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
Natural cycle day 7-9=
750 pg/ml vs. 184
Nevo et al, 2003

SUMMARY
•
•
The lower levels of luteal steroidal and nonsteroidal 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

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 E 2 level daily. Individualized approach.
• Trigger with hCG when E 2 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 corpura lutea.
• No need for additional P and /or E 2 .

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.

200
150
100
50
0 trigger
CASE #1, P POST AGONIST TRIGGER
BETA=316
ET
P levels hCG 1,500 IU
OPU+2
P
OPU+3 OPU+17

CASE #1: E2 AND LH POST AGONIST TRIGGER
E2
20000
15000
10000
5000
0
Trigger OP+2 OPU+3 OPU+17
LH
E2
4
3
2
1
0
Trigger OPU+2 OPU+3
LH

• Moderate OHSS
• Ongoing singleton pregnancy
OUTCOME

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.

200
150
100
50
0
CASE #2, P POST AGONIST TRIGGER
P
ET hCG 1,500 IU
OPU OPU+1 OPU+2 OPU+7
BETA=174
OPU+14
P

CASE #2: E 2 AND LH POST AGONIST TRIGGER
E2
15000
10000
5000
0
OPU OPU+1 OPU+2 OPU+7 OPU+14
E2
LH
8
6
4
2
0
OPU OPU+1 OPU+2 OPU+7
LH

• No OHSS
• Ongoing twin pregnancy
OUTCOME

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