Protocol for COH in PCOS women undergoing IVF cycles

1. Controlled Ovarian
Hyperstimulation for PCOS
ByBy
Osama Abdalmageed, MDOsama Abdalmageed, MD
Assiut University ART UnitAssiut University ART Unit
20172017

2. This presentation will try to cover:
 Introduction: PCOS, COH
 COH in PCOS is challenging
 The Prospective Hyperresponders
 Individualized COH (iCOH) in PCOS
 Success for PCOS in IVF
 Which Protocol?!
The starting dose
GnRH Agonist For Pituitary Downregulation
GnRH Antagonist For Pituitary Downregulation
Advantages of the Antagonist Downregulation in the
Hyperresponders
Criteria for triggering of ovulation in COH
GnRH agonist trigger protocol
Strategies to prevent OHSS
GnRH antagonist to abort OHSS

3. Introduction
PCOS
Common 8-25%
70% infertile.
Rotterdam criteria,
2004.
Lines of infertility
ttt, ASRM,2007.

4. COH in PCOS is Challenging! WHY?!
 Initial poor response.
 Later sudden exaggerated “explosive”
response.
 High risk to develop OHSS. (life
threatening condition)
? Immature oocytes, Fertilization rate,
Cleavage rate, Implantation rate,
Multiple pregnancies, Miscarriage rate,
Birth weight,

5. The Prospective Hyperresponders:
 age < 30 years
 PCO patient (> 24 antral follicles present
on baseline ultrasound examination),
 high number of AFC(>15-20),
 high LH to FSH ratio(>1.5),
 previous episodes of OHSS,
 and/or high AMH levels(> 3.36 ng/mL)
SOGC, 2014
Prediction of ovarian response in PCOS= Combination ofPrediction of ovarian response in PCOS= Combination of
AMH and AFCAMH and AFC

6. Individualized COH (iCOH) in PCOS:
• Improve the cumulative LBR.
• Harvesting fertilizable, good quality oocytes.
• Cryopreservation of good quality embryos.
• Reduce stimulation burden and multiple gestation.
• Avoid OHSS.
Optimization of the total reproductive potentialOptimization of the total reproductive potential viavia
embryo cryopreservationembryo cryopreservation should be considered theshould be considered the
cornerstone targetcornerstone target forfor potentiation the successpotentiation the success of IVF inof IVF in
PCOS.PCOS.
Oehninger et al., 2005

7. Success for PCOS women undergoing IVF
““single live birthsingle live birth without OHSSwithout OHSS””
Sunkara et al.
(2011)
Je et al.
(2013)
Baker et al.
(2015)
Retrospective
400,135 cycles
Large retrospective study SART data analysis
231,815 cycles
Increase LBR till 15 retrieved
oocytes.
Plateau LBR between 15 and
20 retrieved oocytes.
Declining LBR after 20
retrieved oocytes.
Optimum number of
retrieved oocytes is between
6 and 15.
LBR has been increased
significantly with the increase
in the number of the
retrieved eggs.
The more retrieved oocytes
associated with significant
decrease in the life birth
weight.

8. Pre. COH for IVF workup
 Weight loss
 Metformin
 Pre ttt with COCs

9. Which Protocol?!!
The starting dose
““Theory of FSH threshold for follicle rescuing”Theory of FSH threshold for follicle rescuing”

10. Which Protocol?!!
The starting dose

11. Which Protocol?!!
The starting dose
““Usual starting dose is 75-150 units of FSH, butUsual starting dose is 75-150 units of FSH, but
the total dose of FSH should not exceed 150the total dose of FSH should not exceed 150
units.”units.”
oLow dose step up protocol.
oLow dose step down protocol.
oSequential low dose protocol.
Polat et al. , 2014
Balasch et al., 2001
Hugues et al., 1996

12. Which Protocol?!!
GnRH Agonist For Pituitary Downregulation

13. Which Protocol?!!
GnRH Antagonist For Pituitary Downregulation

14. Which Protocol?!!
Advantages of the Antagonist Downregulation in the Hyperresponders
 Simple (with similar pregnancy rates to GnRH
agonist-long-down regulation).
 Lower incidence of OHSS and cycle cancelation.
 Give the opportunity to trigger oocyte maturation
using GnRH agonist (prevent OHSS).
““GnRHGnRH antagonistantagonist protocol isprotocol is preferredpreferred by manyby many
programs for COH in the prospective hyperrespondersprograms for COH in the prospective hyperresponders
including PCOS women for the advantage of usingincluding PCOS women for the advantage of using GnRHGnRH
agonist triggeragonist trigger for oocyte maturation whichfor oocyte maturation which preventprevent
the development ofthe development of OHSSOHSS in considerable number of thein considerable number of the
high risk women.”high risk women.”

15. Which Protocol?!!
Criteria for triggering of ovulation in COH
 More than two follicles measurement
was > 17 mm.
 Two follicles measurement > 17mm & at
least two follicles measurement 15-17
mm.
 Premature P4 rise (cutoff point should be
1.5 to 1.7 in the hyperresponders: no
consistent agreement !!!).
 Can we delay the trigger for one or two
days?!!!

16. GnRH agonist trigger protocol
Assiut University IVF Center Experience
1.Trigger: Lucrin 1 mg (20 units) 36 hours prior to
planned oocyte retrieval.
2.Measure Progesterone and LH on the day after
Lucrin trigger to ensure adequate luteinization.
3.Give hCG 1500IU IM in the recovery room post
retrieval.
4.Start estradiol beginning the day after egg
retrieval.
5.Start progesterone in oil 50 mg IM daily starting the
day after egg retrieval.
6.Continue estradiol and progesterone support till 10
weeks gestation (8 weeks from the day of egg
retrieval).

17. Strategies to prevent OHSS
Primary prevention
 Tailoring of personalized stimulation
protocol.
 Adjuvant agents : Metformin,
Cabergoline

18. Strategies to prevent OHSS
Secondary prevention
• Reducing the triggering hCG dose.
• Cycle cancellation.
• Coasting.
• GnRH antagonist downregulation +
GnRH agonist trigger (+/- Embryo
freezing).

19. Conclusions
 PCOS is challenging and high risk case
during COH.
 Careful starting dose is a cornerstone part
in the success of COH in PCOS.
 Antagonist protocol is the best current
available option to have the opportunity to
prevent OHSS using GnRH agonist trigger.
 Aggressive luteal phase support Vs. freeze
all strategy should be discussed with the
patient when GnRH agonist trigger is used.