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O&G TopicsReproductive endocrinology & infertility

O&G · Reproductive endocrinology & infertility

IVF and ART techniques: stimulation, trigger, transfer, luteal support, OHSS prevention and cumulative success

Also known as In vitro fertilisation · IVF · ART · Assisted reproductive technology · ICSI · Controlled ovarian stimulation · Ovarian hyperstimulation syndrome · Luteal phase support

Exam-exhaustive FRANZCOG fellowship topic on IVF and ART techniques: the controlled ovarian stimulation protocols (long agonist vs antagonist), the trigger decision (hCG vs GnRH agonist trigger and the OHSS risk window), freeze-all and the OHSS prevention bundle, embryo culture and transfer (day 3 vs day 5 blastocyst, fresh vs frozen), the luteal phase support (vaginal, oral, IM progesterone with doses), the live-birth rate by maternal age and cycle number, the OHSS severity grading, and the cumulative success after up to 6 cycles. Anchored to the Cochrane 2021/2022 reviews, the Malizia 2009 cumulative live-birth data, and the regional guidelines (NICE NG257, RANZCOG, ASRM, ESHRE, HFEA).

high18 referencesUpdated 28 July 202618 min readVerification in progress

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FRANZCOGMRCOGABOGFRCSCMRCPI

Red flags

  • A high responder (high follicle count, markedly elevated oestradiol, PCOS, high AMH) — use antagonist + GnRH agonist trigger + freeze-all to minimise OHSS risk
  • Severe OHSS — admit, IV crystalloid, paracentesis for tense ascites, thromboprophylaxis; never give hCG trigger with markedly elevated oestradiol and a high follicle count
  • A woman over 40 — counsel on the age cliff (cumulative 42%/23% by 6 cycles at 40 and over, with further decline by age); donor oocyte is the realistic option over 43
  • A poor responder (advanced age, prior poor response or cancellation, abnormal reserve tests) — use antagonist, dual trigger, increased gonadotropin dose, or natural cycle
  • A couple with severe male factor (very low count, surgically retrieved sperm, prior failed fertilisation) — ICSI, not IVF
  • Vaginal or pelvic bleeding after egg collection — call the on-call team; crossmatch and prepare for theatre
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Practise this topic14 MCQs with explanations

Target exams

FRANZCOGMRCOGABOGFRCSCMRCPI

Red flags

  • A high responder (high follicle count, markedly elevated oestradiol, PCOS, high AMH) — use antagonist + GnRH agonist trigger + freeze-all to minimise OHSS risk
  • Severe OHSS — admit, IV crystalloid, paracentesis for tense ascites, thromboprophylaxis; never give hCG trigger with markedly elevated oestradiol and a high follicle count
  • A woman over 40 — counsel on the age cliff (cumulative 42%/23% by 6 cycles at 40 and over, with further decline by age); donor oocyte is the realistic option over 43
  • A poor responder (advanced age, prior poor response or cancellation, abnormal reserve tests) — use antagonist, dual trigger, increased gonadotropin dose, or natural cycle
  • A couple with severe male factor (very low count, surgically retrieved sperm, prior failed fertilisation) — ICSI, not IVF
  • Vaginal or pelvic bleeding after egg collection — call the on-call team; crossmatch and prepare for theatre
One-line fellowship answer

IVF and ICSI are the two ART procedures — ICSI for severe male factor and surgically retrieved sperm, IVF otherwise. The cycle is built on three decisions: (1) stimulation protocol — the GnRH antagonist is now first-line for most (shorter, lower OHSS risk, allows agonist trigger) while the long GnRH agonist remains standard for some indications; (2) trigger — hCG 5000 to 10,000 IU in standard risk, GnRH agonist (leuprolide or triptorelin 0.2 mg) in OHSS risk; (3) fresh or frozen transfer — element of the OHSS prevention bundle (antagonist + agonist trigger + freeze-all + metformin in PCOS). Luteal support is vaginal progesterone (8% gel 90 mg, 180 mg total daily) — with similar ongoing pregnancy to oral dydrogesterone 40 mg total daily and IM progesterone 100 mg daily — started the day of egg collection and continued to 10 to 12 weeks gestation. Cumulative live birth is around 72% by 6 cycles (optimistic) but falls from 32% per fresh transfer under 35 to under 2% over 44; the age cliff is the single most important modifier of success.[9][13][14][16][17]

It is 08:00 on the IVF unit. A 32-year-old woman with PCOS has produced 24 follicles on day 12 of an antagonist cycle, her oestradiol is 4800 pg/mL, and the lead follicles are 18 mm. The embryologist is on standby. The decision you make before going to theatre is the one that decides whether the cycle ends in a healthy singleton or a week in hospital with tense ascites. The same three questions will be on the exam: which protocol, which trigger, and which transfer. Get the trigger wrong in a high responder and you have caused OHSS; get the luteal support wrong after an agonist trigger and you have caused luteal phase failure; transfer the day a hydrosalpinx is found and you have wasted the cycle.[1][9][16]

Overview and definition

IVF is the in vitro fertilisation of oocytes with sperm, with subsequent embryo culture and transfer to the uterus. ICSI is the microinjection of a single spermatozoon into each mature oocyte. Both are part of the broader category of assisted reproductive technology (ART) — treatments involving the in vitro handling of oocytes, sperm, or embryos; this includes IVF, ICSI, intrauterine insemination (IUI), gamete and embryo cryopreservation, and donor gametes. The clinic's modern bundle is built on three decisions — the protocol, the trigger, and the transfer — and the OHSS prevention bundle is the audit point for every high responder. Since the birth of Louise Brown in 1978, IVF has become the single most effective treatment for intractable infertility, with cumulative live-birth rates around 72% by 6 cycles in women under 35 (Malizia 2009).[4][16]

