Human Reproduction and Pregnancy

0 · Exam Blueprintread first

The course arc is Pringle's "make a baby → grow a baby → deliver a baby." Side 1 = make & cycle; side 2 = conceive → deliver.

Assessment: Assignment 1 educational resource (group) 40% · 5× online tests 10% · Formal Exam 50%.

Exam shape: 120 min · 80 marks = 30 MCQ (30) + 19 short-answer (50), Zoom-invigilated. Short-answer carries most marks ⇒ this sheet privileges mechanisms, feedback loops & sequences. Possible ~10-min Zoom viva on your rationale.

1 · Male Systemanatomy + glands

Scrotum keeps testes 2–3 °C below core (needed for spermatogenesis). Dartos (smooth, wrinkles skin) + cremaster (skeletal, raises testis) thermoregulate. Heat ↓ sperm (fever, varicocele, cryptorchidism).

Sperm pathway (memorise): seminiferous tubules → rete testis → efferent ductules → epididymis (mature + store) → vas deferens → ejaculatory duct → urethra.

Glands → semen: seminal vesicles (~60–70%; fructose, prostaglandins, alkaline) · prostate (citrate, PSA) · bulbourethral (pre-ejaculate mucus).

TRAP: sperm are made in tubules but mature & gain motility in the epididymis, not the testis. Vasectomy = cut vas deferens (production continues, no exit).

2 · Sertoli vs Leydighigh-yield

Mnemonic: FSH→Sertoli (Support); LH→Leydig. Blood–testis barrier (Sertoli tight junctions) hides haploid sperm from the immune system. ABP keeps local testosterone high for spermatogenesis.

2b · Sementhe ejaculate

Sperm + seminal plasma. ~1.5–5 mL, ~200 million sperm per ejaculate; only a few hundred reach the ampulla. Lost to vaginal acidity, leukocytes, wrong tube and the journey.

Plasma = fructose (energy), prostaglandins (stimulate female-tract motility), alkaline buffer (protects against vaginal acid), coagulation/liquefaction enzymes.

Low count/motility or abnormal morphology = common male-factor infertility — addressed by IUI, IVF or ICSI.

2c · Sex Determinationmodule 1

Bipotential gonad (~wk 6) branches on SRY (Y chromosome). SRY present → testis → Sertoli (AMH) + Leydig (testosterone → DHT) → Wolffian duct persists, Müllerian regresses → male.

SRY absent → ovary, no AMH → Müllerian persists (uterus, tubes) → female = the default pathway.

3 · Spermatogenesis2n → n · 4 sperm

In the seminiferous tubule wall, continuous from puberty, ~64–74 days. Cells move periphery → lumen as they mature.

1. Spermatogonium (2n) → mitosis → keeps stem pool + primary spermatocyte (2n)
2. Primary spermatocyte → meiosis I → 2× secondary spermatocyte (n)
3. Secondary spermatocyte → meiosis II → 2× spermatid (n)
4. Net 1 → 4 spermatids (4 functional sperm)

Spermiogenesis = final remodelling of round spermatid → spermatozoon: builds the acrosome (enzyme cap), condenses the nucleus, grows the flagellum + mitochondrial midpiece, sheds cytoplasm. No cell division.

TRAP: spermatogenesis = whole process; spermiogenesis = only the maturation step.

Mature sperm parts: head (condensed haploid nucleus + acrosome) · midpiece (mitochondria → ATP for the tail) · flagellum (propulsion). Meiosis I = reduction (2n→n, homologues separate); meiosis II separates sister chromatids.

4 · Female Systemtube + uterus

Ovary: cortex (follicles = reserve) + medulla; makes oestrogen, progesterone, inhibin. Tube: fimbriae → infundibulum → ampulla (fertilisation site) → isthmus → uterus.

Uterus wall: perimetrium → myometrium (labour muscle) → endometrium = functional layer (sheds) + basal layer (regenerates).

TRAP: fertilisation in the ampulla, not the uterus. Implantation in the endometrial functional layer. Ectopic = implantation outside the uterus (usually the tube).

