Menstruation & Ovulation
Dr.Suresh Babu Chaduvula
Professor
Department of OBGYN
College of Medicine
Menstruation
• Definition: The visible manifestation of cyclic
physiologic uterine bleeding due to shedding
of the endometrium.
• Due to invisible interplay of hormones
through hypo-thalamo-pituitary-ovarian axis.
• For menstruation to occur axis should be
active , endometrium should be receptive and
outflow tract should be patent.
Menstrual Cycle
• The period extending from first day of period
until the 1st day of next period.
• Normal length of a cycle is between 28-32
days. Mean – 28 days.
• It occurs cyclically between 21-35 days.
• Menarche: First menstruation
• Age of onset – 11-15 years &average is 13
years
Menstruation is an
external indicator of
ovarian events controlled
by the hypothalamicpituitary axis
Hypothalamus
GnRH
Pituitary
(gonadotrophin
releasing hormone)
LH
FSH
Feedback
Ovaries
+
Steroids
(oestradiol,
progesterone).
MENSTRUATION
Reproductive tract
Other targets
(“gonadotrophins”)
Roles of the ovary
1. Gametes (ova)
2. Hormones
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•
•
•
Menstruation ceases between 45-50 years.
Duration – 4-5 days
Amount – 20-80 ml
Menstrual discharge consists of blood, mucus,
epithelial cells, fragments of endometrium,
prostaglandins, enzymes and bacteria.
• Menstrual cycle is divided into
• 1] Ovarian
• 2] Endometrial cycle
Timing events in the menstrual cycle.
2. LH surge
Days before
LH
Days after
Day 1
Day 1
Follicular phase
0
4
8
12
Luteal phase
16
Menstruation
OVULATION
20
24
28
Ovarian Cycle
• Development and maturation of a follicle,
ovulation and formation of corpus luteum and its
degeneration
• All these events occur in 4 weeks
• 1] Recruitment of group of follicles
• 2] Selection and maturation of dominant follicle
• 3] Ovulation
• 4] Corpus luteum formation and degeneration
Recruitment of Follicles
• Out of many primordial follicles only 20 antral
follicles are developed in each cycle.
• All these follicles from 2-5 mm size are influenced
by FSH.
• Those follicles not influenced by FSH will become
atretic.
• Oocyte of each follicle grow out of
proportion.Oocyte is surrounded by acellular
glycoprotein from follicular cells called Zona
pellucida
• Flattened outer pregranulosa cells will
become Granulosa cells. These cells contain
FSH receptors.
Selection of a Dominant follicle and
maturation
• Dominant follicle is called as Graafian Follicle
out of 30-50 follicles from many primordial
follicle.
• Starts from 5-7 days
• Follicle with high oestrogen and with
maximum FSH receptors in granulosa cells will
become a dominant one.
• Rest of follicles will become atretic by 8th day.
Animated ovarian events
Key events in the ovarian cycle
LH
1. Follicular
growth
Day 1
0
4
Menstruation
8
12
16
Oestradiol
OVULATION
20
24
28
Growth of follicles:
Antral follicle
Graafian
follicle
Primordial
follicle
Oocyte
Granulosa
cells
Antrum
(fluid filled
space)
Thecal
cells
Ovulation
Many! 30-50
How many follicles are
growing at the start of the
cycle?
When do
follicles start
growing?
2-3
months
earlier!
Why is only 1 selected
and becomes
“dominant”?
Ovulation
Menstruation
What controls
follicular growth?
OVULATORY FOLLICLE
??????
Gonadotrophin
independent
FSH
+ LH
Ovulation
Menstruation
OVULATORY FOLLICLE
FSH
+ LH
Ovulation
OESTRADIOL
Menstruation
As each follicle grows, it produces increasing
amounts of oestradiol.
