Appearance
15.4 — Egg Production and the Menstrual Cycle
A female fetus has about 6 to 7 million eggs at 20 weeks of gestation. That is the peak, and it occurs before she is born. By birth there are 1 to 2 million; by puberty around 300,000 to 400,000; and around 1,000 at menopause.
Only about 400 are ever ovulated. The rest are lost by attrition — a continuous programmed die-off that runs from before birth until the supply is exhausted, regardless of pregnancies, contraception or anything else.
Menopause is therefore not the ovaries switching off. It is running out (Chapter 12.6).
Eggs, and why maternal age matters
All eggs enter meiosis before birth and then stop, arrested in prophase of meiosis I (Chapter 1.7).
They stay arrested until the month they are ovulated.
So an egg ovulated at 40 has been held in mid-division for four decades.
And that is the mechanism behind the maternal age effect. The protein complexes holding the chromosome pairs together degrade over time, so separation errors become progressively likelier — hence the rise in trisomy with maternal age (Chapter 1.7).
Meiosis I completes only at ovulation, and meiosis II only if fertilisation occurs (Chapter 4.3). An unfertilised egg never finishes dividing.
And the division is deliberately unequal. One daughter cell takes almost all the cytoplasm and the other becomes a tiny polar body that is discarded. The egg needs its stores — everything the embryo runs on for the first days comes from it — so the material is not split evenly. Sperm discard their cytoplasm; eggs hoard it.
Follicle development
A follicle is an egg plus its surrounding support cells, and its development takes far longer than one cycle.
The full journey from a dormant primordial follicle to ovulation takes around 6 months — so the follicle ovulated this month began developing half a year ago, and anything affecting egg quality has been acting over that period.
Around 15 to 20 follicles begin the final race each cycle. One is selected. The rest die.
And the selection mechanism is elegant. All the recruited follicles compete for FSH. As they grow they produce oestrogen and inhibin, which suppress FSH. The follicle with the most FSH receptors keeps growing on the falling FSH level; the others cannot and undergo atresia.
So the cohort collectively switches off the signal they all depend on, and only the most sensitive survives it. A self-limiting competition with no external referee.
Which is exactly what fertility drugs override. Giving high-dose FSH prevents the level falling, so the whole cohort continues developing — producing the multiple eggs needed for IVF, and the multiple pregnancies that occur when ovulation induction is not carefully controlled.
The cycle
Average 28 days, and normal is 21 to 35 days, with substantial variation between and within individuals.
The convention is that day 1 is the first day of bleeding.
And there is an asymmetry worth knowing. The luteal phase — after ovulation — is fixed at 14 days, give or take a day. The follicular phase varies.
So a woman with a 35-day cycle ovulates around day 21, not day 17. Which means "ovulation happens on day 14" is only true for a 28-day cycle, and assuming it is a common source of error in both conception attempts and calendar-based contraception.
Follicular phase (day 1 to ovulation)
FSH rises, recruiting follicles.
Growing follicles produce oestrogen, which rises steadily.
Oestrogen does three things: it thickens the endometrium, it thins the cervical mucus, and it feeds back to suppress FSH.
Ovulation (around day 14 in a 28-day cycle)
And here the system does something it does nowhere else: it switches to positive feedback.
Oestrogen normally suppresses LH. But when oestrogen exceeds a threshold and stays there for around 48 hours, the effect reverses and it stimulates LH instead (Chapter 4.7).
The result is an explosive LH surge, and it triggers everything:
Meiosis I completes.
Enzymes digest the follicle wall.
The follicle ruptures and the egg is released, swept up by the fimbriae (Chapter 15.3).
Ovulation occurs about 36 hours after the LH surge begins and about 12 hours after its peak.
Which is exactly what an ovulation predictor kit detects — LH in the urine. A positive test means ovulation in roughly the next 24 to 36 hours, which is why it is used to time intercourse rather than to confirm it happened.
Mittelschmerz — mid-cycle pain — occurs in around 20 percent of women, from the follicle rupturing and a small amount of blood irritating the peritoneum. Usually one-sided, and it alternates unpredictably between sides rather than regularly.
Luteal phase (ovulation to day 28)
The ruptured follicle becomes the corpus luteum — "yellow body" — which produces progesterone and oestrogen.
Progesterone:
Converts the endometrium from proliferative to secretory — the glands become tortuous and secrete glycogen, preparing to nourish an embryo before the placenta exists.
Thickens the cervical mucus into a barrier.
Raises basal body temperature by 0.3 to 0.5 °C — which is the basis of temperature-based cycle tracking, and note that the rise confirms ovulation after the fact rather than predicting it.
And the corpus luteum has a built-in lifespan of about 14 days.
If there is no pregnancy, it degenerates. Progesterone and oestrogen collapse.
If there is a pregnancy, hCG from the implanting embryo rescues it (Chapter 4.3), and it continues producing progesterone until the placenta takes over at around 8 to 10 weeks.
Which is why hCG is what a pregnancy test detects, and why its whole purpose is to prevent the period that would otherwise end the pregnancy before it was known.
Menstruation
Falling progesterone causes the spiral arteries to constrict.