Mammary gland: alveoli (milk-secreting) → lobules → lactiferous ducts → sinus → nipple; myoepithelial cells wrap the alveoli for ejection. Oestrogen grows ducts, progesterone grows alveoli.

The endometrium has a functional layer (the part that cycles, thickens and sheds) over a permanent basal layer that regenerates it each month from its stem cells.

5 · Oogenesisarrests · polar bodies

Begins in fetal life, finishes only at fertilisation.

1. Oogonium (2n) → mitosis (fetal) → primary oocyte (2n) starts meiosis I then ARRESTS at prophase I before birth (finite reserve)
2. Each cycle the LH surge → completes meiosis I → secondary oocyte (n) + 1st polar body
3. Secondary oocyte starts meiosis II then ARRESTS at metaphase II — this is ovulated
4. Meiosis II completes only if fertilised → ovum + 2nd polar body

Net 1 oogonium → 1 ovum (+ up to 3 polar bodies; cytoplasm conserved). Polar bodies take the discarded chromosomes.

Why arrest? Conserving cytoplasm gives the ovum its nutrient/organelle store; the long prophase-I arrest is also why older oocytes mis-segregate → ↑aneuploidy with maternal age.

Two LH-triggered events: the cycle's LH surge completes meiosis I (→ secondary oocyte); only fertilisation completes meiosis II — so the ovulated cell is always paused at metaphase II.

5b · Sperm vs Eggclassic compare

Both make haploid (n) gametes; differences are timing, number, symmetry, arrests.

6 · Folliculogenesismemorise the order

1. Primordial — oocyte + flat granulosa (resting reserve)
2. Primary — cuboidal granulosa; zona pellucida forms
3. Secondary — many granulosa layers + theca cells
4. Antral (tertiary) — fluid antrum appears
5. Graafian — mature, bulging → ovulation
6. Corpus luteum — luteinised remnant → progesterone + oestrogen
7. Corpus albicans — scar if no pregnancy → hormones fall → menses

Two-cell, two-gonadotropin model: LH → theca → androgens → diffuse to granulosa, where FSH → aromatase → oestrogen. Granulosa inhibin (⊖ FSH) selects ONE dominant follicle; rest undergo atresia.

TRAP: corpus luteum secretes mainly progesterone; rescued by hCG in pregnancy, else → corpus albicans.

Timing nuance: early follicle growth (months) is gonadotropin-independent; only the final ~2 weeks are FSH/LH-driven. The zona pellucida (laid down at the primary stage) is the same coat later bound by sperm at fertilisation.

Atresia: the dominant follicle's inhibin + oestrogen lower FSH, starving the other recruited follicles, which die by atresia — a built-in mechanism that usually limits ovulation to one egg per cycle.

7 · HPG Axis3 nodes

Hypothalamus → GnRH (pulsatile) → anterior pituitary → FSH + LH → gonads → steroids + inhibin.

Classes: GnRH/FSH/LH/prolactin/oxytocin = peptide (membrane receptors, fast). Oestrogen/progesterone/testosterone = steroid (intracellular receptors, slow).

TRAP: GnRH must be pulsatile — continuous GnRH downregulates the pituitary (basis of GnRH-agonist drugs).

HPG cascade (♀)Hypothalamus —GnRH→ Pituitary
—FSH/LH→ Ovary → E / P / inhibin
⊖ back on both nodes (default)

GnRH pulse frequency also tunes output: fast pulses favour LH, slow pulses favour FSH — the hypothalamus shapes the cycle by changing its rhythm, not just its amount.

7b · The Feedback Switch⊖ ⇄ ⊕

The same hormone (oestrogen) is inhibitory or stimulatory by its level + duration:

• Most of cycle: low/moderate E → ⊖ → GnRH/LH damped
• Mid-cycle: sustained HIGH E → ⊕ → GnRH/LH amplified → LH SURGE

This sign-flip makes ovulation a discrete, once-per-cycle event. Both the level and the duration of the oestrogen signal must cross threshold to flip the sign.

