______________________________________________________ obstetrics 1

1.02
PHYSIOLOGY OF FEMALE REPRODUCTIVE SYSTEM
Dr. JANDOC/AUGUST 17, 2016
PRELIMS:QUIZ 1
Bold red letters- emphasized during lecture; Italic blue letters-
Audio; Green- Taken from the book/OT
MENSTRUAL CYCLE
 Periodic discharge of blood, mucus and cellular debris
from the uterine mucosa
 Classic:
- Interval: 28 Days (+/- 7d)- average
o Menstrual cycle may range from
21-35 days
o If a patient has a 21 day cycle,
she can have her period 2x a
month and still it is considered
normal
o Before you say that the patient
has an IRREGULAR CYCLE you
have to ask the first day of her
cycle and the first day of her
PREVIOUS cycle in order to
establish the INTERVAL
o Clinical application:
 If she has a 28 day
cycle: 28-14(14 days:
average life span of
corpus luteum)= 14
 day of
ovulation/fertility:
day14
 Compute: 14 +/- 2 days:
12-16 days- Range of
Luteal Phase
 Luteal phase: always
constant
- Duration: 2-8 days
- Menstrual blood loss: 60 mL (MBL)- ask
how many pads per day to estimate blood
loss
o 1-3 fully soaked pads/day:
around 50 ml of blood loss
o 13 mg iron lost each period
C. OVARY
 Estrogen, Progesterone and acts on UTERINE
ENDOMETRIUM
 controls the secretion of the hypothalamus, pituitary
gland, endometrium
 normal size of uterus:
o non pregnant depends on parity:
a. gravida 0=5-6 cm
b. gravida 1= 6-7cm
c. multi gravida= 8-9cm
*Gravida- # of pregnancies
 patients with problems in the uterus like a tumor or
myoma that may complain of heavy bleeding, pain
or pressure symptoms they can try medications but
if they do not respond, the treatment is
hysterectomy (removal of uterus) but does not
necessarily follow that the ovaries are also removed
 if ovaries are also removed patients undergo surgical
menopause which leads to patients complaining of hot
flushes
o drawbacks: (if no estrogen)
a. wrinkles
b. no more lubrication by glands
 if (+)ovarian cyst → removal of entire ovary
 bilateral ovarian cyst → if both ovaries removed may
cause osteoporosis, CVD
o solution: cystectomy; preserve any part of the
ovary that is still normal so that fertilization
and ovulation would be preserved
o 1/16th of an ovarian tissue is still capable of
functioning like a normal sized ovary
 there are medications that are given that would have an
effect on the different levels like the hypothalamus,
pituitary gland or even the ovaries

PURPOSE
1. Provide a fully mature fertilizable ovum for
achievement of pregnancy.
2. Provide an endometrial bed for potential inidation or
implantation of the fertilized ovum.
-If no fertilization would take place then the initial
endometrial bed that was prepared for the ovum or
zygote will be shed of as menstrual blood

HPO AXIS
A. HYPOTHALAMUS
 Gonadotropin Releasing Hormone (GnRH)
- acts on the anterior pituitary gland

B. ANTERIOR PITUITARY GLAND

 -Gonadotropins- acts on specific site of the ovary
o FSH(acts on granulosa cells)- estrogen
o LH (acts on theca cells)-progesterone