The endometrium becomes ischaemic and dies. The arteries then relax and the necrotic tissue is shed with bleeding.
So a period is the shedding of a lining that was built for an implantation that did not happen.
Blood loss is normally 30 to 40 ml — "heavy" is defined as over 80 ml, though in practice it is defined by whether it interferes with life.
Duration 3 to 7 days.
And menstrual blood does not clot in the normal way, because the endometrium releases fibrinolytic enzymes. Clots that do appear indicate flow heavy enough to overwhelm them — which is why passing clots larger than a 10-pence coin is one of the practical markers of heavy bleeding.
And humans are unusual in menstruating at all. Most mammals reabsorb the endometrium rather than shedding it. Menstruation occurs in humans, some other primates, a few bats and the elephant shrew.
The leading explanation is that human implantation is unusually invasive (Chapter 4.3) — so the endometrium must be prepared in advance rather than in response to an embryo, and preparing it every cycle means discarding it every cycle. The maternal–fetal relationship in humans is closer to a negotiation than a partnership, and menstruation appears to be part of the cost.
Period problems
Dysmenorrhoea — painful periods.
Primary — no underlying disease. Caused by prostaglandins produced by the shedding endometrium, causing intense uterine contractions and local ischaemia — the pain is genuinely ischaemic, like angina in the uterus.
Which is exactly why NSAIDs work well, and why they work best started before the pain becomes established, since they block prostaglandin production rather than the pain (Chapter 13.4).
Secondary — from endometriosis, fibroids, adenomyosis, or infection. Suggested by pain that begins later in life, worsens over time, occurs outside periods, or is accompanied by pain during sex.
And the most important point here is a cultural one. Period pain severe enough to prevent school, work or normal activity is not normal and should be investigated. Normalising it is the main reason endometriosis takes 7 to 10 years to diagnose (Chapter 15.3).
Heavy menstrual bleeding — affects around 1 in 4 women.
Causes: fibroids, adenomyosis, polyps, bleeding disorders — von Willebrand disease is found in a meaningful proportion of women with heavy periods since menarche and is frequently undiagnosed — thyroid disease, and often none identified.
And it is a leading cause of iron deficiency anaemia in women (Chapter 7.1), which is worth checking rather than assuming.
Treatments, in order of invasiveness: tranexamic acid, which reduces loss by around 50 percent taken only during the period; NSAIDs, around 30 percent; the hormonal intrauterine system, around 90 percent and now first-line for most women; hormonal contraception; and surgical options.
Amenorrhoea — absent periods.
Primary — no period by 15 with normal secondary sexual development, or by 13 with none.
Secondary — periods stopping for 3 months or more.
And the first test in secondary amenorrhoea is always a pregnancy test, whatever the history.
Other causes: functional hypothalamic amenorrhoea — from low body weight, excessive exercise, or stress, in which GnRH pulsing shuts down; polycystic ovary syndrome (Chapter 12.6); high prolactin (Chapter 12.2); thyroid disease; and premature ovarian insufficiency.
Functional hypothalamic amenorrhoea deserves emphasis because it is common in athletes and in restrictive eating, and it is not benign. The oestrogen deficiency causes bone loss at exactly the age peak bone mass should be accumulating (Chapter 5.1), and that loss is not fully recoverable. The combination of low energy availability, menstrual disturbance and low bone density is a recognised syndrome and is a genuine health problem rather than a sign of fitness.
Premenstrual syndrome — physical and mood symptoms in the luteal phase, resolving with the period. Affects a large proportion of women to some degree.
Premenstrual dysphoric disorder is the severe form, affecting 3 to 8 percent, with mood symptoms severe enough to disrupt functioning and relationships.
And it is not a normal cycle experienced badly. The evidence indicates an abnormal central response to normal hormonal fluctuation rather than abnormal hormone levels — which is why measuring hormones is unhelpful and why treatment targets the response.
SSRIs are effective, often at low dose and often taken only in the luteal phase — which is unusual, since in depression they take weeks. Suppressing ovulation with hormonal contraception also works.
Tracking the cycle
Three signs, and their reliability differs.
Cervical mucus — the most useful single sign. Dry or sticky after the period; then increasingly wet, clear and stretchy — like raw egg white — around ovulation; then thick and scant afterwards.
Basal body temperature — a rise of 0.3 to 0.5 °C after ovulation. Confirms rather than predicts.
Calendar tracking — least reliable alone, given the variability described above.
Fertility awareness methods combining all three, taught properly and used consistently, achieve failure rates of around 1 to 5 percent with perfect use and considerably higher with typical use (Chapter 15.11).
And cycle tracking apps deserve a caution. Most predict ovulation from calendar data alone using an assumed 14-day pattern, which is exactly the assumption that fails. Apps used for contraception should be ones that incorporate temperature or mucus data and have been formally evaluated.
There is also a genuine privacy dimension: cycle app data is health data, has been commercially shared, and in some jurisdictions has legal implications. It is worth knowing what an app does with it.
What the next page fixes
The reproductive systems of both sexes have now been described. Chapter 15.5 covers what happens when they meet — the physiology of arousal and orgasm, what is actually known and what is asserted, and the common problems and their treatments.