• Cumulus oophorus or Discus proligerous anchors
the ovum to to the wall of follicle
• Corona radiata – radially arranged cells around
the ovum
• At this stage FSH induces LH receptors in
granulosa cells of dominant follicle
• LH receptor induction is essential for mid cycle LH
surge for ovulation and lutenisation of granulosa
cells to form corpus luteum and secretion of
progesterone
Graafian Follicle
• Graafian follicle measures 20 mm before
ovulation
• It has following layers from outside inward
• 1] Theca externa
• 2] Theca interna
• 3] Membrana granulosa
• 4] granulosa cell layer
• 5] discus proligerous
• 6] corona radiata woth ovum inside
• And 7] antrum with fluid
The follicle is the fundamental element of the ovary:
Blood vessels
Theca
Granulosa
cells
Antrum
Cumulus
cells
Oocyte
Zona pellucida
(non-cellular glycoprotein coat)
Graafian Follicle and its Fluid
•
•
•
•
•
•
•
•
•
•
Fluid contains:
1]Oestrogens
2] FSH
3] traces of androgens
4] Prolactin
5] OMI-oocyte maturation inhibitor
6] LI – lutenisation inhibitor
7] Inhibin
8] Proteolytic enzymes
9] Plasmin
Time for development of a Follicle
•
•
•
•
Total duration - 3 months
Upto antral stage of 1mm – 2months
Upto 5 mm stage – 2 weeks
Upto 20 mm – 2 weeks
Ovulation
• Causes:
• 1] LH surge – secondary to sustained peak
level of estrogens in the late follicular phase.
This will cause completion of reduction
division in the oocyte and lutenisation of
granulosa cells, synthesise progesterone
andprostaglandins.
• 2] FSH rise- leads to plasminogen and it helps
in lysis of follicle.
• 3] Stretching factor – Necrobiosis of wall due
to passive stretching
• 4] Contraction of micromuscles in theca
externa
Effects of Ovulation
• Following ovulation the follicle is changed to
corpus luteum.
• Ovum will be picked up by fallopian tube and
may fertilise or degenerate.
Corpus Luteum
•
•
•
•
•
Life cycle is divided into 4 stages:
1] stage of proliferation
2] stage of vascularisation
3] stage of maturation and
4] stage of regression
• Stage of Proliferation:
• Granulosa cells will become polyhedral and enlarged and
with lipids –looks greyish yellow called granulosa lutein
cells
• Stage of vascularisation: small capillaries grow towards
granulosa layer.
• Stage of maturation:
• After 1 week reaches 1-2cm and a carotene pigment will
give a yellow color
• Stage of regression: on 22 -23 day regression starts.Lutein
cells become atrophic and will become white called Corpus
Albicans / if pregnancy occurs it will become Corpus
luteum of pregnancy.
Hormones for formation and
maintenance of corpus luteum
• 1] FSH induces LH receptors and LH surge
causes lutenisation of granulosa cells and
progesterone secretion.LH scretion should be
continuous for function of corpus luteum
• 2]17 alfa–OH–progesterone and estradiol
• 3] Low level of prolactin
• Life span of Corpus luteum is 12-14 days.
Hormones from Corpus luteum
•
•
•
•
•
1] Progesterone
2] Oestrogen
3] Inhibin
4] Relaxin
In absence of pregnancy levels of O+P+I
decreases leading to rise in FSH and this in
turn leads to recruitment of new follicles
Luteal- Placental Shift
• At 7- 10 weeks corpus luteum function will be
taken up by Placenta
Endometrial or Uterine Cycle
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•
•
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Endometrium contains
surface epithelium,
glands,
stroma and
blood vessels
Endometrium has 2 zones:
1] Basal [ stratum basalis ]
2] Superficial functional zone
Uterine changes in the menstrual cycle.
Endometrial
depth
More secretion from
the glands – hence
the term “secretory
phase”
Oestradiol
causes an
increase in
thickness (the
“proliferative
phase”)
0
4
Menstruation
8
12
16
OVULATION
20
24
28
Terminal differentiation of
stromal cells – “decidualisation”
Characteristic “spiral arteries”
0
4
Menstruation
8
12
16
20
Optimal time for
implantation
24
28
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Stratum Basalis:[ 1mm ]
Ocupies 1/3 of endometrium – basal arteries+
Not influenced by hormones
Regeneration occurs from it.
Functional zone:
Responds to hormones like O+P
In an ovulatory cycle four stages are seen.
Functional Zone stages
• 1] Stage of regeneration
• 2] Stage of Proliferation
• 3] Secretory phase
• 4] Menstrual phase
• Stage of regeneration:
• Starts before menstruation and completes after 2-3
days after periods. Measures 2mm.
