Prepared by : Muhammad Azam bin Mohd Niza [ Group 13 ]

Menstrual Cycle
Definition of menstruation

The visible manifestation of cyclic physiologic uterine bleeding due to shedding of the endometrium
following invisible interplay of hormones mainly through hypothalamo-pituitary-ovarian axis.

Anatomical aspect

The first menstruation (menarchy) occurs between 11-15 years with a mean of 13 years. For the past
couples of decades, the age of menarche gradually declining with improvement of nutrition and
environmental condition. Once the menstruation starts, it continues cyclically at intervals of 21 – 35
days (with the mean of 28 days).

The duration of menstruation (mens) is about 5 to 7 days (or 3 to 5 days) and the amount of blood
loss is estimated to be 20 to 80 mL with an average of 35 mL.

Nearly 70 % of total menstrual blood loss occurs in the first 2 days. The menstrual discharge consists
mainly of dark altered blood, mucus, vaginal epithelial cells, fragments of endometrium,
prostaglandins, enzymes and bacteria.

Physiology

The germ cells migrate from the endoderm of the yolk sac in the region of hindgut. It undergoes
rapid mitotic division and by 20 weeks, the number reaches 7 million. Some of the oogonia enter
into prophase of first meiotic division and are called primary oocytes (these are surrounded by flat
cells from the stroma (pregranulosa cells) and are called primordial follicles). Primary oocytes
continue grows through various stages of prophase and ultimately reach the stage of diplotene or
else become atretic. It then arrested in the diplotene stage of prophase of first meiotic division until
ovulation.

Total number of oocytes at 20th weeks on intrauterine life is about 6 – 7 million.

At birth, the total number of primordial follicles is estimated to be about 2 million.

At puberty, some 400000 primary oocytes are left behind, the rest become atretic.

During the entire reproductive period, 400 primary oocytes are likely to ovulate.

Maturation

The primary oocyte remains in diplotene phase until shortly before ovulation unless it undergoes
atresia. It is the mudcycle LH surge that initiates the resumption of meiosis-1. The primary oocyte
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undergoes first meiotic division giving rise to secondary oocyte and one polar body. Both are
unequal in size. The formation of secondary oocyte occurs with full maturation of Graafian follicle
just prior to ovulation. The secondary oocyte immediately begins second meiotic division but stop at
metaphase (It only completes the second meiotic division after fertilization by a sperm in the
fallopian tube. The result of fertilization is the formation of two unequal daughter cells, each
possessing 23 chromosomes (23, X). One is called ovum and the other is second polar body.

In the absence of fertilization, the secondary oocyte does not complete the second meiotic division
and degenerate as such.

Primordial follicle

It consists of an oocyte, which is surrounded by a single layer of flattened granulose cells. It

Morphology of the oocyte

With the stimulation of the follicle, there is a simultaneous enlargement of the oocyte. While the
follicle continues to enlarge until just prior to ovulation, the oocyte ceases to enlarge around the
time of antrum formation. Mature ovum measures about 130 microns and the nucleus with 20 – 25
microns. Corona radiate is the radially arranged granulose cells surrounding the oocyte. The oocyte
is surrounded by an outer envelope called zona pellucid (glycoprotein layer secreted by the growing
oocyte). The cytoplasm (vittelus) contains nutrition yolk granules and is limited by a definite
membrane (perivitelline membrane). Perivitteline space is the space between vitteline membrane
and zona pellucida. The nucleolus is large with sparsely distributed chromaffin. Shortly before
ovulation, meiosis is reinitiated.

Ovarian Cycle
The development and maturation of a follicle, ovulation and formation of corpus luteum and its
degeneration constitute an ovarian cycle. All these event occur within 4 weeks.

Ovarian cycle consists of :

1. Follicular phase (recruitment of groups of follicles and selection of the dominant follicle and
its maturation)
2. Ovulation
3. Luteal phase (Corpus luteum formation and demise of the corpus luteum)

I. Follicular phase

The initial recruitment and growth of primordial follicles are not under control of any hormone. After
a certain stage (2 – 5 mm in size) the growth and differentiation of primordial follicles are under the
control of FSH. The predominant change occurs in oocyte (pregranulosa cells becomes cuboidal and
multilayered (granulose cells). There is also differentiation of theca interna layer surrounding the
follicle. The granulose cells now acquire FSH receptors
Prepared by : Muhammad Azam bin Mohd Niza [ Group 13 ]

The development of antrum containing secondary or vesicular follicle from the solid primary follicle
depends on FSH. There is an accelerated growth of all the components of the follicles of preantral
phase. There is production of follicular fluid which is primarily an ultra filtrate blood from the vessels
within theca interna. The fluid-filled space coalesce to form an antrum.