The numbers that anchor every IVF counselling conversation

~46-51%Donor-oocyte pregnancy per transferfresh 51.3% / thawed 45.7% (ESHRE 2020)
72% (51%)Cumulative live birth, 6 cyclesoptimistic / conservative; 86%/65% under 35 (Malizia 2009)
~11% / ~8%Twin delivery, fresh vs FETESHRE 2020; eSET is the answer
OR 0.61OHSS, antagonist vs long agonist36 RCTs; LBR comparable (Cochrane 2016)
→ near 0%OHSS reduction, agonist triggercompared to hCG in antagonist cycles
21% vs 3%Multiple birth, ART vs naturalUS 2018 (CDC)
[4] [5] [6] [1] [13]
The six situations that change the cycle todayA high responder (over 20 follicles, oestradiol over 3000 pg/mL, PCOS, AMH over 35 pmol/L) — use antagonist + GnRH agonist trigger + freeze-all. A severe OHSS admission — IV crystalloid, paracentesis, thromboprophylaxis, dopamine if oligo-anuric. A woman over 40 — counsel on the age cliff; donor oocyte is the realistic option over 43. A poor responder (Bologna criteria) — antagonist, dual trigger, increased gonadotropin dose, or natural cycle. Severe male factor (concentration under 5 million/mL, surgically retrieved sperm, prior failed fertilisation) — ICSI, not IVF. Vaginal or pelvic bleeding after egg collection — call the on-call team; crossmatch and prepare for theatre.[9][1]
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References18ShowHide
  1. [1]Youssef MA, Van der Veen F, Al-Inany HG, Mochtar MH, Griesinger G, Nagi Mohesen M, Aboulfoutouh I, van Wely M. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist-assisted reproductive technology. Cochrane Database Syst Rev, 2014.PMID 25358904
  2. [2]Zaat T, Zagers M, Mol F, Goddijn M, van Wely M, Mastenbroek S. Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev, 2021.PMID 33539543
  3. [3]Glujovsky D, Quinteiro Retamar AM, Alvarez Sedo CR, Ciapponi A, Cornelisse S, Blake D. Cleavage-stage versus blastocyst-stage embryo transfer in assisted reproductive technology. Cochrane Database Syst Rev, 2022.PMID 35588094
  4. [4]Malizia BA, Hacker MR, Penzias AS. Cumulative live-birth rates after in vitro fertilization. N Engl J Med, 2009.PMID 19144939
  5. [5]Smeenk J, Wyns C, De Geyter C, Kupka MS, Bergh C, et al. ART in Europe, 2020: results generated from European registries by ESHRE. Hum Reprod, 2025.PMID 40985526
  6. [6]Sunderam S, Kissin DM, Zhang Y, Jewett A, Boulet SL, Warner L, et al. Assisted Reproductive Technology Surveillance - United States, 2018. MMWR Surveill Summ, 2022.PMID 35176012
  7. [7]Kadoura S, Alhalabi M, Nattouf AH. Conventional GnRH antagonist protocols versus long GnRH agonist protocol in IVF/ICSI cycles of polycystic ovary syndrome women: a systematic review and meta-analysis. Sci Rep, 2022.PMID 35292717
  8. [8]Haahr T, Roque M, Esteves SC, Humaidan P. GnRH Agonist Trigger and LH Activity Luteal Phase Support versus hCG Trigger and Conventional Luteal Phase Support in Fresh Embryo Transfer IVF/ICSI Cycles-A Systematic PRISMA Review and Meta-analysis. Front Endocrinol (Lausanne), 2017.PMID 28638367
  9. [9]Leathersich S, Roche C, Hart R. Minimising OHSS in women with PCOS. Front Endocrinol (Lausanne), 2025.PMID 40182629
  10. [10]Mizrachi Y, Horowitz E, Farhi J, et al. Ovarian stimulation for freeze-all IVF cycles: a systematic review. Hum Reprod Update, 2020.PMID 31867625
  11. [11]Ganer Herman H, Feferkorn I, Dahan MH, Reinblatt S, Demirtas E, Buckett W. A meta-analysis and systematic review of advanced maternal age patients in IVF. Hum Reprod Update, 2025.PMID 40803331
  12. [12]Pabuccu E, Kovanci E, Israfilova G, Tulek F, Demirel C, Pabuccu R. Oral, vaginal or intramuscular progesterone in programmed frozen embryo transfer cycles: a pilot randomized controlled trial. Reprod Biomed Online, 2022.PMID 36153226
  13. [13]Al-Inany HG, Youssef MA, Ayeleke RO, Brown J, Lam WS, Broekmans FJ. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev, 2016.PMID 27126581
  14. [14]Humm KC, Dodge LE, Wu LH, et al. In vitro fertilization in women under 35: counseling should differ by age. J Assist Reprod Genet, 2015.PMID 26371056
  15. [15]Romualdi D, Ata B, Bhattacharya S, Bosch E, Costello M, Gersak K, Homburg R, Mincheva M, Norman RJ, et al. Evidence-based guideline: unexplained infertility. Hum Reprod, 2023.PMID 37599566
  16. [16]Brinsden PR, Brinsden PR Thirty years of IVF: the legacy of Patrick Steptoe and Robert Edwards. Hum Fertil (Camb), 2009.PMID 19925325
  17. [17]Al-Inany H, Aboulghar M. GnRH antagonist in assisted reproduction: a Cochrane review. Hum Reprod, 2002.PMID 11925376
  18. [18]Walls ML, Hart RJ In vitro maturation. Best Pract Res Clin Obstet Gynaecol, 2018.PMID 30056110

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