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  1. 1. Infertility Version 1
  2. 2. Infertility: Introduction <ul><li>Significant social and medical problem affecting couples worldwide </li></ul><ul><ul><li>Average incidence of infertility is about 15% globally </li></ul></ul><ul><ul><ul><li>varies in different populations </li></ul></ul></ul><ul><ul><li>Some causes can be detected and treated, whereas others cannot </li></ul></ul><ul><ul><ul><li>unexplained infertility constitutes about 10% of all cases </li></ul></ul></ul>
  3. 3. Definition of Infertility <ul><li>Inability to conceive after 12 months of having sexual intercourse with average frequency (2 to 3 times per week), without the use of any form of birth control </li></ul>
  4. 4. Types of Infertility <ul><li>Primary infertility </li></ul><ul><ul><li>couple has never produced a pregnancy </li></ul></ul><ul><li>Secondary infertility </li></ul><ul><ul><li>woman has previously been pregnant, regardless of the outcome, and </li></ul></ul><ul><ul><li>now is unable to conceive </li></ul></ul>
  5. 5. Conception and Fertility <ul><ul><li>The chances of conceiving in any given menstrual cycle is less than 20% </li></ul></ul><ul><ul><li>Main events necessary for pregnancy to occur are: </li></ul></ul><ul><ul><ul><li>ovulation </li></ul></ul></ul><ul><ul><ul><li>fertilization </li></ul></ul></ul><ul><ul><ul><li>implantation </li></ul></ul></ul>Any condition that interferes with these events may result in infertility
  6. 6. Factors Affecting Fertility: Frequency of Intercourse <ul><li>Coital frequency is positively correlated with pregnancy rates </li></ul>17% Frequency of intercourse Probability of conception (within 6 months) 1 time per week 3 times per week 50%
  7. 7. Factors Affecting Fertility: Timing of Intercourse <ul><li>Intercourse just before ovulation maximizes the chance of pregnancy </li></ul><ul><ul><li>Sperm survives as long as 5 days in the female genital tract </li></ul></ul><ul><ul><li>Ovum life expectancy is about 1 day if not fertilized </li></ul></ul><ul><ul><li>Sperm should be available in the female genital tract at or shortly before ovulation </li></ul></ul>
  8. 8. Factors Affecting Fertility: STIs and Other Infections <ul><li>Gonorrhea and chlamydia can cause: </li></ul><ul><ul><li>in women: pelvic inflammatory disease (major cause of tubal infertility) and cervicitis </li></ul></ul><ul><ul><li>in men: urethritis, epididymitis, accessory gland infection </li></ul></ul><ul><li>Mumps, leading to orchitis, may cause secondary testicular atrophy </li></ul><ul><li>Other infections that may affect fertility include tuberculosis, toxoplasmosis, malaria, schistosomiasis and leprosy </li></ul>
  9. 9. Factors Affecting Fertility (Continued) <ul><li>Age of the woman </li></ul><ul><ul><li>after 40 the fertility rate decreases by 50% while the risk of miscarriage increases </li></ul></ul><ul><li>Age of the man </li></ul><ul><ul><li>increased age affects coital frequency and sexual function </li></ul></ul><ul><li>Nutrition </li></ul><ul><ul><li>for women, weight 10% to15% below normal or obesity may lead to less frequent ovulation and reduced fertility </li></ul></ul>
  10. 10. Factors Affecting Fertility (Continued) <ul><li>Factors that can contribute to fertility problems include: </li></ul><ul><ul><li>toxic agents, such as lead, toxic fumes and pesticides </li></ul></ul><ul><ul><li>smoking and alcohol </li></ul></ul><ul><li>All these factors may cause: </li></ul><ul><ul><li>in women: reduced conceptions and increased risk of fetal wastage </li></ul></ul><ul><ul><li>in men: reduced sex drive and sperm count </li></ul></ul>
  11. 11. Infertility: Female and Male Factors <ul><li>Infertility may be a result of one or more male or female factors </li></ul><ul><li>Female and male factors are equally responsible for infertility (30% to 40% each) </li></ul><ul><ul><li>in 20% of cases there is a combination of both factors </li></ul></ul><ul><li>Evaluating both partners is essential </li></ul>
