction 1 - 5% n Developmental 1 - 5% n Lifestyle: smoking, diet, heat ?% nAbout 70 % of men with congenital bilateral absence of the vas deferens are carriers of cystic fibrosis mutations. Causes of Male Subfertility Etiology of Male Infertility Multi-factorial Prevalence n Varicocele 35% n Idiopathic 25% n Infection genito-urinary tract 10% n Genetic 10% n Endocrine 1 - 5% n Immunologic 1 - 5% n Obstruction 1 - 5% n Developmental 1 - 5% n Lifestyle: smoking, diet, heat ?% Etiology of Male Infertility Multi-factorial Prevalence n Varicocele 35% n Idiopathic 25% n Infection genito-urinary tract 10% n Genetic 10% n Endocrine 1 - 5% n Immunologic 1 - 5% n Obstruction 1 - 5% n Developmental 1 - 5% n Lifestyle: smoking, diet, heat ?% Male Infertility: Evaluation uHistory (Questionnaire) uPhysical examination uStandard semen analysis uHormonal evaluation uGenetic counseling and evaluation uImaging studies Semen Analysis: World Health Organization Guidelines ParametersNormal range Volume 1.5 - 5 mL Sperm conc. 20 million/mL Sperm motility 50% Sperm morphology30% normal forms Leukocyte density 20 million/mL Sperm motility 50% Sperm morphology30% normal forms Leukocyte density 20 million/mL Sperm motility 50% Sperm morphology30% normal forms Leukocyte density 20 million/mL Sperm motility 50% Sperm morphology30% normal forms Leukocyte density 20 million Motility50% Morphology50% normal (strict criteria 15%) Male Factor Infertility Evaluation: Repeat semen analysis Physical exam- varicocele, testicular size Lab testing- testosterone, FSH, LH Genetics for special cases IUI (intrauterine insemination) ICSI (intracytoplasmic sperm injection) Donor sperm Etiologies nMale Factor40% nTubal Factor40% nOvulation Problem10% nUnexplained10% Sperm transport, Fertilization, & Implantation nThe female genital tract is not just a conduit ufacilitates sperm transport ucervical mucus traps the coagulated ejaculate uthe fallopian tube picks up the egg nFertilization must occur in the proximal portion of the tube uthe fertilized oocyte cleaves and forms a zygote uenters the endometrial cavity at 3 to 5 days nImplants into the secretory endometrium for growth and development Acquired Disorders nAcute salpingitis uAlters the functional integrity of the fallopian tube tN. gonorrhea and C. trachomatis nIntrauterine scarring uCan be caused by curettage nEndometriosis, scarring from surgery, tumors of the uterus and ovary uFibroids, endometriomas nTrauma Endometriosis? ncharacterized by the presence of endometrium-like tissue in ectopic sites outside the uterus, primarily on pelvic peritoneum and ovaries naffects nearly 1 in 7 women of reproductive age nthird most common gynecologic disorder that requires hospitalization, and a leading cause of hysterectomy. Commonly affected organs and structures: Ovaries and the sacral ligament Endometriosis Affected Pelvis Congenital Anatomic Abnormalities Hysterosalpingogram nAn X-ray that evaluates the internal female genital tract uarchitecture and integrity of the system nPerformed between the 7th and 11th day of the cycle nDiagnostic accuracy of 70% HSG: Unilateral Blocked Tube Etiologies nMale Factor40% nTubal Factor40% nOvulation Problem 10% nUnexplained10% Ovulation Physiology nThe LH (lutenizing hormone) surge occurs 34-36 hours prior to follicle rupture nProgesterone is increasingly produced after the LH surge nSecretory changes to the endometrium occur secondary to the increased progesterone levels Evaluation of Ovulation Menstruation nOvulation occurs 13-14 times per year nMenstrual cycles on average are Q 28 days with ovulation around day 14 nLuteal phase udominated by the secretion of progesterone ureleased by the corpus luteum nProgesterone causes uThickening of the endocervical mucus uIncreases the basal body temperature (0.6 F) nInvolution of the corpus luteum causes a fall in progesterone and the