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HYPOTHALAMUS: GnRH
 Arcuate nucleus – primary site of GnRH producing
neurons
 GnRH- released from the median eminence and
released into the portal system
 Internal carotid arteries- blood supply of the
pituitary gland
Actions:
1. stimulates synthesis and storage of FSH and LH
2. stimulates the release of FSH and LH
Pulsatile manner of secretion:
 Folicular phase (first half): 1 pulse/hour
 Luteal phase (second half): 1 pulse/2-3 hrs
Gonadotropes respond only to GnRH pulses
- Gonadaotropins will only respond if it is released at
pulsatile manner. If for example, GnRH was given
continuously, such as exogenous sources of GnRH, it will
now affect the release .
 Low levels of GnRH
- increase in number of its own receptors
- it would potentiate pituitary response to
subsequent pulse of GnRH
 High Levels of GnRH:
- Opposite effect
- DOWN REGULATION in concentration of
GnRH receptors which decreases
sensitivity to GnRH
- Appreciated in the treatment of gynaecologic problems
such as endometriosis, dysmenorrhea etc.
GnRH is regulated by:
1. Inhibitory feedback effect of Gonadotropins
( FSH and LH)
2. Stimulatory and inhibitory effect of ovarian
hormones (estrogen and progesterone)
3. Inhibition of GnRH by GnRH itself
4. Neurotransmitters/Neuromodulators
ANTERIOR PITUITARY GLAND
Gonadotropins: FSH and LH
 FSH (Follicular phase)- Act on GRANULOSA
CELLS to stimulate follicular growth
- Produces ESTROGEN
 LH (Luteal Phase)- Act on THECA CELLS to
stimulate ANDROGEN synthesis
- Stimulates PROGESTERONE synthesis by
CORPUS LUTEUM
 In extreme luteinization, there is increased
ANDROGEN synthesis which will have
masculinizing effects
OVARY
 Master Gland- one that dictates the amount of
hormones to be produced
 Ovarian Cycle- controls the secretion of the
hypothalamus, pituitary gland, endometrium
STAGES IN THE CONTROL OF REPRODUCTIVE FUNCTION
1. Fetal life to infancy
- GnRH, gonadotropin, and gonadal sex
hormones are secreted at high levels
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obstetrics 1
2. Infancy to puberty
- sex hormones secretions are low
- reproductive function is quiescent
- Sexual characteristics are not being developed
yet.
3. Puberty
- hormonal secretion rate increases
- shows cyclical variations during the
menstrual cycle.
- period of active reproduction
4. Menopause
- reproductive function diminishes and
ceases
- Gonads are less responsive
OVARIAN CYCLE
2 PHASES:
A. Follicular phase
- not constant
- upon release of the ovum it will enter the
luteal phase
- formation and mutation of the Graafian
follicle
B. Luteal phase
- always constant, predictable
- occurs after ovulation,
- corpus luteum (life span: 2 wks -/+ 2d)
- ex. 30d cycle: ovulation - 16th day
32d cycle: 18th day
- For irregular pt’s: we can give medications or hormones to keep
the cycle in a 28 day period for easier prediction of ovulation
FOLLICULOGENESIS: STAGES
 From the presence of follicles until selection of one
ovum →ovulation → presence of corpus luteum
a. Recruitment
b. Selection
c. Dominance
d. Demise
1. RECRUITMENT
- day 1 to day 4
- while the woman is menstruating the ovary is
already selecting the follicles that will already be
selected for ovulation during that cycle
- small antral follicles will be mustered into the next
growth phase (called COHORTS)
- principle behind the giving of oral contraceptive pills
(to prevent ovulation before the next follicle will be
selected), so give the pill prior to recruitment so that
selection would not occur
- no selection= no ovulation
COHORTS
- 10/15 but only 1 will be selected
- Which cohort will be selected: follicle with the lowest
FSH threshold
o It will undergo activation of the aromatase
system and begin estradiol production
- increased estrogen from recruited follicles
gives a negative feedback on FSH
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2 cell 2 Gonadotropin Theory of ovarian Steroidogenesis
- 2 different cells will be able to produce more Estrogen
binding of LH to its receptor on ovarian theca
cells : stimulates conversion of cholesterol to
androstenedione- androstenidione is able to diffuse in
the granulosa cells
binding of FSH to its receptor on ovarian granulosa
cells – stimulates aromatization (by aromatase
enzyme) of androgens (from theca cell) then further
converted to estrogen (common board exam question)
2. SELECTION
- day 5 to 7
- a single follicle becomes destined to ovulate
(the cohort that has the lowest threshold for FSH)
- FSH decreases due to increased Estrogen
(feedback mechanism)
- the rest of the cohorts that are not selected will still
produce estrogen
3. DOMINANCE
- one cohort was already selected called as Graafian
Follicle
- day 8 to 12: Graafian Follicle
- day 16 to 24: corpus luteum
- Graafian follicle retains its responsiveness to decrease
FSH
- proliferation of granulosa and theca layers
