Ovulation induction with gonadotropins causes increased sister chromatid exchanges.

Summary: Ovulation induction with gonadotropins causes increased sister chromatid exchanges: Gonadotropins are widely accepted agents for ovulation induction in infertile women. On the other hand, several authors discuss the possible effect of gonadotropins on the developmental mechanism of ovarian cancer. SCE is a method of genotoxicity investigation and it is an excellent parameter to monitor the DNA damage and repair. There are numbers of studies showing the relationship between endogenous or exogenous hormones and SCEs. The aim of this study was to investigate with SCE techniques the effects of long-term (6 months) use of gonadotropins on DNA as we couldn't find any other study on the effect of long term use. We found increased sister chromatid exchange rates in a study group as compared to a control group. This may be one of the causes of increased ovarian cancer risk in infertile population. Key-words: Gonadotropins - Sister Chromatid Exchange (SCE) - Ovarian cancer Reproductive hormones Estradiol. INTRODUCTION Gonadotropins are widely accepted agents for ovulation induction in infertile women. On the other hand, several authors discuss the possible effect of gonadotropins on the developmental mechanism of gynecologic cancers, especially on ovarian cancer (7, 21, 27, 28). Many of these reports on the possible link between ovarian cancer and treatment with fertility drugs are epidemiologic studies (7, 21, 28). As the frequency of ovarian cancer is low in our patients, it is hard to collect adequate data to consistently assess the presence or absence of a relationship. Nevertheless, in addition to the known risk factors like low parity and infertility, the effect of ovulation induction is generally also discussed. Sister chromatid exchange (SCE) is a reciprocal exchange of DNA segments between sister chromatids at identical loci (16). This phenomenon takes place during DNA synthesis. Although the mechanism underlying the SCE formation is not clear, it is known that this mechanism is related with replication and repair processes (17). Sister chromatid exchange is thus an excellent parameter to monitor the DNA damage and repair. It is used as a method for genotoxicity investigation, and it is considered as a reliable method for such studies. Although there are many epidemiologic data in the literature, no data on genotoxicity studies showing the effect of gonadotropins on DNA stability are available. There are nevertheless several SCE studies on either in vitro chromosome treatment with steroid hormones (6, 15) or in vivo oral contraseptives and postmenoposal hormone replacement therapy (14, 20, 24). All these studies clearly show a relationship between endogenous or exogenous hormones and SCE. There are also studies investigating the effects on SCE of gonadotropins used in the induction of ovulation (3, 13). In these studies, however, only one single ovarian cycle of each patient was examined, and comparisons were made between SCE frequencies observed at different periods of the cycle (basal period and day of either gonadotropin administration or spontaneous LH peak) in treated and control groups. Purpose of this study was to investigate with SCE techniques the effects on DNA of gonadotropins after long-term use (6 months). Furthermore, since native estrogen can also cause an increase in SCEs around the ovulatory period of the patient, frequency of SCE during the basal period of patients were also investigated with the purpose of examining the isolated effects of gonadotropin use. A correlation was found between estrogen and SCE. MATERIAL AND METHODS PATIENTS Twenty-five infertile females using gonadotropins (ree FSH) (Gonnal F,Sereno) were included in the study. Ovulation induction was administered because of unexplained infertility. Conventional step-up protocol was applied to patients to start with 75 ILVmI. Follow-up of E2 and folliculometry was performed, and induction was completed with 150 IU/ ml dosage as a maximum. …