8 · Feedback & the LH SurgeTHE concept

Default = negative feedback: rising steroids ⊖ suppress GnRH + FSH/LH; inhibin ⊖ FSH selectively. Keeps the system stable, prevents over-recruitment.

The female-only switch: sustained HIGH oestrogen near mid-cycle flips to ⊕ positive feedback → massive LH surge (+ smaller FSH rise).

LH surge → ovulation (~within 18 h) · drives the oocyte to complete meiosis I → metaphase-II arrest · luteinises the follicle → corpus luteum.

TRAP: it is HIGH & sustained oestrogen that triggers the surge — low/moderate oestrogen is inhibitory. Males have NO surge (tonic, negative-feedback only, testosterone ~constant; inhibin still ⊖ FSH).

The full mid-cycle chain: dominant follicle → oestrogen climbs past a threshold & stays high → ⊖ flips to ⊕ → GnRH/LH amplified → LH surge → follicle ruptures (ovulation) → the emptied follicle luteinises → progesterone rises and re-imposes ⊖, preventing a second surge.

9 · Male HPG Axisno surge

Hypothalamus → GnRH → pituitary → LH→Leydig→testosterone; FSH→Sertoli→spermatogenesis + inhibin + ABP.

All feedback negative: testosterone ⊖ on both; inhibin ⊖ FSH only. No positive feedback, no LH surge ⇒ continuous, stable output (contrast with the cyclical female axis).

Testosterone is held roughly constant (small ultradian pulses); spermatogenesis runs continuously. The female axis instead builds toward a single monthly surge.

One-line contrast: ♂ = tonic, ⊖ only, continuous gametes; ♀ = cyclical, ⊖ plus one ⊕ surge, one gamete per cycle. Same hormones (GnRH, FSH, LH, inhibin) — different feedback architecture.

10 · Cycle Hormone Curveflagship figure

Read it off: FSH (green) rises early then dips; oestrogen (blue) peaks ~d12–13; LH (red) spikes at d14; progesterone (purple) only climbs after ovulation. The estrogen peak precedes and causes the LH spike. A common short-answer is simply "label the four curves and the surge."

Four-curve cheat: if no pregnancy, the corpus luteum regresses (~d26) → E + P both crash → spiral-artery spasm → menses (d1 of the next cycle). If pregnancy, hCG rescues the corpus luteum → progesterone stays high → no menses.

Colour key: blue = oestrogen, red = LH, green = FSH, purple = progesterone. The single tall red spike at day 14 is the diagnostic feature — narrower and taller than FSH's small mid-cycle bump.

11 · Ovarian Cycle~28 days

Follicular (d1–13): FSH↑ recruits follicles → oestrogen↑; inhibin restricts recruitment; one dominant follicle selected.

Ovulation (~d14): oestrogen peak → LH surge → Graafian follicle ruptures, releases the secondary oocyte.

Luteal (d15–28): corpus luteum → progesterone (+ oestrogen); no pregnancy → regresses (~d26) → P/E fall → menses.

TRAP: luteal phase length is fixed (~14 d) — cycle-length variation is in the follicular phase.

The corpus luteum has a built-in ~14-day lifespan unless rescued by hCG; that fixed timer is why progesterone falls on schedule and menses arrives ~14 d after ovulation.

12 · Uterine (Menstrual) Cycleendometrium

Integrated: FSH→follicles+E · E→proliferative + (high & sustained) the LH surge · LH surge→ovulation · P→secretory + maintains lining + ⊖ feedback · P falls → menstruation.

TRAP: progesterone peaks in the luteal/secretory phase (NOT ovulation); oestrogen peaks just before ovulation. Falling progesterone (not oestrogen alone) causes menses. Peak endometrial receptivity ~7 days post-ovulation.

13 · Puberty & the Switchmodule 3

Childhood HPG is suppressed; puberty = reawakening of pulsatile GnRH (kisspeptin-driven) → rising FSH/LH → gonadal steroids → secondary sex characteristics, growth spurt, menarche/spermarche.

