260 likes | 430 Views
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.
E N D
Luteal support post agonist trigger for OHSS prevention: The introduction of "luteal coasting" as a novel approach. ShaharKol 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 Natural cycle day 7-9= 750 pg/ml vs. 184 Nevo et al, 2003
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
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
Conclusion: complete luteolysis by day of OPU + 5 Implication: luteal support is mandatory
Luteal phase post agonist trigger in high responders • Freeze all • Fresh transfer
LUTEAL PHASE: INTENSIVE E+P OHSS high-risk patients Engmann et al, 2008
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
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
hCG (1,500IU) day 3 after oocyte retrieval Haas et al, 2014
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???
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.
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.
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.
Case #1, P post agonist trigger BETA=316 ET hCG 1,500 IU
Outcome • Moderate OHSS • Ongoing singleton pregnancy
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.
Case #2, P post agonist trigger BETA=174 ET hCG 1,500 IU
Outcome • No OHSS • Ongoing twin pregnancy
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?
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