Summary of Advanced Assisted Reproductive Technologies
Advanced Assisted Reproductive Technologies: A Student's Guide
Introduction
In vitro maturation (IVM) is an assisted reproductive technique in which immature oocytes (typically at the germinal vesicle, GV, stage) are collected from antral follicles and matured in the laboratory to metaphase II (MII) before fertilisation. IVM reduces or avoids ovarian stimulation, lowering medication exposure, cost, and risk of ovarian hyperstimulation syndrome (OHSS). Modern IVM encompasses a spectrum from true IVM (no hormonal priming) to so-called "pseudo" or truncated IVF approaches that use minimal gonadotropins or hCG priming.
Definition: In vitro maturation (IVM) — laboratory maturation of oocytes from GV or MI to MII, performed outside the body with minimal or no prior ovarian stimulation.
Why IVM matters
- Reduces number of injections, clinic visits, and medication cost compared with conventional controlled ovarian hyperstimulation (COH) IVF.
- Useful for patients at high risk of OHSS (e.g., polycystic ovary syndrome, PCOS), fertility preservation when stimulation is contraindicated, poor responders, or when rapid treatment is needed.
Basic biology: what changes during oocyte maturation
Two linked processes
- Nuclear maturation — progression through meiosis from GV to metaphase II (MII) and extrusion of the first polar body.
- Cytoplasmic maturation — biochemical, organelle, and molecular changes that prepare the oocyte for fertilisation and embryo development. Cytoplasmic maturation often lags behind nuclear maturation and is critical for developmental competence.
Definition: Nuclear maturation — the chromosomal and spindle events that take the oocyte from GV through MI to MII.
Definition: Cytoplasmic maturation — changes in cytoplasmic organelles, mRNA/protein stores, and signalling pathways required for successful fertilisation and embryo development.
When can a human oocyte mature in vitro?
- Oocyte size: an oocyte must have reached near-full growth (typically >90 µm) to acquire competence to resume meiosis.
- Follicle status: oocytes must be from antral follicles (approx. 2–12 mm) to be suitable for IVM.
- Cycle timing: oocytes can be collected at various times in the menstrual cycle for IVM — strict follicular-phase timing is not always required.
Clinical variants and definitions
Use this table to compare common approaches:
| Term | Oocyte stage at retrieval | Hormonal exposure before retrieval | Typical use case |
|---|---|---|---|
| True IVM (biological) | GV → MII | No hCG/LH exposure; minimal or no FSH | Patients avoiding stimulation; fertility preservation |
| FSH-primed IVM (pseudo IVM) | GV/MI → MII | Minimal FSH priming, no hCG | PCOS/PCO patients to improve yield |
| Truncated IVF / mild-stimulation IVF | GV/MI → MII | Minimal FSH and early hCG to prime intermediate follicles | Reduced stimulation IVF comparator |
| Rescue IVM | Any immature oocytes after COH | Retrieved during COH when immature oocytes present | Salvage when cycle yields immature oocytes |
Definition: Pseudo IVM — IVM performed after minimal FSH priming and/or hCG trigger to improve follicle and oocyte readiness; not true zero-hormone IVM.
Practical aspects of human IVM (clinical technique)
- Follicle size for aspiration: typically 2–12 mm; many centres target 10–12 mm for aspirating leading follicles after priming.
- Needle and aspiration adjustments: use smaller needles (19–21G rather than 17G) and lower suction pressures (e.g., ~7.5 kPa) to reduce follicular trauma.
- Lab handling: aspirates filtered (e.g., 70 µm filters) and collected cumulus–oocyte complexes (COCs) maintained with cumulus intact when possible.
- Maturation period: incubation for 24–48 h depending on protocol; biphasic (pre‑maturation with meiotic arrest modulators followed by maturation) is increasingly used.
Example IVM protocol used in clinical s
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In vitro maturation (IVM) overview
Klíčové pojmy: IVM matures GV/MI oocytes in lab to MII without full ovarian stimulation, True IVM uses no hCG/LH exposure; pseudo IVM uses minimal FSH and/or hCG priming, Typical follicle size for IVM retrieval: ~2–12 mm (often 10–12 mm after priming), Biphasic/CAPA‑IVM adds a prematuration step to improve cytoplasmic competence, IVM significantly reduces medication, visits, and OHSS risk compared with COH‑IVF, Clinical outcomes in PCOS cohorts: ~69% MII, ~71% fertilisation, ~41% blastocyst rates, Rescue IVM has poorer outcomes due to aged/defective oocytes and lack of cumulus support, Animal models showed benefits of meiotic arrest strategies but raised epigenetic concerns, CAPA‑IVM and refined protocols have produced encouraging results in specialist centres, IVM is useful for fertility preservation when stimulation is contraindicated