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Female reproductive system & male and female infertility
1. LEARNING OBJECTIVES
1. PHYSIOLOGICAL ANATOMY.
2. THE MONTHLY OVARIAN CYCLE
3. HORMONES INFLUENCING THE
FEMALE REPRODUCTIVE SYSTEM
Dr. Misbah-ul-Qamar
2. FEMALE REPRODUCTIVE SYSTEM
⢠Femaleâs role in reproduction is more
complicated than the maleâs. The essential
functions include:-
ďProduction of ova, reception of sperm and their
transport to a common site for union
(fertilization)
ďMaintenance of the developing fetus (gestation
or pregnancy).
ďFormation of placenta that serves as the organ of
exchange between mother and fetus.
ďParturition (delivering the baby)
ďNourishing the infant after birthDr. Misbah-ul-Qamar
3. PHYSIOLOGICAL ANATOMY OF FEMALE
REPRODUCTIVE ORGANS
⢠Female Reproductive Organs Include the
Ovaries and Accessory Sex Organs.
Dr. Misbah-ul-Qamar
6. Function of Female Reproductive
System
⢠Produce sex hormones
⢠Produce functioning gametes [ova]
⢠Support & protect developing embryo.
Dr. Misbah-ul-Qamar
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
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. 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. ⢠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
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
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. UTERUS
⢠Functional zone â layer closest to the
cavity â contains majority of glands.
Thicker portion â undergoes changes with
monthly cycle
⢠Basal zone â layer just under myometrium,
attaches functional layer to myometrial
tissue, has terminal ends of glands.
Remains constant
Dr. Misbah-ul-Qamar
17. UTERINE ARTERIES
⢠Arcuate arteries - encircle endometrium
⢠Radial arteries â connect arcuate to
straight
⢠Straight arteries â deliver blood to basilar
zone
⢠Spiral arteries â deliver blood to functional
zone
Dr. Misbah-ul-Qamar
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 âfriendly environmentâ 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. 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
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
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. 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. PHYSIOLOGIC Anatomy OF FEMALE
REPRODUCTIVE SYSTEM
⢠The principle organs include:-
ďOVARIES:- lie within the pelvic cavity.
ďOVIDUCTS:- 2 oviduct (uterine or fallopian tubes)
lie in close association with the ovaries. It is the
site for fertilization.
ďUTERUS:- Thick walled hollow organ. Responsible
for maintaining the fetus during development
and expelling it out at the end of pregnancy.
ďVAGINA:- A muscular expandable tube that
connects uterus to external environment.ď .
Dr. Misbah-ul-Qamar
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:
â Phase I
â Phase II
Dr. Misbah-ul-Qamar
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. 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:
â A large ovum
â 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. 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
â Half remain in fertilized ovum
â Other half are released in a 2nd polar body which then
disintegrates.
Dr. Misbah-ul-Qamar
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. 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. 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
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. 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. ⢠Secreted in short(5-25 minutes) pulses
averaging once every 90 minutes(1-2hours)ď
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
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. Psychic control of GnRH
⢠Multiple neuronal centers in higher brainâs
limbic system transmit signals into arcuate
nucleiď modify both the intensity of GnRH
release & the frequency of pulses
⢠Thatâs how the psychic factors often modify
female sexual function.
Dr. Misbah-ul-Qamar
43. GONADOTROPINS
(female sex hormones)
⢠Ovarian changes during sexual cycle depend
completely on gonadotropins(FSH &LH)
⢠During childhood, almost no pituitary
gonadotropins are secretedď ovaries remain
inactive
⢠At age 9-12, pituitary begins to secrete
progressively more FSH & LHď 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 & LHď cyclical ovarian changes.
Dr. Misbah-ul-Qamar
44. Functions of gonadotropins
⢠Both FSH & LH have stimulatory effects on
target ovarian cells:
⢠Increase in cellsâs rate of secretion
⢠Growth & proliferation of target cellsď
ovaries begin to grow
Dr. Misbah-ul-Qamar
48. SYNTHESIS
⢠from
â mainly Cholesterole (derived from blood)
â Acetyl coenzyme A (to a slight extent)
⢠PROGESTERONE AND androgens
FORMED BY THE OVARIES ď
CONVERTED TO ESTROGEN BY THE
GRANULOSA CELLS (not theca cells) IN
THE FOLLICULAR PHASE (by action of
aromatase).
Dr. Misbah-ul-Qamar
50. Transport of estrogens & progesterone
⢠Transported in blood bound with:
â Mainly albumin
â 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. Fate of ovarian sex hormones
ESTROGEN & PROGESTERONE
ELIMINATED BY THE LIVER.
