Potential clinical implications of iron metabolism in ovarian endometriosis.

OBJECTIVE: The purpose of this study was to investigate iron metabolism indices in ovarian endometriosis (OEMs) and to demonstrate the potential clinical implications in the initiation and development of OEMs. METHODS: Three datasets in Gene Expression Omnibus (GEO) database were selected to assess the expression levels of iron metabolites in endometrial tissues from patients with EMs and the health. To evaluate the differential expression of serum iron indices , hospitalized patients with OEMs and health examinees in Jilin University Second Hospital from November 2018 to December 2019 were recruited. Serum samples were obtained from 38 patients with OEMs and 36 health examinees. To compare the iron metabolism between peripheral circulation blood and local ectopic lesion, cyst fluid samples were obtained from 15 patients with ovarian chocolate cyst at the time of surgery. Iron metabolism indices include iron, transferrin (TF), ferritin, and unsaturated iron-binding capacity (UIBC)), which were measured by automatic biochemical analyzer. RESULTS: The present study indicated the increased levels of the iron storage protein, ferritin, in the endometriotic tissues of patients with EMs. The expression of iron and ferritin in cyst fluid of patients with OEMs showed higher than that in serum, the results of TF and UIBC were opposite (P < 0.05). There was no statistical difference in the content of iron metabolites between patients with OEMs and the healthy examinees(P > 0.05). CONCLUSION: The ovarian chocolate cyst fluid and endometriotic tissues in patients with OEMs could more directly reflect the pathological changes of local ectopic lesion, which usually manifested as high levels of free iron and/or iron deposits in the ectopic sites. The implications of our work suggest iron metabolites in the serum may have potentially limited value as circulating biomarkers for OEMs. The iron variation in local lesions may be not only regulated by liver that mainly manipulate the systematic iron homeostasis, but also be tuned by the iron regulatory protein (IRP)/ iron responsive element (IRE) system. In summary, the iron metabolites, especially the iron and ferritin in the cyst fluid and endometriotic tissues, are meaningful biomarkers involved in the process of pathophysiology and pathogenesis of OEMs.

The prediction of surgical intervention in patients with tubo-ovarian abscess.

The aim of this study was to compare the clinical characteristics of patients with tubo-ovarian abscess (TOA) who responded to medical treatment and those who underwent surgical intervention due to medical treatment failure. Electronic medical records were evaluated retrospectively to identify patients who were diagnosed with TOA. Demographic, clinical, and laboratory data including white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were compared between the medical treatment group and the surgical intervention group. Patient age, TOA diameter, WBC count, CRP, and ESR were significantly different between the groups. On multiple regression analysis, significant correlations were identified between age (p = .001), ESR (p = .045), and failure of medical treatment. TOA diameter (p = .065) showed a borderline association with surgical intervention. The risk of needing surgical intervention in TOA patients can be predicted using ESR in addition to age and TOA size as risk factors.IMPACT STATEMENTWhat is already known on this subject? For patients diagnosed with a tubo-ovarian abscess (TOA), the size of TOA and the patient's age are helpful for early identification of patients who are likely to need surgical treatment. Inflammatory markers such as C-reactive protein and white blood cell are also associated with the risk of surgical intervention.What do the results of this study add? Erythrocyte sedimentation rate (ESR) in addition to the size of TOA and the patient's age is a useful marker in determining whether to undergo surgery in patients with TOA.What are the implications of these findings for clinical practice and/or further research? ESR combined with the patient's age and the size of TOA is clinically useful in predicting the need for early surgical intervention in patients with TOA. Large prospective controlled studies are required to establish relationship between inflammatory markers and the risk of surgical intervention.

The effect of prophylactic bilateral salpingectomy on ovarian reserve in patients who underwent laparoscopic hysterectomy.

