1. © Fertility Centers of Illinois1 Freeze-All Policy: Fresh vs. Frozen- Thawed embryo transfer in PCOS patients Jane Nani, M.D. November 17, 2015

2. © Fertility Centers of Illinois2 PCOS: most common endocrinopathy in women of reproductive age.

3. © Fertility Centers of Illinois3 Bilaterally Enlarged Ovaries

4. © Fertility Centers of Illinois4 PCOS and IVF

5. © Fertility Centers of Illinois5 Overt Ovarian Enlargement

6. © Fertility Centers of Illinois6 Hyperstimulation Syndrome Ovarian enlargement Bloating and swelling of the abdomen Blood clots Ovarian torsion Free fluid in the pelvis

7. © Fertility Centers of Illinois7 PCOS and OHSS PCO patients are inherently at risk of OHSSPCO patients are inherently at risk of OHSS Early OHSSEarly OHSS - Late OHSSLate OHSS – Early: pre-ovulatory response to gonadotropins Late: occurrence of pregnancy – more severe Mathur RS, et al., F&S (2000 May)

8. © Fertility Centers of Illinois8 OHSS Strategies Prevention!!

9. © Fertility Centers of Illinois9 Prevention Strategies Cycle cancellation Coasting Pellicer A, Hum Reprod (2014 Jul) GnRH agonist trigger Manzanares MA, et al., F&S, (2010 Mar) Metformin Palomba S, et al,. BJOG (2013 Feb) Cabergoline Guvedag ES, et al., Gyne Endo (2013 Aug) Albumin infusion Chen CD, et al., F&S (1997 Aug)

10. © Fertility Centers of Illinois10 FCI: Policy for Freeze-All vs. Cycle cancellation Standards for patient using HCG E2: 5000-6000 If < 35 eggs, auto. Day 5 ET If > 35 eggs retrieved, FA If E2 > 6000, cance l Standards for pts. using Lupron If < 35 follicles, and E2 < 7500, ok to proceed with ET, per MD If E2 > 7500, cancel IF 50 or more follicles, cancel

11. © Fertility Centers of Illinois11 IVF: 1/2014- 8/2015. 346 PCOS pts Defined by Rotterdam criteria Ages: range 22-43 Average Age: 32.9 yrs. BMI: range 19-49 Average BMI: 28.2 Range In egg number: 6-60 Average number of eggs: 21 22 had more than one retrieval

12. © Fertility Centers of Illinois12 PCOS Diagnosis Rotterdam (2003) Diagnostic criteria for PCOS- two out of three of : Clinical Hyperandrogenism (Ferriman-Gallwey Score >8) or Biochemical Hyperandrogenism (Elevated Total/Free Testosterone) OR Oligomenorrhea (Less Than 6-9 Menses per Year) or Oligo-Ovulation OR Polycystic Ovaries on Ultrasound (>= 12 Antral Follicles in One Ovary or Ovarian Volume >= 10 cm3)

13. © Fertility Centers of Illinois13 Ovulation Triggers HCG: 172 Ovidrel: 53 Lupron: 86 Lupron + HCG: 55 Ovidrel + HCG: 2 TOTAL: 368

14. © Fertility Centers of Illinois14 Severe OHSS: Culdocentesis 14 PCOS patients met criteria for severe OHSS All required culdocentesis for symptomatic relief 8 required more than one culdocentesis –1 had 5 taps –1 had 4 taps –2 had 2 taps –6 had single taps –4 had 3 taps each

15. © Fertility Centers of Illinois15 Culdocentesis

16. © Fertility Centers of Illinois16 OHSS Patients : 3 Taps 1.H.P.: 55 eggs retrieved FA cycle Lupron + HCG trigger 2.N.S.: 20 eggs retrieved Fresh ET Positive HCG Live birth HCG trigger 3. R.T.: 24 eggs retrieved FA cycle HCG trigger 4. D.M.: 21 eggs retrieved Fresh ET HCG trigger Ongoing pregnancy

17. © Fertility Centers of Illinois17 Outcomes Fresh: PR/TR: 129/225 = 57.3% (CI: 0.508 to 0.636) / 3.5% OHSS Frozen: PR/TR: 84/121 = 69.4% (CI: 0.607 to 0.769) / 0.5% OHSS Difference between OHSS rates: non-significant: p = 0.572 Combined Fresh + Frozen = 213/346 = 62% (CI: 0.563 to 0.665) Difference between Fresh vs Frozen: Statistically significant: p=0.028* (Fisher’s Exact test/2 tailed p-value)

18. © Fertility Centers of Illinois18 Conclusions PCOS pts are at risk for OHSS with COH Avoidance of ET does not eliminate OHSS Avoid HCG trigger FET results exceed fresh ET

19. © Fertility Centers of Illinois19 Collaborators Angeline N. Beltsos, MD Eve C. Feinberg, MD Jennifer Hirshfeld-Cytron, MD Laurence A. Jacobs, MD Brian R. Kaplan, MD Edward L. Marut, MD John J. Rapisarda, MD Allison K. Rogers, MD Christopher S. Sipe, MD Meike L. Uhler, MD Sue Jasulaitis: clinical research Embryology: Juergen Liebermann Eliss Pelt Rebecca Brohammer Sara Sanchez Yuri Wagner

20. © Fertility Centers of Illinois20 Thank You