TRAP: the capacity to reproduce (menarche/first ovulation, viable sperm) lags the first visible milestones — early puberty signs ≠ full fertility.

Adrenarche (adrenal androgens) and gonadarche (HPG reactivation) drive the visible changes; leptin signals adequate energy stores, linking body fat to the timing of puberty.

13b · Cycle Timing Mathscalculator OK

Luteal phase is fixed (~14 d), so ovulation ≈ cycle length − 14:

Longer cycles ⇒ later ovulation because the follicular phase lengthens, not the luteal one. Fertile window ≈ the 5 days before + day of ovulation (sperm survive ~3–5 d, oocyte ~24 h).

Ovulation signs: a urinary LH-surge test predicts ovulation ~1 day ahead; basal body temperature rises ~0.3–0.5 °C after ovulation (progesterone is thermogenic) — so BBT confirms, it does not predict. Cervical mucus turns clear & stretchy near ovulation (oestrogen effect).

14 · Hormone Source → Actionside-1 belt

15 · Steroid vs Peptidewhy it matters

Peptide (GnRH, FSH, LH, oxytocin, prolactin, hCG, inhibin): water-soluble, surface receptors, 2nd messengers (cAMP), fast & brief; stored in vesicles.

Steroid (oestrogen, progesterone, testosterone): lipid-soluble from cholesterol, intracellular receptors → alter gene transcription, slow & long-lasting; carried bound to plasma proteins.

Exam use: steroid lag explains why the proliferative/secretory endometrium responds over days, while the LH surge (peptide) acts within hours to trigger ovulation.

It also explains drug design: synthetic steroids (the pill) silently reset feedback over weeks; a peptide hCG "trigger" in IVF mimics the LH surge within hours.

Receptor logic: peptide hormones need a surface receptor on the target cell, so a tissue without that receptor ignores the signal; steroids diffuse into any cell but only act where the matching nuclear receptor + co-factors exist — selectivity comes from receptor expression, not hormone distribution.

This is why oestrogen acts on the endometrium, breast and bone alike (all express its receptor) while a peptide like FSH only hits gonadal cells carrying the FSH receptor.

16 · Side-1 Trap Listone glance

1. FSH→Sertoli (Support); LH→Leydig. Inhibin ⊖ FSH only.
2. Spermatogenesis = 4 sperm; oogenesis = 1 ovum + polar bodies. Arrests: prophase I then metaphase II.
3. HIGH sustained oestrogen = ⊕ → LH surge → ovulation. Low oestrogen = ⊖.
4. Two-cell model: theca→androgen (LH), granulosa→oestrogen (FSH).
5. Fertilisation in the ampulla. Progesterone peaks luteal, not ovulation.
6. Falling progesterone drives menstruation. Luteal phase fixed ~14 d.
7. GnRH must be pulsatile; continuous = pituitary shutdown.
8. Males: no LH surge, tonic axis.
9. Folliculogenesis order: primordial → primary → secondary → antral → Graafian → corpus luteum → albicans.
10. Sperm pathway: tubules → epididymis (mature) → vas → ejaculatory duct → urethra.

17 · Capacitation & Fertilisationin the ampulla

Epididymal maturation (in testis→duct): sperm gain motility, condensed DNA, zona-binding ability. Capacitation happens in the female tract: cholesterol/inhibitory proteins removed → ↑membrane fluidity, ↑Ca²⁺/cAMP → hyperactivated motility. Only capacitated sperm fertilise.

Fertilisation sequence:

1. Cumulus penetration by hyperactivated sperm
2. Zona binding to ZP glycoproteins (classically ZP3)
3. Acrosome reaction — releases acrosin/hyaluronidase to digest the zona
4. Membrane fusion with the oolemma

Fusion → oocyte completes meiosis II → maternal + paternal pronuclei → fuse → 2-cell zygote. Mitochondria are maternally inherited (paternal destroyed).

Sequence why it matters: capacitation enables hyperactivation; hyperactivation powers cumulus penetration; only zona contact triggers the acrosome reaction (so it cannot fire prematurely) — each step gates the next, securing one sperm into one receptive egg. Fertilisation also restores diploidy via pronuclear fusion.

