Exposure to 7,12-dimethylbenz[a]anthracene impacts ovarian DNA damage sensing and repair proteins differently in lean and obese female mice and weight loss may mitigate obesity-induced ovarian dysfunction.

Obesity impairs oocyte quality, fertility, pregnancy maintenance, and is associated with offspring birth defects. The model ovotoxicant, 7,12-dimethylbenz[a]anthracene (DMBA), causes ovarian DNA damage and follicle loss. Both DMBA-induced chemical biotransformation and the DNA damage response are partially attenuated in obese relative to lean female mice but whether weight loss could improve the DNA damage response to DMBA exposure has not been explored. Thus, at six weeks of age, C57BL/6 J female mice were divided in three groups: 1) Lean (L; n = 20) fed a chow diet for 12 weeks, 2) obese (O; n = 20) fed a high fat high sugar (HFHS) diet for 12 weeks and, 3) slim-down (S; n = 20). The S group was fed with HFHS diet for 7 weeks until attaining a higher body relative to L mice on week 7.5 and switched to a chow diet for 5 weeks to achieve weight loss. Mice then received either corn oil (CT) or DMBA (D; 1 mg/kg) for 7 d via intraperitoneal injection (n = 10/treatment). Obesity increased (P < 0.05) kidney and spleen weight, and DMBA decreased uterine weight (P < 0.05). Ovarian weight was reduced (P < 0.05) in S mice, but DMBA exposure increased ovary weight in the S mice. LC-MS/MS identified 18, 64, and 7 ovarian proteins as altered (P < 0.05) by DMBA in the L, S and O groups, respectively. In S and O mice, 24 and 8 proteins differed, respectively, from L mice. These findings support weight loss as a strategy to modulate the ovarian genotoxicant response.

Comparison of ovarian reserve after cystectomy of ovarian endometrioma by bipolar coagulation, suture method, or hemostatic sealants: An updated meta-analysis.

AIM: The purpose of the study was to compare the ovarian reserve after cystectomy of ovarian endometrioma by bipolar coagulation, suture method, or hemostatic sealants (HSs). METHODS: We performed a meta-analysis of studies in which post-cystectomy serum anti-Müllerian hormone (AMH) values were compared between bipolar coagulation and suture method or between bipolar coagulation and HSs. Through a literature search, we retrieved 14 articles which met inclusion criteria and were eligible for final analysis. The articles included 10 randomized trials, 3 prospective studies, and 1 retrospective study (n = 1435). The primary outcome was post-cystectomy serum AMH values. RESULTS: Both bipolar coagulation and suture methods showed significantly lower post-cystectomy AMH values at 3, 6, and 12 months. However, post-cystectomy serum AMH values at 12 months were significantly higher in the suture method group compared to the bipolar coagulation (weighted mean difference [WMD]: -1.10, 95% confidence interval [CI]: -1.83, -0.38, p = 0.003, I2 = 89, n = 3). The suture method also showed a lower decline rate at 3 months post-cystectomy compared to the bipolar coagulation group (WMD: -25.13%, 95% CI: -49.56 to -0.70, p = 0.04, I2 = 95%, n = 2). Overall, pregnancy rates were similar between the two groups. Between the bipolar coagulation and HSs group, serum AMH values at 3 months post-cystectomy were similar (WMD: -0.46, 95% CI: -1.04 to 0.13, p = 0.13, I2 = 0%, n = 3). However, the HSs group showed a less decline rate at 3 months post-cystectomy compared to the bipolar coagulation group (WMD: -17.02%, 95% CI: -22.81, -11.23, p < 0.00001, I2 = 0%, n = 3). CONCLUSIONS: Both the suture method and HSs may have potential benefits in the preservation of ovarian reserve over the bipolar coagulation method when cystectomy for ovarian endometrioma is performed.

Tocilizumab is effective in preventing ovarian injury induced by ischemia- reperfusion in rats.

