Effects of resveratrol on VEGF & HIF1 genes expression in granulosa cells in the angiogenesis pathway and laboratory parameters of polycystic ovary syndrome: a triple-blind randomized clinical trial.

OBJECTIVES: Management options for PCOS, as the most prevalent endocrine disorder in women of reproductive age, using natural supplements have a high priority for physicians, especially based on the etiological pathways. Therefore, this study was conducted to describe the effect of resveratrol on the angiogenesis pathway, for management of PCOS through assessing VEGF, HIF1 gene expression, and laboratory parameters. METHODS: In this triple-blind RCT, PCOS was confirmed in ICSI candidates based on the Rotterdam criteria. Sixty-two patients that met the inclusion criteria were randomly assigned to two groups. All patients took resveratrol 800 mg/day or placebo for 40 days orally from the beginning of their previous menstruation cycle until the oocyte retrieval day. The serum levels of different hormones were measured, and the expression of HIF1 & VEGF genes was quantified by real-time PCR. RESULTS: As for the laboratory hormone assay in 61 PCOS patients, a significant mean difference was seen in the FSH, LH, TSH, and testosterone between the two groups (P < 0.05). The results showed a reduction in the expression of VEGF & HIF1 genes under the effect of resveratrol in the granulosa cells (P = 0.0001). The number of mature oocytes, cleavage rate, fertilization rate, and fertility rate were not significantly different between the two groups (P > 0.05), but the high-quality oocyte rate and high-quality embryo rate were higher in the resveratrol group (P < 0.05). CONCLUSIONS: Based on the results, resveratrol may improve some outcomes of PCOS patients, probably through changing the serum levels of some sex hormones and expression of VEGF & HIF1 genes in the angiogenesis pathway of granulosa cells.

Metadata Correction: Uterine Fundectomy in Patients with Benign Etiology Undergoing Hysterectomy: New Surgical Technique.

[This corrects the article DOI: 10.2196/resprot.7536.].

Comparing Serum Levels of Th17 and Treg Cytokines in Women with Unexplained Recurrent Spontaneous Abortion and Fertile Women.

BACKGROUND: Increased evidences have shown that unexplained recurrent spontaneous abortion (URSA) is associated with inflammatory responses and breakage of immunological autotolerance. Therefore, the balance between Th17 and Treg cells may elucidate the pathophysiology of URSA. OBJECTIVE: To investigate the serum concentration of regulatory and inflammatory cytokines associated with Treg and Th17 in both normal and URSA females. METHODS: Forty-six women with URSA and 28 non-pregnant control women with at least one successful pregnancy were included. Serum was obtained from both groups and stored at -7º C. The serum concentrations of IL-17, IL-21, IL-22, IL-10, and TGF-ß were quantitatively determined by ELISA. RESULTS: The levels of IL-17, IL-21, and IL-22 in sera were significantly higher (P<0.001, P=0.01 and P<0.001, respectively) and TGF-ß serum concentration was significantly lower (P=0.02) in URSA women compared with normal controls. CONCLUSION: Our results suggest that enhancement in Th17-associated cytokine levels and reduction in TGF-ß may be one of the factors involved in URSA.

Uterine Fundectomy in Patients With Benign Etiology Undergoing Hysterectomy: New Surgical Technique.

BACKGROUND: Hysterectomy is the most common surgical procedure in gynecology, not only in cases of malignancies but also in many benign cases. Many uterine preservation techniques have been introduced as alternatives to hysterectomy. OBJECTIVE: We aimed to propose a new uterine surgical procedure. In this paper, we compare the utility of this new technique to the limitations of current procedures. METHODS: Uterine fundectomy may be considered as a subtotal hysterectomy. In this new technique, the uterine fundus including all pathologic tissue is cut as a reverse trapezoid by monopolar cautery. The upper side of the trapezoid, which includes the whole uterine fundus, is removed, but the fallopian tubes and cornual segment are preserved. A small uterine cavity remains, as well as the endometrial tissue lining it. RESULTS: Patient recruitment for this study began in April 2017 and is expected to end approximately 12 months later. Assessment of the primary outcomes is expected to take place in April 2018. CONCLUSIONS: Uterine preservation is particularly critical in developing new surgical approaches that can lead to a positive impact on patient satisfaction. This protocol outlines the first attempt to prospectively test surgical fundectomy in candidates for hysterectomy for benign indications.