- continues to produce estrogen until estradiol peak is
reached prior to ovulation
ESTRADIOL PEAK/SURGE
- should be maintained for24 hours, so LH surge to take
place
- causes pulsatile frequency of GnRH to be more rapid
enhancing the sensitivity of pituitary Gn
- 24hrs after,it will lead to LH SURGE then ovulation
- Patients who have the same level of estrogen all
througout the follicular phase—there will be no LH
surge—no OVULATION: they are having menstruation
but they are not fertile
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LH SURGE
(Stimulates 3 major events)
- Should be sustained for 24-48 hours followed by
OVULATION
a. Resumption of meiosis 1 allowing oocyte to
undergo maturation
- from conception until puberty it stays
at meiosis 1
- puberty- resumption of meiosis 1 until
it reaches meiosis 2
b. Luteinization of granulosa and theca cells to
produce progesterone
- with ovulation what would be left is
the corpus luteum that would start to produce
progesterone to get ready for implantation and
development of the conceptus, needed for implantation
c. Follicle rupture with extrusion of mature oocyte -
OVULATION
- there is a specific site in the ovary where rupture
occurs, but in some patients there is a condition called
unruptured so they undergo the stages of recruitment,
selection and dominance but there is no ovulation
because the area of rupture is very thick such that the
ovum is trapped
LUTEAL PHASE
- time between ovulation and menses
OVULATION/ FOLLICLE RUPTURE
- If there is fertilization corpus luteum will take over:
corpus luteum of pregnancy extends its life until about 8
weeks (covering the placental development)
- 24 to 36 hours after LH surge
- can be documented by ultrasound
MECHANISMS OF RUPTURE
1. proteolytic digestion of wall: plasmin
2. prostaglandin: hydrolases
3. mucification: hyaluronic acid
4. muscle activity- expel the ovum
Clinical application:
- During menstruation, Selection period is already
happening. While the patient is shedding, there is already
a follicle destined to ovulate (basis of contraception)
- oral contraceptives (prevents ovulation) are given at a
first 5 days of the cycle, not at any time. If the patient
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takes it at 7th day, the follicles might already recruited
and at 5-7 days, follicle might had been selected= chance
of positive pregancy
CLINICAL ASPECTS OF OVULATION
1. Mittleschmertz
- In the extrusion of a mature ovum, the antral fluid that is
present is also being released, thus the body reacts via
spasm—14th day: pain in the hypogastric area
- Clinical Application: For couples who are trying to
conceive, mid-cycle pain can be one indicator that the
woman has ovulated
o Other method: Follicle monitoring via
Ultrasound
- mid cycle pain; sharp pain
- pain associated with ovulation
- usually 14th day of cycle
2. Spinnbarkheit phenomenon
- follicular phase- short distance- estrogen being
predominant
- Progesterone makes the cervical mucus more watery
- the formation of an elastic thread by mucus of the
uterine cervix when it is drawn out
- the time of maximum elasticity usually precedes or
coincides with ovulation ability of the cervical mucus to
be stretched
3. Ferning of air-dried cervical mucus
- clue that pt has already ovulated
4. Bi-phasic temperature rise/Symptothermal Effect
- Temperature is maintained due to Progesterone
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Summary:
From the hypothalamus, it will produce GnRH—GnRH will act on
the Anterior pituitary gland-- Anterior pituitary gland will
produce FSH and LH—Gonadotropins will act on the ovaries to
stimulate estrogen and progesterone production (FSH will act on
the granulosa cells to produce estrogen, LH will act on the Theca
cells to produce progesterone . But the with 2 cell theory, Theca
cells will be able to produce estrogen by virtue of aromatization of
androstenidione)-- increase estrogen level-- estradiol peak—at
24 hours, it should be maintained-- LH surge—after 24-36 hours—
Ovulation
CORPUS LUTEUM
Developmental stages:
a. proliferation
b. vascularization: capillaries + fibroblasts
- in ovulation, it’s not only the antral fluid that is
extruded out but there’s also the hemorrhagic corpus
luteum—signifies certain amount of bleeding
o Some patients may not need medical treatment
but in patients who are presenting signs of
acute abdomen, they might need to be
operated to removethehemorrhage, however,
medical treatment can be sufficient
c. maturation: active secretion of progesterone
d. regression: if there is no fertilization
**CORPUS LUTEUM of pregnancy: (+) fertilization
- continues estrogen and progesterone production
- dependent on the presence of hCG from the
syncitiotrophoblast (placenta 10-12 weeks AOG)
- (+) PT is due to hCG from placenta
- if no baby is formed after 12 wks the body would
recognize it as an abnormal pregnancy so it tries to
