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Shahar Kol August 2014

Luteal support post agonist trigger for OHSS prevention: The introduction of "luteal coasting" as a novel approach. Shahar Kol August 2014. Agonist trigger and OHSS prevention. The secret is simple: quick and irreversible luteolysis. Luteal phase. Natural cycle day 7-9= 75 pg /ml vs. 18.

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Shahar Kol August 2014

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  1. Luteal support post agonist trigger for OHSS prevention: The introduction of "luteal coasting" as a novel approach. ShaharKol August 2014

  2. Agonist trigger and OHSS prevention • The secret is simple: quick and irreversible luteolysis.

  3. Luteal phase Natural cycle day 7-9= 75 pg/ml vs. 18 Natural cycle day 7-9= 750 pg/ml vs. 184 Nevo et al, 2003

  4. Summary • The lower levels of luteal steroidal and non-steroidal hormones reflect luteolysis, and may explain the mechanism of OHSS prevention by GnRH-a. • Pregnancy post agonist trigger does not rescue the CL!!! Nevo et al, 2003

  5. Four oocyte donors, each underwent 4 consecutive cycles (same protocol) • hCG trigger (10,000) + LPS (600 mg vag P+ 4 mg oral E2) • Agonist trigger (triptoreline 0.2 mg) , 1,500 hCG 35 hours later + LPS • Agonist trigger + LPS • Agonist trigger without LPS. Fatemi et al, 2013

  6. Conclusion: complete luteolysis by day of OPU + 5 Implication: luteal support is mandatory

  7. Luteal phase post agonist trigger in high responders • Freeze all • Fresh transfer

  8. LUTEAL PHASE: INTENSIVE E+P OHSS high-risk patients Engmann et al, 2008

  9. Dual trigger of oocyte maturation with gonadotropin-releasing hormone agonist and low-dose human chorionic gonadotropin to optimize live birth rates in high responders • Patients <40 years old with peak E2 <4,000 pg/mL at risk of OHSS • Triggered with GnRHa alone or GnRHa plus 1,000 IU hCG (dual trigger) for oocyte maturation Griffin et al ,2012

  10. Griffin et al, 2012

  11. The concept of “tailored” luteal phase support: • Extreme response (>25 follicles >11 mm): freeze all • High response (15-25 follicles): a bolus of 1,500 IU hCG on retrieval day • Normal response: an alternative to hCG trigger Humaidan and plyzos F&S 2014

  12. hCG (1,500IU) day 3 after oocyte retrieval Haas et al, 2014

  13. HCG-based luteal support: fixed time points • 1,000 IU with trigger (Griffin) • 1,500 IU with OPU (Humaidan) • 1,500 IU 3 days post OPU (Haas) • Can we be more patient specific??? • Can we tailor hCG support to a specific patient endocrine response???

  14. Coasting • A popular OHSS prevention strategy. • So far, follicular phase only. • In OHSS high risk situation: stop gonadotropin. • Follow E2 level daily. Individualized approach. • Trigger with hCG when E2 drops below a cutoff level. • Mechanism: partial follicular demise.

  15. Luteal coasting post agonist trigger • Suggested strategy: follow P level, when drops below a certain cutoff level, add 1,500 (?) IU of hCG • Mechanism: patient-specific, partial rescue of corpuralutea. • No need for additional P and /or E2.

  16. Case #1 • 30 year old, mechanical + male factors, AFC=15 • Short antagonist protocol, starting dose Menopur 112.5 daily, last 3 days 75. • On trigger (0.2 mg triptorelin) day E2=19017 pmol/l, P=2.5 nmol/l, LH=2.1 IU, >20 follicles >11 mm • OPU=20 oocytes., 12 injected, 4 normal fertilization, 2 embryos transferred on day 2, 2 frozen.

  17. Case #1, P post agonist trigger BETA=316 ET hCG 1,500 IU

  18. Case #1: E2 and LH post agonist trigger

  19. Outcome • Moderate OHSS • Ongoing singleton pregnancy

  20. Case #2 • A 27 year old patient, severe OTA syndrome. • A previous IVF cycle 7 years ago resulted in live birth. • Three IVF trials failed during the last 4 years. • Stimulation: antagonist-based, 150 IU Menopur. • A day before trigger E2=15768 P=3.2 LH=1.2, with >30 follicles >11 mm. • Trigger with triptorelin 0.2 mg • 25 oocytes were retrieved, 23 injected with sperm, 11 normal 2pn fertilizations. • 2 embryos transferred 48 hours post retrieval, 8 were frozen.

  21. Case #2, P post agonist trigger BETA=174 ET hCG 1,500 IU

  22. Case #2: E2 and LH post agonist trigger

  23. Outcome • No OHSS • Ongoing twin pregnancy

  24. The question of implantation potential post excessive ovarian response • Clinical evidence for a detrimental effect on uterine receptivity of high serum oestradiol concentrations in high and normal responder patients. Simon et al, 1995 • Lower implantation rates in high responders: evidence for an altered endocrine milieu during the preimplantation period. Pellicer et al, 1996 • Is it secondary to insufficient P during implantation window?

  25. Conclusion • Luteal coasting in high responders is a viable option if fresh transfer is desirable. • Cutoff P levels yet to be determined. • LH activity –dependent luteal support does not require additional E2 and/or P : patient comfort. • Despite extreme E2 levels, good clinical outcome is possible if endogenous P secretion is high enough during implantation window. Thank you

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