Dium, provided the original work is BLU-554 supplier properly cited.Takasaki et al.
Dium, provided the original work is properly cited.Takasaki et al. Journal of Ovarian Research 2013, 6:94 http://www.ovarianresearch.com/content/6/1/Page 2 ofBackground Clomiphene citrate (CC) has been widely used to stimulate follicular growth in the treatment of infertility. CC has an antiestrogenic effect on the hypothalamus by binding to estrogen receptors. This stimulates a gonadotropin-releasing hormone (GnRH) pulse that induces gonadotropin secretion from the anterior pituitary gland. CC is most commonly used as a first-line treatment of infertility [1,2]. However, several adverse effects of the CC treatment have been recognized. One of them is a disturbance of endometrial growth by the antiestrogenic effect. In fact, endometrial thickness is significantly thinner in women taking CC than women not taking CC [3-5]. Since a thin endometrium is recognized as a critical factor of implantation failure [6-9], preventing CC-induced thinning of the endometrium is important. Since the endometrium grows by estrogen during the follicular phase, endometrial growth is impaired by antiestrogenic effects of CC [10]. Impaired epithelial cell proliferation and delayed glandular maturation are often found in endometrial biopsies from patients treated with CC [11]. Some reports also indicate that the number and diameter of the gland were lower in the CC PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28506461 treatment cycle than in the control cycle [12]. These results strongly suggest that a thin endometrium caused by the CC treatment PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28388412 is due to impaired endometrial growth and that this is a major cause of poor pregnancy rates in women who showed a thin endometrium by the CC treatment. Therefore, these patients receive the next step therapy such as gonadotropin therapy, which potentially causes multiple pregnancies or ovarian hyperstimulation syndrome (OHSS). To reduce the adverse effect of CC on endometrial growth, some clinical trials have been tested so far. Unfer et al. reported that ethinyl estradiol treatment reversed the antiestrogenic effect of CC on the endometrium [13]. High dose of phytoestrogens [14] and transdermal estradiol [15] were also tested in clinical trials to improve endometrial thickness in patients undergoing CC treatment. However, there are no established treatments to reduce or to reverse the adverse effect of CC on the endometrium. In this study, we focused on the dosage and timing of CC treatment. Reduced amounts of CC (half dose) may diminish the antiestrogenic effect of CC because the antiestrogenic effect of CC is dose-dependent [16]. Furthermore, since the antiestrogenic effect of standard CC treatment continues until the late follicular phase when endometrial growth is still active, early administration of CC may reduce the adverse effect of CC on the endometrium. Therefore, this study was undertaken to investigate whether the modified CC treatments are useful to prevent a thin endometrium in patients undergoing CC treatments.Methods This study (UMIN000007959) is a prospective, randomized controlled study. The study was conducted according to guidelines as stated in the Declaration of Helsinki and the protocol was approved by the Institutional Review Board of Saiseikai Shimonoseki General Hospital. Informed consent was obtained from all the patients. Patients were randomized at the beginning of each cycle by sealed opaque envelopes containing random generated numbers. The study was performed at the Saiseikai Shimonoseki General Hospital during a 4-month period (May 2012.

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