• Glands are lined by cubical cells
• Stage of Proliferation:
• Extends from 5-6th day to 14th day due to
Estrogens.Glands are tubular and perpendicular to
surface.
• Epithelium is columnar with nuclei at base, stromal
cells are spindle shaped with spiral vessels upto
epithelium. Subepithelial congestion +. Measures 3-4
mm.
• Secretory Phase:
• Effects of O+P
• Oestrogen induces Progesterone receptors and
progesterone is responsible for secretory phase.
• Starts at 15th day to 5-6 days prior to
menstruation.
• Epithelium is more columnar and ciliated.
• Glands increase in size with taller epithelium with
vacuoles formation- subnuclear vacuolation.
• First and earliest effect of progesterone is
appearence of subnucleolar vacuolation.It will
persist upto 21 days.
• Saw toothed glandular epithelium, glands
become corkscrew shaped with marked spiralling
of vessels.
• Measures 6-8 mm.
• Regresssion of endometrium starts 24-48 hrs
prior to periods.
• Marked spiralling of vessels and withdrawl of
hormones causes tissue hypoxia and anoxia.
Menstrual phase
• Degeneration and casting off endometrium
due to regression of corpus luteum with fall in
level of O+P.
• Degeneration is due to stasis of blood and
spasm of vessels leading to damage of vessels
with escape of blood.
• Proteolytic enzymes from lysosomes causes
local damage.[ Enzymatic autodigestion ]
What causes the onset of menstruation?
Steroid
levels
fall
This is followed by
the onset of
menstruation
How does menstruation stop?
•
•
•
•
Prolonged vasoconstriction
Myometrial contraction
Local aggregation of platelets
Endothelin and platelet activating factor are
potent vasoconstrictors.
Regeneration of Endometrium
• Oestrogens
• Growth factors
Hormones of ovarian and
endometrial cycle
• At menstruation Oestrogen and inhibin are at low levels and high
FSH.
• Oestrogen increases gradually and FSH decreases and remains static
at day 5.
• O+ LH and androgen increases.
• Matuaration of follicle is combined effect of FSH and LH/
• Peptides –Inhibin, Activin and Follistatin
• Growth Facors – IGF, EGF from theca cells – modulate FSH,LH and
peptide actions.
• IGF stimulates aromatase activity and progesterone synthesis.
• Progesterone will increase in secretory phase until 5 days before
periods.
• LH will start declining
Hormones and Ovulation
• It occurs after 10-12 hrs following LH surge.
• It occurs after 24-36 hrs following Oestradiol
peak of 200 pg/ml
• Progesterone peaks at 8th day after LH surge.
• Datting of endometrium – Examination of
endometrium
• Luteal phase defect – A discrepancy of more
than 2 days in the postovulatory phase when
endometrium is examined
• A woman can have periods without ovulation.
Cervical mucus
Abundant mucus - like
“raw egg white”
Production
of low
viscosity
mucus
increases
Cervical
mucus
Thick, rubbery, high viscosity
- impenetrable to sperm.
Variable
number of
“dry” days
0
4
Menstruation
8
12
16
OVULATION
20
24
28
With increasing oestradiol:
1. The mucus becomes more abundant - up to
30x more and its water content increases.
2. Its pH becomes alkaline.
3. Increased elasticity – ("spinnbarkeit test")
5. “Ferning pattern” caused by the interaction of
high concentrations of salt and water with
the glycoproteins in the mucus.
Characteristic fernlike pattern as
the mucus dries on a glass slide.
A small (0.5 oC) rise in BBT
typically follows ovulation.
38
LH
37.8
37.6
37.4
37.2
37
36.8
36.6
Basal body temperature
36.4
36.2
36
0
4
Menstruation
8
12
16
OVULATION
20
24
28
Basal body temperature
Plasma oestradiol
Plasma progesterone
Volume of cervical mucus – and
sperm penetration
Uterine endometrium
There are a number of potential ways of trying to identify the
“fertile” period..:
a) Calendar Method - which is essentially based on the
previous menstrual history.
b) Temperature method - using a midcycle rise in body
temperature as a sign when ovulation has occurred.
c) Cervical changes - which can be detected by feeling the
cervix and cervical mucus.
d) Hormonal methods - using over-the-counter "kits" to
assess urinary hormone levels.