18 · Blocks to Polyspermymonospermy

Fast block — transient oolemma depolarisation (seconds). Slow block (cortical / zona reaction) — Ca²⁺ wave → cortical granules harden the zona + alter ZP receptors → no further sperm bind. Polyspermy → lethal triploidy.

Zona roles: species-specific binding · polyspermy block · embryo protection · implantation timing.

Why monospermy matters: two sperm sets → triploid (3n), which is lethal/non-viable. The cortical (zona) reaction is the durable guarantee; the fast block just buys seconds.

The Ca²⁺ wave that triggers the cortical reaction also activates the egg — restarting meiosis II and beginning development. ICSI works because injecting the sperm reproduces this Ca²⁺ activation directly.

19 · Pre-Implantationtimeline

Zygote (d1) → cleavage (smaller cells, no growth) → d2 2-cell → d3 4–8-cell → d4 morula (solid) → d5 blastocyst (blastocoel + ICM + trophoblast) → hatches from zona (d5–6) before implanting.

Blastocyst: inner cell mass → embryo; trophoblast → placenta. TRAP: morula = solid; blastocyst = cavity + ICM/trophoblast split. Must hatch before implanting.

Anatomical track: ovary → ampulla (fertilisation) → oviduct (cleavage) → uterus (arrives ~blastocyst stage). Cilia + smooth muscle move it along; tube blockage (e.g. post-chlamydia) → ectopic risk.

Compaction (~d4): blastomeres maximise contact and polarise → this is the first cell-fate decision, splitting outer cells (→ trophectoderm/placenta) from inner cells (→ ICM/embryo). Totipotency is lost as cells specialise.

Twinning: two ovulated eggs → dizygotic (fraternal); one zygote splitting → monozygotic (identical) — timing of the split sets shared membranes.

Hatching: the blastocyst enzymatically thins and escapes the zona pellucida (~d5–6); only the now-exposed trophectoderm can contact and adhere to the endometrium.

20 · Implantation~day 6–7 · 3 stages

Into the endometrial functional layer during the secretory phase (progesterone-primed, receptive, pinopods present).

1. Apposition / adplantation — loose contact; ICM faces the endometrium
2. Adhesion — stable attachment via adhesion molecules; no longer dislodged
3. Invasion — syncytiotrophoblast breaches epithelium + basement membrane into stroma

Trophoblast splits: inner cytotrophoblast + outer multinucleate syncytiotrophoblast (invades AND makes hCG). Decidualisation = stromal cells → nutrient-rich, immune-tolerant decidua (progesterone-supported).

TRAP: order = Apposition → Adhesion → Invasion.

Implantation window: implantation needs BOTH a competent hatched blastocyst AND a receptive endometrium (secretory, progesterone-primed, pinopods) — a mistimed window is a cause of early loss/failed IVF transfer.

Normal site = posterior/superior uterine wall. Placenta praevia = low implantation over the cervix (bleeding risk); deep/abnormal invasion = placenta accreta.

21 · Placenta Structuremodule 8

Fetomaternal organ; functional unit = chorionic villus (fetal tissue bathed by maternal blood in the intervillous space). Haemochorial — maternal blood directly bathes the villi.

Maternal–fetal barrier (out→in): syncytiotrophoblast → cytotrophoblast → basal lamina → villous stroma → fetal capillary endothelium.

EVT & spiral arteries: extravillous trophoblast remodels maternal spiral arteries into wide, low-resistance, high-flow vessels. Failed remodelling → preeclampsia / IUGR.

TRAP: maternal & fetal blood do NOT mix — exchange is across the barrier only.

The barrier thins as pregnancy advances (cytotrophoblast becomes discontinuous) → shorter diffusion distance for late-gestation O₂/nutrient demand. Hofbauer cells in the villus stroma are placental macrophages. Umbilical cord = 2 arteries (deoxygenated, fetus→placenta) + 1 vein (oxygenated) in Wharton's jelly.