Ovarian torsion can be defined as the bending of the ovaries on the supporting ligament, disrupting both venous and arterial blood circulation. Insufficient blood flow causes ovarian tissue hypoxia and leads to ischemia. This study aimed to investigate whether tocilizumab has a protective effect on ischemia-reperfusion injury due to ovarian torsion in rats. Eighteen female Wistar albino rats were divided into three equal groups (Sham (SG), ischemia-reperfusion (OIR), and ischemia-reperfusion+tocilizumab (OIRT)). Degeneration, necrosis, vascular dilatation/congestion, interstitial edema, hemorrhage, and polymorphonuclear lymphocyte (PMNL) infiltration scores were significantly different between the groups (p=0.001 for all parameters). Moreover, the OIRT group had a significant improvement in these criteria compared to the OIR group (p<0.05). Additionally, there was a considerable difference between OIRT and OIR groups in the number of primordial, developing, and atretic follicles groups (p<0.05), while there was no difference in the number of corpus luteum (p=0.052). Stress markers or cytokines, such as MDA, tGSH, NF-κB, TNF-α, IL-1ß, and IL-6, were significantly different between groups (p<0.05). Furthermore, a significant improvement was found in the measured variables when the OIRT group was compared with the OIR group (p<0.05). Tocilizumab may be an alternative option for treating ischemia-reperfusion injury due to ovarian torsion.

Protective effect of astaxanthin on experimental ovarian damage in rats.

This study aimed to investigate the protective effect of astaxanthin (AS) on 3-nitropropionic acid (3-NPA) induced experimental ovarian damage in rats. Thirty two female Wistar rats were divided into four equal groups of eight each: control group (C); phosphate-buffered saline, AS group; AS (80 mg/kg) for 14 days, 3-NPA group; 3-NPA (6.25 mg/kg) twice a day for 7 days, 3-NPA + AS group; administered AS (80 mg/kg) for 14 days and 3-NPA (6.25 mg/kg) for 7 days. All injections were administered intraperitoneally. Rats were fed ad libitum with standard rat chow and tap water. Plasma and ovarian tissue total antioxidant capacity (TAC), total oxidant capacity (TOC) and oxidative stress index (OSI) levels, whole blood reduced glutathione (GSH), plasma paraoxonase 1 (PON1) activity, lipid profile, malondialdehyde (MDA), nitric oxide (NO), total sialic acid (TSA) and total thiol (TT) concentrations were analysed spectrophotometrically. Also, ovarian tissue histopathology was performed. We observed 3-NPA-induced histopathological ovarian damage significantly decreased the TAC (p < 0.001), GSH (p < 0.001), high-density lipoprotein (p < 0.01) levels and PON1 activity (p < 0.01), and significantly increased TOC, OSI (p < 0.001), MDA, NO, TSA, cholesterol, low-density lipoprotein (p < 0.01) and triglyceride (p < 0.05) levels. In conclusion, cotreatment with AS restored the negative effect of 3-NPA on all biochemical parameters cited above and improved the histopathological ovarian damage. Ovarian toxicity induced by 3-NPA might be due to oxidative damage. The improvement of AS seems to be related to its antioxidant properties.

The effect of protection of platelet-rich plasma against experimental ischemia/reperfusion injury in the rat ovary on in vitro fertilization outcomes.

OBJECTIVE: Ovarian torsion is a common cause of local ischemic damage, reduced follicular activity and infertility. This study aimed to investigate how well platelet-rich plasma (PRP) protects against experimental ischemic (I) and ischemia-reperfusion (I/R) injury in rat ovaries and its effect on in vitro fertilization (IVF) outcomes. METHOD: Fifty-six adult female Sprague-Dawley albino rats were randomly assigned to six groups of eight animals each: Sham, Ischemia, I/R, Sham + PRP, I + PRP, and I/R + PRP. The remaining eight animals were used to prepare the PRP. The ischemia groups were subjected to bilateral adnexal torsion for 3 h, while the I/R and I/R + PRP groups received subsequent detorsion for 3 h. Intraperitoneal (i.p.) PRP was administered 30 min prior to ischemia (I + PRP) or reperfusion (I/R + PRP). The ovaries were stimulated through an intraperitoneal injection of 150-300 internal units of IU/kg PMSG. After ovulation induction, oocytes were taken from the ovaries, and IVF was performed. RESULTS: The number of MII oocytes reached the highest number with 4.63 ± 0.74 in the S group and had the lowest number with 0.50 ± 0.53 in the I/R group. There were statistically significant differences for the number of embryos obtained on the second day between the I and I + PRP groups and the I/R and I/R + PRP groups (p = 0.000). In comparing anti-Müllerian hormone 1 (AMH1) and AMH2 values within the group, the highest decrease was observed in the I and I/R groups. CONCLUSION: PRP is effective in minimizing ovarian damage and preserving ovarian reserves following ovarian torsion.

