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Female reproductive system & male and female infertility

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Female reproductive system & male and female infertility

  1. 1. LEARNING OBJECTIVES 1. PHYSIOLOGICAL ANATOMY. 2. THE MONTHLY OVARIAN CYCLE 3. HORMONES INFLUENCING THE FEMALE REPRODUCTIVE SYSTEM Dr. Misbah-ul-Qamar
  2. 2. FEMALE REPRODUCTIVE SYSTEM • Female’s role in reproduction is more complicated than the male’s. The essential functions include:- Production of ova, reception of sperm and their transport to a common site for union (fertilization) Maintenance of the developing fetus (gestation or pregnancy). Formation of placenta that serves as the organ of exchange between mother and fetus. Parturition (delivering the baby) Nourishing the infant after birthDr. Misbah-ul-Qamar
  3. 3. PHYSIOLOGICAL ANATOMY OF FEMALE REPRODUCTIVE ORGANS • Female Reproductive Organs Include the Ovaries and Accessory Sex Organs. Dr. Misbah-ul-Qamar
  4. 4. Dr. Misbah-ul-Qamar
  5. 5. Dr. Misbah-ul-Qamar
  6. 6. Function of Female Reproductive System • Produce sex hormones • Produce functioning gametes [ova] • Support & protect developing embryo. Dr. Misbah-ul-Qamar
  7. 7. General Physical Changes • Axillary & pubic hair growth • Changes in body conformation [widening of hips, development of breasts] • Onset of first menstrual period [menarche] • Mental changes Dr. Misbah-ul-Qamar
  8. 8. Major Organs • Ovaries [ gonads] • Uterine tubes [ fallopian tubes] • Uterus • Vagina • Accessory glands • External genitalia • Breasts Dr. Misbah-ul-Qamar
  9. 9. OVARIES • Each ovary is about the size and shape of an almond. • In young women the ovaries are about 1½ - 2 inches long, 1 inch wide & 1/3 inch thick. After menopause they tend to shrink. • They produce eggs (also called ova) - every female is born with a lifetime supply of eggs. • They also produce hormones: Estrogen & Progesterone Male Homolog = testesDr. Misbah-ul-Qamar
  10. 10. FALLOPIAN TUBES. • Stretch from the uterus to the ovaries and measure about 8 to 13 cm in length. • Range in width from about one inch at the end next to the ovary, to the diameter of a strand of thin spaghetti. • The ends of the fallopian tubes lying next to the ovaries feather into ends called fimbria. Dr. Misbah-ul-Qamar
  11. 11. • Millions of tiny hair-like cilia line the fimbria and interior of the fallopian tubes. • The cilia beat in waves hundreds of times a second catching the egg at ovulation and moving it through the tube to the uterine cavity. • Fertilization typically occurs in the fallopian tube Dr. Misbah-ul-Qamar
  12. 12. Dr. Misbah-ul-Qamar
  13. 13. UTERUS • Pear-shaped muscular organ in the upper female reproductive tract. • The fundus is the upper portion of the uterus where pregnancy occurs. • The cervix is the lower portion of the uterus that connects with the vagina and serves as a sphincter to keep the uterus closed during pregnancy until it is time to deliver a baby. • The uterus expands considerably during the reproductive process. the organ grows to from 10 to 20 times its normal size during pregnancy. Dr. Misbah-ul-Qamar
  14. 14. Dr. Misbah-ul-Qamar
  15. 15. UTERUS • The main body consists of a firm outer coat of muscle (myometrium) and an inner lining of vascular, glandular material (endometrium). • The endometrium thickens during the menstrual cycle to allow implantation of a fertilized egg. • Pregnancy occurs when the fertilized egg implants successfully into the endometrial lining. If fertilization does not occur, the endometrium sloughs off and is expelled as menstrual flow. Dr. Misbah-ul-Qamar
  16. 16. UTERUS • Functional zone – layer closest to the cavity – contains majority of glands. Thicker portion – undergoes changes with monthly cycle • Basal zone – layer just under myometrium, attaches functional layer to myometrial tissue, has terminal ends of glands. Remains constant Dr. Misbah-ul-Qamar
  17. 17. UTERINE ARTERIES • Arcuate arteries - encircle endometrium • Radial arteries – connect arcuate to straight • Straight arteries – deliver blood to basilar zone • Spiral arteries – deliver blood to functional zone Dr. Misbah-ul-Qamar
  18. 18. CERVIX • The lower portion or neck of the uterus. • The cervix is lined with mucus, the quality and quantity of which is governed by monthly fluctuations in the levels of the estrogen and progesterone. • When estrogen levels are low, the mucus tends to be thick and sparse, hindering sperm from reaching the fallopian tubes. But when an egg is ready for fertilization, estrogen levels are high, the mucus then becomes thin and slippery, offering a “friendly environment” to sperm • At the end of pregnancy, the cervix acts as the passage through which the baby exits the uterus into the vagina. The cervical canal expands to roughly 50 times its normal width in order to accommodate the passage of the baby during birth Dr. Misbah-ul-Qamar
