Membership of the Royal College of Obstetricians and Gynaecologists (MRCOG) Basic and Applied Sciences for Reproductive Health (Part 1 Foundations) Syllabus

What endocrine changes define the menopause?

Ovarian follicular depletion causes a fall in oestradiol and inhibin B, releasing the pituitary from negative feedback so FSH rises (diagnostic FSH $> 30\ \text{IU/L}$, and $> \text{LH}$). Menopause is defined retrospectively after $12$ months of amenorrhoea; average age ~$51$ years.

Outline the stages of spermatogenesis and its duration.

Spermatogonia (mitosis) → primary spermatocytes (meiosis I) → secondary spermatocytes (meiosis II) → spermatids → spermatozoa (spermiogenesis). The full cycle takes ~$70\text{-}74$ days, occurring in seminiferous tubules supported by Sertoli cells; Leydig cells produce testosterone under LH.

What are the roles of FSH and LH in the male, and of Sertoli versus Leydig cells?

LH acts on Leydig cells to produce testosterone. FSH acts on Sertoli cells to support spermatogenesis and produce inhibin (negative feedback on FSH) and androgen-binding protein. Sertoli cells form the blood-testis barrier.

Summarise the maternal cardiovascular adaptations to pregnancy (cardiac output, SVR, BP, blood volume).

Cardiac output rises ~$40\text{-}50\%$ (increased stroke volume then heart rate); systemic vascular resistance falls; blood pressure drops in the 2nd trimester then returns to baseline; plasma volume increases ~$50\%$ and red cell mass ~$20\text{-}30\%$.

Why does physiological anaemia of pregnancy occur and what defines anaemia in each trimester?

Plasma volume rises proportionally more than red cell mass, causing a dilutional fall in haemoglobin concentration. WHO/UK thresholds: $1^{st}$ trimester $< 110\ \text{g/L}$, $2^{nd}/3^{rd}$ trimester $< 105\ \text{g/L}$, postpartum $< 100\ \text{g/L}$.

Describe the respiratory adaptations to pregnancy.

Tidal volume rises ~$40\%$ (driven by progesterone) increasing minute ventilation; this causes a compensated respiratory alkalosis ($\text{PaCO}_2 \approx 4.0\ \text{kPa}$, $\approx 30\ \text{mmHg}$). Functional residual capacity falls ~$20\%$; respiratory rate is largely unchanged; oxygen consumption rises ~$20\%$.

Outline the renal adaptations to pregnancy.

Renal plasma flow and GFR rise ~$50\%$, lowering serum creatinine and urea; there is mild glycosuria and proteinuria, increased renin/aldosterone (sodium and water retention), and physiological dilatation of the renal pelves and ureters (right $>$ left).

Describe the structure of the placental villus and the layers separating maternal and fetal blood.

At term, maternal blood in the intervillous space is separated from fetal capillary blood by: the syncytiotrophoblast, (thinning) cytotrophoblast, villous stroma, and fetal capillary endothelium — the vasculosyncytial membrane allowing efficient exchange.

List the mechanisms of placental transfer with an example of each.

Simple diffusion ($\text{O}_2$, $\text{CO}_2$, water); facilitated diffusion (glucose via GLUT transporters); active transport (amino acids, iron, calcium — against gradient, energy-dependent); pinocytosis (immunoglobulins, e.g. IgG); and bulk flow/solvent drag for water and electrolytes.

Which hormones are produced by the placenta and what are their main roles?

hCG (maintains the corpus luteum early, peaks ~$10$ weeks); human placental lactogen (hPL, anti-insulin/diabetogenic, lipolysis); progesterone (maintains pregnancy after the luteo-placental shift ~$8\text{-}10$ weeks); and oestrogens (oestriol, requiring the fetal adrenal/liver).

Describe fetal circulation and the three key shunts.

Oxygenated blood from the placenta enters via the umbilical vein. Ductus venosus bypasses the liver to the IVC; foramen ovale shunts blood right atrium → left atrium (bypassing lungs); ductus arteriosus shunts pulmonary artery → aorta. Two umbilical arteries return deoxygenated blood to the placenta.

