Transcript Does endometriosis effect implantation?

Bilgin GURATES, MD
IMPLANTATION IS OR IS NOT AFFECTED BY
ENDOMETRIOSIS
 It’s a common disease and an enigmatic disease
 This database gives us the dimension of this problem, which is a huge
problem,
 Many different experimental moldels, even animal models, that show
that, this disease decreses fertility.
THE MECHANISM OF INFERTILITY
 Altered folliculogenesis,
 Ovulatory dysfunction,
 Hyperprolactinemia,
 Luteal phase defect,
 Accelerated ovum transport,
 Sperm phagocytosis,
 Impaired fertilization,
 Embryotoxicity against early embryonic development,
 Defective implantation
IMPLANTATION
 Embryo quality,
 This is a high indicator of
how pregnancy rates can be more or less.
 Endometrial receptivity,
 Which is a crucial event.
 Transfer efficiency,
 That it is actually very important
step in the implantation rate.
control of
hyper
stimulation
Presence of Endometriosis Decreases Pregnancy
Rates
 Without
 Padigas K, Fertil Steril 1996
 assisted reproductive
 Kodama H, Fertil Steril 1996
technologies or
 with ovulation induction
 Guzick DS, Fertil Steril 1994
 Adamson GD, Semin Reprod
Endocrinol 1997
 Tummon IS, Fertil Steril 1997
 Falcone T, Curr Opin Obstet
Gynecol 1996
 Lu PY, Mayo Clinic Proc 1995
ENDOMETRIOSIS &FERTILITY(IVF)
SAME
 GEBER, S., 1995. Hum. Reprod.
 JONES, H.W., 1984. Fertil. Steril
 OLIVENNES, F., 1995. Fertil. Steril.
 OEHNINGER, S., 1988. J. InVitro Fertil.
 FIVNAT (French In Vitro National):
French national IVF registry: analysis of
1986 to 1990 data. 1993. Fertil. Steril.
WORSE
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MAHADEVAN M.M., 1983. Fertil. Steril
WARDLE, P.G., 1986. Lancet
WARDLE, P.G., 1985. Lancet
YOVICH, J.L., 1985, Lancet
MATSON, P.L., 1986.Fertil. Steril.
O’SHEA, R.T., 1985. Lancet
PAL, L., 1998. J. Assist.Reprod. Genet.
ARICI , A., 1996. Fertil. Steril
Impact of ovarian endometrioma on oocytes and
pregnancy outcome in in vitro fertilization
aspirated
Takahiro Suzuki, Fertility and Sterility 2005
Endometriosis
L/S
tubal factor
Effect of endometriosis on in vitro
fertilization
Christos Coutifaris,
Effect of endometriosis on in vitro fertilization
Christos Coutifaris,
Effect of endometriosis on in vitro fertilization
Christos Coutifaris,
Impaired parameters
 Number of oocytes retrieved,
 Peak E2 concentration,
 Fertilization rate,
 PR, and
 IR
Poor oocyte quality
Defective implantation
capacity
ENDOMETRIAL RECEPTIVENESS
 Theoretically, endometriosis might affect endometrial
receptiveness by altering the
 local biochemical environment
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paracrine
endocrine
immune response.
ENDOMETRIOSIS IN OOCYTE
RECIPIENTS
 Simon C, Gutierrez A, Vidal A, de los Santos MJ, Tarın JJ, Remohı
J, et al. Outcome of patients with endometriosis in assisted
reproduction: results from in-vitro fertilization and oocyte
donation. Hum Reprod 1994;9:725–9.
 Sung L, Mukherjee T, Takeshige T, Bustillo M, Copperman A.
Endometriosis is not detrimental to embryo implantation in
oocyte recipients. J Assist Reprod Genet 1997;14:152–6.
 Dıaz I, Navarro J, Blasco L, Simon C, Pellicer A, Remohı J. Impact
of stage III–IV endometriosis on recipients of sibling oocytes:
matched case-control study. Fertil Steril 2000;74:31–4.
