The Menstrual Cycle

Question 1

Follicular phase

Answer 1

the phase of the menstrual cycle associated with growth of the follicles and selection of the dominant follicle. It is characterised by oestrogen production.

Question 2

Ovulation

Answer 2

the release of a mature haploid oocyte from the dominant follicle in response to a surge in LH

Question 3

Luteal phase

Answer 3

the phase of the menstrual cycle associated with formation the corpus luteum after ovulation. It is characterised by progesterone production

Question 4

Dominant follicle

Answer 4

the follicle that is selected from the growing cohort of antral follicles to become the pre-ovulatory follicle and release a mature egg at ovulation

Question 5

Corpus luteum

Answer 5

the structure formed from the granulosa and theca cells of the follicle after ovulation, which is triggered by the surge in LH and causes luteinisation of the granulosa and theca cells.

Question 6

Menses

Answer 6

the shedding of the endometrial tissue lining along with blood

Question 7

Polar body

Answer 7

the small structure contains half the chromosomes after the completion of meiosis I.

Question 8

What are the aims of the menstrual cycle?

Answer 8

• selection of a single oocyte
• correct number of chromosomes in eggs i.e. haploid
• regular spontaneous ovulation
• cyclical changes in the vagina, cervix and Fallopian tube
• preparation of the uterus
• support of the fertilised dividing egg

Question 9

Control of Menstrual Cycle

Answer 9

diagram

Question 10

GnRH has to be pulsatile

Answer 10

diagrams

Question 11

the menstrual cycle summary

Answer 11

diagram
•In a 28-day cycle day 1 is typically the 1st day of menses
•Follicular phase = growth of follicles up to ovulation → dominated by
oestradiol production from follicles
•Luteal phase = formation of corpus luteum from the empty follicle →
dominated by progesterone production from corpus luteum

Question 12

Menstrual Cycle

Answer 12

• 2 phases separated by ovulation
• Cycle begins on day 1=first day of bleeding
• Next 14 days are follicular phase i.e. growth of antral
follicles
• Ovulation occurs at end of the follicular phase (i.e. in
the middle of the cycle)
• Remnant of the follicle becomes the corpus luteum
• Next 14 days are luteal phase i.e dominated by corpus
luteum
• Menstruation occurs at the end if there is no pregnancy

Question 13

hypothalamic/ pituitary/ ovarian axis

Answer 13

diagram
Luteal phase=Negative feedback → Progesterone
Follicular phase=variable
1. Release of negative feedback
2. Negative feedback then reinstated, then
3. Switch from negative to positive feedback

Question 14

phases and cycle

Answer 14

diagram

Question 15

The Inter-Cycle Rise in FSH

Answer 15

diagram
The inter-cycle rise and fall in FSH is very important because it allows selection of a single follicle, which will go onto become the dominant follicle that will ovulate

Question 16

The window of opportunity

Answer 16

diagram

Question 17

Follicle Selection

Answer 17

• Raised FSH present a “window” of opportunity to recruit antral follicles that are at the right stage to continue growth
• FSH threshold hypothesis
– One follicle from the group of antral follicles in ovary is just at the right stage at the right time to survive declining FSH
– This becomes the dominant follicle which goes onto ovulate
– Known as “selection”
– Can be in either ovary
• Oestradiol levels rise reinstating negative feedback at pituitary causing FSH levels to fall prevents further follicle growth
How does the dominant follicle survive the fall in FSH?

Question 18

Dominant Follicle Selection - LH

Answer 18

diagram
• As FSH falls, LH increases. Dominant follicle acquires LH receptors on granulosa
cells
• Other follicles do not, so they lose their stimulant and die
*(look at the steroidogenesis slide in the folliculogenesis lecture)

Question 19

The Dominant Follicle characteristics

Answer 19

Dominant follicle survives fall in FSH by
• increases sensitivity to FSH = increased FSH receptors
• increased numbers of granulosa cells
» 2-5 million GC in EFP and 50-100 million at ovulation
» increases E2 production because of increased aromatase levels
» 200x more E2 in DF than in others
• acquisition of LH receptors
» the LHR (LH receptor) gene is switched on by FSH

Question 20

steroidogenesis

Answer 20

diagram

Question 21

LH surge

Answer 21

• Throughout follicular phase E2 feedback was negative
• At end of follicular phase if E2 levels raised for long enough
(48h) and high enough (>300pM) enough → feedback switches from negative to positive
• Causes massive release of LH from pituitary
• Exponential rise in LH in serum
• Triggers ovulation cascade
- Egg is released
- Above result in changes in follicle cells = luteinisation i.e. formation of
the corpus luteum
- Corpus luteum has both luteinised granulosa and theca cells
- E2 production falls, but still produced and P is stimulated & dominates