Dr. Misbah-ul-Qamar
52. Role of liver in ovarian hormone
degradation
⢠It conjugates the estrogens
â 1/5 of conjugated estrogen is excreted in bile,
remainder in urine
⢠Coverts potent estrogens (estradiol & estrone)
into almost totally impotent estrogen (estriol)
â Diminished liver functionď increased activity of
estrogens in bodyď hyperestrinism
⢠It degrades progesterone to other steroids
with no progestational effect.
Dr. Misbah-ul-Qamar
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. FEMALE REPRODUCTIVE
HORMONES
⢠ON BODY METABOLISM AND FAT
DEPOSITION
⢠ON HAIR DISTRIBUTION.
⢠ON SKIN.
⢠ON ELECTROLYTE BALANCE.
Dr. Misbah-ul-Qamar
57. Monthly ovarian cycle
(less accurately called menstrual
cycle)
Function of the gonadotropic
hormones
Dr. Misbah-ul-Qamar
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 ovariesâŚâŚ.
Dr. Misbah-ul-Qamar
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
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. 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. Follicular phase
âThe phase of ovarian cycle dominated by the
presence of maturing folliclesâ
It shows the progressive stages of follicular
growth in ovaries.
Dr. Misbah-ul-Qamar
64. FOLLICULAR PHASE
ďA cohort of follicles begin to develop.
ďThe others, lacking hormonal support
undergo atresia.
ďDuring this phase the primary oocyte is
synthesizing and storing material for future
use.
Dr. Misbah-ul-Qamar
66. When a female child is born
PRIMORDIAL FOLLICLE
Each ovum is surrounded by a thin layer of cells
ď the granulosa cells
The ovum with this granulosa cell layer is known as
PRIMORDIAL FOLLICLE.
ďAt puberty pulsatile release of GnRH causes the
release of FSH & LH, under the effect of which
some ovarian follicles to grow.
ďOvum increases twofold to threefold in diameter,
followed by additional layer of granulosa cells.
called as PRIMARY FOLLICLE
Dr. Misbah-ul-Qamar
67. At puberty
ď pulsatile release of GnRH causes the
release of FSH & LH, under the effect of
which some ovarian follicles to grow.
ďOvum increases twofold to threefold in
diameter, followed by additional layer of
granulosa cells. called as PRIMARY FOLLICLE
Dr. Misbah-ul-Qamar
68. ďThe 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. 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. 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 ď follicular cells.
⢠They function as a unit to secrete estrogen.
Dr. Misbah-ul-Qamar
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. 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. 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. 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. 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 âve
feedback effect of estrogen during remainder of
cycle.
2. Increasing quantities of progesterone from
granulosa cells (a day or so before LH
surge)ď could possibly stimulates the excess
LH secretion
Dr. Misbah-ul-Qamar
76. How to assess if ovulation has occured
⢠Urine analysis in latter half of cycle
â Measurement for a surge in pregnanediol (end
product of progesterone metabolism)
â Lack of this substance indicates ovulation failure
⢠Charting of body temperature throughout the
cycle.
â Secretion of progesterone during latter half raises
body temperature about 0.5oF
Dr. Misbah-ul-Qamar
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. 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. 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. ⢠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. Results of female sexual cycle
1. Only a single ovum is normally released from
the ovaries each monthď 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. 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. Cause of corpus luteum involutionď
Loss of feedback inhibition of pituitary
⢠How anterior pituitary gland is uninhibited?
â Sudden cessation of secretion of estrogen &
progesterone
â Inhibin by corpus luteum
⢠Pituitary inhibition causes it to begin secreting
increasing amounts of FSH & LH.
Dr. Misbah-ul-Qamar
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
folliclesď beginning a new ovarian cycle.
2. Menstruation by uterus due to paucity of
progesterone, estrogen secretion.
Dr. Misbah-ul-Qamar
87. Uterine CYCLE OR MENSTURAL CYCLE
⢠âThe cyclical changes in the uterus that
accompany the hormonal changes in the
ovarian cycleâ.
⢠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. 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
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. 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. 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. 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 thicknessď
resulting in a net thickness of 3 to 5mm of the
endometrium due to increase in:
â Stromal cells
â Growth of endometrial glands
â New endometrial BVs
Dr. Misbah-ul-Qamar
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
â Only a thin layer of endometrial stroma remains
â Only epithelial cells that are left are those located
in remaining deeper portions of glands/crypts
Dr. Misbah-ul-Qamar
95. There is an additional advantage also
⢠Endometrial glands (especially those of
cervical region) secrete thin stringy mucusď
mucus strings align themselves along the
length of cervical canalď forming channels
that help guide sperm in proper direction
from vagina to uterus.
