Assisted reproductive technology — structured SAQ (15 marks)

(a) Definitions and ICSI indication (3 marks)

• Infertility is a disease of the male or female reproductive system, clinically the failure to achieve a pregnancy after 12 months or more of regular unprotected intercourse (International Glossary, 2017).^[1]
• Assisted reproductive technology (ART) is any intervention involving the in vitro handling of human oocytes, sperm or embryos to establish a pregnancy.^[1]
• ICSI is indicated for severe male factor (his severe oligoasthenoteratozoospermia): it bypasses the fertilisation barriers that conventional IVF cannot overcome, injecting a single spermatozoon into each mature oocyte — first reported by Palermo in 1992. ICSI is not a blanket upgrade over IVF.^[2]

(b) The staged IVF/ICSI pathway (4 marks)

One mark per named pair of steps, maximum four. ^[3]

• Pituitary suppression — prevent a premature LH surge (GnRH agonist or antagonist).^[3]
• Ovarian stimulation — gonadotrophins to recruit multiple follicles.^[3]
• Trigger — hCG or a GnRH agonist (in an antagonist cycle) to induce final oocyte maturation.
• Oocyte retrieval — transvaginal ultrasound-guided pickup about 36 hours after the trigger.
• Fertilisation — ICSI here (given severe male factor); conventional IVF otherwise.^[2]
• Embryo culture — to cleavage (day 3) or blastocyst (day 5).
• Embryo transfer with luteal phase support — catheter transfer, then progesterone.^[5]

(c) Protocol and embryo-transfer decisions with OHSS prevention (5 marks)

• Protocol: use a GnRH antagonist protocol rather than the long agonist — Cochrane shows comparable live birth (OR 1.02) with a substantial reduction in OHSS (OR 0.61).^[3]
• Trigger: use a GnRH agonist trigger in place of hCG to reduce early OHSS, with modified luteal support or a freeze-all strategy.^[3]
• Luteal support: progesterone, never hCG — hCG carries a higher OHSS risk and should be avoided (Cochrane).^[5]
• Embryo transfer number: follow ASRM/SART guidance to promote singleton gestation — elective single embryo transfer given her good prognosis, transferring surplus embryos as frozen-thawed cycles.^[6]
• OHSS prevention ladder: individualise the gonadotrophin dose; antagonist protocol with agonist trigger; cabergoline if high response; metformin if PCOS; and a low threshold to freeze-all in high-risk cycles.^[3][6]

(d) Counselling on success and complications (3 marks)

• Cumulative live birth: quote Malizia — at 40 years or older, cumulative live birth after up to six cycles was 23% (conservative) to 42% (optimistic), versus 65% to 86% under 35. IVF may largely overcome infertility in younger women but does not reverse the age-dependent decline.^[4]
• Complications to name: OHSS (the iatrogenic emergency), multiple pregnancy (prevented by elective single embryo transfer), and the procedural risks of retrieval (bleeding, infection, torsion, anaesthetic).^[6]
• Perinatal risk: ART singletons carry slightly higher perinatal risk than non-ART singletons, but far less than ART multiple births, and much reflects the underlying subfertility rather than the technique itself.^[6]