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

Nevo et al, 2003

Natural cycle day 7-9=75 pg/ml vs. 18

Natural cycle day 7-9=

750 pg/ml vs. 184

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 + 5Implication: luteal support is mandatory

LUTEAL PHASE POST AGONIST TRIGGER IN HIGH RESPONDERS

• Freeze all• Fresh transfer

Engmann et al, 2008

LUTEAL PHASE: INTENSIVE E+P

OHSS high-risk patients

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 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 corpura lutea.

• 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

trigger OPU+2 OPU+3 OPU+170

40

80

120

160

200

P levels

P

hCG 1,500 IU

ET

BETA=316

CASE #1: E2 AND LH POST AGONIST TRIGGER

Trigger OP+2 OPU+3 OPU+170

5000

10000

15000

20000

E2

E2

Trigger OPU+2 OPU+30

1

2

3

4

LH

LH

OUTCOME

• Moderate OHSS

• Ongoing singleton pregnancy

• 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

CASE #2, P POST AGONIST TRIGGER

OPU OPU+1 OPU+2 OPU+7 OPU+140

20406080

100120140160180200

P

PhCG 1,500 IU

ET

BETA=174

CASE #2: E2 AND LH POST AGONIST TRIGGER

OPU OPU+1 OPU+2 OPU+7 OPU+140

2000400060008000

1000012000

E2

E2

OPU OPU+1 OPU+2 OPU+701234567

LH

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