Fertilisation and implantation
Fertilisation, implantation and placental hormones (hCG, hPL)
Fertilisation in the ampulla is followed by a week of cleavage and travel before the blastocyst implants, and the trophoblast immediately starts making hCG to keep the corpus luteum alive. CPSP asks about capacitation, the acrosome and cortical reactions, the timing and site of implantation, and what hCG, hPL, progesterone and oestriol tell us in normal and abnormal pregnancy.
Before fusion
- The oocyte can be fertilised for about 12–24 hours after ovulation; sperm survive up to 5 days. Fertilisation normally occurs in the ampulla.
- Capacitation (in the female tract, or after washing and incubation in IVF) removes cholesterol and surface glycoproteins from the sperm head membrane over several hours, allowing hyperactivated motility and the acrosome reaction.
- Sperm pass the cumulus (hyaluronidase helps), then bind ZP3 of the zona pellucida, which triggers the acrosome reaction; acrosin digests a path through the zona. Sperm without an acrosome (globozoospermia) cannot penetrate.
Fusion and the block to polyspermy
- Fusion releases a wave of calcium in the oocyte. This completes meiosis II (second polar body).
- The calcium wave also triggers the cortical reaction: cortical granules modify the zona (zona reaction) so no further sperm bind or pass. Failure gives polyspermy and a triploid zygote.
- At 16–18 hours a normal zygote shows two pronuclei and two polar bodies.
- Genetic sex is decided by the sperm: every ovum carries X, the sperm carries X or Y.
Cleavage and transport
| Day after fertilisation | Stage | Where |
|---|---|---|
| 1 | Zygote | Ampulla |
| 2–3 | 2–8 cells; each division halves cell size inside the zona (no growth) | Tube |
| 3–4 | Morula (about 16 cells) | Enters the uterus |
| 4–5 | Blastocyst: inner cell mass, trophoblast, cavity | Uterine cavity, fed by gland secretions |
| 5–6 | Hatching from the zona (assisted in some IVF cycles) | Cavity |
| About 6 | Attachment at the embryonic pole | Endometrium |
| 10–12 | Interstitial implantation complete; surface closed by a fibrin plug | Endometrial stroma |
- Damaged tubal cilia slow transport, so the morula may implant in the tube: ectopic pregnancy.
- Normal site: posterior wall of the upper uterine body. Implantation in the lower segment gives placenta praevia.
- The window of implantation is mid-luteal, about days 20–24 of a 28-day cycle, when progesterone has made the endometrium receptive.
- The trophoblast over the inner cell mass makes first contact and differentiates into:
| Layer | Features |
|---|---|
| Cytotrophoblast (inner) | Pale, distinct cell borders, mitoses: the stem layer |
| Syncytiotrophoblast (outer) | Dark, multinucleated, no cell borders, no mitoses; invades and makes the hormones |
- Extravillous trophoblast expresses HLA-G rather than classical HLA-A and B, so uterine natural killer cells do not destroy this semi-allograft. Progesterone converts endometrial stroma into decidua.
hCG
- Glycoprotein (alpha subunit shared with LH, FSH and TSH; specific beta subunit) made by syncytiotrophoblast.
- Detectable in serum about 8–10 days after ovulation, before the missed period; serum immunoassay is the most sensitive test.
- Doubles about every 48 hours in early pregnancy, peaks at 8–10 weeks, then falls to a plateau.
- Actions: acts on LH receptors to rescue the corpus luteum until the placenta takes over progesterone production at about 7–10 weeks; drives fetal Leydig cells in the first trimester; weak TSH-like action.
- A gestational sac should be seen by transvaginal ultrasound once hCG exceeds about 1,500–3,500 IU/L (discriminatory zone): an empty uterus above this suggests ectopic pregnancy.
| hCG | Situations |
|---|---|
| Higher than expected | Molar pregnancy, multiple pregnancy, Down syndrome |
| Slow rise | Ectopic pregnancy, failing pregnancy |
- Clinical uses: the IVF trigger (mimics the LH surge and lasts days). hCG-secreting testicular tumours cause gynaecomastia by stimulating testicular oestradiol production. Placental hCG can stimulate a fetal ovarian cyst.
hPL (human chorionic somatomammotropin)
- Single-chain polypeptide from syncytiotrophoblast, structurally closest to growth hormone (also prolactin-like). It rises steadily with placental mass.
