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INFERTILITY

INFERTILITY. female reproductive system. 1.Uterus.. 2.Falopian tubes.. 3.Ovaries.. 4.Cervix.. 5.Vagina.. 6.Endometrium. physiology. menstural cycle. male reproductive system. spermatogensis. The basic workup to evaluate male factors : Is semen analysis

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INFERTILITY

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  1. INFERTILITY

  2. female reproductive system

  3. 1.Uterus.. 2.Falopian tubes.. 3.Ovaries.. 4.Cervix.. 5.Vagina.. 6.Endometrium..

  4. physiology

  5. menstural cycle

  6. male reproductive system

  7. spermatogensis

  8. The basic workup to evaluate male factors : Is semen analysis Semen sample should be collected after 48 h of abstinence and examined within 2 to 3 h of collection. .

  9. Normal values of semen variables: Standard Tests ..

  10. normal fertalization

  11. What’s needed to Conceive? • The right Time, The right Situation : • 1- Hypothalamic- pituitary- gonadal axis intact. • 2- Reproductive systems of both intact, physiologically & anatomically. • 3- Juxtaposition of male & female gametes, at the ampulla. • 4- At the optimal stage of maturation, normal preovulatory oocyte & normal enough sperms. • 5- following, Transportation to the uterine cavity. • 6- when the Endometrium is supportive to develop & implant. • 7- Coital frequency is enough to let semen be deposited in close temporal relationship to release of oocyte.

  12. *Fertility: The capacity to reproduce. *Fecundability: The probability of achieving a pregnancy each month. Rate : 0.22/mo *Fecundity: The ability to achieve a live birth within one menstrual cycle. Rate : 0.15-0.18/mo

  13. When to conceive? After that there’s low monthly conception rate without treatment

  14. Probability of conception (fecundability) : Factors influncing : 1.Age : Maximum at 24 y/o. Slight decrease : 24-30 y/o. Rapid decrease : 30+ y/o. 2.Frequency : 4-5 times at week : maximum chance. 3.Age of man : Maximum fertility at 24 y/o. Slight decrease after 40 y/o. Spermatogenesis upto age 70.

  15. The following ADVERSELY affect fertility: Menstrual FSH > 10. Oligospermia. No previous conception.

  16. INFERTILITY

  17. What’s infertility? Sterility: absolute inability to conceive . Infertility: inability of couple of reproductive age to achieve conception after 1 y of sexual intercourse without contraception . 1ry infertility: infertility that occurs without any prior pregnancies . 2ry infertility: infertility that occurs after previous conception . Subfertility: relative state of decrease capacity to conceive . 70% of fertilization fails . So, 10-15% of couples experience infertility 23% of them without treatment conceive within 2 years, 10% more conceive within 4 years End of spectrum… Sterility

  18. CAUSES

  19. 40% Multiple causes… Causes Female 32% Male 18% (30% undiagnosed) Both 18.5% Idiopathic 11.1%

  20. MALE FACTORS • 90% is related to sperm production and function • Coital factor is 40 %

  21. Pretesticular causes of infertility Congenital or acquired • - Hypothalamus • No GnRH release> No Gonadotrpin> hypogonadotropic hypogonadism. • Idiopathic hypogonadotropic hypogonadism: may be due to defective migration of GnRH neurons> isolated or Kallmann syndrome • Prader-Willi syndrome • Laurence-Moon-Biedl syndrome • Other: as CNS tumors, temporal lobe seizures, and many drugs (eg, dopamine antagonists)

  22. Pituitary • congenital or acquired • caused by tumor (functional or nonfunctional)*, infarction, radiation, infection, or granulomatous disease: • Prolactinoma: Adenoma> most common functional pituitary tumor, gynecomastia and galactorrhea, bilateral hemanopia. • Isolated LH deficiency (fertile eunuch): eunuchoidal body habitus, large testis, and a low ejaculatory volume. • Isolated FSH deficiency: This is a very rare cause. oligospermia. • Thalassemia: Excess iron in the pituitary gland and testis • Cushing disease: negative feedback on the hypothalamus

  23. Peripheral organstumors or exogenous • Cortisol excess: by adrenal hyperplasia, adenomas, carcinoma, lung tumors or cushing syndrome> negative feedback on pitutary • Congenital adrenal hyperplasia (CAH)*: inefficient cortisol production with short stature, precocious puberty, small testis, and occasional bilateral testicular rests. • High Estrogen: due to Sertoli cell tumors, Leydig tumors, liver failure, or massive obesity> negative feedback on the pituitary. • Iatrogenic: High cortisol due to steroid therapy for ulcerative colitis, asthma, arthritis, or organ transplant> inhibition of GnRH release.