  19. 19. VAGINA • vagin = sheath • a muscular, ridged sheath connecting the external genitals to the uterus. • Functions as a passageway for sperms and serves as the birth canal. Dr. Misbah-ul-Qamar
  20. 20. Dr. Misbah-ul-Qamar
  21. 21. MAMMARY GLANDS • Present in both sexes - normally only functional in females. • Developmentally they are derived from sweat glands. • Contained within a rounded skin-covered breast anterior to the pectoral muscles of the thorax. • Slightly below center of each breast is a ring of pigmented skin, the areola - this surrounds a central protruding nipple. • Internally - they consist of 15 to 25 lobes that radiate around and open at the nipple. • Each lobe is composed of smaller lobules- these contain alveoli that produce milk when a women is lactating. • Non-pregnant women - glandular structure is undeveloped - hence breast size is largely due to the amount of fat deposits. Dr. Misbah-ul-Qamar
  22. 22. Dr. Misbah-ul-Qamar
  23. 23. GLANDS • Lesser Vestibular (Paraurethral, Skene's) ( Male Homolog = prostate) located on the upper wall of the vagina, around the lower end of the urethra. They drain into the urethra and near the urethral opening • Function - mucus production to aid lubrication during intercourse Dr. Misbah-ul-Qamar
  24. 24. GLANDS • Greater Vestibular (Bartholin's) (Male Homolog = bulbourethral glands) located slightly below and to the left and right of the opening of the vagina. They secrete mucus to provide lubrication. Dr. Misbah-ul-Qamar
  25. 25. PHYSIOLOGIC Anatomy OF FEMALE REPRODUCTIVE SYSTEM • The principle organs include:- OVARIES:- lie within the pelvic cavity. OVIDUCTS:- 2 oviduct (uterine or fallopian tubes) lie in close association with the ovaries. It is the site for fertilization. UTERUS:- Thick walled hollow organ. Responsible for maintaining the fetus during development and expelling it out at the end of pregnancy. VAGINA:- A muscular expandable tube that connects uterus to external environment. . Dr. Misbah-ul-Qamar
  26. 26. Dr. Misbah-ul-Qamar
  27. 27. CERVIX:- The lowest portion of uterus. It contains a small opening  CERVICAL CANAL. Dr. Misbah-ul-Qamar
  28. 28. Dr. Misbah-ul-Qamar
  29. 29. Oogenesis • It is a series of steps through which a developing egg differentiates into a mature egg. • The process completes itself in 2 phases: – Phase I – Phase II Dr. Misbah-ul-Qamar
  30. 30. Phase I • Phase I: Starts during early embryonic development of female fetus & ends by the 5th month of fetal development. • What is achieved in phase I? formation of primary oocyte & only 1st stage of meiosis! • At birth: ovary contains about 1-2 million primary oocytes Dr. Misbah-ul-Qamar
  31. 31. Phase II • Development of egg to maturity after puberty • comprises of 2 divisions of meiosis. • The phase starts with 1st meiotic division of oocyte which occurs after puberty. • In this division: each oocyte divides into 2 cells: – A large ovum – A small 1st polar body • 2nd division: as a result of this division, sister chromatids separate from each other in the same cell Dr. Misbah-ul-Qamar
  32. 32. Relation of oogenesis with ovulation • Ovulation is the release of ovum from the ovary • Before ovulation, the ovum is in an arrested state of pause in meiosis • After ovulation, If the ovum is fertilized, the final step in meiosis occurs • This final step dispatches the sister chromatids of ovum to separate cells – Half remain in fertilized ovum – Other half are released in a 2nd polar body which then disintegrates. Dr. Misbah-ul-Qamar
  33. 33. Outcome of Oogenesis • At puberty, only about 300,000 oocytes remain in the ovaries. • Only a small percentage of these oocytes become mature. • Many thousands of oocytes that do not mature, degenerate. Dr. Misbah-ul-Qamar
  34. 34. Female reproductive years • Between about 13 and 46 years of age. • During these years of adult life, 400-500 of primordial follicles develop enough to expel their ova • Only one ovum is expelled each month • Remainder of developing follicles become acretic by degeneration Dr. Misbah-ul-Qamar
  35. 35. Menopause • It is the end of female reproductive capability. • What happens at follicular level? • Only a few primordial follicles remain in the ovaries, and even these follicles degenerate soon thereafter. Dr. Misbah-ul-Qamar
  36. 36. Dr. Misbah-ul-Qamar