- Actions: maternal insulin resistance and lipolysis, so the mother burns fatty acids and ketones while glucose and amino acids are spared for the fetus; breast development; weak growth activity.
Steroids of the placenta
- Progesterone: made by the placenta from maternal cholesterol (LDL), so it stays high even after fetal death. Needed for myometrial quiescence and decidua.
- Oestrogens: the placenta lacks 17-alpha-hydroxylase and cannot make androgens itself; it relies on fetal adrenal DHEA sulphate, 16-hydroxylated in the fetal liver, to make oestriol (the fetoplacental unit).
| Event | Progesterone | Oestriol |
|---|---|---|
| Fetal death | Remains high | Falls sharply |
| Anencephaly (adrenal hypoplasia) | Normal | Very low |
| Placental sulphatase deficiency | Normal | Very low |
- Other placental products: placental GH variant, CRH (rises towards term, linked to labour timing), inhibin A, PAPP-A.
Remember hCG keeps the corpus luteum alive; hPL makes the mother insulin resistant.
Exam trap hPL resembles growth hormone, while hCG resembles LH; do not swap them.
Exam trap Fetal death lowers oestriol but not progesterone, because progesterone is made from maternal cholesterol.
Test yourself on this topic
5 of the 27 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
On day 3 of IVF culture, an embryo has eight cells but is no larger overall than the zygote was on day 1. What explains this?
Answer: Each division halves the cell size
Cleavage divisions of the zygote are rapid mitoses without growth in between. Each division splits the existing cytoplasm, so the blastomeres become progressively smaller while the total volume within the zona stays about the same. The embryo relies largely on stored maternal resources until its own genome is activated around the 4–8 cell stage. Growth in size begins after the blastocyst hatches and implants.
Cleavage
- Rapid mitoses
- No growth between divisions
- Blastomeres get smaller
- Total size unchanged within zona
Remember Cleavage divides the cake; it does not bake more.
Exam trap Cell number rises quickly in the first days, but embryo size does not.
Why the other options are wrong
- Most cells have died by apoptosis Healthy embryos do not lose most cells.
- The zona pellucida compresses the cells The zona limits shape, but the cause is lack of growth.
- The cells are fusing into a syncytium Syncytium forms in trophoblast after implantation.
- The embryo has not yet taken up water Fluid enters at the blastocyst stage, but cleavage itself adds no growth.
Between meals in late pregnancy, a woman's plasma free fatty acids and ketones rise more than they did before pregnancy. Which effect of human placental lactogen (hPL) explains this, and how does it help the fetus?
Answer: Maternal lipolysis spares glucose for the fetus
hPL is made by the syncytiotrophoblast in amounts proportional to placental mass. It promotes lipolysis and causes insulin resistance in the mother, so she burns more fat and ketones between meals. This leaves glucose, which crosses the placenta readily by facilitated diffusion, available for the fetus, whose main fuel is glucose. The same effects explain the fasting tendency to ketosis and the post-meal rise in glucose in late pregnancy.
hPL actions
- Made by syncytiotrophoblast
- Maternal lipolysis and FFA
- Maternal insulin resistance
- Glucose spared for the fetus
Remember hPL makes the mother burn fat so the baby gets sugar.
Exam trap hPL's insulin resistance is purposeful: it diverts glucose to the fetus.
Why the other options are wrong
- Fat storage builds energy reserves for labour Fat storage dominates early pregnancy, not under hPL in late pregnancy.
- Hepatic gluconeogenesis supplies the fetus with fat Gluconeogenesis makes glucose, not fat, and is not hPL's main effect.