  24. Primary testicular causes of infertility • Chromosomal abnormalities • 1.Klinefelter syndrome*: most common, 1 per 500-1000 male births, Classically 47,XXY, most are azoospermic with 20% show presence of residual spermatogenesis, many of 2ry spermatocytes & spermatids with normal patterns. • Increased gonadotropin, while 60% have decreased testosterone • 2.XX male (sex reversal syndrome)*: often short, small firm testis and gynecomastia, normal-sized penis. Seminiferous tubules show sclerosis.

  25. XYY male: 0.1-0.4% of newborn.often tall and severely oligospermic or azoospermic, aggression, maturation arrest or germ cell aplasia. Might have some normal functional sperm. Noonan syndrome (46,XY): as male Turner syndrome, webbed neck, short stature, low-set ears, ptosis, shieldlike chest, lymphedema of hands and feet, cardiovascular abnormalities, and cubitus valgus. Leydig cell function is impaired. Mixed gonadal dysgenesis (45,X/46,XY): ambiguous genitalia, a testis on one side, and a streaked gonad on the other. Down syndrome: mild testicular dysfunction, varying degrees of reduction in germ cell. LH and FSH are usually elevated. Myotonic dystrophy: 75% testicular atrophy

  26. 2. Nonchromosomal testicular failure • Varicocele • A varicocele is defined as a dilation of the veins of the pampiniform plexus of the scrotum. Although varicoceles are present in 15% of the male population, they have been associated with and implicated as a factor responsible for male infertility in 30-35% of infertile men and the cause of 75-85% of secondary infertility. Varicoceles are observed more commonly on the left side than the right. Those with isolated right-sided varicoceles should be evaluated for retroperitoneal pathology.

  27. Cryptorchidism: • An estimated 3-4% of full-term males are born with an undescended testicle; however, less than 1% remain undescended by the age of 1 year. Risks for cryptorchidism include family history and prematurity. It may be observed as part of syndromes such as prune belly syndrome. Patients have an increased risk of infertility. The higher and longer the testicle resides outside the scrotum, the greater the likelihood of damage to the seminiferous tubules. • Trauma: • Testicular trauma is the second most common acquired cause of infertility. The testes are at risk for both thermal and physical trauma because of their exposed position

  28. Sertoli-cell-only syndrome (germinal cell aplasia): Patients with germinal cell aplasia have LH and testosterone levels within the reference range but have an increased FSH level. The etiology is unknown but is probably multifactorial. small- to normal-sized testes and azoospermia. Secondary sex characteristics are normal. • ChemotherapySuch as cyclophosphamide • Radiation therapy

  29. Orchitis • The most common cause of acquired testicular failure in adults is viral orchitis, usually caused by the mumps virus, echovirus, or group B arbovirus • Granulomatous diseaseleprosy & sarcoidosis • Sickle cell diseasemicroinfarction & secondary testicular failure

  30. Posttesticular causes of infertility • Posttesticular causes of infertility include problems with sperm transportation through the ductal system (congenital or acquired). it is observed in 7% of infertile patients. Additionally, the sperm may be unable to cross the cervical mucus or may have ultrastructural abnormalities.

  31. Congenital blockage of the ductal system: observed in children of mothers who were exposed to DES during pregnancy. called segmental dysplasia • Cystic fibrosis: congenital bilateral absence of the vas deferens. • Acquired blockage of the ductal system: • infections, such as chlamydia, gonorrhea, tuberculosis, and smallpox. • Trauma, previous attempts at sperm aspiration, and inguinal surgery may also result in ductal blockage. • Small calculi may block the ejaculatory ducts, or prostatic cysts may extrinsically block the ducts. • Scrotal surgery

  32. Antisperm antibodies: Antisperm antibodies bind to sperm and impair motility. • Immotile cilia syndrome: Patients experience sinusitis, bronchiectasis, and infertility. • Retrograde ejaculation: This is caused by an open bladder neck during ejaculation. Retrograde ejaculation may be due to causes such as diabetes, bladder neck surgery, alpha-antagonists, transurethral prostatectomy (TURP), colon or rectal surgery, multiple sclerosis, or spinal cord injury.

