FreezeAll Policy Fresh vs Frozen Thawed embryo transfer

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

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

Bilaterally Enlarged Ovaries 3 © Fertility Centers of Illinois

PCOS and IVF Exaggerated response to Ovulation induction 4 © Fertility Centers of Illinois

Overt Ovarian Enlargement 5 © Fertility Centers of Illinois

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

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

OHSS Strategies Prevention!! 8 © Fertility Centers of Illinois

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

FCI: Policy for Freeze-All vs. Cycle cancellation Standards for patient using HCG Standards for pts. using Lupron E 2: 5000 -6000 If < 35 eggs, auto. Day 5 ET If > 35 eggs retrieved, FA If E 2 > 6000, cancel • If < 35 follicles, and E 2 < 7500, ok to proceed with ET, per MD • If E 2 > 7500, cancel • IF 50 or more follicles, cancel • • 10 © Fertility Centers of Illinois

IVF: 1/2014 - 8/2015. • • • 11 346 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 © Fertility Centers of Illinois

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 cm 3) 12 © Fertility Centers of Illinois

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

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 14 © Fertility Centers of Illinois

Culdocentesis 15 © Fertility Centers of Illinois

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

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) 17 © Fertility Centers of Illinois

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

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 19 © Fertility Centers of Illinois Sue Jasulaitis: clinical research Embryology: Juergen Liebermann Eliss Pelt Rebecca Brohammer Sara Sanchez Yuri Wagner