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      Luteal blood flow and luteal function

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          Blood flow in the corpus luteum (CL) is associated with luteal function. The present study was undertaken to investigate whether luteal function can be improved by increasing CL blood flow in women with luteal phase defect (LFD).


          Blood flow impedance in the CL was measured by transvaginal color-pulsed-Doppler-ultrasonography and was expressed as a resistance index (RI). The patients with both LFD [serum progesterone (P) concentrations < 10 ng/ml during mid-luteal phase] and high CL-RI (≥ 0.51) were given vitamin-E (600 mg/day, n = 18), L-arginine (6 g/day, n = 14) as a potential nitric oxide donor, melatonin (3 mg/day, n = 13) as an antioxidant, or HCG (2,000 IU/day, n = 10) during the subsequent menstrual cycle.


          In the control group (n = 11), who received no medication to increase CL blood flow, only one patient (9%) improved in CL-RI and 2 patients (18%) improved in serum P. Vitamin-E improved CL-RI in 15 patients (83%) and improved serum P in 12 patients (67%). L-arginine improved CL-RI in all the patients (100%) and improved serum P in 10 patients (71%). HCG improved CL-RI in all the patients (100%) and improved serum P in 9 patients (90%). Melatonin had no significant effect.


          Vitamin-E or L-arginine treatment improved luteal function by decreasing CL blood flow impedance. CL blood flow is a critical factor for luteal function.

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          Most cited references 41

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          Vascular endothelial growth factor is essential for corpus luteum angiogenesis.

          The development and endocrine function of the ovarian corpus luteum (CL) are dependent on the growth of new capillary vessels. Although several molecules have been implicated as mediators of CL angiogenesis, at present there is no direct evidence for the involvement of any. Here we report the unexpected finding that treatment with truncated soluble Flt-1 receptors, which inhibit vascular endothelial growth factor (VEGF) bioactivity, resulted in virtually complete suppression of CL angiogenesis in a rat model of hormonally induced ovulation. This effect was associated with inhibition of CL development and progesterone release. Failure of maturation of the endometrium was also observed. Areas of ischemic necrosis were demonstrated in the corpora lutea (CLs) of treated animals. However, no effect on the preexisting ovarian vasculature was observed. These findings demonstrate that, in spite of the redundancy of potential mediators, VEGF is essential for CL angiogenesis. Furthermore, they have implications for the control of fertility and the treatment of ovarian disorders characterized by hypervascularity and hyperplasia.
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            Effect of vaginal sildenafil on the outcome of in vitro fertilization (IVF) after multiple IVF failures attributed to poor endometrial development.

            To evaluate the effects of vaginally administered sildenafil on endometrial thickness and IVF outcome in a large cohort of infertile women with poor endometrial development. Retrospective cohort analysis. Private practice setting. A cohort of 105 infertile women aged /=9 mm, whereas 32 (30%; Group B) did not. Implantation and ongoing pregnancy rates were significantly higher for Group A (29% and 45%) than for Group B (2% and 0). Of 11 women in Group B who had embryos transferred in that cycle, only one conception occurred, which resulted in a miscarriage. In Group B, 59% of women had a history of endometritis, compared with 44% in Group A. Vaginal administration of sildenafil enhanced endometrial development in 70% of patients studied. High implantation and ongoing pregnancy rates were achieved in a cohort with a poor prognosis for success. Previous endometritis may decrease the response to sildenafil.
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              Vaginal sildenafil (Viagra): a preliminary report of a novel method to improve uterine artery blood flow and endometrial development in patients undergoing IVF.

               Michael Fisch,  G Sher (2000)
              Endometrial growth is thought to depend on uterine artery blood flow and the importance of endometrial development on in-vitro fertilization (IVF) outcome has been previously reported. Nitric oxide (NO) relaxes vascular smooth muscle through a cGMP-mediated pathway and NO synthase isoforms have been identified in the uterus. Sildenafil citrate (Viagra), a type 5-specific phosphodiesterase inhibitor, augments the vasodilatory effects of NO by preventing the degradation of cGMP. In this preliminary report we describe the use of vaginal sildenafil to improve uterine artery blood flow and sonographic endometrial appearance in four patients with prior failed assisted reproductive cycles due to poor endometrial response. The uterine artery pulsatility index (PI) was measured in a mock cycle after pituitary down-regulation with Lupron. The PI was decreased after 7 days of sildenafil (indicating increased blood flow) and returned to baseline following treatment with placebo. The combination of sildenafil and oestradiol valerate improved blood flow and endometrial thickness in all patients. These findings were reproduced in an ensuing gonadotrophin-stimulated cycle. Three of the four patients conceived. Although greater numbers of patients and randomized evaluation are needed to validate this treatment, vaginal sildenafil may be effective for improving uterine artery blood flow and endometrial development in IVF patients with prior poor endometrial response.

                Author and article information

                J Ovarian Res
                Journal of Ovarian Research
                BioMed Central
                14 January 2009
                : 2
                : 1
                [1 ]Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube, 755-8505 Japan
                [2 ]Department of Obstetrics and Gynecology, Saiseikai Shimonoseki General Hospital, Kifunecho 3-1-37, Shimonoseki, 751-0823, Japan
                Copyright © 2009 Takasaki et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


                Obstetrics & Gynecology


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