  33. Other Factors • A. Environmental & Occupational • toxins like: tobacco & marijuana, heroin, cocaine, and crack cocaine, alchol, radiation, exposure to lead, other heavy metals, and pesticides • 2. Social trends IUD, sexual revolution & salpingitis!! • 3. Psychological effects stresses have No significant effect on fertility

  34. B. Age • decreases coital frequency & affects fertility, • For females, • in 1/3 of female between 35-45yrs old • (Chromosomal abnormalities and poor oocyte quality, poor embryonic quality, low implantation rate, increased miscarriage, and low birth rates) • For males, • (Testosterone decrease, gonadotropin increase, sperm concentration and semen volume change, libido decreases, and incidence of birth defects increases) • Despite this, male fertility is not as much affected as female… It only takes them longer…

  35. C. Exercise • Compulsive exercise> • excessive endorphins> interferes with FSH and LH production> ovulatory disorders and LPD. • In males, oligospermia. • D. Extreme weight loss or gain • hypothalamic-pituitary-ovarian axis • *Anorexia nervosa or bulimia> hypothalamic amenorrhea, • *Weight gain> a low FSH level, and low LH secretion> tolerated better • F. Systemic diseases • e.g. *CRF, SCA • Affecting both hormones & gonadal tissue

  36. 1. Ovulation Factors Ovulatory dysfunction: alteration in the frequency and duration of the menstrual cycle. Pathophysiology: The most common problem is the absence of ovulation (irregular or delayed)

  37. Classification of premature ovarian failure • Ovarian follicle depletion • Pure gonadal dysgenesis • Idiopathic • Congenital ovarian torsion • Turner syndrome • Fragile X chromosome • Galactosemia • Autoimmune • Viral oophoritis • Ovarian follicle dysfunction • 17,20-desmolase deficiency • Gonadotropin-receptor blocking immunoglobulins • Antibodies to gonadotropins • Idiopathic - Resistant ovary syndrome

  38. Endometrial & Ovulation factors LPD (luteal phase dysfunction) - Ovulatory dysfunction due to, At time of ovulation, follicle size is small < 23-24mm in diameter Preovulatory LH surge is rather blunt, high enough to induce resumption of myosis of the oocyte but not to induce follicular rupture and normal corpus luteum function Decreased sensitivity of progestrone receptors at endometrial level (Soules, 1989- Saracoglu, 1985).

  39. 2.Tubal Factors A. Congenital: - absence of the fallopian tube(s) can be due to spontaneous torsion in utero followed by necrosis and reabsorption. B. Acquired: - salpingitis: chlamydia, gonorrhea - Elective tubal ligation and salpingectomy

  40. 3.Uterine Factors: • A. Congenital: • Müllerian duct abnormalities: 1. total absence of the uterus and vagina (ie, Rokitansky-Küster-Hauser syndrome) 2. minor defects such as arcuate uterus, blind horn and vaginal septa (transverse or longitudinal). .

  41. B. Acquired: • Endometritis: due to a traumatic delivery, D&C, IUD, or any instrumentation (eg, myomectomy, hysteroscopy) of the endometrial cavity  intrauterine adhesions or synechiae (ie, Asherman syndrome), partial or total obliteration of the endometrial cavity. • Placental polyps: from placental remains. • Intramural and submucous fibroids: 1. distortion of the cavity; compromise the blood supply; a lack of embryo implantation, 2. Early miscarriages, premature delivery, and abruptio placentae.

  42. 4.Cervical Factors • 1- Bacterial infection (cervicitis) • 2- Autoimmune antibodies • 3- previous surgery for abnormal pap smears and • 4- Congenital, narrow cervical opening.

  43. 5.Pelvic or Peritoneal Factors Inflammation, adhesions encapsulating ovaries, reducing tubal motility, blockage of cul-de-sac result from: 1. abdominal or pelvic surgery, 2. appendicitis, 3. pelvic infections such as STDs, leading to pelvic inflammatory disease (PID): mostlyChlamydia, gonorrhea

  44. 4. Endometriosis*: intrauterine tissue grows outside of the uterus> pelvic pain & reproductive failure or incidental finding *The incidence of endometriosis in primary infertility is 26%, and secondary infertility 13% *7 folds increased risk of endometriosis with family history Mechanism: *Severe endometriosis mechanical or adhesions *mild to moderate “immune abnormalities & embryo toxic serum”

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