The Effect of Sildenafil on Embryo Development - Literature review Example

 The Effect of Sildenafil on Embryo Development Fertility problem is one of the major problems of couples in the United Kingdom. According to Gurunath et al. (2011), roughly 72.4 million people around the world and close to 15% of the couples in UK are facing infertility problems. To solve problems related to fertility problems, Assisted Reproduction Technology (ART) was developed as a promising solution. The in virto fertilization (IVF) is a good example of ART. To increase the success rate of IVF, the clinical and laboratory procedures were enhanced in order to reduce the risk of side-effects on the part of thepatients (Gupta and Agarwa, 2010). Despite the effort to improve the use of IVF, Diedrich et al. (2007) revealed that successful pregnancy rates remain low. The common problems encountered with the use of the IVF procedure includes: (1) inadequate supply of nutrients and oxygen necessary to make the embryo implant itself in the endometrium lining (Forbes and Westwood, 2010; Raine-Fenning et al., 2004a; Kennedy, 1997); (2) lack of endometrial receptivity (Forbes and Westwood, 2010; Kennedy, 1997); (3) failed ovarian responses to the IVF protocols (Oudendijk et al., 2012; Tarlatzis et al., 2003); and (4) uterine blood flow abnormalities caused by poor angiogenesis or vasculogenesis (Satterfield et al., 2010; Huppertz et al., 2006). Due to the failure of the embryo implant itself in the endometrium lining, women can either experience a miscarriage, a recurrent miscarriage, implantation failure, or a recurrent implantation failure (Christiansen et al., 2006; Margalioth et al., 2006; Tomassetti et al., 2006). Based on the study of Achache and Revel (2006), approximately 2/3 of failed IVF is caused by the inability of the embryo implant itself in the endometrium lining. To avoid experiencing a failed IVF intervention, the women’s endometrium lining should not only have more than 6 mm thickness but also show patterns similar to a trilaminar either during her ovulation period or when hCG is being administered to the patient (Killick, 2007). Furthermore, the women’s endometrium lining should not only have more than 2 cm2 in volume but also have an endometriual vascularity of not more than 3.3 pulsatility index (Killick, 2007; Friedler et al., 1996). One of the pharmacological drugs that are being considered in treating problems related to the endometrium lining is the sildenafil citrate (Hattori and Tabata, 2006). Through the use of this particular drug, the presence of nitric oxide can will not only create a positive affect on the endometrium lining during the implantation stage but also help in preventing the presence of intrauterine adhesions during menstruation and maintain normal blood pressure during pregnancy (Nakatsuka et al., 2002; Sher et al., 2000; Norman and Cameron, 1996). Based on the study of Sher et al. (2000), the use of 25 mg of sildenafil citrate vaginal suppository for at least four (4) times each day for a period of one week prior to ovarian stimulation will not only increase the endometrium thickness by more than 8 mm but also improve the uterine blood flow. In a similar study, Paulus et al. (2002) examined the effects of 25 mg of sildenafil citrate vaginal suppository on ten (10) women with poor endometrial response to IVF. After administering the vaginal suppository for at least four (4) times each day, the authors noted a 9 mm increase in the endometrium thickness of nine (9) patients but no such improvements in the patients’ uterine blood flow (Paulus et al., 2002). Aside from havng a trilaminar pattern during the ovulation period, Chanona et al. (2004) found that that it is possible to increase the endomentrium thickness up to more than 10 mm after administering 50 mg of sildenafil citrate vaginal suppository each day between the 9th to 12th day of menstruation cycle. Several studies revealed that between 10 % to 25% of women who had IVF intervention have low follicular responses to the treatment (Sunkara et al., 2012; Tarlatzis et al., 2003). In most cases, the presence of non-responsive FSH receptors on guanyl cyclase (GC), poor ovarian reserve, or impaired vascular follicles can lead to poor ovarian responses (Venetis et al., 2010; Tarlatzis et al., 2003). To solve this problem, several studies suggest that the administration of pharmacological intervention is necessary to maintain a controlled ovarian stimulation (Hillier, 2000; Miller et al., 1996). Using this particular intervention, it is possible to induce the growth of multiple follicles and maintain its growth up to the time wherein the oocyte is retrieved. The use of sildenafil citrate is also being considered as a possible treatment for low follicular responses (Hattori and Tabata, 2006; Tarlatzis et al., 2003; Tamanini et al., 2002). Although the use of sildenafil citrate may not have direct effects on womens’ ovarian function, several studies revealed that the use of sildenafil citrate can lead to positive developments in the patients’ folliculogenesis (i.e. a significant increase not only on the size of the follicles but also in the secretion of oestrogen) (Bruno et al., 2009; Hattori and Tabata, 2006; Tamanini et al., 2002). As a result, Bruno et al. (2009) explained that the follicles are able to develop well because of the presence of sufficient nutrients and hormones. Likewise, several studies found out that the use of sildenafil citrate can help develop a mature oocyte (Li et al., 2012; Hanna et al., 2011; Jee et al., 2009). Today, the use of sildenafil citrate is being considered as a potential therapeutic intervention that can increase not only the endometrial receptivity but also the ovarian responses to IVF procedure (Li et al., 2012; Hanna et al., 2011; Bruno et al., 2009; Jee et al., 2009; Hattori and Tabata, 2006; Chanona et al., 2004; Tarlatzis et al., 2003; Nakatsuka et al., 2002; Paulus et al., 2002; Tamanini et al., 2002). Despite the fact that most of the research studies today acknowledges the potential benefits of using sildenafil citrate together with IVF procedures, there is no single study that can prove its safety over the development of the embryo. Therefore, this study will focus on identifying the possible side-effect(s) of sildenafil citrate over the embryonic development. Read More