Postoperative hormonal treatment for prevention of endometrioma recurrence after ovarian cystectomy: a systematic review and network meta-analysis.

BACKGROUND: The efficacy of hormonal regimens for the prevention of endometrioma recurrence in women who have undergone conservative surgery is still controversial. OBJECTIVE: To compare the efficacy of different hormonal regimens in this context and to rank them. SEARCH STRATEGY: MEDLINE and Scopus databases were searched through January 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) or cohorts, comparing the effect of any pair of interventions (i.e. cyclic oral contraceptives [OC], continuous OC, gonadotropin-releasing hormone agonist [GnRHa], dienogest [DNG], levonorgestrel-releasing intrauterine system [LNG-IUS] and expectant management) on endometrioma recurrence were selected. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two reviewers. Relative treatment effects were estimated using network meta-analysis (NMA) and ranked in descending order. MAIN RESULTS: Six RCTs (675 patients) and 16 cohorts (3089 patients) were included. NMA of the RCTs involving expectant management, cyclic OC, continuous OC, GnRHa and GnRHa + LNG-IUS, showed that all hormonal regimens had a nonsignificant lower risk of endometrioma recurrence compared with expectant management. NMA of the cohorts involving expectant, cyclic OC, continuous OC, GnRHa, DNG, LNG-IUS, GnRHa + OC, and GnRHa + LNG-IUS indicated that LNG-IUS, DNG, continuous OC, GnRHa + OC and cyclic OC had a significantly lower risk of endometrioma recurrence than expectant management. LNG-IUS was ranked highest, followed by DNG and GnRHa + LNG-IUS. Long-term use of hormonal treatment either OC or progestin had a significantly lower risk of endometrioma recurrence than expectant treatment. CONCLUSION: In the NMA of RCTs, there was no evidence supporting hormonal treatment for postoperative prevention of endometrioma recurrence. This was at odds with the cohort evidence, which found the protective effect of OC and progestin regimens, especially long-term treatment. Large-scale RCTs of these agents are still required. TWEETABLE ABSTRACT: Hormonal regimens given as long-term treatment tend to reduce risk of endometrioma recurrence after conservative surgery.

The protective effects of resveratrol pretreatment in cyclophosphamide-induced rat ovarian injury: an vivo study.

OBJECTIVES: To explore whether resveratrol (Res) pretreatment could exert a protective effect on cyclophosphamide (Cy) induced ovarian toxicity in a rat model. METHODS: Twenty-four female 7-week old Sprague-Dawley rats were randomly divided into four groups: Con, administered with vehicle solutions; Cy, treated with Cy; Res + Cy, treated with Cy + Res combined; Res, treated with Res. After 21 d of treatments, the rats were euthanized and blood samples were collected to evaluate the levels of anti-Müllerian hormone (AMH). The Ovaries were processed for immunohistochemical and western blotting. RESULTS: Cy-treat caused the decrease of body weights and ovarian weight. AMH was lower in Cy group, whereas AMH levels were similar among other groups. Histomorphology showed a large number of primordial follicles were activated in Cy groups, whereas the primordial follicles were inhibited in the Res and Res + Cy groups. The expressions of Sirt1, Foxo3a were up-regulated and p53, Caspase-3, and Bax were down-regulated in Res + Cy and Res groups (p < .05). CONCLUSIONS: Res can prevent the primordial follicle activation and decrease apoptosis induced by Cy. Res may be an effective protection for ovarian function during chemotherapy, which means a new nonsurgical application for protection of ovarian reserve.

