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Patient Management and Outcome of IVF/ICSI in Patients with Peritoneal Endometriosis and Endometriomas PowerPoint PPT Presentation


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Patient Management and Outcome of IVF/ICSI in Patients with Peritoneal Endometriosis and Endometriomas. Timur G ü rgan , MD Head and Professor Division of Reproductive Medicine and Infertility Faculty of Medicine , Hacettepe University Ankara , Turkey. pelvic factors.

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Patient Management and Outcome of IVF/ICSI in Patients with Peritoneal Endometriosis and Endometriomas

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PatientManagementandOutcome of IVF/ICSI in PatientswithPeritonealEndometriosisandEndometriomas

Timur Gürgan, MD

HeadandProfessor

Division of ReproductiveMedicineandInfertility

Faculty of Medicine,Hacettepe University

Ankara,Turkey


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pelvic factors

Pelvic inflammation (microphages producing cytokines):

interferes w/ sperm-oocyte interaction.

Affect in-vivo fertility


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pelvic factors

Pelvic inflammation (microphages producing cytokines):

interferes w/ sperm-oocyte interaction.

Affect in-vivo fertility

ovarian factors

endometriomas and

Sx. for OMAS:

affects ovarian reserve and (?) oocyte quality.


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pelvic factors

uterine factors

Pelvic inflammation (microphages producing cytokines):

interferes w/ sperm-oocyte interaction.

Affect in-vivo fertility

Increase E2 prod

and P4 resistance

Medical treatment:

favors IVF outcome (endom. Receptivity)

ovarian factors

endometriomas and

Sx. for OMAS:

affects ovarian reserve and (?) oocyte quality.


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pelvic factors

uterine factors

Pelvic inflammation (microphages producing cytokines):

interferes w/ sperm-oocyte interaction.

Affect in-vivo fertility

Increase E2 prod

and P4 resistance

Medical treatment:

favors IVF outcome (endom. Receptivity)

Sx

med TT

ovarian factors

endometriomas and

Sx. for OMAS:

affects ovarian reserve and (?) oocyte quality.

ov. Res.


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Treatment options

  • Expectant management

  • Analgesia

  • Hormonal medical therapy

    • Combined oral contraceptive pills, cyclic or continuous

    • Gonadotropin-releasing hormone (GnRH) agonists

    • Progestins, given by an oral, parenteral, or intrauterine route

    • Danazol

    • Aromatase inhibitors

  • Surgical intervention, which may be

    • conservative (retain uterus and ovarian tissue)

    • definitive (removal of the uterus and possibly the ovaries)

  • Combination therapy in which medical therapy is given before and/or after surgery


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Expectant management for infertility

Cumulative probability of a pregnancy carried beyond 20 weeksin the 36 weeks after the diagnostic laparoscopy of infertile women with minimal or mild endometriosis is not significantly lower than that of women with unexplained infertility.

Berube et al,Fertil Steril 1998;69:1034-41.


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Resection or ablation of visible endometriosis or diagnostic laparoscopy only

p<0.05

N Engl J Med 1997;337:217-22.


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Thebeneficaleffect of Laparoscopicsurgery on pregnancy rate


Resection or ablation of visible endometriosis or diagnostic laparoscopy only14 l.jpg

Resection or ablation of visible endometriosis or diagnostic laparoscopy only

N Engl J Med 1997;337:217-22.


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a

Marcoux S et al.NEJM 1997;337:217-22.

Consider

Sx + 6-18 Mo

in vivo

b

Akande VA, et al.Hum Reprod. 2004;19:96-103.

c

Vercellini P, et al. Hum Reprod. 2009;24:254-69.

Vercellini et al. Human Reprod 2009;24:254-69.


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a

Marcoux S et al.NEJM 1997;337:217-22.

Consider

Sx + 6-18 Mo

in vivo

b

Akande VA, et al.Hum Reprod. 2004;19:96-103.

c

Vercellini P, et al. Hum Reprod. 2009;24:254-69.

50%

Overall weighted mean

Vercellini et al. Human Reprod 2009;24:254-69.


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Fertil Steril 2006;86:566–71


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IUI success after surgically untreated minimal to mild endometriosis than in women with unexplained infertility.

Fertil Steril 2006;86:566–71.


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ESHRE guidelines-infertility


Eshre guidelines infertility21 l.jpg

ESHRE guidelines-infertility


Eshre guidelines infertility22 l.jpg

ESHRE guidelines-infertility


Eshre guidelines infertility23 l.jpg

ESHRE guidelines-infertility


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Med

Efficacy

No benefit

med treatment is contraceptive

Conclusion

Medical treatment of endometriosis is contraceptive.

No rebound-effect on fertility upon stopping.