22 · Placental Transportmatch the mode

TRAP: amino acids are active ⇒ fetal AA can exceed maternal. Maternal IgG crosses (newborn passive immunity); IgM does not. Many drugs/alcohol/viruses cross.

Other roles: waste removal (urea, creatinine), an endocrine organ (§23), and an immune interface that must tolerate the semi-allogeneic fetus (progesterone is immunomodulatory/anti-inflammatory).

Gradient rule: diffusion (O₂, CO₂, glucose) always runs down a gradient; only active transport (amino acids, Ca²⁺, Fe) can move solute up a gradient, using ATP — which is why fetal levels of those can exceed maternal.

23 · Pregnancy Hormonesplacental endocrine

Luteal–placental shift (~wk 6–9): early progesterone from the hCG-rescued corpus luteum; then the placenta takes over (CL no longer essential).

TRAP: hCG keeps the corpus luteum alive (not the placenta directly). hPL causes the insulin resistance behind gestational diabetes. Low estriol can signal fetal compromise.

Estriol needs both: the fetal adrenal makes DHEAS, the placenta aromatises it → estriol is a read-out of a healthy fetoplacental unit, which is why it falls with fetal compromise.

Progesterone = "pro-gestation": relaxes the myometrium, supports the decidua, blocks lactation until birth, and is anti-inflammatory/immunomodulatory — its functional withdrawal is what later permits labour.

24 · Maternal Adaptationsmodule 9

• CV: blood volume ↑30–50% (plasma ↑ > RBC ↑ → dilutional anaemia); CO ↑30–50% (early ↑HR, later ↑SV); ↓SVR → BP falls, lowest mid-pregnancy
• Resp: ↑tidal volume (progesterone) → mild respiratory alkalosis (↓PaCO₂ aids fetal CO₂ offload)
• Renal: ↑GFR/RPF ~50% → ↓creatinine/urea; mild glucosuria
• Metabolic: insulin resistance (hPL) spares glucose for fetus

TRAP: pregnancy anaemia is dilutional = normal, not pathology. A failure of BP to fall, or rising BP, flags preeclampsia.

Cardiac outputCO = HR × SV
↑ ~30–50% in pregnancy
(early via ↑HR, later via ↑SV)

24b · DOHaDBarker

An adverse in-utero environment programmes later disease (CVD, T2DM, obesity). Thrifty phenotype: a nutrient-restricted fetus adapts to scarcity; a postnatal mismatch with plenty → metabolic disease. Mediated by epigenetic change (DNA methylation), e.g. reduced nephron number.

TRAP: it is the mismatch that harms; low birth weight is the classic marker.

Screening vs diagnostic: screening (e.g. NIPT, combined first-trimester) estimates risk — judged by sensitivity/specificity/false-positive rate; diagnostic (CVS, amniocentesis) is definitive but invasive (miscarriage risk). A positive screen needs a confirmatory diagnostic.

Calculator note: sensitivity = true positives / all affected; specificity = true negatives / all unaffected; a false positive is a high-risk screen in an unaffected pregnancy — high sensitivity catches cases, high specificity avoids needless invasive tests.

25 · Onset of Labour4 drivers

1. Progesterone functional withdrawal — its quiescence action falls near term → myometrial excitability ↑
2. Oestrogen priming — ↑oxytocin receptors + ↑gap junctions (coordinated contraction)
3. Oxytocin positive feedback (the loop, §26)
4. Prostaglandins — fetal membranes → cervical ripening + ↑contraction strength

TRAP: in humans it is a functional/relative progesterone withdrawal (not always a blood-level drop). Oestrogen primes, it does not directly contract. Contrast: many animals show an absolute progesterone fall before labour.

Triggers behind the functional withdrawal: inflammation, placental senescence, uterine distension and fetal/maternal stress (fetal cortisol via the HPA axis) — together they convert a quiescent uterus to a contractile one.