An assessment of the protective effect of gonadotropin-releasing hormone agonist and antagonist on bleomycin-induced ovarian toxicity in rats.

The aim of this study is to evaluate the effect of GnRH agonist or GnRH antagonist therapy on bleomycin-administered rats by examining ovarian follicle counts and AMH levels. A total of 30 female Wistar albino rats aged 4-6 months were randomly divided into 4 groups. First, an intramuscular injection of bleomycin (30 mg/m2) was administered to all except the control group on the 1st, 8th and 15th days. The control group (Group I) was administered 0.1 mL intramuscular saline on those days. The bleomycin group (Group II) was followed up without any further treatment. The bleomycin + GnRH agonist group (Group III) was administered subcutaneous GnRH agonist triptorelin (1 mg/kg) at the same time as the bleomycin injections. The bleomycin + GnRH antagonist group (Group IV) was administered 1 mg/kg cetrorelix acetate subcutaneously, concurrently with the bleomycin. Although AMH levels were lower in the bleomycin group than in all the other groups, there was no statistically significant difference between the groups in terms of AMH levels (p > .05). In the bleomycin + cetrorelix acetate and bleomycin + triptorelin groups, significantly higher primordial, secondary and tertiary follicle counts were determined compared to the bleomycin group (p < .001). In conclusion the harmful effects of bleomycin on ovarian reserve can be reduced by the simultaneous administration of GnRH agonist or GnRH antagonist.

Decision regret and associated factors following oocyte cryopreservation in patients with diminished ovarian reserve and/or age-related fertility decline.

PURPOSE: To evaluate the prevalence and factors associated with decision regret following oocyte cryopreservation (OC) in women with diminished ovarian reserve (DOR) and/or age-related fertility decline (ARFD). METHODS: A cross-sectional survey study was conducted to five hundred fifty-two women with DOR and/or ARFD who underwent OC between 2014 and 2019 in two private-assisted reproductive units in Istanbul, Turkey. Decision regret was measured using the validated Decision Regret Scale (DRS). RESULTS: The median and mean DRS scores were 10 (interquartile range: 25) and 13.4 (SD: 13.2, range 0-70), respectively. Eighty-five (52.5%) women reported mild regret and 26 (16%) had moderate to severe regret. Decision regret was inversely associated with the belief in fate regarding childbearing and trust in the efficacy of OC. CONCLUSIONS: The prevalence of severe decision regret among patients with DOR and/or ARFD undergoing OC is low. Women who had belief in fate and trusted in the efficacy of oocyte cryopreservation had significantly lower decisional regret.

Protective effects of nebivolol on ovarian ischemia-reperfusion injury in rat.

AIM: Ovarian torsion is a common gynecological emergency of reproductive ages, occurring at rates of 2.7-7.4%. This study aimed to evaluate the antioxidant effects of Nebivolol (NEB) and histopathological changes in experimental ischemic (I) and ischemic-reperfusion (I/R) injury in rat ovaries. METHODS: Forty-eight adult female rats were randomly separated into six groups as group 1 (control) receiving an oral saline solution for 3 days; group 2 (I) that underwent ischemia for 3 h with the application of atraumatic vascular clips; group 3 (I/R); group 4 (I + NEB) receiving 10 mg/kg NEB by oral gavage 30 min prior to the ischemia induction; group 5 (I/R + NEB) receiving 10 mg/kg NEB, and group 6 (control + NEB) receiving oral 10 mg/kg NEB for 3 days before ischemia induction followed by consequent reperfusion. Ovarian tissue damage was scored by histopathological analysis. Ovarian tissue malondialdehyde (MDA) and glutathione (GSH) levels were measured biochemically. RESULTS: The levels of MDA and tumor necrosis factor-alpha (TNF-α), and TUNEL assay positivity scores increased in the I and I/R groups. GSH levels decreased in all case groups (P < 0.05). The oral administration of NEB (10 mg/kg) to the I- and I/R-groups reduced the levels of MDA and TNF-α and TUNEL assay immunopositivity scores (P < 0.05). GSH levels increased in the treatment groups. CONCLUSION: The current experimental ovarian torsion study suggests a protective role for NEB against I and I/R injury in rat ovaries. NEB may be a novel agent for decreasing ovarian I/R injury.