onset of menses Ovulation nA history of regular menstruation suggests regular ovulation nThe majority of ovulatory women experience ufullness of the breasts udecreased vaginal secretions uabdominal bloating nAbsence of PMS symptoms may suggest anovulation mild peripheral edema slight weight gain depression Diagnostic studies to confirm Ovulation nBasal body temperature uInexpensive uAccurate nEndometrial biopsy uExpensive uStatic information nSerum progesterone uAfter ovulation rises uCan be measured nUrinary ovulation- detection kits uMeasures changes in urinary LH uPredicts ovulation but does not confirm it Basal Body Temperature nExcellent screening tool for ovulation uBiphasic shift occurs in 90% of ovulating women nTemperature udrops at the time of menses u rises two days after the lutenizing hormone (LH) surge nOvum released one day prior to the first rise nTemperature elevation of more than 16 days suggests pregnancy Serum Progesterone nProgesterone starts rising with the LH surge udrawn between day 21-24 nMid-luteal phase u10 ng/ml suggests ovulation Anovulation Anovulation Symptoms Evaluation* nIrregular menstrual cycles nAmenorrhea nHirsuitism nAcne nGalactorrhea nIncreased vaginal secretions nFollicle stimulating hormone nLutenizing hormone nThyroid stimulating hormone nProlactin nAndrostenedione nTotal testosterone nDHEAS *Order the appropriate tests based on the clinical indications Ovulation Predictor Kits Salivary Estrogen: TCI Ovulation Tester- 92% accurate Add Saliva Sample Non-Ovulatory Saliva Pattern High Estrogen/ Ovulatory Saliva Pattern Approach to Ovulation Disorders nEvaluate- Hypothyroidism Prolactin Disorder Hyperandrogenism- PCOS Weight loss/ weight gain nInduce Ovulation Clomid (clomiphene citrate) Unexplained infertility n10% of infertile couples will have a completely normal workup nPregnancy rates in unexplained infertility uno treatment 1.3-4.1% uclomid and intrauterine insemination 8.3% ugonadotropins and intrauterine insemination 17.1% Treatment of the Infertile Couple Inadequate Spermatogenesis nEliminate alterations of thermoregulation nClomiphene citrate is occasionally used for induction of spermatogenesis u20% success nIn vitro fertilization may facilitate fertilization nArtificial insemination with donor sperm is often successful Husband Donor Artificial insemination with husbands sperm (AIH) Therapeutic donor insemination (TDI) In vitro fertilization (IVF) Intracytoplasmic sperm injection (ICSI) Testicular sperm aspiration Pre-therapy cryopreservation (ex - chemotherapy) ASSITED REPRODUCTIVE TECHNOLOGIES for MALE INFERTILITY Sperm DNA Quality: Assisted Reproduction IVF/ICSI (Intra-cytoplasmic sperm injection) Pregnancy rate: 30 to 40% Costly: $10,000 per attempt Safety: Some reports suggest increased risk of birth defects and genetic abnormalities in children? Anovulation nRestore ovulation uAdminister ovulation inducing agents nClomiphene citrate uAntiestrogen uCombines and blocks estrogen receptors at the hypothalamus and pituitary causing a negative feedback uIncreases FSH production tstimulates the ovary to make follicles Clomid Given for 5 days in the early part of the cycle Maximum dose is usually 150mg t50mg dose - 50% ovulate t100mg -25% more ovulate t150mg lower numbers of ovulation No changes in birth defects If no pregnancy in 6 months refer for advanced therapies t7% risk of twins 0.3% triplets tSAB rate 15% Superovulatory Medications nIf no response with clomid then gonadotropins- FSH (e.g. pergonal) can be administered intramuscularly uThis is usually given under the guidance of someone who specializes in infertility nThis therapy is expensive and patients need to be followed closely nAdverse effects uHyperstimulation of the ovaries uMultiple gestation uFetal wastage Anatomic Abnormalities nSurgical treatment
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