Dr. Misbah-ul-Qamar
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. 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. 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. 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. ⢠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. 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. 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. ⢠If fertilization and implantation do not occur
the corpus luteum degenerates and new
follicular phase and menstrual cycle starts
Dr. Misbah-ul-Qamar
104. Menstruation
⢠It occurs if the ovum is not fertilized.
⢠Cause: low levels of ovarian hormones
(estrogen & progesterone)
Dr. Misbah-ul-Qamar
105. Changes occuring in menstrual phase
⢠Reduction in estrogens & progesteroneď
Decreased stimulation of endometrial cells by
ovarian hormonesď involution of
endometrium (to about 65% of its previous
thickness)ď vasospasm in mucosal layers of
endometrium by vasoconstrictor
prostaglandins (involution induced release)ď
necrosis of endometrium & its BVs.
Dr. Misbah-ul-Qamar
106. Causes of endometrial necrosis
â Vasospasm
â Decrease in nutrient supply
â Loss of hormonal stimulation
Dr. Misbah-ul-Qamar
107. Outcome of endometrial necrosis
⢠Due to this necrosis, blood seeps into vascular
endometrial layerď hemorrhagic areas grow
rapidly (over a period of 24-36 hours)ď 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. 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. 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. 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. 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. After Menstruation
⢠Within 4-7 days, loss of blood ceases.
⢠Reason: by this time, endometrium has
become re-epithelialized.
Dr. Misbah-ul-Qamar
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. OVERALL MECHANISM
â the hypothalamus secretes GnRH, which
causes the anterior pituitary gland to secrete
LH & FSH.
âĄNegative feedback effects of estrogen &
progesterone to decrease LH & FSH secretion
â˘Positive feedback effect of estrogen before
ovulationď the preovulatory luteinizing
hormone surge
Dr. Misbah-ul-Qamar
117. Anovulatory cycles
⢠When does this occur?
â The 1st few cycles after the onset of puberty
â Cycles occuring several months to years before
menopause
Cause
⢠LH surge is not potent enough.
Dr. Misbah-ul-Qamar
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
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:
â Menopause
â Other factors causing hypogonadism, such as
hypothyroidism
Dr. Misbah-ul-Qamar
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. MALE AND FEMALE INFERTILITY
⢠Infertility is âinability to conceive after one
year of conjugal life without use of
contraceptive methods.â
⢠The term "primary infertility" is applied to
âthe couple who has never achieved a
pregnancy.â
⢠"secondary infertility" implies that âat least
one previous conception has taken place.â
Dr. Misbah-ul-Qamar
124. origin of problem:
â35% female
â35% male
â20% both partners
â10% unexplained
Dr. Misbah-ul-Qamar
136. HISTORY
⢠Previous children
ďInfections: prostatitis, STD
ďTrauma to testicles
ďSurgery to testicles or hernia
ď Chemo or Radio therapy
ďEthanol or Smoking
ďMedication
ďPrevious investigations
Dr. Misbah-ul-Qamar
138. INVESTIGATIONS
âsemen analysis
âAt least 2 samples over different period of
time
âIf abnormal:
⢠Blood work: testosterone
⢠Testicular U/S
⢠Chromosomal analysis
Dr. Misbah-ul-Qamar
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
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. Classification of causes of FEMALE INFERTILITY
⢠Production
⢠Storage
⢠Delivery
Dr. Misbah-ul-Qamar
146. PITUITARY
ďTumors: Pituitary adenoma, metastatic
ďInappropriate gonadal feedback
âestrogen excess: obesity/ tumors
âestrogen deficiency
âPituitary hyposecretion can be treated
by appropriately timed administration
of hCG.
Dr. Misbah-ul-Qamar
147. OVARY
âXRT / Chemo for childhood malignancies
âPremature ovarian failure
âThick ovarian capsules occasionally exist on
the outside of ovaries, making ovulation
difficult.
Dr. Misbah-ul-Qamar
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. 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. How salpingitis could cause infertility
⢠It is inflammation of fallopian tubes which
causes fibrosisď 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. 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:
â Low grade infection /inflammation of cervix
â Abnormal hormonal stimulation of cervix
Dr. Misbah-ul-Qamar
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