Treatment of adenomyomectomy in women with severe uterine adenomyosis using a novel technique.

The advised treatment for severe adenomyosis is hysterectomy, but for patients wishing to preserve their uterus, novel conservative surgery, adenomyomectomy, can be performed. The technique needs to be developed to reduce spontaneous uterine rupture, adhesion and recurrence rates. This study aimed to investigate the safety and therapeutic outcomes of adenomyomectomy. Prospectively, 103 Iranian patients with documented severe adenomyosis were candidates for adenomyomectomy over a period of 7 years (from April 2004 to March 2011). The surgical procedure involved resection of adenomatosis lesions with a thin (⩽ 0.5 cm) margin (wedge-shaped removal) after sagittal incision in the uterine body. Reconstruction of the layers was performed and inverted sutures were used for the serosal layer ends. Of 103 patients, 55.34% presented with infertility, 16.50% with IVF failure, 8.74% with recurrent abortion and 19.42% with abnormal uterine bleeding. Of 70 patients who attempted pregnancy, naturally (n=21) or by assisted reproduction treatment (n=49), 30% achieved a clinical pregnancy, and 16 resulted in a full-term live birth. Dysmenorrhoea and hypermenorrhoea were reduced post surgery. Only one patient had relapsed adenomyosis. Adenomyomectomy is a conservative and effective treatment for adenomyosis. This study describes an efficient procedure to treat severe adenomyosis. Adenomyosis is uterine thickening that occurs when endometrial tissue, which normally lines the uterus, moves into the outer muscular walls of the uterus. The advised treatment for the severe forms of adenomyosis is hysterectomy (removal of the patient's uterus), but for the patient who wishes to preserve her uterus, a novel conservative surgery referred to as 'adenomyomectomy' (removal of the abnormal tissues) can be performed. This technique must be developed for reduction of spontaneous uterine rupture, adhesions and recurrence rate. This study aims to investigate the safety and therapeutic outcomes of adenomyomectomy. Prospectively, 103 Iranian patients with documented severe adenomyosis were candidates for adenomyomectomy over a period of 7 years (from April 2004 to March 2011). The surgical procedure was resection of adenomatosis lesions with a thin margin. Of 103 patients, 55.34% presented with infertility, 16.50% with IVF failure, 8.74% with recurrent abortion and 19.42% with abnormal uterus bleeding. Of 70 patients who attempted pregnancy either naturally (n=21) or using assisted reproduction technology (n=49), 30% became pregnant, and 16 pregnancies reached full term. There was a significant reduction in dysmenorrhoea and hypermenorrhoea. Only one patient had relapsed adenomyosis. Based on these results, we conclude that adenomyomectomy is the conservative and effective option to treat adenomyosis with preservation of the uterus. The procedure described in this study can be an efficient procedure to treat severe adenomyosis.

Correlation between serum zinc levels and successful immunotherapy in recurrent spontaneous abortion patients.

BACKGROUND: Immunotherapy with paternal lymphocytes plays an important role in preventing recurrent spontaneous abortion (RSA) and is an effective treatment for it. This kind of treatment is performed as an immunotherapy method in several centers in the world. It attributes to the production of anti-paternal cytotoxic antibodies (APCAs) in women with RSA. Production of APCA after lymphocyte immunotherapy (LIT) in RSA patients gives them a better chance for successful pregnancy. Regarding the important effect of trace elements on the function of the immune system, we tried to investigate the correlation between serum zinc level and the success of LIT in RSA. MATERIALS AND METHODS: Serum zinc concentration was determined in two groups of RSA patients using atomic absorption spectrophotometer systems. Group (a) that responded to the paternal lymphocytes and their cross-match test was positive, and group (b) that had no response to the paternal lymphocytes immunizations and their cross-match test was negative. RESULTS: Serum zinc levels in group (a) patients were 74.98 ± 11.88 µg/dl, which was significantly higher than those in group (b) with the zinc concentration of 64.22 ± 9.22 µg/dl. CONCLUSIONS: Zinc deficiency may be one of the substantial causes of negative results for LIT in RSA patients. Therefore, compensation of zinc defect before LIT can be a promising approach to improve the immune response in patients.

