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 Padigas K, Fertil Steril 1996 Kodama H, Fertil Steril 1996 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 Without assisted reproductive technologies or with ovulation induction

ENDOMETRIOSIS &FERTILITY(IVF) GEBER, S., Hum. Reprod. JONES, H.W., Fertil. Steril OLIVENNES, F., Fertil. Steril. OEHNINGER, S., J. InVitro Fertil. FIVNAT (French In Vitro National): French national IVF registry: analysis of 1986 to 1990 data Fertil. Steril. MAHADEVAN M.M., Fertil. Steril WARDLE, P.G., Lancet WARDLE, P.G., Lancet YOVICH, J.L., 1985, Lancet MATSON, P.L., 1986.Fertil. Steril. O’SHEA, R.T., Lancet PAL, L., J. Assist.Reprod. Genet. ARICI, A., Fertil. Steril SAMEWORSE

aspirated Endometriosis L/S tubal factor Impact of ovarian endometrioma on oocytes and pregnancy outcome in in vitro fertilization Takahiro Suzuki, Fertility and Sterility 2005

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 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.

n=178 retrospective premature ovarian failure (n = 54), low response (n = 77) endometriosis (n = 10) No difference pregnancy rate per woman, per cycle, per implantation. SIMÓN, C Hum. Reprod. 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 OOCYTE DONATION IN PATIENTS WITH ENDOMETRIOSIS

N=25 stage III–IV endometriosis (n=25) Healthy recipient (n =33) Impact of stage III–IV endometriosis on recipients of sibling oocytes: matched case-control study Israel Dı´az, Fertility and Sterility 2000

Infertility outcome comparing endometriosis and tubal infertility. SIMÓN, C., A. GUTIERREZ, A. VIDAL, et al Outcome of patients with endometriosis in assisted reproduction: results from in vitro fertilization and oocyte donation. Hum. Reprod. 9: 725–729 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 Arrested embryos 59 women78 women IVF IN PATIENTS WITH ENDOMETRIOSIS

Simon C, Hum Reprod 1994, Sung L, J Assist Reprod Genet 1997, Dıaz I, Fertil Steril 2000

ENDO(-)ENDO(+) ENDO(-) Grup 1(n=44)Grup 11(n=14)Grup 111(n=16) ENDO(-) ENDO(+) DONORS RECIPIENTS Preg Rate Per Tansfer 61.4 % 28.6 % 60 % Pellicer, 1994 OOCYTE DONATION IN PATIENTS WITH ENDOMETRIOSIS

Follicular-oocyte-embryo quality in endometriosis Ovlatory dysfonction(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. 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.

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