Disclosure

Lyubov MykhaylshynIVF department“Alternativa” clinicLviv, 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.

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

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

Proportion of FET cycles compared with fresh IVF, ICSI cycles in the US 2005 - 2014

Proportion of FETcycles compared with fresh IVF, ICSI cycles in the Netherlands 1996-2015

The reasons of the rise in the number of FETs

• developments in laboratory techniques increased a number of anembryos 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 thedetrimental aspects

• concerns for detrimental effect of controlled ovarian stimulation onendometrial receptivity in a fresh cycle

Effect of COS on endometrial receptivityin a fresh cycle

Nucleolar channel systems, G. Zapantis

Subnuclear vacuole, P. Devroey

Expression of pinopodes, NikasProgesterone levels, E. Bosch

Freeze-all vs conventional IVFLive birth rate

Freeze-all vs conventional IVFMiscarriage rate

OHSS

Freeze-all vs conventional IVFBirth weight of babies born

Pregnancy complications

↓ risks of placenta previa, placentalabruption, LBW, VLBW, VPTB, SGA,and perinatal mortality with frozenembryos↑ LGA,PIH, postpartum hemorrhagewith frozen embryos

↓ risks PTB, LBW and SGA withfrozen embryos↑ LGA, PIH, placenta accreta withfrozen embryos

VOL. 101 NO. 1 / JANUARY 2014VOL. 109 NO. 2 / FEBRUARY 2018

↓ preterm birth risks of SGA, LBW, APH, perinatal mortality with frozen

embryos

↓ risks of LBW, VLBW, perinatalmortality, ↑HBW, VHBW with frozen

embryos

The risk ratio for LGA neonates in SP resulting from blastocyst- vscleavage-stage ET

VOL. 104 NO. 6 / DECEMBER 2015

↑LBR, risks of LGA, pre-eclampsia↓OHSS, PL with frozen embryos

↑ risks of LGA in SP, pre-eclampsia in TP with frozen embryos

August 11, 2016

VOL. 109 NO. 2 / FEBRUARY 2018

VOL. 107 NO. 3 / MARCH 2017

Freeze all for slower developing blastocysts

El-Toukhy et al, BJOG 2011; 118; 1551-1556

Premature progesterone elevation in COS

Types of endometrial preparation protocols for FET

NC-FET

mNC-FET

AC-FET OS-FET

tNC-FET withouta-GnRH

witha-GnRH

Gn

Cl

AI

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

Luteal phase support in tNC-FET

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 priorhCG triggering

• The necessity for luteal phase support

What is your prefered monitoring approach in patients undergoing mNC-FET?

E.R. Groenewoud, N.S. Macklon, B.J. Cohlen et all, Hum Reprod. 2016; 31: 1483-1492 ‘ANTARCTICA’ trial, NTR 1586

The impact of elevated progesterone levels prior to hCGtriggering in mNC-FET cycles

LPS in tNC-FET, mNC-FET

S. Mackens, S. Santos-Ribeiro et all Human Reproduction, Vol.32, No.11 pp. 2234–2242, 2017

M. Montagut, S. Santos-Ribeiro et all Human Reproduction, Vol.31, No.12 pp. 2803–2810, 2016

tNC-FET vs mNC-FET

Eva R. Groenewoud, 2013

AC-FET, AC-FET+a-GnRH

• What type of estrogen administration route?

• What is the minimal and maximum duration ofestrogen supplementation in follicular phase?

• What is the incidence of premature ovulation in AC-FET?

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

The cost-efficiency analysis

Protocol

Cost, € p

mNC-FET 617,50

0,54

AC-FET 625,73

AC vs OS with Gn or AI: pooled results of all studies

Hakan Yarali, Mehtap Polat et all. J Assist Reprod Genet (2016) 33:1287–1304

Take-home message

• Freeze all is not yet for all patients

• Freeze all for: patients with a risk of OHSS, PGT, RIF ?(window ofimplantation);

• FET results in lower risks of preterm delivery, LBW, SGA andhigher risk of a LGA, hypertensive disoders, high birth weight

• It is not possible to recommend one method of endometriumpreparation over another now

• Routine use of luteal phase support in tNC-FET, mNC-FET hasnot been shown to be advantageous

• Minimal duration of both estrogen and progesteronesupplementation need further clarification

One size does not fit all

Thank you!