  12. 12. Requirements for Female Fertility <ul><li>Vagina capable of receiving sperm </li></ul><ul><li>Normal cervical mucus to allow sperm passage </li></ul><ul><li>Ovulatory cycles </li></ul><ul><li>Patent fallopian tubes </li></ul><ul><li>Uterus capable of developing and sustaining pregnancy </li></ul><ul><li>Adequate hormonal status to maintain pregnancy </li></ul>
  13. 13. Requirements for Female Fertility (Continued) <ul><li>Adequate sexual drive and sexual function </li></ul><ul><li>Normal immunologic responses to accommodate sperm and conceptus </li></ul><ul><li>Adequate nutritional and health status to maintain nutrition and oxygenation of placenta and fetus </li></ul>
  14. 14. Requirements for Male Fertility <ul><li>Normal spermatogenesis in order to fertilize egg: </li></ul><ul><ul><li>sperm count </li></ul></ul><ul><ul><li>motility </li></ul></ul><ul><ul><li>biological structure and function </li></ul></ul><ul><li>Normal ductal system to carry sperm from the testicles to the penis </li></ul>
  15. 15. Requirements for Male Fertility (Continued) <ul><li>Ability to transmit sperm to vagina achieved through </li></ul><ul><ul><li>adequate sexual drive </li></ul></ul><ul><ul><li>ability to maintain erection </li></ul></ul><ul><ul><li>ability to achieve normal ejaculation </li></ul></ul><ul><ul><li>placement of ejaculate in vaginal vault </li></ul></ul>
  16. 16. Causes of Female Infertility <ul><li>Pelvic inflammatory disease (PID) leading to blocked or damaged fallopian tubes </li></ul><ul><ul><li>may interfere with fertilization and transport of egg </li></ul></ul><ul><li>Ovarian dysfunction resulting in absent or diminished egg production </li></ul>
  17. 17. Causes of Female Infertility (Continued) <ul><li>Local factors in the uterus and cervix </li></ul><ul><ul><li>may interfere with implantation and woman’s ability to carry pregnancy to term </li></ul></ul><ul><li>Luteal phase defect </li></ul><ul><ul><li>results in low production of progesterone </li></ul></ul><ul><ul><li>may lead to early miscarriage </li></ul></ul><ul><li>Production of anti-sperm antibodies </li></ul><ul><ul><li>can interfere with fertilization </li></ul></ul>
  18. 18. Causes of Male Infertility <ul><li>Conditions that affect quality or quantity of sperm may lead to infertility </li></ul><ul><li>These conditions include: </li></ul><ul><ul><li>varicocele </li></ul></ul><ul><ul><li>primary testicular failure </li></ul></ul><ul><ul><li>accessory gland infection </li></ul></ul><ul><ul><li>idiopathic low sperm motility </li></ul></ul>
  19. 19. Causes of Infertility Affecting Both Partners <ul><li>Psychological </li></ul><ul><ul><li>sexual behavior may reflect couple’s desire not to have children </li></ul></ul><ul><li>Immunological incompatibility </li></ul><ul><ul><li>may cause sperm agglutination </li></ul></ul><ul><li>Unknown causes </li></ul>
  20. 20. Basic Work-up for Infertility <ul><li>Evaluating both partners is essential </li></ul><ul><li>Detailed history and physical examination for both </li></ul><ul><li>Semen analysis </li></ul><ul><li>Evidence of ovulation </li></ul><ul><li>Evidence of fallopian tubes patency </li></ul><ul><li>Postcoital test </li></ul><ul><ul><li>still performed by some clinicians </li></ul></ul><ul><ul><li>not found valid by some studies </li></ul></ul>Roque Carvajal/Agencia Fotográfica
  21. 21. Fertility Evaluation Procedure <ul><li>Couple should be informed about: </li></ul><ul><ul><li>different causes of infertility </li></ul></ul><ul><ul><li>tests and procedures required to make a diagnosis </li></ul></ul><ul><ul><li>various therapeutic possibilities </li></ul></ul><ul><li>Couple’s interview is conducted together as well as separately to obtain confidential information </li></ul>Richard Lord
  22. 22. Fertility Evaluation: General and Sexual History <ul><li>General history </li></ul><ul><ul><li>occupation and background </li></ul></ul><ul><ul><li>use of tobacco, alcohol and drugs </li></ul></ul><ul><ul><li>history of abdominal surgery and earlier diseases/infections </li></ul></ul><ul><li>Sexual history </li></ul><ul><ul><li>sexual disturbances or dysfunction such as vaginismus, dyspareunia or erectile dysfunction </li></ul></ul><ul><ul><li>sexually transmitted infections </li></ul></ul>