What circulatory changes occur at birth (transition), and what do the fetal shunts become?

Lung expansion drops pulmonary vascular resistance; cord clamping raises systemic resistance, so left atrial pressure exceeds right, closing the foramen ovale. The ductus arteriosus closes (rising $\text{PaO}_2$, falling prostaglandins) → ligamentum arteriosum; ductus venosus → ligamentum venosum; umbilical vein → ligamentum teres.

Describe amniotic fluid production, circulation and volume changes across gestation.

Early fluid is a dialysate of fetal/maternal plasma; from ~$16$ weeks it is mainly fetal urine, balanced by fetal swallowing and lung secretion. Volume rises to ~$800\text{-}1000\ \text{mL}$ around $34$-$36$ weeks then declines. Polyhydramnios suggests reduced swallowing (e.g. atresia); oligohydramnios suggests reduced urine (e.g. renal agenesis/IUGR).

Distinguish symmetrical from asymmetrical fetal growth restriction.

Symmetrical FGR: early insult (e.g. chromosomal, infection) affecting head and body equally — globally small fetus. Asymmetrical FGR: later insult (e.g. placental insufficiency) with head-sparing — abdominal circumference falls before head circumference, raised cerebroplacental redistribution.

How does maternal carbohydrate metabolism change in pregnancy and why?

Pregnancy is progressively insulin-resistant (driven by hPL, progesterone, cortisol, prolactin), promoting maternal hyperglycaemia and facilitated glucose transfer to the fetus. The mother becomes hyperinsulinaemic; fasting state shows accelerated starvation with ketosis.

How do lipid and protein metabolism change in pregnancy?

Lipids: hyperlipidaemia with raised triglycerides, cholesterol and free fatty acids; the fed state is anabolic (fat storage) and fasting is catabolic (lipolysis). Protein: net positive nitrogen balance to support fetal/maternal tissue growth; amino acids are actively transported to the fetus.

Name the phases of the cell cycle and the key checkpoints.

$G_1 \to S$ (DNA synthesis) $\to G_2 \to M$ (mitosis), with $G_0$ as a quiescent state. Checkpoints: $G_1/S$ (restriction point, governed by p53/Rb), $G_2/M$ (DNA damage check), and the spindle/metaphase checkpoint in mitosis. Cyclin-CDK complexes drive transitions.

Contrast apoptosis with necrosis.

Apoptosis: programmed, energy-dependent, single-cell, membrane blebbing, chromatin condensation, apoptotic bodies, NO inflammation. Necrosis: passive, pathological, affects cell groups, cell swelling and lysis, releases contents causing inflammation.

Describe the intrinsic and extrinsic pathways of apoptosis.

Extrinsic: death-receptor ligands (e.g. Fas/FasL, TNF) activate caspase-8. Intrinsic (mitochondrial): cellular stress shifts Bcl-2/Bax balance, releasing cytochrome c → apoptosome → caspase-9. Both converge on executioner caspases ($3$, $6$, $7$).

List the main types of membrane transport across a cell membrane.

Passive: simple diffusion and facilitated diffusion (channels/carriers, down gradient, no energy). Active: primary active transport (ATP-driven, e.g. $\text{Na}^+/\text{K}^+$-ATPase) and secondary active transport (symport/antiport using an ion gradient). Plus endocytosis/exocytosis for bulk transport.

Describe the Henderson-Hasselbalch equation and normal arterial values.

$$\text{pH} = \text{p}K_a + \log_{10}\frac{[\text{HCO}_3^-]}{0.03 \times \text{PaCO}_2}$$ Normal arterial pH $= 7.35\text{-}7.45$, $\text{PaCO}_2 \approx 4.7\text{-}6.0\ \text{kPa}$ ($35\text{-}45\ \text{mmHg}$), $[\text{HCO}_3^-] \approx 22\text{-}26\ \text{mmol/L}$.

How is the anion gap calculated and what does a raised value suggest?

$$\text{Anion gap} = ([\text{Na}^+] + [\text{K}^+]) - ([\text{Cl}^-] + [\text{HCO}_3^-])$$ Normal ~$8\text{-}16\ \text{mmol/L}$. A raised anion gap metabolic acidosis suggests lactate, ketones, renal failure or toxins (mnemonic MUDPILES).

