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    In Vivo Evaluation of the Genotoxic Effects of Gonadotropins on Rat Reticulocytes
    (Elsevier Science Inc, 2011) Duran, Bulent; Koc, Onder; Ozdemirci, Safak; Topcuoglu, Ata; Özdemir, Öztürk
    BACKGROUND: Gonadotropins, as ovulation-inducing drugs, have been used widely to treat infertility. An epidemiologic correlation between infertility therapy and ovarian cancer development has been reported. However, the effect of gonadotropins in the formation of reproductive tract cancers is controversial. OBJECTIVE: The aim of the study was to determine the in vivo genotoxic effects of gonadotropins on rat reticulocytes. METHODS: In this prospective, randomized, controlled study, rats were randomly assigned to 1 of 5 groups. The calculated rat doses of 0.65 human menopausal gonadotropin (hMG), 0.95 hMG, 0.65 follitropin beta (FB), 0.95 FB, or normal saline (control group) were injected, respectively. These calculated rat doses (U/g) are based on average human gonadotropin doses of 150 and 225 IU/d for a 70-kg woman given in 2-mL saline (the control group received 2 mL of saline). Injections were administered once per day for 5 days, followed by 5 days of rest. Each treatment was repeated for 6 estrus cycles in the rats for a total of 12 estrus cycles. Six months after the last day of the 12(th) cycle, the rats were euthanized. Bone marrow tissues were removed, and pluripotent reticulocyte cells with micronuclei, nuclear buds, and binuclear abnormalities were analyzed using an in situ micronuclei assay under light microscopy. The proportion of micro-nucleated cells, cells with anaphase bridge, nuclear buds, and other nuclear abnormalities were measured. RESULTS: The number of cells with nuclear buds and binuclear abnormalities in the hMG 225 and FB 225 groups was significantly higher (P < 0.05) than that from the hMG 150, FB 150, and control groups in the cytogenetic analysis of bone marrow stem cells. An increased rate of genotoxicity in all gonadotropin groups versus that of placebo was found. CONCLUSION: In rats, the micronucleus genotoxicity assay suggests a dose-dependent gonadotropin effect on genomic instability in bone marrow stem cells in vivo. (Curr Ther Res Clin Exp. 2011;72:60-70) (C) 2011 Elsevier HS Journals, Inc. All rights reserved.
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    Use of progestogens in pregnant and infertile patients
    (Springer Heidelberg, 2012) Ozlu, Tulay; Gungor, Aysenur Cakir; Donmez, Melahat Emine; Duran, Bulent
    Progesterone is an essential hormone in the occurence and maintenance of pregnancy. Natural or synthetic progestogens are commonly used in pregnant patients or patients undergoing infertility treatments for various indications. Most frequently put indications for the use of progestogens in these patient populations are the prevention of spontaneous preterm birth, the prevention of pregnancy loss in pregnancies with an unexplained recurrent pregnancy loss and in patients with threatened abortion. It is also used in pregnant women undergoing nonobstetric surgery, for infertility or recurrent pregnancy loss that is thought to be due to luteal phase defect or as a luteal support in stimulated IVF cycles. We aimed to review the current evidence for the use of progestogens in each of these settings.