Is embryo cryopreservation causing

macrosomia – and what else?

Raoul Orvieto M.D.

- Department of Obstetrics and Gynecology,

Chaim Sheba Medical Center, Ramat Gan, Israel

- The Tarnesby-Tarnowski Chair for Family Planning and Fertility

Regulation, Sackler Faculty of Medicine, Tel-Aviv University, Israel.

1

No relevant financial relationships

to disclose

Ratio of FET VS fresh cycles RR live birth FET/fresh

Frozen ET

Improvement in Cryopreservation

technology

Transferring fewer embryos

Advantages of Cryopreservation

• Increase cumulative pregnancy rate per cycle

• Facilitate elective single ET

• Prevent late OHSS

• Endometrial pathology / substandard endometrium

• Simplify donor oocyte process

• Fertility preservation

PR/LBR Pregnancy complications

Fresh vs Frozen ET

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FETFresh

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(2019)

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The underlying mechanisms

-----------------------------------------------------ART procedures Maternal factors

COH- high E2

Culture media

The length of time in culture

Manipulation of gametes and embryos

Freezing….

Subfertile women who conceived

without the aid of ART and yet

exhibited an increased risk of

obstetrics complications (Hayashi et al 2012; Marino et al 2014; Zhu et al 2006; 2007).

14Luke et al 2017

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(2019)

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The supraphysiological hormone levels produced by ovarian stimulation in fresh

cycles may affect implantation as well as growth and development of the embryo.

(Imudia et al 2012)

Synchronization between the endometrium and embryos at the time of transfer is

more accurate in frozen cycles and that the uterine environment in frozen cycles

is generally more natural than that following hormonal stimulation of the ovaries

in fresh cycles.

Epigenetic changes during the early embryonic stages as a result of the freezing

and thawing procedures might alter developmental processes and intrauterine

growth potential in FET offspring .Frozen embryos yielding epigenetic patterns

and gene expression more similar to natural conception. (Estill et al 2016; Ghosh et al 2017)

The cause of increased risk of macrosomia and

LGA

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IVF group- mice embryos

resulting from superovulation,

IVF, in vitro culture, and

embryo transfer

Vitrified group- embryos that

were vitrified

Control group- day 14 fetuses

that arose from copulation

Both IVF groups showed loss of methylation in both genes’ DMDs, although a greater loss

was seen in the vitrified group.

This suggests a potential mechanism of vitrification resulting in reversal of the epigenetic

effects of superovulation on the oocyte, with consequentially larger babies.

(2010)

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FET and other pregnancy complications

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Type of endometrial preparation

(2013)

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(2017)

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(2019)

(2019)

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(2019)

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THANK YOU

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