1. Triggers and Luteal Support What, Why and How?
Paul Brezina, MD/MBA
Director of Reproductive Genetics: Fertility Associates of Memphis
Consulting Gynecologist: St. Jude Children's Research Hospital
Assistant Clinical Professor: Vanderbilt University School of Medicine
Director of clinical genetic applications: advagenix, llc

2. Disclosures Advagenix LLC Minority Partner
Director of Clinical Genetic Applications
PGS
PGD
Preconception Carrier Screening
Non Invasive Prenatal Testing
Other Genetic Testing

3. Case: “Jenny and Bob T” 32 year old G0 Male factor infertility
AFC = 25
AMH = 3.1
FSH= 6.2
LH = 5.9
E2=42
BMI = 28

4. Big Questions What is the best protocol? What is the best trigger
Pregnancy outcomes
Cost
Safety
What is the best trigger
hCG
Lupron
What is the best luteal support?
Injectable progesterone
Vaginal progesterone

5. Progesterone: What’s the big deal?
Maintenance of early pregnancy depends on the production of progesterone by the corpus luteum
Between 7 and 9 weeks of gestation the developing placenta takes over the progesterone production

6. Luteal Phase Deficiency
Progesterone
Estrogen
Fetus
Placenta
Corpus
Luteum
Ovary
Uterus
HCG

7. Luteal Phase Deficiency
Progesterone
Estrogen
Fetus
Placenta
Corpus
Luteum
Ovary
Uterus

8. So…. We treat most everybody with progesterone
IUI
RPL
IVF
Why is it different in IVF?

9. (Removes Granulosa Cells)
Luteal Support in IVF
Fresh Embryo Transfer IVF
Frozen Embryo Transfer IVF
Extra
Progesterone
Added
Estrogen
Progesterone
Added
Progesterone
Estrogen
Ovary
Ovary
Fetus
Fetus
Placenta
HCG
Placenta
Uterus
Uterus
Retrieval
(Removes Granulosa Cells)
Supplementation
Replacement

10. Fresh IVF Progesterone
Progesterone support is superior to no support
Best method of support: Debated
Optimal support
Work well
Minimal side effects
Ease of administration
Hubayter ZR, Muasher SJ. Luteal supplementation in in vitro fertilization: more questions than answers. Fertil Steril 2008; 89(4):749–758
Yanushpolsky EH. Luteal phase support in in vitro fertilization. Semin Reprod Med Mar;33(2):

11. Fresh IVF Progesterone
IM Progesterone
Pro
Long track record
“It has to be getting in”
Cons
Big Needle
Disturb surrounding tissue
Vessels (Hematoma)
Nerves
Vaginal Progesterone
Pro
Ease of use (no needles)
No disturbance of surrounding tissues
Excellent outcome data
Cons
Less long term data
Administration errors
Messy
Hubayter ZR, Muasher SJ. Luteal supplementation in in vitro fertilization: more questions than answers. Fertil Steril 2008; 89(4):749–758
Yanushpolsky EH. Luteal phase support in in vitro fertilization. Semin Reprod Med Mar;33(2):

12. Fresh IVF Progesterone: In our center
In our center we use Vaginal progesterone as 1st line for fresh ET
We still utilize IM Progesterone if patient prefers

13. Frozen ET Progesterone
IM Progesterone
Pro
Long track record
“It has to be getting in”
Cons
Big Needle
Disturb surrounding tissue
Vessels (Hematoma)
Nerves
Vaginal Progesterone
Pro
Ease of use (no needles)
No disturbance of surrounding tissues
Cons
Less long term data
? Efficacy concerns
Administration errors
Messy
Hubayter ZR, Muasher SJ. Luteal supplementation in in vitro fertilization: more questions than answers. Fertil Steril 2008; 89(4):749–758
Yanushpolsky EH. Luteal phase support in in vitro fertilization. Semin Reprod Med Mar;33(2):

14. Triggers
GnRH
FSH LH E2
Progesterone

15. Lupron Down Regulated Cycle
Triggers
Lupron Down Regulated Cycle
Antagonist Cycle
Lupron
Trigger
GnRH
GnRH
FSH LH
FSH LH
HCG
Trigger E2
Progesterone E2
Progesterone

16. Lupron Trigger Principally utilized to prevent OHSS
Only several case reports with Lupron trigger
Only with antagonist cycles
Reduced pregnancy rates with FRESH transfers
Some data shows improvement with aggressive E2 and P4 luteal support
Some have utilized low dose hCG concurrently with Lupron trigger
Reported lower OHSS rates while preserving rates of pregnancy success.
Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C. Comparison of "triggers" using leuprolide acetate alone or in combination with low-dose human chorionic gonadotropin. Fertil Steril Jun 30;95(8):
Griffin D, Benadiva C, Kummer N, Budinetz T, Nulsen J, Engmann L.Dual trigger of oocyte maturation with gonadotropin-releasing hormone agonist and low-dose human chorionic gonadotropin to optimize live birth rates in high responders. Fertil Steril Jun;97(6):
Lin MH, Wu FS, Lee RK, Li SH, Lin SY, Hwu YM. Dual trigger with combination of gonadotropin-releasing hormone agonist and human chorionic gonadotropin significantly improves the live-birth rate for normal responders in GnRH-antagonist cycles. Fertil Steril Nov;100(5):
Casper RF. Basic understanding of gonadotropin-releasing hormone-agonist triggering. Fertil Steril Apr;103(4):
Shapiro BS, Andersen CY. Major drawbacks and additional benefits of agonist trigger-not ovarian hyperstimulation syndrome related. Fertil Steril Apr;103(4):
Youssef MA, Van der Veen F, Al-Inany HG, Mochtar MH, Griesinger G, Nagi Mohesen M, Aboulfoutouh I, van Wely M. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist-assisted reproductive technology. Cochrane Database Syst Rev. 2014
Yding Andersen C, Vilbour Andersen K. Improving the luteal phase after ovarian stimulation: reviewing new options. Reprod Biomed Online May;28(5):552-9.
Engmann L, Benadiva C. Agonist trigger: what is the best approach? Agonist trigger with aggressive luteal support. Fertil Steril Mar;97(3):531-3 .

17. hCG Trigger Standard method of triggering
Any type of IVF stimulation cycle
Exposure to OHSS
Coasting
May minimize dose of hCG trigger
Seyhan A, Ata B, Polat M, Son WY, Yarali H, Dahan MH. Severe early ovarian hyperstimulation syndrome following GnRH agonist trigger with the addition of 1500 IU hCG. Hum Reprod Sep;28(9):2522-8
Lin YH, Huang MZ, Hwang JL, Chen HJ, Hsieh BC, Huang LW, Tzeng CR, Seow KM. Combination of cabergoline and embryo cryopreservation after GnRH agonist triggering prevents OHSS in patients with extremely high estradiol levels--a retrospective study. J Assist Reprod Genet Jun;30(6):753-9.

18. Case: “Jenny and Bob T” 32 year old G0 Male factor infertility
AFC = 25
AMH = 3.1
FSH= 6.2
LH = 5.9
E2=42
BMI = 28

19. Big Questions What is the best protocol? What is the best trigger
Pregnancy outcomes
Cost
Safety
What is the best trigger
hCG
Lupron
What is the best luteal support?
Injectable progesterone
Vaginal progesterone