  23. 23. Fertility Evaluation: Obstetric and Gynecological History <ul><li>Reproductive history </li></ul><ul><li>Gynecological history </li></ul><ul><li>Age at menarche </li></ul><ul><li>Menstrual periods: duration and intervals </li></ul><ul><li>Previous contraceptive use </li></ul><ul><li>Previous testing and treatment for infertility </li></ul>
  24. 24. Fertility Evaluation: General and Gynecological Examination Visual evaluation and pelvic exam for women to rule out: Visual evaluation and penile exam for men to rule out: Endocrinopathy Congenital anomalies Uterine hypoplasia Cervical lesions Dyspareunia Hypogonadism Tumors Epididymal cysts Cryptorchidism Hydrocele Varicocele
  25. 25. Fertility Evaluation of Female Partner: Evidence of Ovulation <ul><li>Ovulation can be established based on: </li></ul><ul><li>Urine test </li></ul><ul><ul><li>measures the LH in urine to detect if and when ovulation occurred </li></ul></ul><ul><li>Basal body temperature chart </li></ul><ul><ul><li>temperature is measured every morning, before woman gets out of bed </li></ul></ul><ul><ul><li>elevation in temperature indicates ovulation </li></ul></ul>
  26. 26. Fertility Evaluation of Female Partner: Evidence of Ovulation (Continued) <ul><li>Progesterone test </li></ul><ul><ul><li>progesterone level in blood is measured on days 21 or 22 of 28-day cycle </li></ul></ul><ul><li>Endometrial biopsy </li></ul><ul><ul><li>done during premenstrual phase </li></ul></ul><ul><ul><li>detects if endometrium undergoes expected changes (consistent with ovulation and production of progesterone) </li></ul></ul>
  27. 27. Fertility Evaluation of Female Partner: Other Tests <ul><li>Hysterosalpinogram (HSG) </li></ul><ul><ul><li>to determine whether fallopian tubes are blocked </li></ul></ul><ul><li>Laparoscopy </li></ul><ul><ul><li>to evaluate for pelvic disease, such as endometriosis, and check patency of fallopian tubes </li></ul></ul><ul><li>Hysteroscopy </li></ul><ul><ul><li>to evaluate condition of uterine cavity (polyps, fibroids) </li></ul></ul>
  28. 28. Fertility Evaluation of Male Partner: Semen Analysis <ul><li>Semen is studied for a number of factors including: </li></ul><ul><ul><li>Volume (1.5 cc to 5.0 cc) </li></ul></ul><ul><ul><li>Number of sperm present (> 20 million/ml) </li></ul></ul><ul><ul><li>Sperm motility (> 60%) and forward progression (more than 2 on scale 1 to 4) </li></ul></ul><ul><ul><li>Morphology (> 60% normal forms) </li></ul></ul><ul><ul><li>Presence of any infection </li></ul></ul>
  29. 29. Fertility Evaluation of Male Partner: Other Tests <ul><li>Urine analysis: to rule out infection </li></ul><ul><li>Endocrine tests: to measure concentrations of hormones testosterone, FSH and LH </li></ul><ul><li>Anti-sperm antibodies </li></ul><ul><li>Sperm penetration assay: to establish ability of sperm to penetrate egg </li></ul><ul><li>Postcoital test (low validity): to establish ability of sperm to penetrate cervical mucus </li></ul>
  30. 30. Treatment Possibilities: Female Infertility Ovulation disorders Ovulation-inducing drugs Hyperprolactinemia Prolactin-suppressing drugs Uterine and tubal abnormalities Surgical procedures Cervical mucus problems Intrauterine insemination Endometriosis Suppressing hormones or surgical procedure
  31. 31. Treatment of Female Infertility: Induction of Ovulation <ul><li>Involves the use of medication to stimulate development of one or more mature follicles </li></ul><ul><li>Success rates vary considerably and depend on age of the woman, the type of medication used, whether there are other infertility factors present in the couple and other reasons </li></ul>
