Improving endometrial receptivity f

WelComeWelCome

“ DR. MANJUSHREE BOOB” M.B.B.S. M.D. D.N.B. F.I.C.M.C.H.

DIPLOMATE OF NATIONAL BOARDS

CONSULTANT OBSTETRICIAN GYNAECOLOGIST

AND INFERTILITY EXPERT

“SHUBHAM HOSPITAL”

BADNERA ROAD

AMRAVATI

By,…By,…

IMPROVING ENDOMETRIAL RECEPTIVITY IMPROVING ENDOMETRIAL RECEPTIVITY

WILL IT CHANGE IVF SUCCESSWILL IT CHANGE IVF SUCCESS

INTRODUCTION1) Definition of Endometrial Receptivity

2) Fertilization

3) Window of Receptivity

4) Formation of Decidua :

I)Nk Cells – Like

a) CD – 56 – Bright

b) CD – 16

c) CD – 3

i) Formation of –

a)Phosphoethanolamine [PE]

b) Phosphoserine [PS]

c) Cardiolipin

For SYNCYTILIZATION which is important for foetal survival

THE IMPLANTATION PROCESS

ENDOMETRIUM AT IMPLANTATION

1) Apposition

2) Adhesion

3) Invasion

1) HISTOLOGICAL CHANGES :

a) Formation of Pinpodes

b) Decrease in cell polarity and tight junction between cell.

ENDOMETRIUM AT IMPLANTATION

C) INVASION – PROTEOLYTIC ENZYMES

• Serineproteases

• Metalloproteases

• Collagenases

1) BIOCHEMICAL & MOLECULAR CHANGES-

a)APPOSITION –> Chemokinase

1) IL8 – Interlukin 8

2) MCPI – Monocyte chemo attractant protein-1

3) RANTES – Regulated on activation, T- Cell expressed and secreted

CHEMOKINES – DIRECT EMBRYO TOWARDS ITS SPECIFIC SITE OF IMPLANTATION.

b) ADHESIONS – CYTOKINES ARE RESPONSIBLE, Eg..

• LIF

• IC-I Systems

• HBGF

• INTEGRINS

• HOXA – 10

IMMUNOLOGICAL ASPECT OF IMPLANTATIONIMMUNOLOGICAL ASPECT OF IMPLANTATION

1) Increase no of Leukocytes, T-cell, mcrophages and large Granular Lymphocyte [LGL] is seen in endometrium, believed to play a role in Implantation and maintainance of Pregnancy.

2) Combination 4 & B3 integrins subunits are seen in secretary endometrium

B3 is reliable marker in opening

“WINDOW OF IMPLANTATION”

ENDOMETRIAL VASCULAR CHANGES

1) The lowest impedonce to blood flow is seen in implantation phase – Increase Vascularity – increase endometrial and stromal growth which permitts expression & efficient distribution of biochemical markers in endometrium for implantation .

ENDOMETRIAL RECEPTIVITYENDOMETRIAL RECEPTIVITY

ASSESSING ER –

1) Test to assess Endometrial change

a) Endometrial Histology

b) TV - USG & Doppler

c) Harmonal levels.

2) Evaluation of Marker’s of Embryo – Endometrial dialogue

Natural conception cycle - Implantation rate is 30%

IVF CYCLE - 12 - 20%

ENDOMETRIAL HISTOLOGY

1) By Electron Microscopy

2) Timings – Late luteal phase

3) Pitfalls – a) Reflects only regional variation in endometrium but whole morphology is not seen

b) Cannot be done in routine IVF cycle.

4) Study – STUDY OF PINPODES BY SEM i.e.. – (Scanning electron microscopy)

Its important for oocyte donation or frozen embryo transfer cycle.

There is corelation between apical projection seen on LEM [Light electron Microscopy] with pinpodes as visualised in SEM which incrcases the effectivity of routine Embreyo Transfer.

ULTRASOUND – TVS is simple non-invasive modality which is most commonly used to assess ER.

1) Endometrial thickness < 7mm- Poor endometrium

> 15mm- Poor endometrium

2) Endometrial volume < 2.5ml- Poor response

3) Echogenicity -

1. Endometrium is hypoechoic in proliferative phase

2. As thickness increase - Triple or multilayered endometrium.

3. Secretary phase - Isoechoic / hyperechoic

DOPPLER – MID LUTEL PHASE

Uterine perfusion is maximum.

• Uterine Artery flow (p1) P1 < 3 – Increased pregnancy rate in IVF Cycle.

• Sub- endometrial Blood Flow – Presence of pulsatile SE blood flow signifies Increased Implantation rate

ULTRASOUND AND DOPPELER – TO EVALUATE ER

Endometrium is divided in 4 Zones

Good Vascularity in zone 3/4th /EE in relation to uterine lumen

suggest good ER.