Describe the inheritance pattern and recurrence risk of an autosomal recessive condition.

Both parents are unaffected carriers; affected offspring are homozygous. Each child of two carriers has a $\frac{1}{4}$ ($25\%$) risk of being affected, $\frac{1}{2}$ of being a carrier, and $\frac{1}{4}$ unaffected non-carrier. Risk is increased by consanguinity; e.g. cystic fibrosis, sickle cell.

Contrast X-linked recessive inheritance with autosomal dominant inheritance.

X-linked recessive: males affected, females usually carriers, NO male-to-male transmission, all daughters of an affected male are carriers (e.g. haemophilia). Autosomal dominant: each child of an affected heterozygote has a $\frac{1}{2}$ risk, both sexes affected, male-to-male transmission occurs (e.g. Huntington's).

Define non-disjunction and give the recurrence risk of trisomy 21 by maternal age.

Non-disjunction is failure of chromosome pairs (meiosis I) or sister chromatids (meiosis II) to separate, producing aneuploid gametes. Trisomy 21 risk rises with maternal age: ~$1\text{ in }1500$ at age $20$, ~$1\text{ in }900$ at $30$, ~$1\text{ in }100$ at $40$.

Compare the karyotypes and key features of Turner, Klinefelter, Down, Edwards and Patau syndromes.

Turner $45,\text{X}$ (short stature, streak ovaries); Klinefelter $47,\text{XXY}$ (tall, hypogonadism); Down (trisomy 21); Edwards (trisomy 18, rocker-bottom feet); Patau (trisomy 13, holoprosencephaly/cleft). Edwards and Patau carry very poor prognosis.

Distinguish a Robertsonian translocation from a reciprocal translocation.

Robertsonian: fusion of two acrocentric chromosomes ($13,14,15,21,22$) at the centromere with loss of short arms; a balanced carrier has $45$ chromosomes and risks trisomic offspring (e.g. translocation Down syndrome). Reciprocal: exchange of segments between two non-homologous chromosomes; balanced carriers are usually phenotypically normal but risk unbalanced gametes.

Outline how PCR works and the steps of each cycle.

PCR amplifies a DNA target through repeated cycles: (1) denaturation (~$95^{\circ}\text{C}$, strands separate), (2) annealing (~$50\text{-}65^{\circ}\text{C}$, primers bind), (3) extension (~$72^{\circ}\text{C}$, Taq polymerase synthesises new strands). Amplification is exponential — $n$ cycles give up to $2^{n}$ copies.

Differentiate karyotyping, FISH, microarray (CGH) and NIPT in prenatal genetic testing.

Karyotyping detects aneuploidy and large structural rearrangements. FISH gives rapid targeted detection of specific chromosomes/loci. Microarray (array CGH) detects sub-microscopic copy-number variants but not balanced rearrangements. NIPT analyses cell-free fetal DNA in maternal plasma — a high-sensitivity SCREENING test for common trisomies.

State the Hardy-Weinberg equations and the assumptions required for equilibrium.

$$p + q = 1 \quad\text{and}\quad p^{2} + 2pq + q^{2} = 1$$ where $p^{2}$ and $q^{2}$ are homozygote frequencies and $2pq$ heterozygotes. Assumptions: large population, random mating, no mutation, no migration, no selection.

For an autosomal recessive disease with incidence $1\text{ in }2500$, calculate the carrier frequency using Hardy-Weinberg.

$q^{2} = \frac{1}{2500}$, so $q = \frac{1}{50} = 0.02$. Then $p \approx 0.98$, and carrier frequency $2pq = 2 \times 0.98 \times 0.02 \approx 0.039$, i.e. about $1\text{ in }25$.

Name important organisms causing chorioamnionitis/preterm labour and neonatal early-onset sepsis.

Group B Streptococcus ($\textit{Streptococcus agalactiae}$) is the leading cause of early-onset neonatal sepsis; others include $\textit{E. coli}$, $\textit{Listeria monocytogenes}$, and ascending genital tract anaerobes/$\textit{Ureaplasma}$ in chorioamnionitis.