BACKGROUND: Bilateral salpingectomy has been proposed to reduce the risk of ovarian cancer, but it is not clear whether the surgery affects ovarian reserve. This study compares the impact of laparoscopic hysterectomy for benign disease with or without prophylactic bilateral salpingectomy on ovarian reserve. METHODS: Records were reviewed for 373 premenopausal women who underwent laparoscopic hysterectomy with ovarian reserve for benign uterine diseases. The serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and three-dimensional antral follicle count (AFC) were assessed before surgery and 3 and 9 months postoperatively to evaluate ovarian reserve. Patients were divided into two groups according to whether they underwent prophylactic bilateral salpingectomy. The incidence of pelvic diseases was monitored until the ninth month after surgery. RESULTS: There was no significant difference between the two surgery groups in terms of baseline AMH, E2, FSH, LH, and AFC (all P > 0.05). There was no difference in potential bias factors, including patient age, operative time, and blood loss (all P > 0.05). There was also no significant difference between the two groups 3 months after surgery with respect to AMH (P = 0.763), E2 (P = 0.264), FSH (P = 0.478), LH (P = 0.07), and AFC (P = 0.061). Similarly, there were no differences between groups 9 months after surgery for AMH (P = 0.939), E2 (P = 0.137), FSH (P = 0.276), LH (P = 0.07) and AFC (P = 0.066). At 9 months after the operation, no patients had malignant ovarian tumors. The incidences of benign ovarian tumors in the salpingectomy group were 0 and 2.68 % at 3 and 9 months after surgery, respectively, and the corresponding values in the control group were 0 and 5.36 %. The incidences of pelvic inflammatory disease in the salpingectomy group were 10.72 and 8.04 % at 3 and 9 months after surgery, respectively, while corresponding values in the control group were 24.13 and 16.09 %. CONCLUSIONS: Prophylactic bilateral salpingectomy did not damage the ovarian reserve of reproductive-age women who underwent laparoscopic hysterectomy. Prophylactic bilateral salpingectomy might be a good method to prevent the development of ovarian cancer. Larger clinical trials with longer follow-up times are needed to further evaluate the risks and benefits.

Copenhagen Index versus ROMA in preoperative ovarian malignancy risk stratification: Result from the first Vietnamese prospective cohort study.

OBJECTIVES: This study aimed to evaluate the diagnostic performances of the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA) in the preoperative prediction of ovarian cancer. METHODS: In a prospective cohort study, data were collected from 475 patients with ovarian masses diagnosed by gynecologic examination / ultrasound who were hospitalized at the Departments of Obstetrics and Gynecology, Hue University of Medicine and Pharmacy Hospital and Hue Central Hospital, Vietnam, between January 2018 and June 2020. ROMA and CPH-I were calculated based on measurements of serum carbohydrate antigen (CA-125) and human epididymis protein (HE4). The final diagnosis was based on clinical features, radiologic and histologic findings, and the International Federation of Gynecology and Obstetrics (FIGO) 2014 stages of ovarian cancer were recorded. Matching the values of ROMA and CPH-I to postoperative histopathology reports resulted in the preoperative prediction values. RESULTS: Among the 475 women, 408 had benign tumors, 5 had borderline tumors and 62 had malignant tumors. The two indices showed similar discriminatory performances with no significant differences (p > 0.05). At an optimal cut-off, the sensitivities/specificities of ROMA and CPH-I for ovarian cancer diagnosis were 74.2% and 91.8%, 87.1% and 78.5%, respectively. The optimal cut-off for CPH-I was 1.89%. The areas under the ROC curves (AUCs) of ROMA and CPH-I were 0.882 (95% CI: 0.849-0.909) and 0.898 (95% CI: 0.867-0.924), respectively. CONCLUSIONS: The introduction of the Copenhagen Index to help stratify the malignancy risk of ovarian tumors, irrespective of menopausal status, might be applied as a simple alternative with a similar efficacy to ROMA in clinical practice.

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.

Large ovarian endometriomas are associated with high pre-operative anti-Müllerian hormone concentrations.

RESEARCH QUESTION: Are large ovarian endometriomas associated with high pre-operative anti-Müllerian hormone (AMH) concentrations? DESIGN: Data from 332 women who underwent AMH measurement before surgery for endometriosis were prospectively recorded in a large database. Univariate analysis compared AMH concentrations in terms of the patients' baseline characteristics. A multivariate model was used to identify variables having an independent relationship with AMH concentration. RESULTS: Among 332 women included in the study, 47.6% were aged 18-30 years, 67.8% were infertile and 85.5% were nulliparous. A total of 66.3% had ovarian endometriomas, and 10.8% had cysts measuring over 6 cm. Bilateral cysts over 3 cm were recorded in 24.7% of the women. Univariate analysis identified two variables that had a statistically significant relationship with AMH concentration: the woman's age (P = 0.01) and cyst size (P < 0.001). Multivariate analysis revealed that ages of 36-40 years and over 40 years showed a significant association with lower AMH concentrations (P = 0.02 and P = 0.009, respectively), while a cyst size of over 6 cm was statistically associated with high AMH concentrations (P < 0.001), after adjustment for smoking, parity, rectosigmoid endometriotic nodules and a bilateral location of endometriomas. CONCLUSIONS: Pre-operative AMH concentration was significantly increased in women with large endometriomas of over 6 cm, independent of their age or the presence of bilateral endometriomas. This is relevant for both surgeons and patients when planning surgery in women with an intention to conceive post-operatively.

The Protective Effects of L-Carnitine and Zinc Oxide Nanoparticles Against Diabetic Injury on Sex Steroid Hormones Levels, Oxidative Stress, and Ovarian Histopathological Changes in Rat.