  37. 37. FEMALE HORMONAL SYSTEM • Normal reproduction in females is achieved through monthly rhythmical changes in rates of secretion of female hormones & corresponding physical changes in ovaries & other sexual organs. • Hormonal system consists of 3 hierarchies of hormones: 1. GnRh (Gonadotropin-releasing hormone) 2. Anterior pituitary sex hormones (Gonadotropins) 3. Ovarian hormones These various hormones are secreted at drastically differing rates during different parts of monthly sexual cycle. Dr. Misbah-ul-Qamar
  38. 38. GnRH • It is a releasing hormone from hypothalamus • FSH & LH are secreted in response to its release • It is formed in the hypothalamus & then transported to anterior pituitary gland by way of hypothalamic-hypophysial portal system. Dr. Misbah-ul-Qamar
  39. 39. • Secreted in short(5-25 minutes) pulses averaging once every 90 minutes(1-2hours) stimulate pulsatile release of LH • The pulsatile nature of GnRH release is essential to its functions • If it is infused continuously, its ability to cause the release of LH & FSH is lost Dr. Misbah-ul-Qamar
  40. 40. Dr. Misbah-ul-Qamar
  41. 41. Hypothalamic centers for GnRH release • Neuronal activity that causes its release occurs primarily inarcuate nuclei of medio-basal hypothalamus • Additionally neurons in preoptic area of anterior hypothalamus also secrete GnRH in moderate amounts Dr. Misbah-ul-Qamar
  42. 42. Psychic control of GnRH • Multiple neuronal centers in higher brain’s limbic system transmit signals into arcuate nuclei modify both the intensity of GnRH release & the frequency of pulses • That’s how the psychic factors often modify female sexual function. Dr. Misbah-ul-Qamar
  43. 43. GONADOTROPINS (female sex hormones) • Ovarian changes during sexual cycle depend completely on gonadotropins(FSH &LH) • During childhood, almost no pituitary gonadotropins are secreted ovaries remain inactive • At age 9-12, pituitary begins to secrete progressively more FSH & LH onset of normal monthly sexual cycle (menarche) beginning b/w ages 11 & 15(puberty). • During each cycle, there is a cyclical increase & decrease of FSH & LH cyclical ovarian changes. Dr. Misbah-ul-Qamar
  44. 44. Functions of gonadotropins • Both FSH & LH have stimulatory effects on target ovarian cells: • Increase in cells’s rate of secretion • Growth & proliferation of target cells ovaries begin to grow Dr. Misbah-ul-Qamar
  45. 45. Dr. Misbah-ul-Qamar
  46. 46. Ovarian sex hormones • CHEMISTRY: STEROID HORMONES. ESTROGEN: , ESTRIOL, ESTRONE. PROGESTERONE: PROGESTERONE, 17 OH PROGESTERONE. Dr. Misbah-ul-Qamar
  47. 47. FEMALE REPRODUCTIVE HORMONES: Dr. Misbah-ul-Qamar
  48. 48. SYNTHESIS • from – mainly Cholesterole (derived from blood) – Acetyl coenzyme A (to a slight extent) • PROGESTERONE AND androgens FORMED BY THE OVARIES  CONVERTED TO ESTROGEN BY THE GRANULOSA CELLS (not theca cells) IN THE FOLLICULAR PHASE (by action of aromatase). Dr. Misbah-ul-Qamar
  49. 49. Production of estrogens Dr. Misbah-ul-Qamar
  50. 50. Transport of estrogens & progesterone • Transported in blood bound with: – Mainly albumin – Specific estrogen & progesterone binding globulins • This binding is loose enough to release the hormones to tissues over a period of 30 minutes or so. Dr. Misbah-ul-Qamar
  51. 51. Fate of ovarian sex hormones ESTROGEN & PROGESTERONE ELIMINATED BY THE LIVER. Dr. Misbah-ul-Qamar
  52. 52. Role of liver in ovarian hormone degradation • It conjugates the estrogens – 1/5 of conjugated estrogen is excreted in bile, remainder in urine • Coverts potent estrogens (estradiol & estrone) into almost totally impotent estrogen (estriol) – Diminished liver function increased activity of estrogens in body hyperestrinism • It degrades progesterone to other steroids with no progestational effect. Dr. Misbah-ul-Qamar
  53. 53. FEMALE REPRODUCTIVE HORMONES: • FUNCTIONS OF THE ESTROGEN: ON UTERUS AND EXTERNAL FEMALE SEXUAL ORGANS. ON THE FALLOPIAN TUBULES. ON THE BREASTS. ON THE SKELETON. ON PROTEIN DEPOSITION. Dr. Misbah-ul-Qamar
  54. 54. FEMALE REPRODUCTIVE HORMONES • ON BODY METABOLISM AND FAT DEPOSITION • ON HAIR DISTRIBUTION. • ON SKIN. • ON ELECTROLYTE BALANCE. Dr. Misbah-ul-Qamar
  55. 55. Dr. Misbah-ul-Qamar
  56. 56. FEMALE REPRODUCTIVE HORMONES: • FUNCTIONS OF PROGESTERONE: ON UTERUS. ON FALLOPIAN TUBULES. ON THE BREASTS. Dr. Misbah-ul-Qamar
  57. 57. Monthly ovarian cycle (less accurately called menstrual cycle) Function of the gonadotropic hormones Dr. Misbah-ul-Qamar
  58. 58. Introduction to Ovarian cycle • This cycle corresponds to physical changes in ovaries & other sexual organs • Duration: 28 days (average) • Abnormal cycle length is frequently associated with decreased fertility • Gonadotropic hormones cause 8-12 follicles to begin to grow in ovaries……. Dr. Misbah-ul-Qamar
