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Chronic endometritis, endometriosis and the microbiota’s role in implantation

Dominique de Ziegler

Foch-ART Center Suresnes France

Pr Jean Marc AyoubiPr René FrydmanPr Philippe BouchardDr Paul PirteaDr Marine Poulain

Disclosures: D. de Ziegler, MD

Served on the advisory board of: • IBSA Pharmaceuticals

• Ferring Pharmaceuticals• Teva Pharmaceuticals• Seventure Partners

• Nath Goldberg and Myer, LLC

Holds equity interest in:• Ultrast Inc.

• Medicalship Sagl.

Donor egg and frozen embryo transfer (FET)

Inflammation: Chronic endometritis (CE)

Role of the microbiota

Window of endometrial vulnerability

Endometriosis and the uterus


35 years later:Never surpaased


0 1 2 3 4 weeks

E2

P4300

0.4

0.2

(mg)

20 24-6

Day 20 Day 24

Endometrial glands Endometrial stroma

(mg)

Window of receptivity (WOR): controlled by duration of exposure to P4

0 1 2 3 4 weeks

E2

P4300

0.4

0.2

(mg)

20 24-6


(mg)

WOR


Parenteral Oral Vaginal Transdermic

Poorbioavailability

Poor permeability

First described


http://www.acclaimimages.com/usepolicy.html

Parenteral Oral Vaginal Transdermic

Poorbioavailability

Poor permeability

First described

New self-injectable P4 (25mg/d)


http://www.acclaimimages.com/usepolicy.html

25 & 50mg: 100% decidua-lized endomriumNo difference between the 2 doses tested

de Ziegler et al. Fertil Steril 2013

The Endometrium and IVF

Sator et al. Gyn End 2013;29:205-8.

de Ziegler et al. Fertil Steril 2013

0

2

4

6

8

10

12

0 1 2 3 4 5 6 7 8 9 10 11

Days since the beginning of treatment

Pro

gest

ero

ne n

g/m

l

MEAN progesterone level

(ng/ml)x 50 mg

MEAN progesterone level

(ng/ml)x 25 mg

steady state


Fertil Steril 2019

Progesterone production increases during early pregnancy

Progesterone production luteal phase 25mg/day

de Ziegler D, Borghese B, Chapron C. The Lancet 2010;376:730-8..

Chronic endometritis (CE): Often associated w/ endometriosis

Fertil Steril 2017


Reproductive Sciences 2016

Endometrial stromal fibroblasts gene expression when exposed to E2 and P4 in women w/ (red) and w/o endometriosis (blue).

Resistance to progesterone lifted by ovarian suppression


Reprod Biomed Online 2015;31:647–54.

We can, therefore conclude, that the endometrial

receptivity gene signature during the window of

implantation, as determined by the ERA array, is similar

in infertile women with and without endometriosis, also after sub-analysis for different stages of endometriosis.

The deferred ET option (Def-ET)

The bottle neck of ART

The GnRH trigger option

no hCGAntagonist

temporary ovarian suppression

GnRH-a vs. OC


de Ziegler D, Borghese B, Chapron C. The Lancet 2010;376:730-8..

Endometrial receptivity in endometriosis

Ovarian effects on endometrium

Our workinghypothesis

To optimize endometrial receptivity, disconnect uterus from ovaries


Fertil Steril 2016;105:844-54.

Chronic EndometritisHistology on endometrial biopsies

Bacteriology

Hysteroscopy: micropolyps

Classical

Genic Signature

Fertil Steril 2018 in press

Ongoing PROngoing PR

Clinical PR

Implantation R

CE

Ongoing PR

Clinical PR

Implantation R

curedCE

Plus One 2014

2014


Fertil Steril 2017


Fertil Steril 2017

42.338.5 38.5

15.4 14.1 14.1

0

20

40

60


Fertility Sterility 2019


2019


Fertility Sterility 2017


2017


2019


The endometrium is vulnerable to alterations created by hormone imbalances that are susceptible of inducing lasting obstetrical consequences


0 1 2 3 4 weeks

E2

P4300

0.4

0.2

(mg)

20 24-6


(mg)

WOR

Window of endometrial vulnerability (WEV)

New concept: Window of Endometrial Vulnerability (WEV)


Low birth weight


The results of this cumulative meta-analysis confirm that the

decreased risks of small for gestational age, low birth weight and

preterm delivery and increased risks of large for gestational age

and high birth weight associated with pregnancies conceived from

frozen embryos have been consistent in terms of direction

and magnitude of effect over several years, with increasing

precision around the point estimates.


Munro et al. MHR, 2010



Dominique de Ziegler

Foch-ART Center Suresnes France

Pr Jean Marc AyoubiPr René FrydmanPr Philippe BouchardDr Paul PirteaDr Marine Poulain

chronic endometritis, endometriosis and the …cme-utilities.com/mailshotcme/material for...

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