Menstrual cycle

Question 1

What are the aims of the menstrual cycle?

Answer 1

• selection of a single oocyte
• correct number of chromosomes in eggs i.e. haploid
• regular spontaneous ovulation

Question 2

What are the aims of the menstrual cycle? part 2

Answer 2

• cyclical changes in the vagina, cervix and Fallopian tube
• preparation of the uterus
• support of the fertilised dividing egg

Question 3

What is the relationship between GnRH and LH for the menstrual cycle?

Answer 3

GnRH needs to be pulsatile, this leads to an increase (and decrease) of LH

Question 4

The menstrual cycle

Answer 4

• 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 5

Cycle length

Answer 5

Clinically you should ask a women how long there cycle is from the 1st day of bleeding to the 1st day of bleeding in the next cycle – NOT do you have regular cycles!
• 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 6

Hypothalamic/pituitary/ovarian axis

Answer 6

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 7

Window of opportunity

Answer 7

Key part of whole thing………not anything wrong with the other follicles – they are just at the exact stage of development when FSH goes up and then as FSH declines, other follicles die. This occurs because selected follicle double in size every 24hrs and makes lots of E2 – which exerts negative feedback on H-P to decrease FSH.

Question 8

Follicle selection

Answer 8

• 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

Question 9

Dominant follicle selection

Answer 9

• As FSH falls, LH increases. Dominant follicle acquires LH receptors on granulosa cells
• Other follicles do not, so they lose their stimulant and die

Question 10

Dominant follicle

Answer 10

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 11

LH surge

Answer 11

• 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 12

Ovulation part 1

Answer 12

• 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

Question 13

Meiosis & Extrusion of the Polar Body

Answer 13

• 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 14

Secondary Oocyte

Answer 14

• 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

Question 15

Corpus luteum formation

Answer 15

• 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 16

Ovulation part 2

Answer 16

• 12-18 hrs after peak of LH, the follicle wall is digested and ovulation occurs with release of cumulus-oocyte complex (COC)
• 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

Question 17

Secretions of CL

Answer 17

•	progesterone: 
	supports oocyte in its journey
	Maintains the CL
	prepares the endometrium
	controls cells in Fallopian tubes
	alters secretions of cervix
•	oestradiol:
	for endometrium

Question 18

Demise of CL

Answer 18

• 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 19

Physical aspects of the menstrual cycle

Answer 19

• 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 20

Signs of ovulation

Answer 20

• 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

–      Tender breasts
–	Abdominal bloating
–	Light spotting
–	Changes in cervical mucus
–	Slight pain or ache on one side of the abdomen

Question 21

Ovulation prediction kits

Answer 21

• 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