Disclosure. Lyubov Mykhaylshyn IVF department Alternativa clinic Lviv, Ukraine

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2 Disclosure Lyubov Mykhaylshyn IVF department Alternativa clinic Lviv, Ukraine I do not currently have, nor have I had in the 12 months preceding the activity, a vested interest or affiliation with any organization that may be perceived as a potential conflict of interest, or any affiliation with an organization whose philosophy may bias my presentation.

3 EXCEMED WORKSHOP Improving success in ART: how to define it and key strategies to get the best outcomes Kiev, Ukraine - 21 September 2018 Are we ready for freeze-all strategy for all patients? If so, what is the best frozen embryo transfer protocol? Lyubov Mykhaylyshyn Ukraine

4 Objectives The reasons of the rise in the number of frozen embryo transfers(fets) Fresh versus FET : clinical and safety outcomes What is the optimal endometrial preparation protocol

5 Proportion of FET cycles compared with fresh IVF, ICSI cycles in the US Proportion of FET cycles compared with fresh IVF, ICSI cycles in the Netherlands

6 The reasons of the rise in the number of FETs developments in laboratory techniques increased a number of an embryos available after each treatment cycle elective single embryo transfer replacement of slow freeze cryopreservation by vitrification preimplantation genetic testing introduction of freeze-all strategies to prevent many of the detrimental aspects concerns for detrimental effect of controlled ovarian stimulation on endometrial receptivity in a fresh cycle

7 Nucleolar channel systems, G. Zapantis Effect of COS on endometrial receptivity in a fresh cycle Expression of pinopodes, Nikas Progesterone levels, E. Bosch Subnuclear vacuole, P. Devroey

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10 Freeze-all vs conventional IVF Live birth rate

11 Freeze-all vs conventional IVF Miscarriage rate OHSS

12 Freeze-all vs conventional IVF Birth weight of babies born Pregnancy complications

13 VOL. 109 NO. 2 / FEBRUARY 2018 risks of placenta previa, placental abruption, LBW, VLBW, VPTB, SGA, and perinatal mortality with frozen embryos LGA,PIH, postpartum hemorrhage with frozen embryos VOL. 101 NO. 1 / JANUARY 2014 risks PTB, LBW and SGA with frozen embryos LGA, PIH, placenta accreta with frozen embryos

14 preterm birth risks of SGA, LBW, APH, perinatal mortality with frozen embryos risks of LBW, VLBW, perinatal mortality, HBW, VHBW with frozen embryos

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16 The risk ratio for LGA neonates in SP resulting from blastocyst- vs cleavage-stage ET

17 VOL. 104 NO. 6 / DECEMBER 2015

18 August 11, 2016 VOL. 109 NO. 2 / FEBRUARY 2018 LBR, risks of LGA, pre-eclampsia OHSS, PL with frozen embryos risks of LGA in SP, pre-eclampsia in TP with frozen embryos

19 VOL. 107 NO. 3 / MARCH 2017

20 Freeze all for slower developing blastocysts El-Toukhy et al, BJOG 2011; 118;

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23 Premature progesterone elevation in COS

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25 Types of endometrial preparation protocols for FET NC-FET AC-FET OS-FET tnc-fet mnc-fet without a-gnrh with a-gnrh Gn AI Cl

26 tnc-fet The definition of what constitutes an LH surge -an increase of the level of LH beyond 180% of the mean level observed in the previous 24 h (Frydman et al., 1982) -a concentration of 180% above the latest serum value available in that patient with a continued rise thereafter (Testart et al., 1981) -level of 10 IU/l or more (Groenewoud et al., 2017) LH surge detection Necessity for luteal phase support in tnc-fet

27 Luteal phase support in tnc- FET

28 mnc-fet The effect of hcg on the endometrial quality Monitoring approach in patients undergoing mnc-fet The impact of elevated progesterone and LH level prior hcg triggering The necessity for luteal phase support

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30 What is your prefered monitoring approach in patients undergoing mnc-fet?

31 The impact of elevated progesterone levels prior to hcg triggering in mnc-fet cycles E.R. Groenewoud, N.S. Macklon, B.J. Cohlen et all, Hum Reprod. 2016; 31: ANTARCTICA trial, NTR 1586

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34 LPS in tnc-fet, mnc-fet S. Mackens, S. Santos-Ribeiro et all Human Reproduction, Vol.32, No.11 pp , 2017 M. Montagut, S. Santos-Ribeiro et all Human Reproduction, Vol.31, No.12 pp , 2016

35 Eva R. Groenewoud, 2013 tnc-fet vs mnc-fet

36 AC-FET, AC-FET+a-GnRH What type of estrogen administration route? What is the minimal and maximum duration of estrogen supplementation in follicular phase? What is the incidence of premature ovulation in AC- FET?

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40 What is the incidence of ovulation in AC without a-gnrh?

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43 Protoco l The cost-efficiency analysis Cost, mnc-fet 617,50 p 0,54 AC-FET 625,73

44 AC vs OS with Gn or AI: pooled results of all studies Hakan Yarali, Mehtap Polat et all. J Assist Reprod Genet (2016) 33:

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46 Take-home message Freeze all is not yet for all patients Freeze all for: patients with a risk of OHSS, PGT, RIF?(window of implantation); FET results in lower risks of preterm delivery, LBW, SGA and higher risk of a LGA, hypertensive disoders, high birth weight It is not possible to recommend one method of endometrium preparation over another now Routine use of luteal phase support in tnc-fet, mnc-fet has not been shown to be advantageous Minimal duration of both estrogen and progesterone supplementation need further clarification

47 One size does not fit all Thank you!

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