  59. 59. Effect of gonadotropins on ovaries Follicular development in the ovaries • Reproduction begins with formation of ova in the ovaries. • Every month a single ovum is expelled from ovarian follicle, which passes through the fallopian tubes into the uterus, if fertilization occurs, it is implanted in the uterus, where it develops into fetus, otherwise it undergoes degeneration. Dr. Misbah-ul-Qamar
  60. 60. Dr. Misbah-ul-Qamar
  61. 61. Introduction to ovarian cycle • About every 28 days, gonadotropic hormones cause 8- 12 new follicles to begin to grow in ovaries. • During the growth,estrogen is secreted. • One of follicles become mature & ovulates. • After ovulation, corpus luteum is formed by secretory cells of ovulating follicle • CL secretes progesterone & estrogen for 2 weeks & then degenerate • Menstruation begins upon this degeneration & a new cycle follows. Dr. Misbah-ul-Qamar
  62. 62. Ovarian cycle DEFINITION • The normal cycle that includes development of an ovarian follicle, rupture of the follicle, release of the ovum, and formation and regression of a corpus luteum • PHASES OF OVARIAN CYCLE 1.Follicular phase 2.Luteal phase Dr. Misbah-ul-Qamar
  63. 63. Follicular phase “The phase of ovarian cycle dominated by the presence of maturing follicles” It shows the progressive stages of follicular growth in ovaries. Dr. Misbah-ul-Qamar
  64. 64. FOLLICULAR PHASE A cohort of follicles begin to develop. The others, lacking hormonal support undergo atresia. During this phase the primary oocyte is synthesizing and storing material for future use. Dr. Misbah-ul-Qamar
  65. 65. Dr. Misbah-ul-Qamar
  66. 66. When a female child is born PRIMORDIAL FOLLICLE Each ovum is surrounded by a thin layer of cells the granulosa cells The ovum with this granulosa cell layer is known as PRIMORDIAL FOLLICLE. At puberty pulsatile release of GnRH causes the release of FSH & LH, under the effect of which some ovarian follicles to grow. Ovum increases twofold to threefold in diameter, followed by additional layer of granulosa cells. called as PRIMARY FOLLICLE Dr. Misbah-ul-Qamar
  67. 67. At puberty  pulsatile release of GnRH causes the release of FSH & LH, under the effect of which some ovarian follicles to grow. Ovum increases twofold to threefold in diameter, followed by additional layer of granulosa cells. called as PRIMARY FOLLICLE Dr. Misbah-ul-Qamar
  68. 68. The follicular phase includes:- 1.Proliferation of granulosa cells and formation of zona pellucida 2.Proliferation of thecal cells and estrogen secretion 3.Formation of antrum 4.Formation of a mature follicle 5.Ovulation Dr. Misbah-ul-Qamar
  69. 69. 1.PROLIFERATION OF GRANULOSA LAYER AND FORMATION OF ZONA PELLUCIDA • Single layer of granulosa cells proliferate to form several layers that surround the oocyte and separate it from the surrounding cells. • This innervating membrane is known as ZONA PELLUCIDA. Dr. Misbah-ul-Qamar
  70. 70. PROLIFERATION OF THECAL CELLS AND ESTROGEN SCRETION • As oocyte enlarges and granulosa cells proliferate, the ovarian connective tissue cells in contact with granulosa cells proliferate and differentiate to form an outer layer of thecal cells. • FOLLICULAR CELLS • The thecal cells and granulosa cells are collectively called follicular cells. • They function as a unit to secrete estrogen. Dr. Misbah-ul-Qamar
  71. 71. FORMATION OF ANTRUM • The fluid filled cavity that forms in a developing ovarian follicle. • This stage is characterized by formation of a fluid filled cavity in the middle of granulosa cells. • The follicular fluid originates from two sources:- 1.Transudation of plasma (through capillary pores) 2.Partially from follicular cells secretion • At the time of antrum formation the oocyte has reached its maximum size and this is the period of rapid follicular growth.Dr. Misbah-ul-Qamar
  72. 72. FORMATION OF MATURE FOLLICLE • One of the follicle grows rapidly than the others, developing into mature ( preovulatory, tertiary, or Graffian) follicle within 14 days after the onset of follicular development. • The antrum occupies most of the space in mature follicle. • The oocyte surrounded by zona pellucida and a single layer of granulosa cells, is displaced asymmetrically at one side of growing follicle Dr. Misbah-ul-Qamar
  73. 73. OVULATION It is the release of a mature ovum form a mature ovarian follicle. • Rupture of follicular cells to release ovum is facilitated by the enzymes released from follicular cells that digest the connective tissue in the wall. • The ovum is swept out of the follicular cells by the antral fluid into the abdominal cavity. • The released ovum is quickly withdrawn into the oviduct where fertilization may or may not take place. Dr. Misbah-ul-Qamar