Day 5 – 7, one of the follicles becomes dominant and undergoes further maturation. To become a
dominant follicle, a follicle must contain a highest concentration of oestrogen and lower androgen :
oestrogen ratio (oestrogenic microenvironment) and whose granulose cells contain the maximum
receptors for FSH. The rest of the follicle will become atretic by day 8. FSH also induce LH receptors
on the granulose cells of the dominant follicle. LH receptors is essential for Midcycle LH surge to
induce ovulation, luteinisation of the granulose cells to form corpus luteum and secretion of
progesterone. The follicular fluid contains oestrogens, FSH, trace amount of androgen, prolactin,
OMI (oocyte maturation inhibitor), LI (luteinisation inhibitor), inhibin-which acts centrally to inhibit
FSH, proteolytic enzymes, plasmin, etc.

Fully mature Graafian follicle just prior to ovulation measures about 20 mm and composed of the
following :

1. Theca externa
2. Theca interna
3. Membrane granulosa
4. Granulose cell layer
5. Discus proligerus
6. Antrum containing vesicular fluid

II. Ovulation

The dominant follicle reaches the surface of the ovary. The cumulus detached from the wall so that
the ovum with corona radiate floats freely in the follicular fluid. The oocytes completes the first
meiotic division with the extrusion of the first polar body which is pushed to the perivitelline space.
Follicular wall become thinner. Stigma develops as a conical projection which penetrates the outer
surface layer of the ovary and persists for a while as a thin membrane. The cumulus escapes out of
the follicle by a slow oozing process, taking about 1-2 minutes along with varying amount of fluid.
Stigma is soon closed by a plug of plasma.

Causes

1. Endocrinal
a. LH surge
b. FSH rise
2. Stretching factor
3. Contraction of the micromuscles

Effect of ovulation

Following ovulation, the follicle is changed to corpus lutuem. Ovum is picked up into the Fallopian
tube and undergoes either degeneration or further maturation (if fertilization occurs)
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III. Luteal phase

The luteal phase (or secretory phase) is the latter phase of the menstrual cycle. It begins with the
formation of the corpus luteum and ends in either pregnancy or luteolysis. The main hormone
associated with this stage is progesterone, which is significantly higher during the luteal phase than
other phases of the cycle. Some sources define the end of the luteal phase to be a distinct "ischemic
phase".

Endometrial Cycle
The changes in the internal uterine lining of the uterus, the endometrium, during the menstrual
cycle is termed the uterine cycle of menstruation. These changes occur in response to the hormones,
estrogen and progesterone secreted by the ovaries during menstruation.\

I. The Menstrual Phase :

This phase is also called the ‘bleeding phase’ or the ‘menstrual period’. It usually lasts from the 1st to
the 5th day of the cycle. The duration of bleeding can vary from 2 days to 7 days in different women.
Usually the flow is less on the first day, increases during the 2nd and the 3rd day and peters off on
the 4th and 5th days. The menstrual discharge consists of dead endometrial cells, blood, vaginal
cells, mucous from the cervix and other necrotic tissue.

The lack of hormone causes the endometrium to shrink. The blood vessels of this region become
highly coiled on themselves, blood stagnates, and the cells get necrosed due to unavailability of
blood. The endometrial tissue soon dies off and passes out of the uterus and vagina as menstrual
bleeding.

II. The Proliferative Phase :

Once the menstrual bleeding stops there is a short duration of about 48 hours when the
endometrium rests and repairs itself (‘resting phase’). At this time, the endometrium is disorganized
and chaotic and only about 1mm thick.

Under the influence of oestrogen produced by the growing Graafian follicles in the ovary, the
endometrium proliferates and begins to increase in size and number. New blood vessels grow from
the stumps of the old. The endometrial glands increase in size, though not in number. The stromal
cells assume a compact arrangement. At the end of the proliferative stage, i.e. on the 14th day, the
endometrium is 2-3 mm thick.

III. The Secretory Phase :

This phase begins soon after ovulation occurs. Under the influence of progesterone produced by the
corpus luteum in the ovary during its secretory phase, the endometium continues to grow to reach a
maximum thickness of 5-7 mm as measured from the muscle wall to the endometrial cavity. The
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total measurement from muscle wall to muscle wall as seen on ultrasound during treatment for
infertility will be about 10 mm.

In women with infertility undergoing ultrasonography, the total measurement of the two
endometrial layers with the endometrial cavity in between will come to about 10 – 15 mm. The
stromal cells continue to increase in size and number. Blood supply to the endometrium increases.

The important change in this phase occurs in the endometrial glands. The glands increase in size and
become actively secretory. Hence the name – 'secretory phase'. In the early stage, the secretions
collect in the cells of the glands.

But by the 19th to the 22nd day of the cycle, the secretions are pushed out of the cells and collect in
the endometrial cavity. This secretion is rich in glycogen, fructose and glucose. Its main function is to
supply nutrition to any fertilized ovum reaching the uterus.

Scheme of Ovarian cycle and Uterine cycle