Clomiphene Citrate Versus Tamoxifen for Induction of Ovulation in Women with Polycystic Ovary Syndrome: Randomized Controlled Trial

Abstract

Ovulation induction remains a milestone in the treatment of women with PCOS. For the last 40 years, the first line of induction of ovulation in women with PCOS was Clomiphene Citrate (CC), it was appropriate, because the drug was highly effective in inducing ovulation in selected cases with the advantages of being orally administered, relatively safe, and inexpensive. In spite of the high ovulation rate of CC (60-85%), pregnancy rate was much lower (20-40%)(Palomba et al., 2005;Roy etal., 2012). There is also a higher rate of miscarriage in conception cycles following CC treatment Such discrepancy is believed to be due to the peripheral anti-estrogenic effect of clomiphene citrate, particularly at the level of cervical mucus and endometrium(Steiner et al., 2005). In addition to discrepancy between ovulation and pregnancy rates, 15% to 40% of women with PCOS are resistant to CC and fail to ovulate after6 cycles of CC induction(Zakherahet al., 2010). Tamoxifen (TMX) has been also introduced as a simple oral alternative to CC in ovulation induction. It is also aSERM, but it has 100 to 1000 times lower binding affinity when compared with estrogen, it can induce ovulation in about 50-90% of anovulatory women with pregnancy rate 30-50%. These better results are due to its estrogenic effect on the endometrium and vaginal mucosa, also leads to favorable cervical mucus, better endometrial thickness and may be better endometrial blood flow (Desta et al.,2004;Dhaliwal et al., 2011). Oncologic side effects including numerous endometrial abnormalities have been reported with TMX use, but in small doses of induction of ovulation this cann't happen; as reported in this study. In general, patients should be examined for preexisting endometrial lesions prior to starting tamoxifen therapy(Lorizio et al., 2012). This study revealed that: Ovulation rate wassignificantlybetter under tamoxifen therapy. Pregnancy rate wassignificantlybetter under tamoxifen therapy. Number of stimulated follicleswas not significantly different between the two drugs. Endometrial thickness was significantlybetter under tamoxifen therapy "both preovulatory and midluteal". Endometrial perfusion volume (EV), Vascularization index (VI), and Vascularization flow index (VFI) were significantly better under tamoxifen therapy. Adverse effects with the two drugs were non significant. Endometrial perfusion indices were significantly better in pregnant versus non-pregnant cases.