  74. 74. Necessary factor for ovulation---a surge of luteinizing hormone • LH is necessary for final follicular growth & ovulation • Without this hormone, even when large quantities of FSH are available, the follicle will not progress to the stage of ovulation. • Mechanism responsible for LH surge: • About 2 days before ovulation, rate of LH secretion increases markedly (rising 6-10 fold & peaking about 16 hours before ovulation) Dr. Misbah-ul-Qamar
  75. 75. Causes of LH surge 1. Positive feedback effect of estrogen on LH (& to lesser extent FSH) secretion. 1. This effect is in sharp contrast to normal –ve feedback effect of estrogen during remainder of cycle. 2. Increasing quantities of progesterone from granulosa cells (a day or so before LH surge) could possibly stimulates the excess LH secretion Dr. Misbah-ul-Qamar
  76. 76. How to assess if ovulation has occured • Urine analysis in latter half of cycle – Measurement for a surge in pregnanediol (end product of progesterone metabolism) – Lack of this substance indicates ovulation failure • Charting of body temperature throughout the cycle. – Secretion of progesterone during latter half raises body temperature about 0.5oF Dr. Misbah-ul-Qamar
  77. 77. Initiation of ovulation Dr. Misbah-ul-Qamar
  78. 78. LUTEAL PHASE OF OVARIAN CYCLE • This phase of ovarian cycle dominated by the presence of corpus luteum. • The ruptured follicle left behind changes rapidly. • The thecal and granulosa cells left behind collapse into the emptied antrum that has been partially filled up with blood vessels.. Dr. Misbah-ul-Qamar
  79. 79. The luteal phase includes 1.Formation of corpus luteum and secretion of progesterone and estrogen 2.Degeneration of corpus luteum Dr. Misbah-ul-Qamar
  80. 80. FORMATION OF CORPUS LUTEUM • Corpus means body and luteum means yellow. • It is an ovarian structure that develops from a ruptured follicle following ovulation. • The follicular cells are transformed into corpus luteum • The follicular turned luteal cells are converted into very active steroidogenic tissue. • The abundant presence of cholesterol, steroid precursor molecule and lipid droplets within the corpus luteum gives it a yellowish appearance. Dr. Misbah-ul-Qamar
  81. 81. • Progesterone secretion followed by secretion of estrogen in follicular phase makes the uterus a suitable site for implantation of fertilized ovum Dr. Misbah-ul-Qamar
  82. 82. Results of female sexual cycle 1. Only a single ovum is normally released from the ovaries each month only a single fetus will begin to grow at a time. 2. The uterine endometrium is prepared in advance for implantation of fertilized ovum at the required time of month. Dr. Misbah-ul-Qamar
  83. 83. DEGENERATION OF CORPUS LUTEUM • If the released ovum is not fertilized the corpus luteum degenerates within 14 days after its formation. • The luteal cells degenerate and are phagocytized. • The blood supply is withdrawn and connective tissue fills in to form a fibrous tissue mass known as corpus albicans, white mass. • The luteal phase is now over and one ovarian cycle is complete. • If fertilization and implantation do occur, the corpus luteum is not degenerated , but itDr. Misbah-ul-Qamar
  84. 84. Cause of corpus luteum involution Loss of feedback inhibition of pituitary • How anterior pituitary gland is uninhibited? – Sudden cessation of secretion of estrogen & progesterone – Inhibin by corpus luteum • Pituitary inhibition causes it to begin secreting increasing amounts of FSH & LH. Dr. Misbah-ul-Qamar
  85. 85. Effects of involution • The final involution occurs at end of 12 days of corpus luteum life (26th day of cycle, 2 days before menstruation. 1. Increasing FSH & LH initiate the growth of new follicles beginning a new ovarian cycle. 2. Menstruation by uterus due to paucity of progesterone, estrogen secretion. Dr. Misbah-ul-Qamar
  86. 86. Dr. Misbah-ul-Qamar
  87. 87. Uterine CYCLE OR MENSTURAL CYCLE • “The cyclical changes in the uterus that accompany the hormonal changes in the ovarian cycle”. • The cyclical changes in the uterus results in the menstrual bleeding once during each menstrual cycle (once a month). • Bleeding lasts for about five to seven days after degeneration of corpus luteum. Dr. Misbah-ul-Qamar
  88. 88. Phases • Menstrual cycle coincides in timing with the early phase of ovarian follicular phase.. • It consists of the following phases:- The menstrual phase (menstruation) The proliferative phase The secretory/progestational phase. Dr. Misbah-ul-Qamar
  89. 89. Phases Dr. Misbah-ul-Qamar
  90. 90. THE MENSTURAL PHASE • It is characterized by discharge of blood and endometrial debris form vagina. • It is considered to be the start of a new OVARIAN CYCLE, as it coincides with the end of LUTEAL PHASE and onset of the FOLLICULAR PHASE. • Cause: involution of corpus luteum in ovary. Dr. Misbah-ul-Qamar