remove the products of conception that would lead to
spontaneous abortions (<20wks)
 SPONTANEOUS ABORTION – when
there is not enough production of
progesterone (placenta cannot
produce its own after 10-12 wks; the
fetus should be the one to produce
next)
- life span of corpus luteum: 14 days +/- 2 days
4. DEMISE
- regression of corpus luteum because there is no
fertilization
- day 23
- lutein become pale
- no implantation
 CORPORA ALBICANTIA (corpus albicans)
 dull white body, scar like
 hyalinised
 FATE of COHORTS
 Becomes hyalinized body
 begins intrauterine until
menopause
 CORPUS ATRETICUS
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ENDOMETRIAL CYCLE: PHASES
A. PROLIFERATIVE PHASE
- first half of the cycle
- changes brought about by ESTROGEN
- equated to follicar phase of the ovary
1. Early Proliferative
- after menses
- endometrium increases in thickness at about1-2mm
thick
- mainly basalis layer (left after menstruation)
- small glands, tubular, short, cuboid to columnar
epithelium
- nuclei ovoid, basal/ centrally located
2. Late Proliferative
- gland become more tortuous, elongated
- stroma: dense and more abundant
- nuclei oval with scant cytoplasm
- just before ovulation: estrogen peak cause
Pseudostratification of cells lining lumen
B. SECRETORY PHASE
- second half of the cycle
- changes brought about by PROGESTERONE
1. Early Secretory
- glycogen rich subnuclear vacuoles appear in
base of cells lining lumen
2. Mid - Late
- vascular, succulent, rich in glycogen
- hyperplastic stromal cells
- spiral arteries become coiled
PREMENSTRUAL PHASE
 if no ovulation
 2-3 days before menstruation
 marked decrease in estrogen and progesterone
 collapse of glands due to loss of tissue fluid
 intense coiling of spiral arteries
- resistance to blood flow
- hypoxia
- vasoconstriction (24-36hrs pre menses)
-causes: dysmenorrhea, pelvic pain
- vasodilation (24-36hrs after VC)
- bleeding
PREMENSTRUAL DISCOMFORT
- may or may not occur to all female patient
1. swelling and tenderness of the breasts
2. bloated feeling in the abdomen
3. weight gain up to 5lbs
4. dysmenorrhea
5. low back pain
6. pimples
7. mild fatigue and irritability
8. increased perspiration
MECHANISMS OF REPRODUCTION
MITOSIS
- process of cell division giving rise to 2 daughter cells
that are genetically identical to the parent cell
- each daughter cell receives the complete
- complement of 46 chromosomes
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STAGES
A. Prophase
- chromosomes begin to coil, shorten and thicken
B. Prometaphase
- Each chromosome consists of two parallel subunits
(CHROMATIDS) joined at a narrow region common to
both (CENTROMERE)
C. Metapahase
- chromosomes line up in the equatorial plane
- each chromosome is attached by microtubules
extending from the centromere to the centriole, forming
the mitotic spindle
D. Anaphase
- Centromere of each chromosome divides
- Migration of chromatids to opposite poles of the spindle
E. Telophase
 chromosomes uncoil and lengthen: nuclear envelope
forms
 cytoplasm divides
 each daughter cell receives HALF of all doubled
chromosome material
 maintains the same number of chromosomes as the
mother cell
MEIOSIS
 the cell division that takes place in the GERM CELLS to
generate male and female gametes, sperm and egg cells
 MEIOSIS I and MEIOSIS II
 MEIOSIS II- reduces the number of chromosomes to
the haploid number of 23
Significance:
a. Crossover enhances genetic variablity which
redistributes genetic material
b. each germ cell contains a haploid number of
chromosomes, so that at fertilization the
diploid number of 46 is restored
 completion of meiosis 1 in puberty
A. Primary oocyte produces only ONE mature gamete,
the mature oocyte (1:1)
B. Primary spermatocyte produces FOUR spermatids,
all of which develop into spermatozoa (1:4)
*life span of oocyte: 24 hours
*life span of spermatozoa: 3 days
 female spermatozoa live longer than male but male
sperm moves faster so they die first
OOGENESIS
 Near birth: all primary oocytes have started
prophase of meiosis I
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 instead of proceeding into metaphase, they enter
the DIPLOTENE stage, a resting stage during prophase
and will remain until just before ovulation
 During ovulation: enter metaphase of the first
meiotic division
 Oocyte maturation inhibitor (OMI): a substance
secreted by follicular cells
 primary oocytes at birth - 700,000 to 2M
 puberty - 400,000
 < 500 will be ovulated
obstetrics 1
 4wks and 5 days: (+) Pregnancy Test
 ULTZ= gestational sac only
 5wks= Sac and embryo but no heartbeat (sonologist
can’t say if the pregnancy is viable; ask patient to come
back)
 6wks= sac, baby and heart beat (earliest time to detect
fetal heart tone)
 Transvaginal ULTZ - earlier detection
 10 wks = seen by Transabdominal ULTZ
 10-12 weeks AOG: embryo is able to produce it’s own
hcG