Cilostazol protects against cyclophosphamide-induced ovarian toxicity in female rats: role of cAMP and HO-1.

Purpose: Cancer rates have been increased among women of reproductive age nowadays. Hence, many young female will be exposed to chemotherapeutic agents as cyclophosphamide (CP), carrying the hazards on female fertility. Cilostazol is a selective phosphodiesterase-3 inhibitor drug which exhibits antioxidant, anti-inflammatory, and anti-apoptotic activities. We aimed in this study to explore the possible protective effects of cilostazol against CP-induced ovarian damage in female rats.Methods: Cilostazol (10 mg/kg/day) was administered orally for 10 days in presence and absence of CP (150 mg/kg IP single dose) treatment. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), and anti-Müllerian hormone (AMH) levels were determined. Ovarian oxidative stress parameters along with inflammatory biomarkers were measured. 3,5-Cyclic adenosine monophosphate (cAMP) ovarian level was detected. Ovarian histopathological examination and caspase-3 immunohistochemical study were evaluated.Results: CP-treated rats showed a significant increase in serum levels of FSH and LH with decreased serum E2 and AMH levels with an increase in the ovarian inflammatory and oxidative stress biomarkers besides a significant decrease in cAMP ovarian level with an evident histopathological picture of ovarian damage and a high caspase-3 immunoexpression. Cilostazol pretreatment significantly restored the distributed hormonal levels, the oxidative stress and inflammatory biomarkers to their normal levels with marked improvement in histopathological picture of ovarian damage with a significant decrease in caspase-3 immunoexpression.Conclusions: These data suggest that cilostazol protects against CP- induced ovarian damage, which may be related to an increase in cAMP with subsequent anti-inflammatory, antioxidant, and anti-apoptotic properties.

Surgical Management and Prevention of Ovarian Remnant.

STUDY OBJECTIVE: To provide surgeons with surgical techniques necessary for management and prevention of ovarian remnant syndrome. DESIGN: Instructional video (Canadian Task Force classification III). SETTING: Academic medical center. INTERVENTION: Surgical dissection and retroperitoneal anatomy. MEASUREMENTS AND MAIN RESULTS: Ovarian remnant syndrome occurs when residual ovarian tissue inadvertently remains in situ after salpingo-oophorectomy [1-4]. It can result in pelvic pain and pelvic mass [1-4]. Risk factors include endometriosis, adhesive disease, pelvic inflammatory disease, and prior pelvic surgery [1-4]. Ovarian remnant can also occur as a result of ovarian stroma extending up to 1.4 cm into the infundibulopelvic ligament beyond the visible margin [5]. Medical management and radiotherapy are treatment options but do not provide the definitive management that surgery affords [1-4]. Surgery also avoids missing a potential malignancy within the remnant tissue [1-4]. This video demonstrates the surgical techniques necessary to treat and prevent this condition, including key retroperitoneal anatomy. Mayo Clinic Institutional Review Board approval was not required for this video article. CONCLUSION: Both treatment and prevention of ovarian remnant syndrome follow the same basic surgical principles, including high ligation of the infundibulopelvic ligament, retroperitoneal dissection, and excision of all peritoneum and tissue adherent to the ovary.

What is the protective effect of krill oil on rat ovary against ischemia-reperfusion injury?

AIM: In this study, we aimed to investigate the protective effect of krill oil (KO) against ischemia-reperfusion (I/R) injury on rat ovary. METHODS: This study was conducted with 32 Wistar Albino rats. Rats were divided into four groups, with eight rats in each group-as follows: Sham group, I/R group, I/R + low dose KO group (50 mg) and I/R + high dose KO group (500 mg). The histopathological and follicle counts were performed on the right ovary. The total antioxidant status, total oxidant status and oxidative stress index were evaluated on the left ovary. And also serum N-thiol level, serum T-thiol level, serum disulfide (SDS) level, serum disulfide/N-thiol and serum disulfide/T-thiol ratios were evaluated too. RESULTS: A statistically significant difference was determined between the I/R group and all the other groups for all parameters. There was significant difference between KO groups and the Sham group for the parameters of serum N-thiol, serum T-thiol, SDS, serum disulfide/N-thiol and serum disulfide/T-thiol. SDS, total oxidant status and oxidative stress index were determined to be the highest in the I/R group and the lowest in the low dose KO group. The total antioxidant status values were found to be the highest in the high dose KO group and the lowest in the I/R group. Follicle counts and histological injury scores showed no significant difference between Sham and KO groups. CONCLUSION: This study demonstrated that KO has beneficial effects on decreasing the injury after I/R on rat ovary.