  91. 91. PROLIFERATIVE PHASE (estrogen phase) • The proliferative phase is characterized by repair and proliferation of endometrium. • The endometrial surface is re-epitheliallized within 4-7 days after beginning of menstruation Dr. Misbah-ul-Qamar
  92. 92. Why named estrogen phase • Estrogen plays a key role by stimulating endometrium to proliferate. • Estrogen is secreted in increasing quantities by ovary during 1st part of ovarian cycle Dr. Misbah-ul-Qamar
  93. 93. Effects of estrogen in proliferative phase • Its stimulation causes the proliferation of epithelial cells and blood vessels • Stromal cells also proliferate rapidly • during next week & a half (before ovulation), endometrium increases greatly in thickness resulting in a net thickness of 3 to 5mm of the endometrium due to increase in: – Stromal cells – Growth of endometrial glands – New endometrial BVs Dr. Misbah-ul-Qamar
  94. 94. Proliferative phase • It occurs before ovulation, coincides with the last part of follicular phase. Importance of endometrial proliferation: • At the beginning of each monthly cycle, most of endometrium has been desquamated by menstruation – Only a thin layer of endometrial stroma remains – Only epithelial cells that are left are those located in remaining deeper portions of glands/crypts Dr. Misbah-ul-Qamar
  95. 95. There is an additional advantage also • Endometrial glands (especially those of cervical region) secrete thin stringy mucus mucus strings align themselves along the length of cervical canal forming channels that help guide sperm in proper direction from vagina to uterus. Dr. Misbah-ul-Qamar
  96. 96. Secretory phase • That makes the latter half of monthly cycle • This coincides with the luteal phase of ovarian cycle. Dr. Misbah-ul-Qamar
  97. 97. SECRETORY OR PROGESTational phase • After ovulation, when corpus luteum is formed the uterus enters secretory or progestational phase. • Corpus luteum secretes progesterone (mainly) & estrogen. • Progesterone converts the thickened estrogen primed endometrium into glycogen filled tissue. Dr. Misbah-ul-Qamar
  98. 98. Peak of secretory phase • The peak occurs about 1 week after ovulation • During this part of cycle, endometrium has a thickness of 5-6mm due to: • Progesterone induced effects • Estrogen induced effects (slight additional cellular proliferation) Dr. Misbah-ul-Qamar
  99. 99. Progesterone induced effects • Marked swelling of endometrium • Endometrial secretory development • Glands increase in tortuosity • Accumulation of an excess of secretory substances in glandular epithelial cells • Cytoplasmic increase in stromal cells (not only glycogen but lipids also deposit) • Proportional (secretory activity) increase in blood supply • BVs become highly tortuous Dr. Misbah-ul-Qamar
  100. 100. • This phase is called the secretory phase because the endometrial glands are secreting glycogen or the progestational (before pregnancy), referring to the development of an endometrial lining capable of supporting an early embryo. Dr. Misbah-ul-Qamar
  101. 101. Purpose of endometrial changes • To produce a highly secretory endometrium that contains large amounts of stored nutrients • To provide appropriate conditions for implantation of fertilized ovum (in blastocyst stage) • Availability of great quantities of nutrients to early implanting embryo Dr. Misbah-ul-Qamar
  102. 102. Uterine milk • A name given to the uterine secretions. • It provides nutrition for the early dividing ovum until it implants. • After implantation (7-9 days after ovulation), trophoblastic cells absorb endometrial stored substances Dr. Misbah-ul-Qamar
  103. 103. • If fertilization and implantation do not occur the corpus luteum degenerates and new follicular phase and menstrual cycle starts Dr. Misbah-ul-Qamar
  104. 104. Menstruation • It occurs if the ovum is not fertilized. • Cause: low levels of ovarian hormones (estrogen & progesterone) Dr. Misbah-ul-Qamar
  105. 105. Changes occuring in menstrual phase • Reduction in estrogens & progesterone Decreased stimulation of endometrial cells by ovarian hormones involution of endometrium (to about 65% of its previous thickness) vasospasm in mucosal layers of endometrium by vasoconstrictor prostaglandins (involution induced release) necrosis of endometrium & its BVs. Dr. Misbah-ul-Qamar
  106. 106. Causes of endometrial necrosis – Vasospasm – Decrease in nutrient supply – Loss of hormonal stimulation Dr. Misbah-ul-Qamar