26 · Oxytocin ⊕ Loopthe exemplar

Contraction → fetal head onto cervix → cervical stretch → brain → posterior pituitary releases OXYTOCIN → blood → stronger contraction → more stretch… Self-amplifying; broken only by delivery (the stop signal).

Oxytocin from posterior pituitary (made in hypothalamus). Synthetic oxytocin (Syntocinon) = uterotonic to induce/augment labour & prevent PPH. THE textbook positive-feedback example.

Contrast: most homeostasis is negative feedback (returns to set-point); this ⊕ loop deliberately runs away from set-point to completion — like the LH surge and the clotting cascade.

The afferent limb (cervical stretch → hypothalamus → posterior pituitary) is the Ferguson reflex; oxytocin is the efferent signal that closes the loop on the myometrium.

27 · Stages of Labour3 stages

• 1 · Dilation — onset → full cervical dilation (10 cm); longest
• 2 · Expulsion — full dilation → delivery of baby
• 3 · Placental — delivery of placenta (oxytocin contraction limits bleeding)

TRAP: cervix fully dilated at 10 cm. Stage-3 failure → retained placenta / PPH (postpartum haemorrhage, often uterine atony). Stage 1 = latent (slow, to ~6 cm) then active (faster).

28 · Lactationtwo-hormone split

Pregnancy: oestrogen (ducts) + progesterone (alveoli) + prolactin prepare the breast, but high progesterone blocks milk synthesis. After birth progesterone falls → brake released.

Prolactin (ant. pit.) MAKES milk (sustained by suckling → ↓dopamine → ↑prolactin). Oxytocin (post. pit.) EJECTS milk (let-down: contracts myoepithelial cells). Don't swap them.

Let-down can be conditioned (baby crying) and inhibited by stress. TRAP: retained placental fragments keep progesterone up → delay lactogenesis. Colostrum (IgA-rich) precedes mature milk.

High prolactin during breastfeeding suppresses GnRH → lactational amenorrhoea (a natural, partial fertility brake). Suckling drives both hormones — the more the infant feeds, the more milk is made and ejected (a supply-and-demand loop).

29 · Fetal Circulation3 shunts

Why: lungs fluid-filled, high pulmonary resistance; placenta is the O₂ source → bypass lungs + liver.

1. Placenta → umbilical vein (oxygenated!) → DUCTUS VENOSUS (bypasses liver) → IVC → right atrium
2. FORAMEN OVALE (RA → LA, bypasses lungs) → LV → aorta → brain (best-oxygenated)
3. Pulmonary artery → DUCTUS ARTERIOSUS (PA → aorta, bypasses lungs) → body → umbilical arteries → placenta

Most-oxygenated blood is preferentially streamed (via the foramen ovale) to the left heart → aorta → brain & coronaries, while less-oxygenated blood is shunted through the ductus arteriosus to the lower body and back to the placenta.

At birth: first breath → lungs inflate → PVR drops; LA pressure ↑ → foramen ovale closes (fossa ovalis); ↑O₂ → ductus arteriosus closes (lig. arteriosum); ductus venosus closes (lig. venosum).

TRAP: ductus venosus → liver; foramen ovale + ductus arteriosus → lungs. Umbilical VEIN = oxygenated (reverse of usual). Failures: PFO, PDA.

30 · Fetal HaemoglobinHbF

HbF has higher O₂ affinity than adult HbA → a left-shifted dissociation curve → at the low placental PO₂ it pulls O₂ off maternal Hb across the placenta.

HbF is replaced by HbA over the first ~6 months of life. At the placental working PO₂ (~25–30 mmHg) HbF sits at higher saturation than HbA — the gradient that drives O₂ transfer to the fetus.

Why left-shift: HbF binds 2,3-BPG weakly, so it holds O₂ more tightly. Combined with a higher fetal Hb concentration, this maximises O₂ uptake from the relatively hypoxic maternal blood.

30b · Birth Transitionneonate · module 11

First breath → lungs inflate → PVR drops; cord clamp → SVR rises → pressures reverse → shunts close. Other transitions: thermoregulation begins (brown fat), independent glucose handling, gut/liver take over (jaundice if immature).