- Increased insulin release lowers maternal glucose hPL opposes insulin action.
- Ketones are the main fuel for the fetal brain Glucose is the main fetal fuel.
An infertile man has globozoospermia: his sperm have round heads with no acrosome. They pass through the cumulus poorly and cannot cross the zona pellucida. Which acrosomal enzyme normally digests a path through the zona?
Answer: Acrosin
The acrosome is a cap-like modified lysosome formed from the Golgi apparatus of the spermatid. Hyaluronidase on the sperm surface helps it pass through the hyaluronic acid matrix of the cumulus. After binding to the zona pellucida, the acrosome reaction releases acrosin, a trypsin-like serine protease, which digests a narrow path through the zona for the sperm to reach the oocyte membrane. Sperm without an acrosome need ICSI to fertilise an oocyte.
Acrosome
- Formed from the Golgi apparatus
- Hyaluronidase: through the cumulus
- Acrosin: through the zona
- No acrosome: needs ICSI
Remember Hyaluronidase for the cumulus, acrosin for the zona.
Exam trap Hyaluronidase acts on the cumulus layer; the zona itself is crossed with acrosin.
Why the other options are wrong
- Hyaluronidase Disperses the cumulus cells, not the zona.
- Prostate-specific antigen Prostatic enzyme that liquefies semen.
- Neuraminidase Not the zona-digesting enzyme.
- Collagenase Not an acrosomal enzyme for the zona.
Villi from an 8-week evacuation show an inner layer of pale, well-defined cells with frequent mitoses and an outer layer of dark multinucleated cytoplasm with no cell borders and no mitoses. Which layer is the dividing stem layer that keeps renewing the outer layer?
Answer: Cytotrophoblast
The villous trophoblast has two layers. The inner cytotrophoblast (Langhans layer) consists of discrete mononuclear cells that divide, and these cells fuse into the outer syncytiotrophoblast. The syncytiotrophoblast cannot divide; it makes hCG, hPL and steroids and forms the surface bathed by maternal blood. The cytotrophoblast layer becomes thin and discontinuous later in pregnancy, thinning the placental barrier.
Two trophoblast layers
- Inner cytotrophoblast: dividing
- Outer syncytiotrophoblast: no mitoses
- Cyto fuses into syncytium
- Syncytium makes hCG, hPL
Remember Cyto divides; syncytium secretes.
Exam trap The syncytium is the hormone factory, but new nuclei come only from the cytotrophoblast.
Why the other options are wrong
- Syncytiotrophoblast Non-dividing; formed by fusion of cytotrophoblast.
- Extraembryonic mesoderm Forms the villous core, not the covering.
- Decidua basalis Maternal tissue, not trophoblast.
- Fetal capillary endothelium Inside the villous core.
A woman has placenta praevia, which arises when implantation occurs too low in the uterus. Where does the blastocyst normally implant?
Answer: Posterior wall of the uterine body
The blastocyst normally implants in the endometrium of the upper uterine body, most often on the posterior wall near the fundus. This site has a thick, well-vascularised endometrium and myometrium that contracts strongly after delivery to control bleeding. Implantation in the lower segment leads to placenta praevia. Implantation in the tube, most often the ampulla, is an ectopic pregnancy.
Implantation site
- Normal: posterior wall of body
- Low: placenta praevia
- Tube: ectopic, mostly ampulla
- Cornu: interstitial ectopic
Remember Upper posterior body is the usual home.
Exam trap Fertilisation is in the ampulla; implantation there is ectopic.
Why the other options are wrong
- Lower uterine segment near the os Leads to placenta praevia.
- Internal os of the cervix Leads to cervical pregnancy or praevia.
- Uterine cornu at the tubal opening Interstitial pregnancy, a dangerous ectopic.
- Ampulla of the uterine tube Commonest site of ectopic pregnancy.
Where this sits in the CPSP syllabus
- Obstetrics & Gynaecology, Paper 2: Reproduction, pregnancy and labour, Fertilisation, implantation and placental hormones (hCG, hPL)
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