  107. 107. Outcome of endometrial necrosis • Due to this necrosis, blood seeps into vascular endometrial layerhemorrhagic areas grow rapidly (over a period of 24-36 hours) necrotic outer layers of endometrium separate from the uterus • The separation occurs at the sites of hemorrhages. • As a result, the superficial layers of endometrium are desquamated (about 48 hours after the onset of menstruation. Dr. Misbah-ul-Qamar
  108. 108. How uterine contractions start during menstruation • These contractions are responsible for the expulsion of uterine contents which are: • Mass of desquamated tissue • Blood in uterine cavity • These contents & certain contractile substances cause the contraction Dr. Misbah-ul-Qamar
  109. 109. Degeneration of corpus luteum Decreased level of estrogen and progesterone Decreased level of ovarian hormone stimulates release of prostaglandin prostaglandin causes vasoconstriction of endometrial vessels, disrupting the blood supply to endometrium Dr. Misbah-ul-Qamar
  110. 110. reduced O2 supply to endometrium causes its death including the blood vessels This resulting bleeding alongwith endometrial debris from the uterine cavity is known as Menstrual flow. Dr. Misbah-ul-Qamar
  111. 111. Menstrual fluid • Approximately 40ml of blood & an additional 35ml of serous fluid are lost normally. • Menstrual fluid is non-clotting. Dr. Misbah-ul-Qamar
  112. 112. After Menstruation • Within 4-7 days, loss of blood ceases. • Reason: by this time, endometrium has become re-epithelialized. Dr. Misbah-ul-Qamar
  113. 113. Leukorrhea During Menstruation Dr. Misbah-ul-Qamar
  114. 114. Regulation of females???? • Females have got a monthly rhythm which causes certain cyclical variations • The mechanism responsible for these variations is the interplay b/w ovarian & hypothalamic-pituitary hormones. Dr. Misbah-ul-Qamar
  115. 115. OVERALL MECHANISM ① the hypothalamus secretes GnRH, which causes the anterior pituitary gland to secrete LH & FSH. ②Negative feedback effects of estrogen & progesterone to decrease LH & FSH secretion ③Positive feedback effect of estrogen before ovulation the preovulatory luteinizing hormone surge Dr. Misbah-ul-Qamar
  116. 116. MONTHLY OVARIAN CYCLE Dr. Misbah-ul-Qamar
  117. 117. Anovulatory cycles • When does this occur? – The 1st few cycles after the onset of puberty – Cycles occuring several months to years before menopause Cause • LH surge is not potent enough. Dr. Misbah-ul-Qamar
  118. 118. How does an anovulatory cycle proceeds? The phases of cycle continue but they are altered in following ways: 1. Lack of ovulation causes failure of development of corpus luteum 2. Cycle is shortened by several days, but the rhythm continues Dr. Misbah-ul-Qamar
  119. 119. Abnormalities of ovarian secretion Dr. Misbah-ul-Qamar
  120. 120. Hypogonadism Irregular menses Hypersecretion by ovaries Dr. Misbah-ul-Qamar
  121. 121. Abnormal ovarian cycle • The quantity of estrogens must rise above a critical value to cause rhythmical cycles • Irregularity occurs when the gonads are secreting small quantities of estrogens. • This could be a result of: – Menopause – Other factors causing hypogonadism, such as hypothyroidism Dr. Misbah-ul-Qamar
  122. 122. Effects of irregular cycle • Several months may elapse b/w menstrual periods • Menstruation may cease altogether (amenorrhea) • Failure of ovulation (insufficient LH for preovulatory surge) Dr. Misbah-ul-Qamar
  123. 123. MALE AND FEMALE INFERTILITY • Infertility is “inability to conceive after one year of conjugal life without use of contraceptive methods.” • The term "primary infertility" is applied to “the couple who has never achieved a pregnancy.” • "secondary infertility" implies that “at least one previous conception has taken place.” Dr. Misbah-ul-Qamar
  124. 124. origin of problem: –35% female –35% male –20% both partners –10% unexplained Dr. Misbah-ul-Qamar
  125. 125. Dr. Misbah-ul-Qamar
  126. 126. MALE EITIOLOGY • Idiopathic • Infection – genito-urinary tract,mumps • Genetic/systemic disease • Endocrine • Immunologic • Obstruction • Developmental Dr. Misbah-ul-Qamar
  127. 127. FEMALE ETIOLOGY • Unexplained • DEVELOPMENT • Cervical • Endometrial/uterine • Pelvic • Tubal • Genetic Dr. Misbah-ul-Qamar
  128. 128. Approach to infertility • Production • Storage • Delivery Dr. Misbah-ul-Qamar
  129. 129. Production: –Hypothalamus –Anterior Pituitary –Testes Dr. Misbah-ul-Qamar
  130. 130. Hypothalamic-Pituitary-Gonadal Axis Dr. Misbah-ul-Qamar
  131. 131. hypothalamus • 1Congenital abnormalities of hypothalamus e.g. Kallman’s syndrome • Starvation, stress or severe illness • Tumors (craniopharyngioma, metastatic tumor) • Head injury • Inflammation • Infection • XRT • Drugs: marijuana, Dr. Misbah-ul-Qamar
  132. 132. PITUITARY • . Endocrine: prolactin • Tumors • Inflammation: meningitis • Trauma/XRT • Drugs: anabolic steroids Dr. Misbah-ul-Qamar