Evaluation of the relationship between endometriosis and omega-3 and omega-6 polyunsaturated fatty acids.

BACKGROUND: Endometriosis is a common chronic inflammation causing major problems including infertility. The role of omega-3 and omega-6 fatty acids as their potential anti-inflammatory effects in endometriosis needs to be further explored. The objective of this study was to compare serum phospholipid fatty acid profile in endometriosis patients with controls, and to explore the correlation of this profile with the severity of the disease. METHODS: Sixty-four endometriosis patients and 74 control women, in reproductive age, participated in this study. Among the endometriosis patients, 19 cases were in stage I, 27 cases in stage II, 8 cases in stage III, and 10 cases in stage IV. Each patient underwent laparoscopy. Before surgery, 5 ml of blood was obtained. After extraction of the total lipids, serum total phospholipid fraction was isolated by thin layer chromatography. Fatty acid composition of the phospholipid fraction was determined by gas chromatography and the resulted profile was compared in endometriosis patients and controls. The profile was also compared in the endometriosis group based on the severity of disease. RESULTS: Stearic acid was significantly lower in the endometriosis group as compared to controls (P= 0.030). No other fatty acid compositions were significantly different between patients and controls. Serum ratio of eicosapentaenoic acid (EPA) to arachidonic acid (AA) was in reasonable correlation with the severity of endometriosis (r = 0.34, P = 0.006). CONCLUSION: According to these findings, levels of fatty acids in serum total phospholipids seem not to be a marker for endometriosis, but the EPA to AA ratio was a relevant factor indicating severity of illness.

Effect of polyunsaturated fatty acids on secretory phospholipase A2 type IIa in ectopic endometrial cells.

BACKGROUND: Endometriosis is a common chronic inflammation which leads to infertility and chronic pelvic pain in affected women. Secretory phospholipase A2 type IIa (sPLA2IIa) is an acute phase reactant that is markedly increased in inflammatory disorders. OBJECTIVE: To assess the effects of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) administration in endometrial cells culture on sPLA2IIa level and cell survival comparing homolog ectopic versus eutopic endometrial cells from endometriosis patients. MATERIALS AND METHODS: In this experimental study, ectopic and eutopic endometrial tissue samples obtained from 15 endometriosis patients were immediately frozen. After thawing and tissue digestion, mixed stromal and endometrial gland cells were cultured for 8 days in three different culture media; balanced ω-3/ω-6, high ω-3 and high ω-6 PUFAs ratio. Cell survival was measured using 2, 3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-(phenylamino) carbonyl-2H- tetrazolium hydroxide (XTT) method and sPLA2IIa level assessed with ELISA technique. RESULTS: The sPLA2IIa level was significantly higher in the ectopic endometrial cell culture compared to the eutopic group for each of the three matched treatments (balanced, high ω-3 and high ω-6). Also the sPLA2IIa level in the ectopic endometrial cell group was remarkably increased by each of the three PUFAs treatments compared to control condition (p<0.05, p<0.01, p<0.05 respectively). Cell survival in the eutopic group was significantly decreased by high ω-6 culturing compared to control medium (p<0.05). CONCLUSION: The increase in sPLA2IIa level in ectopic endometrial cells by fatty acid treatments (especially high ω-3), strengthens the hypothesis that PUFAs stimulate secretion of cytokines leading to increased sPLA2IIa level.