  32. 32. Treatment of Female Infertility: Ovulation Induction Agents induces release of gonadotropins Gonadotropins Clomiphene citrate Gonadotropin releasing hormone analogs similar in structure to natural GnRH, provoke a massive release of GnRH into the circulation human menopausal gonadotropin (HMG), which contains equal quantities of FSH and LH Bromocriptine suppresses production of prolactin
  33. 33. Treatment of Female Infertility: Intrauterine Insemination <ul><li>A fertility procedure in which sperm are washed, concentrated and injected directly into a woman’s uterus </li></ul><ul><li>Increases the number of sperm in the fallopian tubes </li></ul><ul><li>Not recommended in cases of tubal blockage, poor egg quality, ovarian failure and severe male factor infertility </li></ul><ul><li>Most successful when coupled with drugs inducing ovulation (success rates of 5% to 20% per cycle) </li></ul>
  34. 34. Treatment of Female Infertility: Assisted Reproductive Technology (ART) <ul><li>Noncoital methods of conception </li></ul><ul><li>Includes all fertility treatments in which both eggs and sperm are manipulated </li></ul><ul><li>Types of ART include: </li></ul><ul><ul><li>In Vitro Fertilization (IVF) </li></ul></ul><ul><ul><li>Zygote Intrafallopian Transfer (ZIFT) </li></ul></ul><ul><ul><li>Gamete Intrafallopian Transfer (GIFT) </li></ul></ul>
  35. 35. ART: In Vitro Fertilization <ul><li>Involves retrieving eggs and sperm from female and male partners and placing them in a lab dish to enhance fertilization </li></ul><ul><li>Fertilized eggs are transferred several days later into the uterus </li></ul><ul><li>Ovarian stimulation drugs are used prior to procedure in order to retrieve several eggs and maximize chances for successful fertilization </li></ul><ul><li>Success rates are about 20% per egg retrieval </li></ul>
  36. 36. ART: Gamete Intrafallopian Transfer (GIFT) <ul><li>GIFT is a procedure that involves: </li></ul><ul><ul><li>ovarian stimulation </li></ul></ul><ul><ul><li>retrieval of eggs </li></ul></ul><ul><ul><li>placing a mixture of sperm and eggs directly into the woman’s fallopian tube </li></ul></ul><ul><li>GIFT does not allow visual confirmation of fertilization </li></ul><ul><li>Success rates per egg retrieval are about 28% (higher than for IVF) </li></ul>
  37. 37. ART: Zygote Intrafallopian Transfer (ZIFT) <ul><li>ZIFT, also called tubal embryo transfer, is another variation of IVF </li></ul><ul><li>As with IVF, the actual fertilization takes place in a lab dish </li></ul><ul><li>Fertilized eggs are placed directly into a fallopian tube </li></ul><ul><li>Success rate is about 29% per egg retrieval </li></ul>
  38. 38. Treatment Possibilities: Male Infertility <ul><li>Surgical treatment in some cases (varicocele) </li></ul><ul><li>Intrauterine insemination can be performed either with patient’s or donor’s sperm </li></ul><ul><li>ART procedures: </li></ul><ul><ul><li>GIFT </li></ul></ul><ul><ul><li>IVF </li></ul></ul><ul><ul><li>ICSI </li></ul></ul><ul><li>Donor semen should be free from STDs/HIV </li></ul>
  39. 39. ART: Intracytoplasmic Sperm Injection (ICSI) <ul><li>Involves injection of single sperm into the egg </li></ul><ul><li>The woman is administered fertility drugs prior to the procedure to aid in the production of multiple eggs </li></ul><ul><li>Only active undamaged sperm are selected for injections </li></ul>
  40. 40. ART: Intracytoplasmic Sperm Injection (ICSI) (Continued) <ul><li>Eggs are observed to see if fertilization takes place </li></ul><ul><ul><li>average fertilization rate is 65% </li></ul></ul><ul><li>Implantation into the uterus takes place within 72 hours after ICSI </li></ul><ul><li>Success rates range from 15% to 35% per egg retrieval </li></ul>
  41. 41. Infertility: Summary <ul><li>Infertility is a significant social and medical problem affecting couples worldwide </li></ul><ul><li>Female and male factors are equally responsible </li></ul><ul><li>Evaluation of both partners is essential </li></ul><ul><li>Treatment depends on the cause of infertility and varies from ovulation-inducing drugs to surgery to ART </li></ul>
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