  133. 133. TESTES • Congenital: Klinefelters (XYY), developmental disorders • Infection: chlamydia, prostatitis. • Autoimmune • Tumors; chemo/XRT Dr. Misbah-ul-Qamar
  134. 134. 2.STORAGE –Temperature • Rise in scrotal temperature • Varicocoele Dr. Misbah-ul-Qamar
  135. 135. . Delivery: Impotence/Ejaculation ○Neurogenic: medications (α-blockers, methyldopa) ○Congenital: absence vas deferens (CF) ○Genetic ○Vasectomy Dr. Misbah-ul-Qamar
  136. 136. HISTORY • Previous children Infections: prostatitis, STD Trauma to testicles Surgery to testicles or hernia  Chemo or Radio therapy Ethanol or Smoking Medication Previous investigations Dr. Misbah-ul-Qamar
  137. 137. • Physical –Morphology –Testes having normal head, neck and tail Dr. Misbah-ul-Qamar
  138. 138. INVESTIGATIONS –semen analysis –At least 2 samples over different period of time –If abnormal: • Blood work: testosterone • Testicular U/S • Chromosomal analysis Dr. Misbah-ul-Qamar
  139. 139. SEMEN ANALYSIS (WHO) • Volume > 2.0 mL • Sperm > 20 million/mL • Motility > 50% forward progression or > 25% rapid progression within 60 min • Morphology> 30% normal forms Dr. Misbah-ul-Qamar
  140. 140. Female sterility About 5-10% of women are infertile! Dr. Misbah-ul-Qamar
  141. 141. Cause of female infertility • Abnormality in genital tract • Abnormal physiological function of genital system • Abnormal genetic development of ova • Ovulation failure is the most common cause Dr. Misbah-ul-Qamar
  142. 142. Classification of causes of FEMALE INFERTILITY • Production • Storage • Delivery Dr. Misbah-ul-Qamar
  143. 143. PRODUCTION –Hypothalamus –Pituitary (hyposecretion of gonadotropic hormones failure to ovulate due to insufficient hormonal stimuli) –Ovary Dr. Misbah-ul-Qamar
  144. 144. Dr. Misbah-ul-Qamar
  145. 145. HYPOTHALAMUS • Stress –Congenital/genetic –Tumors (craniopharyngioma, metastatic tumor) –Head injury –Infection –XRT –Drugs Dr. Misbah-ul-Qamar
  146. 146. PITUITARY Tumors: Pituitary adenoma, metastatic Inappropriate gonadal feedback ○estrogen excess: obesity/ tumors ○estrogen deficiency ○Pituitary hyposecretion can be treated by appropriately timed administration of hCG. Dr. Misbah-ul-Qamar
  147. 147. OVARY –XRT / Chemo for childhood malignancies –Premature ovarian failure –Thick ovarian capsules occasionally exist on the outside of ovaries, making ovulation difficult. Dr. Misbah-ul-Qamar
  148. 148. STORAGE –Uterine abnormalities –Leiomyoma –Luteal phase deficiency Dr. Misbah-ul-Qamar
  149. 149. DELIVERY –Uterine abnormalities (most common is endometriosis) –Tubal Disease (common cause is salpingitis) –Infections/ STD/PID Dr. Misbah-ul-Qamar
  150. 150. Endometriosis • Endometrial tissue almost identical to that of normal uterine endometrium grows (& even menstruate) in the pelvic cavity. • Common sites for the development of endometriosis are surrounding the uterus, fallopian tubes & ovaries. Dr. Misbah-ul-Qamar
  151. 151. Effects of endometriosis • This situation causes fibrosis throughout the pelvis which sometimes so enshrouds the ovaries that an ovum cannot be released in abdominal cavity • Endometriosis also occludes the fallopian tubes, either at fimbriated ends or elsewhere along their extent. Dr. Misbah-ul-Qamar
  152. 152. How salpingitis could cause infertility • It is inflammation of fallopian tubes which causes fibrosis occlusion • Gonococcal infection used to lead to salpingitis in past but it has become less prevelent due to modern therapy. Dr. Misbah-ul-Qamar
  153. 153. Mucus related infertility • Still another cause of infertility is secretion of abnormal mucus by uterine cervix • In this case, failure of fertilization occurs due to a viscous mucus plug • Formation of such abnormal consistency of mucous could result due to: – Low grade infection /inflammation of cervix – Abnormal hormonal stimulation of cervix Dr. Misbah-ul-Qamar
  154. 154. • Ordinarily, at the time of ovulation, the hormonal environment of estrogen causes the secretion of mucus with special characteristics that allow rapid mobility of sperm into uterus. • This environment actually guides the sperm up along mucous threads Dr. Misbah-ul-Qamar
  155. 155. HISTORY Age Regulatory of period Infections, Surgeries Medication, Smoking, Ethanol Medical history Previous investigations Dr. Misbah-ul-Qamar
  156. 156. EXAMINATION –Abdomen (masses, scars) –Vaginal (abnormalities) –Bimanual (Uterus, masses) Dr. Misbah-ul-Qamar
  157. 157. Blood work: FSH  LH Luteal phase Progesterone Imaging: Pelvic Ultrasound (to ensure presence of organs) HSG (hysterosalpingography) Diagnostic Laparoscopy (later)Dr. Misbah-ul-Qamar
  158. 158. PREGNANCY TEST • Beta HCG • LH • FSH Dr. Misbah-ul-Qamar

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