Is not indicated after Sx.

Diagnosis

infertility

time


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Sx

Efficacy

COH-IUI not indicated in case of endometriosis

Conclusion

In early and late stage endometriosis, surgery facilitates in vivo pregnancies.

Indication for surgery implies:

Sperm characteristics permit in vivo pregnancy.

Ovarian reserve authorizes a 12-month waiting

Diagnosis

infertility

time


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Endometriomas

  • Adnexeal mass (14%-44%)

  • Pelvic pain

  • Infertility

    Treatment Options

  • Expectant management

  • Surgery

    Aspiration

    Fenestration

    Ablation,coagulation

    Cystectomy

    Recurrence of the endometriomas is an important issue ! (18%-30%)


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Treatment of Endometriomas

  • Medical therapy alone has a limited role

  • Operative laparoscopy represents the first-line treatment Chapron et al.,2002; Jones and Sutton,2002

  • Better PR and a lower rate of recurrences after laparoscopic ovarian cystectomy

  • PR after surgey vary between 23%-67%

    Elsheikh et al.,2003;Alborzi et al.,2004

  • PR significantly influenced by patients charasteristics,length of follow – up, selection criteria, adhesion score and surgical technics

    (40%-50%)

  • USG guided aspiration associated with high rate of recurrances


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There was a significantly lower pregnancy rate per fresh embryo transfer after pooled cycles (1–4) among women with stage III/IV endometriosis (22.6%) compared to stage I/II group (40.0%) or tubal infertility (36.6%). After 1–4 IVF/ICSI treatments, including frozen embryo transfer, 56.7% of the women with stage III/IV endometriosis were pregnant and 40.3% gave birth.

Kuivasaari et al, Hum Reprod, 2005


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EndometriomaCystectomyand IVF/ICSI

The average time between laparoscopic cystectomy and IVF cycle (6-24 m)


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EndometriomasandOvarianReserve

  • Mechanical streching

    Meneschi et al.,1993

    May cyst per se damage the the surrounding ovarian tissue?

    Yes ! Maneschi et al.,1993- Using pathological sections of the ovarian cortex found reduced number of follicles

    Need for clinical studies in human comparing follicular growth in the affected and contralateral intact gonad !

  • Biochemical negative influence

    Khamsi et al.,2001

  • Adhesions which typically surround affected ovaries.In a rabbit model of endometriosis endometrial implants in the gonads decreased ovulation points

    Kaplan et al.,1989


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Damage Machanisms

  • Surgery-mediateddamage

    Negativeeffect of SURGERY !?

    Presence of healthyovariantissueadjacenttoremovedthecystwall

    Muzzi et al.,2002;HachisugaandKawarabayashi,2002

    Excissionof healthyovariancortexwithfollicles

    Brosens et al.,2004

    Surgeryrelatedlocalinflamationandelectrocoagulationduringhaemostasis

    La Torre et al.,1998;Marconi et al.,2002;Fedele et al.,2004


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EndometriomaCystectomy

  • Recognizable ovarian tissue inadvertently removed 54% of the cases

  • Close to the ovarian hilus ovarian tissue remove by endometriomas consisted of mostly primary and secondary follicles

    GREAT CAUTION SHOULD BE UNDERTAKEN TO AVOID OVARIAN DAMAGE WHİLE STRIPPING THE CYST CAPSULE AND HEMOSTASIS NEAR THE HILUS !

    Muzzi et al. Fertil Steril 2002;Human Reprod,2005


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Endometriomas >3 cm


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Influance of EndometriomaCytectomy on Ovarianreserve

  • Low peak E2 levels and higher gonadotropin requrements were documented in the operated patients

  • Number of oocytes retrieved, number of embryos obtained and pregnancy rates were similar in both groups !!


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Surgery prior to IVF

bilateral endometrioma

1

Somigliana et al. Human Reprod 2009;23:1526-1530.


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Surgery prior to IVF

bilateral endometrioma

1

Casesn= 68

Controlsn= 136

Somigliana et al. Human Reprod 2009;23:1526-1530.


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Surgery prior to IVF

bilateral endometrioma

Casesn= 68

Controlsn= 136

*

PR/ sarting cycle

P=0.037

Somigliana et al. Human Reprod 2009;23:1526-1530.


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AMH?

Ovaries

Decreased ovarian response to COH:

* More FSH/hMG needed

* Less oocytes obtained


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Endometriomas and Ovarian Reserve: Insigths from IVF-ICSI Cycles in Women with Endometriomas

  • Contralateral gonad may adequately compansate for the reduced function of the affected gonad

  • The number of follicles developed in the cystectomized ovary significantly reduced when compared to the contralateral intact gonad!