 Meiosis II is completed only if the oocyte is fertilized  Inadequate corpus luteum- spontaneous abortion may
otherwise, the cell degenerates approximately 24hrs occur; give external sources of hormones
after ovulation  LH kit- sample: urine, to test when ovulation occurred

SPERMIOGENESIS
 from spermatids into spermatozoa
a. formation of the acrosome
b. condensation of the nucleus
c. formation of neck, middle piece, and tail
d. shedding of most of the cytoplasm
- this processes are needed in order for the sperm to swim
 spermatogonium to mature spermatozoon - 64 days

 Fertilization is complete when the haploid nucleus from the

sperm fuses with the haploid egg nucleus creating the
DIPLOID nucleus of the ZYGOTE which happens at the
fallopian tube and it take 6 ½ days to travel from the
Fallopian Tube to the uterus
 Fertilization site: ampullary segment

BLASTOCYST
 cells undergo differentiation and morphogenesis
 cells of the trophoblast mediate the implantation of the
blastocyst into the uterine wall
 Implantation begins when blastocyst comes in contact
with the ENDOMETRIUM

IMPLANTATION
 takes place during the second week of development
 trophoblast cells surrounding the blastocyst secrete
digestive enzymes that break down the endometrial
cells

Syncytiotrophoblast
- the trophoblast that grows into the endometrium
- produces hcg
- That’s why if you have a positive pregnancy test, it means
that you have already a detectable levels of hcG in your
urine. But that’s not always the case. There are cases in
which at 2 months, the patient is pregnant but with no
ovum or embryo. We call this as BLIGHTED OVUM or
ANEMBRYONIC PREGNANCY (it was discovered
because of early ultrasound: as early as 4 weeks)
- Earliest positivepregnancy test: 10 days after the
completed menstrual cycle (e.g 28th day +10 days)

 Cytotrophoblast
- inner layer of the trophoblast

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______________________________________________________ obstetrics 1

MINI QUIZ 1 MINI QUIZ 2 (T/F)

1. It is the periodic discharge of blood, mucus, cellular 1. Hormonal secretion during infancy to puberty is high
debris from the uterine mucosa. 2. Formation and mutation of the Graafian follicle will occur
2. This hormone stimulates the synthesis, storage and during the Luteal Phase
release of FSH and LH. 3. The follicle with the highest FSH threshold will undergo the
3. It acts on granulosa cells to stimulate follicular growth. process of selection
It produces estrogen. 4. There is an intense coiling of the spiral arteries during the
4. It acts on theca cells to stimulate ANDROGEN premenstrual phase
production. It also stimulates progesterone synthesis by 5. Estradiol surge causes pulsatile frequency of GnRH to be more
corpus luteum. rapid enhancing the sensitivity of pituitary Gn
5. In this stage, reproductive function diminishes and
ceases.
6. In this phase of the ovarian cycle, there is a formation
and mutation of the Graafian follicle.
7. Pain associated with ovulation, also known as mid cycle Answer: F, F, F, T, T
pain.
8. The formation of an elastic thread by mucus of the
uterine cervix when it is drawn out.
9. In this phase of the endometrial cycle, the changes are
brought about by estrogen.
10. In this phase of the endometrial cycle, the changes are
brought about by progesterone.

ANSWERS:

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