**5. Reduced embryo quality**

Use of IVF-ET as a therapeutic tool in endometriosis women with infertility could result in information about this disease and reproductive process aspects, such as folliculogenesis, fertilization, embryo development and implantation. The outcome of patients with endometriosis undergoing IVF-ET showed not only the influence of endometriosis on IVF result but also the possible pathomechanisms of infertility in endometriosis (Garrido et al., 2000). The impact of endometriosis in embryo development and quality is still on debate. Various embryo scoring system have been described to assess the developmental potential of embryos, but the most commonly used systems are the blastomeres cleavage rate, the shape and size of the blastomeres and the amount of anucleated fragment (Martynow et al., 2007)

Pellicer (1995) found a significantly reduced number of blastomeres in embryos from endometriosis patients compared with controls, and endometriosis patients had a poor IVF-ET outcome in terms of a reduced pregnancy rate per cycle, reduced pregnancy rate per transfer and reduced implantation rate per embryo replaced (Pellicer et al., 1995). Simon (1994) showed that patients who received embryos derived from endometriosis ovaries

TNF-α caused a significant reduction in both progressive and total sperm motility when compared with controls group. Suggests that this may be a mechanism for the infertility observed in women with minimal endometriosis (Eisermann *et al*., 1989). In the other study stated that the toxic effects of TNF-α could be the result of its ability to stimulate apoptosis in sperm cells through initiation of a caspase cascade. Exposing spermatozoa to pathological concentrations of TNF-α can result in significant loss of sperm function and genomic integrity. Infliximab, an TNF-α inhibitor, could potentially be used to help treat female infertility caused by endometriosis in those with elevated levels of TNF-α in their

Another theory describing pathological effect of endometriosis on sperm function is the role of reactive oxygen species. Oxidative stress has been shown to exert toxic effects on sperm, damaging the sperm cell membrane, inducing DNA damage, and mediating sperm apoptosis (Agarwal *et al.,* 2006). Mansour (2009) found that progressive sperm DNA damage was significantly higher in samples incubated with peritoneal fluid from patients with endometriosis than those from healthy women. Spermatozoa are particularly susceptible to ROS-induced damage because their plasma membranes contain large quantities of polyunsaturated fatty acids and their cytoplasm contains low concentrations of the

Reeve (2005) reported that significantly more spermatozoa bound per unit area to the ampullary epithelium of the uterine tubes taken from women with endometriosis, could potentially hinder fertilization by reducing the number of free spermatozoa in the tubal lumen that are available to take part in fertilization. Numerous studies have shown that spermatozoa that bind to the endosalpinx retain their viability, motility and fertilizing capacity longer than spermatozoa incubated alone or with other cell types. The aberrant expression of integrin in the endometrium of women with endometriosis would be

Use of IVF-ET as a therapeutic tool in endometriosis women with infertility could result in information about this disease and reproductive process aspects, such as folliculogenesis, fertilization, embryo development and implantation. The outcome of patients with endometriosis undergoing IVF-ET showed not only the influence of endometriosis on IVF result but also the possible pathomechanisms of infertility in endometriosis (Garrido et al., 2000). The impact of endometriosis in embryo development and quality is still on debate. Various embryo scoring system have been described to assess the developmental potential of embryos, but the most commonly used systems are the blastomeres cleavage rate, the shape and size of the blastomeres and the amount of anucleated fragment (Martynow et al.,

Pellicer (1995) found a significantly reduced number of blastomeres in embryos from endometriosis patients compared with controls, and endometriosis patients had a poor IVF-ET outcome in terms of a reduced pregnancy rate per cycle, reduced pregnancy rate per transfer and reduced implantation rate per embryo replaced (Pellicer et al., 1995). Simon (1994) showed that patients who received embryos derived from endometriosis ovaries

peritoneal fluid (Said *et al.,* 2005).

scavenging enzymes (Saleh *et al.,* 2002)

**5. Reduced embryo quality** 

2007)

speculated to increased sperm binding (Reeve *et al*., 2005).

showed a significantly reduced ability to implant compared with the remaining groups (Simon et al., 1994). These result above suggest that infertility in endometriosis patients may be related to alterations within the oocyte which, in turn, result in reduced embryos quality (Pellicer et al., 1995).

Endometriosis induces an inflammatory state by activation of macrophages, releasing ROS and cytokines (Gupta *et al.,* 2008). Macrophages, cytokines and other products present in the peritoneal fluid from patients with endometriosis could be responsible for a change in the peritoneal environment that generates embryotoxic activity. Torres (2002) found embryotoxicity was increased in women with endometriosis, but there was little correlation with severity of the disease. These study also found a significant increase in embryotoxicity in the presence of high cytokine concentrations, especially with IL-6 (Torres et al., 2002). Other study by Pellicer found progesterone concentrations in follicular fluid increased with the severity of endometriosis that may be related to the release of the cytokines. The result of the study also showed that IL-6 concentration was significantly increased in follicular fluid of patients with endometriosis, whereas VEGF accumulation in follicular fluid was significantly decreased in women with endometriosis compared with controls. The increased IL-6 means that the immune system may be activated as a marker of altered follicular function that result in reduced oocyte and embryo quality. The decreased VEGF concentration needs further investigation, but in IVF, elevated VEGF concentrations have been shown to be related to good follicular vascularization and health. The study by Pellicer concluded profound differences in the follicular environment of the oocytes of women with endometriosis, compared with those of healthy patients. It may be suspected as a marker of altered follicular function that result in reduced oocyte and embryo quality.