A new approach to prevent ischemia/reperfusion injury in a rat model: remote ischemic conditioning.

PURPOSE: To evaluate the effect of remote ischemic conditioning (RIC) on ovarian ischemia/reperfusion injury in a rat model. METHODS: A total of 36 Wistar albino rats with a body weight of 220-250 g were used for this study. Right adnexal torsion was performed for 180 min, and at the end of the period, the adnex was released and the abdomen was reclosed for 180 min for reperfusion. Torsion and detorsion procedures were applied to all rats except group 1 (sham, control). The right lower extremity was tied to perform remote tissue ischemia in groups 3, 4, 5, and 6. The goal of the procedure, which was purplish discoloration and pulselessness of the extremity, was maintained. After 5 min of ischemia, reperfusion was achieved for 5 min. Repeating this procedure 3 times was defined as hypoxia attacks (RIC). Retrieved ovaries were examined for tissue injury with biochemical, histopathologic, and immunohistochemical analysis. RESULTS: Unlike the control group, vascular congestion, hemorrhage, edema, and inflammatory cell infiltration were observed in group 2 (only I/R [ischemia/reperfusion]). In groups 3 (I/R + RIC), 4 (I/R + RIC), 5 (I/R + RIC), and 6 (I/R + RIC), edema and inflammatory cell infiltration were not observed. However, vascular congestion and hemorrhage that were detected in these groups were higher than in group 1 (Control) and less than in group 2 (I/R). The Caspase-3 Index was found to be increased in all groups compared to group 1 (P < .001). However, the increase in the RIC-performed groups was significantly less than in group 2. The apoptotic index, which was determined by the TUNEL, was also found to be increased in all groups compared to group 1 (P < .001). When the comparison was made in relation to group 2, the decrease of AI in RIC-performed groups was statistically significant, except the decrease in group 6 (P = .29). CONCLUSIONS: It is not clinically conceivable to prepare the tissue for pre-ischemia in ovarian torsion. However, the RIC application, which will be initiated if torsion is suspected when arrangements are made for surgery, might be a simple, effective, and inexpensive approach to prevent I/R injury in the clinic.

A gonadotropin-releasing hormone agonist for the prevention of docetaxel-induced gonadal damage.

This study aimed to evaluate the protective effect of a gonadotropin-releasing hormone (GnRH) agonist against docetaxel-induced gonadotoxicity in a mouse model. Forty mice (female B6, 6-8 weeks old, weighing 16-18 g) were divided randomly into four groups. Groups 1 and 2 were treated with a single intraperitoneal dose of 0.1 mL normal saline; Groups 3 and 4 received 30 mg/kg docetaxel. Groups 2 and 4 were pre-treated with a subcutaneous injection of 0.3 mg leuprolide acetate, 2 weeks before the administration of docetaxel. The ovaries were removed 6 weeks after docetaxel or saline injection. Total follicle number decreased in Group 3 compared to Group 1. There was a significant difference between the Groups 3 and 4 in the total follicle number. Many ovarian follicles were stained for Ki-67 in Groups 1, 2, and 4; however, in Group 3, only a small number were stained and destruction of the ovarian structure was observed. There was no immunohistochemistry staining with γ-H2AX in Groups 1, 2, and 4. However, γ-H2AX staining of the primordial follicles was observed in Group 3. GnRH agonists may protect ovarian follicles from docetaxel-induced ovarian damage considering the total follicle number, follicle proliferation, and double-strand DNA breaks. Impact statement Protection of the ovarian reserve and prevention of infertility are the primary quality of life issues in young cancer patients. In this study, ovarian suppression by gonadotropin-releasing hormone agonists protected ovarian follicles from docetaxel-induced ovarian damage considering the total follicle number, follicle proliferation, and double-strand DNA break. The findings of our study will provide useful information for fertility preservation in women with cancer, undergoing chemotherapy with docetaxel.