Question 22

Ovulation

Answer 22

• ovulation occurs via cascade of events:
– blood flow to the follicle increases dramatically
– appearance of apex or stigma on ovary wall
– Local release of proteases and inflammatory mediators
– Enzymatic breakdown of protein of the ovary wall
• 12-18 hrs after peak of LH, the follicle wall is digested and ovulation occurs with release of cumulus-oocyte
complex (COC)

Question 23

Ovulation cont…

Answer 23

• Oocyte with cumulus cells is extruded from the ovary
• Follicular fluid may pour into Pouch of Douglas
• egg ‘collected’ by fimbria of Fallopian tube
• egg progresses down tube by peristalsis and action of cilia
diagrams

Question 24

Meiosis & Extrusion of the Polar Body

Answer 24

• In response to the LH surge, the nucleus of the oocyte in the dominant follicle completes the first meiotic division.
• ½ the chromosomes are put into a small “package” in the egg called the 1st polar body
• The egg (with most of the cytoplasm) is now a secondary oocyte
• The 1st polar body plays no further part in the process and does not divide again
• Oocyte begins the 2nd meiotic division, but arrests again.

Question 25

Secondary Oocyte

Answer 25

* Unlike sperm we only want a single oocyte * The oocyte is the largest cell in the body (sperm are smallest.....but fastest!) * The oocyte has to support all of the early cell divisions of the dividing embryo until it establishes attachment to the placenta * Spends 2-3 days in the uterine tube * So the oocyte is now on its way into the tube....will it meet a sperm? The story continues later...

Question 26

corpus luteum formation

Answer 26

* after ovulation the follicle collapses * corpus luteum is formed, ‘yellow body’ * progesterone production increases greatly, also E2 * CL contains large numbers of LH receptors * CL supported by LH and hCG (from implanting embryo, if a pregnancy occurs) which also bind to LHR

Question 27

Hormone Changes during Pregnancy

Answer 27

diagrams

Question 28

CL secretion (8) and demise (4)

Answer 28

``` secretions of CL • progesterone: – supports oocyte in its journey – Maintains the CL – prepares the endometrium – controls cells in Fallopian tubes – alters secretions of cervix • oestradiol: – for endometrium ``` demise of CL • If fertilisation does not occur, CL has finite lifespan of 14 days. • removal of CL essential to initiate new cycle • Cell death occurs, vasculature breakdown, CL shrinks • Process is not well understood

Question 29

clinical applications – all centre around the | concept of feedback

Answer 29

diagram

Question 30

Hypothalamic/pituitary/ovarian axis

Answer 30

diagram

Question 31

the menstrual cycle days

Answer 31

• Day 1 is first day of bleeding •Menstruation lasts 3-8 days, written in notes as 7/28 or 5-6/27-32 •Regular cycle should have no more than 4 days variation from month to month

Question 32

How does a patient work out when they are | going to ovulate?

Answer 32

How does a patient work out when they are going to ovulate? • If cycles are regular then it’s easy • But if cycles are irregular? • Question – if a woman has a 32-day cycle on what day will she ovulate? • If having intercourse 3 times/week probably OK....but many will not be • Ultrasound monitoring if having induction of ovulation, How does a patient work out when they are going to ovulate?

Question 33

Signs of Ovulation

Answer 33

• A slight rise in basal body temperature, typically 0.5 to 1 degree, measured by a thermometer – Need to keep a chart of basal body temp from day 1 of LMP – Why? diagrams • Tender breasts • Abdominal bloating • Light spotting • Changes in cervical mucus • Slight pain or ache on one side of the abdomen

Question 34

Ovulation prediction

Answer 34

• Ovulation prediction kits – Fertile period spans 6 days and is affected by: • Lifespan of the egg → up to 24h after ovulation • Lifespan of sperm → median=1.5days but sperm can survive up to 5 days in the sperm supportive mucus of fertile days of cycle » sperm survival is dependent on the type & quantity of mucus within cervix AND the quality of the sperm E3G is urinary metabolite of oestradiol, allowing women to identify days of high fertility leading up to ovulation diagrams

Question 35

Main Points To Remember

Answer 35

* Inter-cycle rise in FSH followed by slow decline * slow rise in LH in follicular phase to exponential mid-cycle rise * 2 peaks in oestradiol- different shapes -------- * single luteal phase rise in progesterone -------- diagrams