TRAP: persistent shunts = PFO / PDA; ductus arteriosus is kept open by prostaglandins (PGE₂) — indomethacin closes it. Closure order: ductus venosus (minutes) → foramen ovale (functional, with the pressure flip) → ductus arteriosus (hours–days). Remnants: fossa ovalis, lig. arteriosum, lig. venosum.

31 · Reproductive Ageingmodule 6

Female: ovarian reserve + oocyte quality fall → ↑aneuploidy with maternal age (non-disjunction in long-arrested oocytes). Menopause = follicle depletion → ↓oestrogen/inhibin → loss of ⊖ → ↑FSH/LH (high FSH = marker).

Male: more gradual decline in testosterone & sperm quality; paternal age raises some new (de novo) mutations. No abrupt "andropause" equivalent of menopause.

TRAP: postmenopausal FSH is HIGH (counterintuitive) — no inhibin/oestrogen to give negative feedback. Trisomy 21 risk rises sharply with maternal age via meiotic non-disjunction.

Reserve markers: AMH (from small follicles) and antral follicle count estimate remaining reserve and predict IVF response; both fall with age. Menopause = ~12 months without menses.

32 · Contraceptionmodule 3

• Hormonal (pill, POP, implant, injection, hormonal IUD) — ⊖ feedback suppresses FSH/LH → no LH surge → no ovulation; thickens cervical mucus; thins endometrium
• Barrier — condoms (only these reduce STIs), diaphragm
• IUD — copper (spermicidal/inflammatory) or hormonal
• Emergency — levonorgestrel delays ovulation
• Sterilisation — tubal ligation; vasectomy (cut vas)
• Emerging male — testosterone ± progestogen suppress spermatogenesis (⊖ feedback)

Common thread: most hormonal methods exploit the same physiology this sheet covers — feed back negatively to block the LH surge, so no ovulation occurs. Only condoms also protect against STIs.

33 · ART / IVFmodule 6

IVF steps: (1) ovarian stimulation (FSH grows many follicles) + GnRH agonist/antagonist to block a premature surge; (2) hCG "trigger" mimics the LH surge → final maturation; (3) oocyte retrieval; (4) IVF; (5) culture; (6) embryo transfer + luteal progesterone support.

ICSI — single sperm injected; for male-factor infertility. PGT/PGD — genetic testing pre-transfer.

TRAP: the hCG trigger substitutes for the natural LH surge. ICSI is for male-factor, not routine.

IVM matures immature oocytes in vitro (avoids high-dose stimulation). IUI = prepared sperm placed in the uterus (mild cases). Luteal progesterone support replaces the corpus luteum the cycle would have made.

34 · Complications & STIsmodule 5/10

Preeclampsia ← failed EVT spiral-artery remodelling → placental ischaemia (HTN + proteinuria >20 wk). IUGR, gestational diabetes (hPL), miscarriage (often chromosomal), placenta praevia vs accreta, preterm labour, PPH.

Drugs: tocolytics STOP contractions; uterotonics CAUSE them. Targeted drug delivery (e.g. to the placenta/uterus) aims to treat the mother or fetus while sparing the other.

STIs: bacterial (chlamydia, gonorrhoea, syphilis) = curable (antibiotics); viral (HIV, HSV, HPV→cervical Ca, HepB) = managed, not cured. Chlamydia = silent cause of PID → tubal infertility & ectopic risk; HPV vaccine prevents.

35 · Side-2 Trap Listone glance

1. Capacitation in the female tract, not before.
2. Implantation Apposition→Adhesion→Invasion; syncytiotrophoblast invades + makes hCG.
3. hCG rescues the corpus luteum; luteal–placental shift wk 6–9.
4. 3 shunts: ductus venosus→liver; foramen ovale + ductus arteriosus→lungs. Umbilical vein = oxygenated.
5. Prolactin makes, oxytocin ejects milk. Oxytocin loop = ⊕ feedback.
6. Pregnancy anaemia = dilutional/normal; postmenopausal FSH high.