Controversial result in evaluating ER & PR in luteal phase in terms of pregnancy.

ENDOMETRIAL ZONES

ESTROGEN AND PROGESTERON RECEPTOR’S=>

PRACTICAL EVALUATION OF ER

1) 2 Endometrial Biopsies:-

a)1st EB :-

During “Window Of Receptivity” to look at factors for apposition and adhesions

SEE For :- Pin podes, mucin integrim, trophonin EGF, HB-EGF, CSF-1, LIF,IL-1b Calcitonin, Hoxa-10, Cox-2

b) 2nd EB:-

In late secretary phase to look for event of invasion.

Screen for- TGF-B, IGF BPI, TIMP, Fibronectin Laminin.

2 ) IMMUNOLOGICAL TEST:-

Like APA, ACA, PT, APTT. is

A must for repeated failure in IVF cycle or Cases of BOH.

TREAMENT TO IMPROVE ERUse of Aspirin, Heparin and I.V. immunologlobulin have increased pregnancy rate. With Aspirin and Heparin failure, use of IVIG has still better success rate.

ASPIRIN-

Dose of 80 mg OD is given preconceptionely and continued during pregnancy.

Mode Of Action:-

It is anti-prostaglandin and antiprostacycline effects, inhibits platelet adhesion and aggregation which increases foetomaternal circulation.

TREATMENT [contd]

B) HEPARIN -

In APA +ve cases-5000 IU of low molecular weight heparin is given twice daily.

Mode Of Action-

It Repels autoantibodies from phospholipid molecules& thus sheild trophoblast , which facilitates syncytialization and promotes proper interaction with decidua.

C) IV IMMUNOGLOBULIN [IVIG]-

APA +ve cases IVIG Should be given 7 day prior to ET and should be repeated in 4-6 weeks time . Very useful in autoimmune hypothyroidism.

D) Sildenafil-

Improves vasular supply to Endometrium giving good result in few centers.

LUTEAL PHASE SUPPORT

1) All ART cycle LPS is must

2) Drugs should be Luteo mimetic and not Luteolytic

DRUGS USED :--

1) Natural micronised Progesterone =>

i) Injectable => Inj. Gestone 100mg OD.

ii) Vaginal Pessary => 200mg. i.e. 600mg/day.

iii) Vaginal gel =>90mg of Gel/Day

2) Injection Human Corionic Gonadotrophins =>2) Injection Human Corionic Gonadotrophins =>As in ART all cases are of superovulation chances of OHSS very high.

Oestradiol Levels => a) > 2500pg/ml => No hcg. b) < 2500pg/ml => Can give hcg.Dose => 5000IU on the Day ET, 5000IU 3days later & 2500IU 6days later.

3)Dydrogesterone => Dose – 30mg/day from day of ET to 15 days after ET. 4)Combnation Regimens => hcg on the Day of Embryo Transfer in combination with vaginal progesterone 600mg/day. 5)Estradiol Valerate => 6mg estradiol Controversial role

ENDOMETRIAL PREPERATIONS IN OOCYTE ENDOMETRIAL PREPERATIONS IN OOCYTE DONATION CYCLE =>OR EMBRYO DONATION CYCLEDONATION CYCLE =>OR EMBRYO DONATION CYCLE

1) ACYCLIC Women =>ET In HRT cycle with natural Oestrogen and Progesterone.

Day of Cycle Oestradiol Valerate( Dose = 2 mg – 1 tablet)

Progesterone

D 1 to D 4Actual dates:…... to….

Nil Nil

D5Actual dates: …. to…….

1 Tablet per day Nil

D 10 to D 11Actual dates: … to.….

2 tablets per day Nil

D 12 and D 14 Actual dates : …. to……


D 15 A Actual dates:

1 tablets (a. m.) Nil

D15A or D15B D15CActual dates ….


D16Actual date……………….

1 tablet Cyclogest 400mg once

D17Actual date……………….

1 tablet Cyclogest 400mg once

D18 to D47Actual dates…… to …….

2 tablets per day Cyclogest 400mg bd







D76 to D80Actual dates….. ..to …….

tablets per day Cyclogest 400mg bd

( Contd. )

Embryo transfer regimen at Bourn Hall

CYCLIC Women =>

1)Natural cycle - as in routine IVF cycle.

2)HRT Cycle.

In the pursuit of optimizing outcome with assisted reproduction, the clinician has profound responsibility to make every attempt to enhance the environment for implantation.

THIS WILL PROMOTE NOBLE OBJECTIVE OF ENHANCING THE SUCCESS RATE OF IVF.

INDEBTED AND THANKFULL

TO ONE AND ALL

FOR

PATIENT LISTENING

Improving endometrial receptivity f

Health & Medicine

Transcript of Improving endometrial receptivity f