OOCYTE DONATION IN PATIENTS WITH ENDOMETRIOSIS
n=178
retrospective
premature ovarian
failure
(n = 54),
low response
(n = 77)
No difference pregnancy rate
per woman,
per cycle,
per implantation.
SIMÓN, C. 1994. Hum. Reprod.
endometriosis
(n = 10)
OOCYTE DONATION IN PATIENTS WITH ENDOMETRIOSIS
239 oocyte
recipient
retrospective
Endometriosis
( n = 55)
without
endometriosis
(n = 184).
pregnancy rates (28 versus 29%)
implantation rates (12 and 13%)
Sung L, . J Assist Reprod Genet 1997
Impact of stage III–IV endometriosis on recipients of sibling
oocytes: matched case-control study
N=25
stage III–IV
endometriosis
(n=25)
Israel Dı´az, Fertility and Sterility 2000
Healthy
recipient
(n =33)
IVF IN PATIENTS WITH ENDOMETRIOSIS
Pregnancy rate per cycle
(34.4% vs. 12.5% ; p <0.0004)
Pregnancy per transfer
(37.3% vs. 15.1% ; p <0.002)
Implantation rate
(13.4% vs. 5.8%; p <0.003)
Decreases Number of
blastomeres
78 women
59 women
Arrested embryos
Infertility outcome comparing endometriosis and tubal infertility.
SIMÓN, C., A. GUTIERREZ, A. VIDAL, et al. 1994. Outcome of patients with endometriosis in assisted reproduction: results from in vitro fertilization and oocyte donation.
Hum. Reprod. 9: 725–729
Simon C, Hum Reprod 1994, Sung L, J Assist Reprod Genet 1997, Dıaz I, Fertil Steril 2000
OOCYTE DONATION IN PATIENTS WITH
ENDOMETRIOSIS
Grup 1(n=44)
Grup 11(n=14)
Grup 111(n=16)
DONORS
ENDO(-)
ENDO(+)
ENDO(-)
RECIPIENTS
ENDO(-)
ENDO(-)
ENDO(+)
Preg Rate
Per Tansfer
61.4 %
28.6 %
60 %
Pellicer, 1994
Follicular-oocyte-embryo quality in
endometriosis
 Ovlatory dysfonction
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(Tummon 1988)
Pituitary-ovarian axis (Chaill 1995)
Over production of progesterone
(Pellicer 1998)
IL-6 IL-1β, VEGF
(Pellicer 1998)
Apoptosis (Toya 2000)
PGF2
(Bergqvist 1997)
MIS
(Fallat 1997)
Inhibins A ,inhibins B, activin B
(Akande 2000)
Endothelin-1 , (Abea 1994)
Conclusions
 Clinic evidence using the oocyte donation model
strongly suggest that the endometrium is NOT altered
in women with endometriosis.
 In-vitro studies on the endometrium of endometriosis
patients do not support the hypothesis of an altered
endometrial environment.
 Rather, decrease oocyte /embryo quality seems to be
cause of endometriosis related infertility .
Conclusions
 None of the alterations described in the in-vitro
studies is relevant for endometrial receptiveness.
 Endometrial priming protocols used in OD cycles
reestablish an adequate uterine cavity environment.
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GnRHa restores the normal apoptotic rate.(Imai A, Am J Obstet Gynecol 2000)
3-month course of GnRH-a(Surrey ES, Fertil Steril 2002)
Artificial endometrial priming for OD could be beneficial in that down-regulation and
the exogenous supply of E and P(Cunha-Filho JS, J Assist Reprod Genet 2003)
Pinopode formation with artificial priming has been demonstrated to be normal in
these patients(Garcıa-Velasco JA, Fertil Steril 2001)
 A question that remains to be answered concerns the
endometrial receptiveness of these patients in natural
cycles.