Aliskiren - a promising strategy for ovarian ischemia/reperfusion injury protection in rats via RAAS.

The aim of this study was to evaluate the effects of aliskiren, direct renin inhibitor, as an antioxidant and tissue protective agent and evaluate the molecular, biochemical, and histopathological changes in experimental ischemia and ischemia/reperfusion injury in rat ovaries. Forty-eight female rats were randomly divided into eight groups: in Group 1, only sham operation was performed. Group 2 received 100 mg/kg aliskiren and sham operated. In Group 3, 3 h-period of bilateral ovarian ischemia was applied. Group 4 received a 3-h period of ischemia followed by 3 h of reperfusion. Groups 5 and 6 received 50 and 100 mg/kg, respectively, of aliskiren and bilateral ovarian ischemia was applied (after a 3-h period of ischemia, both ovaries were surgically removed). To Groups 7 and 8, 50 and 100 mg/kg of aliskiren were administered, respectively, and the induction of ischemia was performed. At the end of a 3-h period of ischemia, bilateral vascular clips were removed, and 3 h of reperfusion continued. After the experiments, IL-1ß, IL-6, TNF-α, and iNOS mRNA expressions and SOD, GSH, MDA, renin, and angiotensin-II levels were determined and histopathological changes were examined in rat ovaries. Aliskiren treatment normalized excessive changes in cytokine and oxidative stress markers in both ischemia and ischemia/reperfusion injury. Histopathologically, treatment with aliskiren ameliorated the development of ischemia and/or ischemia/reperfusion tissue injury. This study concluded that aliskiren treatment is effective in reversing ischemia and/or ischemia/reperfusion induced ovary damage via the improvement of oxidative stress, reduction of inflammation, and suppression of the renin-angiotensin aldosterone system.

Postoperative administration of dienogest for suppressing recurrence of disease and relieving pain in subjects with ovarian endometriomas.

To assess the effect of dienogest on recurrence of ovarian endometriomas and severity of pain after laparoscopic surgery, a retrospective study of 81 patients was performed at three institutions in Osaka, Japan. Patients had a six-month minimum follow-up after laparoscopic surgery for ovarian endometriomas performed between June 2012 and August 2014. Patients who chose to receive 2 mg dienogest daily and those who were managed expectantly postoperatively were included. Recurrence was defined as the presence of endometriomas of more than 2 cm. A visual analog scale (VAS) was used to score the intensity of pelvic pain. The cumulative recurrence rate and absolute VAS score changes between the baseline and at 6, 12, 18 and 24 months after the start of administration were evaluated in both groups. The recurrence rate was 16.5% and 24.0% in the expectant management group at 12 and 24 months, respectively. No recurrences occurred in the dienogest treatment group. The rate of VAS score reduction was significantly higher in the dienogest than in the expectant management group. Dienogest is effective on the recurrence of ovarian endometrioma and relieving pelvic pain after laparoscopic surgery.

Biochemical, Histopathological and Immunohistochemical Evaluation of the Protective and Therapeutic Effects of Thymoquinone against Ischemia and Ischemia/Reperfusion Injury in the Rat Ovary.

