The role of melatonin as an antioxidant in the follicle

Melatonin (N-acetyl-5-methoxytryptamine) is secreted during the dark hours at night by pineal gland, and it regulates a variety of important central and peripheral actions related to circadian rhythms and reproduction. It has been believed that melatonin regulates ovarian function by the regulation of gonadotropin release in the hypothalamus-pituitary gland axis via its specific receptors. In addition to the receptor mediated action, the discovery of melatonin as a direct free radical scavenger has greatly broadened the understanding of melatonin's mechanisms which benefit reproductive physiology. Higher concentrations of melatonin have been found in human preovulatory follicular fluid compared to serum, and there is growing evidence of the direct effects of melatonin on ovarian function especially oocyte maturation and embryo development. Many scientists have focused on the direct role of melatonin on oocyte maturation and embryo development as an anti-oxidant to reduce oxidative stress induced by reactive oxygen species, which are produced during ovulation process. The beneficial effects of melatonin administration on oocyte maturation and embryo development have been confirmed by in vitro and in vivo experiments in animals. This review also discusses the first application of melatonin to the clinical treatment of infertile women and confirms that melatonin administration reduces intrafollicular oxidative damage and increase fertilization rates. This review summarizes our recent works and new findings related to the reported beneficial effects of melatonin on reproductive physiology in its role as a reducer of oxidative stress, especially on oocyte maturation and embryo development

Luteal blood flow in patients undergoing GnRH agonist long protocol

<p>Abstract</p> <p>Background</p> <p>Blood flow in the corpus luteum (CL) is closely related to luteal function. It is unclear how luteal blood flow is regulated. Standardized ovarian-stimulation protocol with a gonadotropin-releasing hormone agonist (GnRHa long protocol) causes luteal phase defect because it drastically suppresses serum LH levels. Examining luteal blood flow in the patient undergoing GnRHa long protocol may be useful to know whether luteal blood flow is regulated by LH.</p> <p>Methods</p> <p>Twenty-four infertile women undergoing GnRHa long protocol were divided into 3 groups dependent on luteal supports; 9 women were given ethinylestradiol plus norgestrel (Planovar) orally throughout the luteal phase (control group); 8 women were given HCG 2,000 IU on days 2 and 4 day after ovulation induction in addition to Planovar (HCG group); 7 women were given vitamin E (600 mg/day) orally throughout the luteal phase in addition to Planovar (vitamin E group). Blood flow impedance was measured in each CL during the mid-luteal phase by transvaginal color-pulsed-Doppler-ultrasonography and was expressed as a CL-resistance index (CL-RI).</p> <p>Results</p> <p>Serum LH levels were remarkably suppressed in all the groups. CL-RI in the control group was more than the cutoff value (0.51), and only 2 out of 9 women had CL-RI values < 0.51. Treatments with HCG or vitamin E significantly improved the CL-RI to less than 0.51. Seven of the 8 women in the HCG group and all of the women in the vitamin E group had CL-RI < 0.51.</p> <p>Conclusion</p> <p>Patients undergoing GnRHa long protocol had high luteal blood flow impedance with very low serum LH levels. HCG administration improved luteal blood flow impedance. This suggests that luteal blood flow is regulated by LH.</p

DNA Double-Strand Breaks Induced by Cavitational Mechanical Effects of Ultrasound in Cancer Cell Lines

Ultrasonic technologies pervade the medical field: as a long established imaging modality in clinical diagnostics; and, with the emergence of targeted high intensity focused ultrasound, as a means of thermally ablating tumours. In parallel, the potential of [non-thermal] intermediate intensity ultrasound as a minimally invasive therapy is also being rigorously assessed. Here, induction of apoptosis in cancer cells has been observed, although definitive identification of the underlying mechanism has thus far remained elusive. A likely candidate process has been suggested to involve sonochemical activity, where reactive oxygen species (ROS) mediate the generation of DNA single-strand breaks. Here however, we provide compelling new evidence that strongly supports a purely mechanical mechanism. Moreover, by a combination of specific assays (neutral comet tail and staining for γH2AX foci formation) we demonstrate for the first time that US exposure at even moderate intensities exhibits genotoxic potential, through its facility to generate DNA damage across multiple cancer lines. Notably, colocalization assays highlight that ionizing radiation and ultrasound have distinctly different signatures to their respective γH2AX foci formation patterns, likely reflecting the different stress distributions that initiated damage formation. Furthermore, parallel immuno-blotting suggests that DNA-PKcs have a preferential role in the repair of ultrasound-induced damage

Usefulness of intermittent clomiphene citrate treatment for women with polycystic ovarian syndrome that is resistant to standard clomiphene citrate treatment

Abstract Purpose Clomiphene citrate (CC) has been used as a first‐line treatment for anovulatory polycystic ovary syndrome (PCOS). However, some patients with PCOS are resistant to standard CC treatment. In this study, a new CC treatment protocol was developed, named “intermittent CC treatment” (ICT) and its efficacy was investigated on the induction of follicular growth in patients with PCOS who were resistant to standard CC treatment. Methods Of the 42 patients with PCOS who were resistant to standard CC treatment (50 mg/day, 5 days), 26 underwent ICT. They were given 100 mg/day of CC for 5 days from the next menstrual cycle day (MCD) 5 (first CC). If follicular growth was not observed on MCD 14, they were given 100 mg/day of CC for 5 days (MCD 14‐MCD 18) (second CC). If follicular growth still was not observed on MCD 23, they were treated with CC again in the same way (third CC). Results The first CC, second CC, and third CC were effective for 3/26 (11.5%) patients, 12/23 (52.2%) patients, and 6/11 (54.5%) patients, respectively. In total, ICT was effective for 21/26 (80.8%) patients with CC‐resistant PCOS. Conclusion Thus, ICT is a useful treatment and could be an alternative to gonadotropin therapy for patients with CC‐resistant PCOS