  • Bilateral cysts may elevated risk of ovarian function impairement (19%-28% bilaterality)

    Prefumo et al.,2002;Al-Fozan and Tulandi,2003.Esiner et al.2006


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OvarianEndometriomas

  • Ovarian endometriosis is unilateral in the vast majority of the cases- 72%-82%

  • The contralateral intact ovary adequately compansate the ovarian function !

  • Overall, studies suggest that surgery does not benefit asymptomatic women preparing to undergo IVF-ICSI who are found to have endometrioma


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Ovarian suppression before COH

2006

meta-analysis


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Ovarian suppression before COH

results

Effects of GnRH-aIVF outcome

The 3 trials retained for study indicate that the administration of GnRH-a for 3-6 months prior to IVF/ICSI in women w/ endometriosis increases the odd of pregnancy >4fold.

1


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Ovarian suppression before COH

results

Effects of GnRH-aIVF outcome

The 3 trials retained for study indicate that the administration of GnRH-a for 3-6 months prior to IVF/ICSI in women w/ endometriosis increases the odd of pregnancy >4fold.

1

Effects on ovarian response

There were no differences between the amounts of FSH/hMG needed in women who received ovarian suppression or not.

2

The mechanism of action

Corrects effects of endmetriosis on etopic endometrium?

3


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ESHRE guidelines-infertility


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Endometriomas and IVF/ICSI

Individualized treatment plan can be developed ,executed and modified as necessary based on :

  • Bilaterality

  • Number of endometriomas

  • Size of the endometrioma

  • Surgical technic

  • Previous ovarian surgery

  • Ovarian reserve

  • Other factor(s) which contribute(s) to infertility


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Infertility

pre ART

Work up


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Infertility

pre ART

Work up

Sx


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Infertility

pre ART

Work up

Sx


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Infertility

pre ART

Work up

ART

1

Ovarian reserve

1

Time available for in vivo

Emergency

I V F

Sx

in principle

NO surgery


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Infertility

pre ART

Work up

ART

1

Ovarian reserve

1

Time available for in vivo

Emergency

I V F

Sx

in principle

NO surgery

ovarian suppression

(3 months)

IVF / ICSI


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Infertility

pre ART

Work up

ART

1

Ovarian reserve

1

Time available for in vivo

Emergency

I V F

2

Semen analysis

2

IVF for severe

male factor

Sx

in principle

NO surgery

ovarian suppression

(3 months)

IVF / ICSI


Slide56 l.jpg

Infertility

pre ART

Work up

ART

1

Ovarian reserve

1

Time available for in vivo

Emergency

I V F

2

Semen analysis

2

IVF for severe

male factor

3

Fallopian tubes

3

IVF for

tubal factor

Sx

in principle

NO surgery

ovarian suppression

(3 months)

IVF / ICSI


Slide57 l.jpg

Infertility

pre ART

Work up

ART

1

Ovarian reserve

1

Time available for in vivo

Emergency

I V F

2

Semen analysis

2

IVF for severe

male factor

3

Fallopian tubes

3

IVF for

tubal factor

Sx

Surgery

in principle

NO surgery

Provide 6-18 mo

for spontaneous preg.

ovarian suppression

(3 months)

IVF / ICSI

No COH-IUI


Slide58 l.jpg

Infertility

pre ART

Work up

ART

1

Ovarian reserve

1

Time available for in vivo

Emergency

I V F

2

Semen analysis

2

IVF for severe

male factor

3

Fallopian tubes

3

IVF for

tubal factor

Sx

Surgery

in principle

NO surgery

Provide 6-18 mo

for spontaneous preg.

ovarian suppression

(3 months)

IVF / ICSI

if not pregnant


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1

2

3

Med

No benefit

improves

med treatment is contraceptive

Sx

Efficacy

COH-IUI not indicated in case of endometriosis

Non-IVF treatments

pre-IVF l

Diagnosis

infertility

time


Slide61 l.jpg

1

2

3

A

Med

improves

improves

IVF outcome

IVF outcome

Sx

Efficacy

COH-IUI not indicated in case of endometriosis

Non-IVF treatments

pre-IVF l

Diagnosis

infertility

time


Slide62 l.jpg

1

2

3

A

B

Med

improves

improves

IVF outcome

IVF outcome

Sx

Efficacy

COH-IUI not indicated in case of endometriosis

Non-IVF treatments

pre-IVF l

Diagnosis

infertility

time


Eshre guidelines infertility63 l.jpg

ESHRE guidelines-infertility


Eshre guidelines infertility64 l.jpg

ESHRE guidelines-infertility


Eshre guidelines infertility65 l.jpg

ESHRE guidelines-infertility


Eshre guidelines infertility66 l.jpg

ESHRE guidelines-infertility


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