AIM: To evaluate the antioxidant effects of thymoquinone (TQ) and to investigate the biochemical, histopathological and immunohistochemical changes in experimental rat ovarian torsion. METHODS: A total of 48 female adult rats were used in this study and randomly divided into 7 groups: (1) sham operation; (2) bilateral 3-hour ovarian ischemia; (3) 3-hour ischemia and 3-hour reperfusion; (4) and (5) rats were administered 20 and 40 mg/kg of TQ, respectively, before 0.5 h of ischemia, and then 3 h of ovarian ischemia was applied; (6) and (7) 3-hour ovarian ischemia was applied; 2.5 h after the induction of ischemia, rats were administered the same doses of TQ; at the end of 3 h of ischemia, a 3-hour reperfusion was applied. Histologic changes under light microscopy, immunoreactivity for anticaspase-3 and serum levels of malondialdehyde, interleukin-6, catalase and glutathione peroxidase were noted and compared between the 7 groups. RESULTS: Ischemia and ischemia/reperfusion cause a deterioration of biochemical and histopathological parameters. Administration of TQ seems to reverse these alterations and alleviate the injury. Antioxidant defense mechanisms appear to be enhanced by the administration of TQ. CONCLUSION: TQ at different doses attenuates ovarian ischemia and ischemia/reperfusion injury in rats.

Protective Effect of Platelet Rich Plasma on Experimental Ischemia/Reperfusion Injury in Rat Ovary.

BACKGROUND/AIMS: Ovarian torsion is a common cause of local ischemic damage, reduced follicular activity and infertility. Platelet-rich plasma (PRP) contains growth factors with demonstrated cytoprotective properties; so we evaluated PRP efficacy in a rat ischemia/reperfusion (I/R) model. METHODS: Sixty adult female Sprague-Dawley albino rats were randomly assigned to 6 groups of 8 animals each: Sham, Ischemia, I/R, Sham + PRP, I + PRP and I/R + PRP; and the remaining 12 used to prepare PRP. Ischemia groups were subjected to bilateral adnexal torsion for 3 h, while I/R and I/R + PRP groups received subsequent detorsion for 3 h. Intraperitoneal PRP was administered 30 min prior to ischemia (Ischemia + PRP) or reperfusion (I/R + PRP). RESULTS: Total oxidant status (TOS), oxidative stress index (OSI) and total ovarian histopathological scores were higher in Ischemia and I/R groups than in the Sham group (p < 0.05). PRP decreased mean TOS, OSI and histopathological scores in I + PRP and I/R + PRP groups compared to the corresponding Ischemia and I/R groups (p < 0.001). There was a strong correlation between total histopathological score and OSI (r = 0.877, p < 0.001). Peritoneal vascular endothelial growth factor was significantly higher in PRP-treated groups than corresponding untreated groups (p < 0.05). CONCLUSION: PRP is effective for the prevention of ischemia and reperfusion damage in rat ovary.

Effects of GnRHa on early embryonic development in mice receiving cyclophosphamide.

PURPOSE: There is a controversy whether GnRH agonist can reduce the deleterious effects of chemotherapy to prevent ovarian failure. We aimed to examine the possible protective effects of a gonadotrophin-releasing hormone agonist (GnRHa) on the fertilization rate and sequential embryonic development in mouse oocytes exposed to Cy. METHODS: Mice were assigned to three groups of six animals each. A single dose of 75 mg/kg Cy was given intraperitoneally to the Cy mice group. The subcutaneous GnRHa injection was initiated 1 week before and continued for 1 week after the Cy injection in the GnRHa + Cy group. The animals given cyclophosphamide mated 1 week after the Cy injection. At the end of the injection period, the animals underwent a superovulation regime with pregnant mare serum gonadotrophin and human chorionic gonadotrophin and were mated. Early embryos were collected at 48 h after mating. The control group received only the superovulation regime and then mated. RESULTS: Cyclophosphamide caused a significant decrease in the fertilization rate (p < 0.001), whereas the GnRHa improved the rate when compared to control group. The GnRHa induced a marked increase in the rate for 2-cell embryos compared with the Cy group (p = 0.003). In both Cy-injected groups, the rates for the 4-cell embryos were lower than those of the control animals (p < 0.001). However, this rate was higher in the GnRHa + Cy group than in the only Cy group. Morphologically abnormal embryos showed such characteristics as condensed cytoplasm, milky cytoplasm, fragmentation, and an empty zona pellucida. CONCLUSION: These results demonstrated that the GnRHa preserved the oocyte capability to develop into an embryo against ovarian toxic chemotherapy. Thus, we suggest that GnRHa cotreatment could increase the number and quality of early embryos in mice.