Which organisms cause the TORCH congenital infections?

Toxoplasma gondii; Other (syphilis/$\textit{Treponema pallidum}$, parvovirus B19, VZV, Listeria); Rubella; Cytomegalovirus (commonest congenital infection); Herpes simplex virus. These cross the placenta and cause congenital anomalies.

Differentiate the cells and timing of innate versus adaptive immunity.

Innate: immediate, non-specific, no memory — neutrophils, macrophages, NK cells, complement, physical barriers. Adaptive: slower, antigen-specific, generates memory — T lymphocytes (cell-mediated) and B lymphocytes/plasma cells (humoral, antibodies).

Why is IgG important in pregnancy and which antibody is the largest?

IgG is the only immunoglobulin actively transported across the placenta (via Fc receptors), giving the fetus/neonate passive immunity — but also mediating haemolytic disease (e.g. anti-D). IgM is the largest (pentamer), does not cross the placenta, and indicates acute/fetal infection if found in cord blood.

List the four types of hypersensitivity reactions with an obstetric/gynaecological example.

Type I (IgE, immediate — anaphylaxis/latex allergy); Type II (antibody-mediated cytotoxic — rhesus haemolytic disease of the newborn); Type III (immune complex — SLE, pre-eclampsia features); Type IV (delayed, T-cell mediated — contact dermatitis, graft rejection).

Define the key pharmacokinetic parameters: bioavailability, volume of distribution, clearance and half-life.

Bioavailability ($F$): fraction of dose reaching systemic circulation. Volume of distribution: $V_d = \frac{\text{dose}}{C_0}$. Clearance ($CL$): volume cleared per unit time. Half-life: $t_{1/2} = \frac{0.693 \times V_d}{CL}$.

Contrast zero-order and first-order kinetics.

First-order: a constant FRACTION of drug is eliminated per unit time (rate proportional to concentration); most drugs follow this. Zero-order: a constant AMOUNT is eliminated per unit time (saturated enzymes), e.g. phenytoin, alcohol — small dose increases cause disproportionate rises in concentration.

How are drugs classified for use in pregnancy regarding placental transfer?

Transfer is greater for drugs that are lipophilic, of low molecular weight ($< 500\ \text{Da}$), un-ionised, and poorly protein-bound. Drug effect on the fetus depends on gestation (organogenesis weeks $3\text{-}8$ carries greatest teratogenic risk).

Define drug potency versus efficacy, and agonist versus antagonist.

Potency = the concentration/dose producing a given effect (reflected by $EC_{50}$); efficacy = the maximal effect achievable. An agonist binds and activates a receptor (full or partial); an antagonist binds without activating — competitive antagonists shift the dose-response curve right (surmountable).

Compare the mechanism of action of the main uterotonics: oxytocin, ergometrine, carboprost and misoprostol.

Oxytocin: binds myometrial oxytocin receptors → contraction (caution: vasodilatation/hypotension). Ergometrine: ergot alkaloid causing sustained contraction (avoid in hypertension). Carboprost ($\text{PGF}_{2\alpha}$): prostaglandin (avoid in asthma — bronchospasm). Misoprostol ($\text{PGE}_1$ analogue): oral/rectal, stable, used for PPH and induction.

Compare the main classes of tocolytics used to suppress preterm labour.

Calcium-channel blockers (nifedipine, first-line in UK); oxytocin-receptor antagonists (atosiban); $\beta_2$-agonists (terbutaline — now less used, cardiac side effects); COX inhibitors (indometacin — risk of ductus arteriosus closure and oligohydramnios); magnesium sulfate (mainly for fetal neuroprotection).

Summarise the mechanisms of the major antimicrobial classes relevant to obstetrics.

$\beta$-lactams (penicillins, cephalosporins): inhibit cell-wall synthesis. Macrolides (erythromycin) and aminoglycosides (gentamicin): inhibit protein synthesis. Metronidazole: damages anaerobic DNA. Avoid tetracyclines (teeth staining), quinolones and trimethoprim (1st trimester, folate antagonist) in pregnancy.