**6. Impaired endometrium receptivity**

There are controversial information regarding implantation alteration in endometriosisassociated infertility. Various studies described three causative factors: an oocyte/embryo impairment, endometrial defect and altered endometrial-embryonic cross-talk (Garrido *et al*., 2002). Implantation depends on an interaction of the trophoblast with the uterine epithelium, whereas a receptive endometrium is characterized by abundant secretory activity such as the presence of several integrins including the αvβ3 integrin. Lessey (1994) reported that the majority of women with abnormal αvβ3 integrin expression had endometriosis stage I or II and stated that αvβ3 integrin expression could be a useful marker of mild endometriosis (Lessey *et al.,* 1994). Inconsistent result pointed by Surrey (2010) that a high prevalence of aberrant endometrial αvβ3 vitronectin expression was noted in a group of infertile endometriosis patients who are IVF candidates but there were no significant differences in ongoing pregnancy or implantation rates in those patients who failed to express integrin αvβ3 vitronectin who were treated with a 3-month course of a GnRH agonist before an IVF cycle in comparison to untreated controls. Endometrial αvβ3 integrin expression did not predict which patients would benefit from prolonged administration of a GnRH agonist before initiation of controlled ovarian hyperstimulation for IVF (Surrey *et al.,* 2010)

The detection of pinopodes as a possible marker of receptivity in humans has been extensively studied. Pinopodes are specialized cell surface formations presumably involved

Pathomechanism of Infertility in Endometriosis 351

Based on several studies reviewed above showed that peritoneal microenvironment of women with endometriosis which contain pro-inflammatory factor and ROS is the main causative factor of the pathomechanism of infertility in endometriosis. They have a key role through autocrine-paracrine communication alteration in the mechanism of pelvic adhesion, abnormal folliculogenesis, reduced oocyte/embryo quality, reduced sperm fuction and implantaion impairment (see figure 2). We hope that the increase of our understanding on the above pathomechanism can increase our attention to the improvement of the complex

The author would like to thank Prof Lila Dewata and Prof Samsulhadi for their assistance in

Agarwal, A., Gupta, S., & Sikkab, S. (2006). The role of free radicals and anti oxidants in reproduction. *Curr. Opin. Obstet. Gynecol.,* Vol. 18, pp. 325–332, ISSN 1040-872x. Agarwal, A., Sharma, R.K., Nallella, K.P., & Thomas, A.J. Jr., Alvarez, J.G., Sikka, S.C. (2006).

American Society for Reproductive Medicine (ASRM). (2006). Endometriosis and infertility.

Arici, A., Tazuke, S.I., Attar, E., Kliman, H.J., Olive, D.L. (1996). Interleukin-8 concentration

Barnhart, K.M., Dunsmoor, R., Su, M.S., & Coutifaris, C. (2002). Effect of endometriosis on in vitro fertilization. *Fertil. Steril.,* Vol. 77, pp. 1148-1155, ISSN 1556-5653. Bedaiwy, M.A., Falcone, T., Sharma, R.K., Goldberg, J.M., Attaran, M., Nelson, D.R., et al.

Carli, C., Leclerc, P., Metz, C.N., & Akoum, A. (2007). Direct effect of macrophage migration

D'hooghe, T.M., Debrock, S. (2002). Endometriosis, retrograde menstruation and peritoneal

associated infertility. *Fertil. Steril*., Vol. 88, pp. 1240–7, ISSN 1556-5653. Cheong, Y.C., Shelton, J.B., Laird, S.M., Richmond, RM., Kudesia, G., Li, T.C., Ledger, W.L.

pelvic adhesions. *Hum. Reprod.*, Vol. 17, pp. 69-75, ISSN 1460-2350.

Reactive oxygen species as an independent marker of male factor infertility. *Fertil.* 

The Practice Committee of The American Society for Reproductive Medicine. *Fertil.* 

in peritoneal fluid of patients with endometriosis and modulation of interleukin-8 expression in human mesothelial cells. *Mol. Hum. Reprod.,* Vol. 2, pp. 40 –5, ISSN

(2002). Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial. Hum. Reprod., Vol. 17, pp. 426–31, ISSN 1460-2350. Carlberg, M., Nejaty, J., Froysa, B., Guan, Y., Soder, O., & Bergqvist, A. (2000). Elevated

expression of TNFα in cultured granulosa cells from women with endometriosis.

inhibitory factor on sperm function: possible involvement in endometriosis-

(2002). IL-1, IL-6 and TNF-α concentrations in peritoneal fluid of women with

inflammation in women and in baboons. *Hum. Reprod. Update.*, Vol. 8, pp. 84-88,

management of infertility in endometriosis.

*Steril.,* Vol. 86, pp. 878–85, ISSN 1556-5653.

*Steril*., Vol. 86, pp. 156-60, ISSN 1556-5653.

*Hum. Reprod*., Vol. 15, pp. 1250-5, ISSN 1460-2350.

**8. Acknowledgments** 

1460-2407.

ISSN 1460-2369.

**9. References** 

the preparation of the manuscript.

in the adhesion of blastocysts to the luminal epithelium. Scanning electron microscopy in sequential endometrial biopsies showed that pinopodes formed briefly (1–2 days) and that their numbers correlate with implantation (Nikas *et al.,* 1999). Garcia-Velasco (2001) found pinopode expression in women with endometriosis did not differ from that of patients without endometriosis undergoing artificial cycles. Similarly, the clinical outcome in these women was comparable to that of the general population included in the oocyte donation program and this study stated that pinopode expression is not altered, suggesting that endometrial receptivity in women with this disease remains unaltered (Garcia-Velasco *et al*., 2001).

Endometrial aspects and molecular studies on the receptivity status of endometrium resulted in conflicting data. Several studies suggest that an altered follicular microenvironment could be responsible for a defective folliculogenesis, and subsequently reduced oocyte/embryo quality, and in turn, result in altered embryo implantation but the debate still ongoing (Garrido *et al.,* 2002).

Fig. 2. Pathomechanism of infertility in endometriosis (Hendarto, 2011)