Diabetes mellitus is a common chronic metabolic disorder. This study aimed to investigate the effects of co-treatment with L-carnitine (LC) and zinc oxide nanoparticles (ZnONPs) on serum levels of sex hormones, oxidative stress, and ovarian histopathology in streptozotocin (STZ)-induced diabetic rats. Female Wistar rats (n = 56, 180-220 g) received a single intraperitoneal (IP) injection of STZ (65 mg/kg). They were randomly assigned into the following groups: diabetic group (Dia), Dia+Met group (100 mg metformin/kg/day), Dia+LC group (200 mg/kg/day), Dia+ZnONPs group (10 mg/kg/day), and Dia+LC+ZnONPs group (200 mg LC/kg/day and 10 mg ZnONPs/kg/day). Control group (Ctl) received the same volume of STZ solvent. After 21 days of treatment, blood serum was centrifuged for sex hormone assays. The right ovary was used for biochemical analysis, and the left ovary was fixed in 10% neutral buffered formalin for histological assessment. The levels of estradiol, progesterone, FSH, and LH significantly increased in the Dia+ZnONPs+LC group (P < 0.001) compared with the Dia group. Co-treatment with LC and ZnONPs reduced malondialdehyde and carbonyl protein and increased glutathione, catalase, and superoxide dismutase activities in ovarian tissue compared with the Dia group (P < 0.05). Moreover, the number of all ovarian follicles significantly increased in this group compared with the Dia group (P < 0.05). The results of this study indicated that co-treatment with LC and ZnONPs could preserve ovarian function by increasing sex hormones levels and antioxidant activity and decreasing lipid peroxidation in diabetic rats. Therefore, this compound supplementation may improve ovulation and fertility in people with diabetes mellitus.

Is Ovarian Reserve Impacted in Anorexia Nervosa?

STUDY OBJECTIVES: Hypothalamic amenorrhea is common in adolescents and young adults (AYAs) with anorexia nervosa (AN), and ovarian reserve is not routinely assessed. AN increases rates of fertility problems, but how or when AN negatively influences future fertility is unclear. We sought to determine whether biomarkers of ovarian reserve were impacted in AYA with AN. DESIGN: Cross-sectional study. SETTING: Tertiary care center. PARTICIPANTS: Females with AN and amenorrhea (n = 97) at the pre-intervention visit of a clinical trial, n = 19 females without an eating disorder or menstrual dysfunction. MAIN OUTCOME MEASURES: Serum anti-Müllerian hormone (AMH) concentrations. RESULTS: AMH levels were higher in AYA with AN than unaffected adolescents (4.7 vs. 3.2 ng/mL; P = .03). Neither FSH nor inhibin B differed between groups. In 19.6% of participants with AN, AMH levels were elevated above the normal range (>6.78 ng/mL). These subjects had a longer disease duration than those with normal AMH levels (9 vs. 3 mos; P = .03); age or degree of malnutrition did not differ between AN subjects with normal or elevated AMH. CONCLUSIONS: AMH levels appear to be normal or elevated in AYA with AN. Low AMH in a patient with AN should raise clinical concern regarding ovarian reserve, and should not be attributed to degree of malnutrition alone. Currently, AMH is not regularly assessed during routine AN clinical care. However, our findings suggest some clinical utility in identifying those patients with reduced ovarian reserve. Potential links between the hypothalamic amenorrhea suffered by patients with AN and PCOS should be explored.

Changes in tumor markers, coagulation function and serum VEGF in patients with ovarian cancer and benign ovarian disease.

PURPOSE: To investigate the changes in tumor markers (TMs), coagulation function and vascular endothelial growth factor (VEGF) in patients with ovarian cancer (OC) and benign ovarian disease (BOD). METHODS: A total of 68 OC patients admitted to and treated in our hospital were selected (OC group), and another 68 BOD patients in the same time period were enrolled (BOD group). The variations in TMs, coagulation function and VEGF in OC and BOD patients were explored by analyzing the TMs, coagulation function and expression levels of serum VEGF and D-dimer in OC group and BOD group as well as the differences in TMs and coagulation function in patients in different stages. RESULTS: The values of TMs such as cancer antigen 125 (CA125), carbohydrate antigen 19.9 (CA19.9) and human epididymis protein 4 (HE4) in OC group were remarkably higher than those in BOD group, with significant differences (p<0.05). The values of those TMs were relatively low in the patients in stage I-II but relatively high in the patients in stage III-IV, and the patients in stage I-II had evidently lower values of those TMs than those in stage III-IV (p<0.05). The coagulation function was similar in both groups (p>0.05), while OC group exhibited a notably higher serum fibrinogen (FIB) level than BOD group (p<0.05). The levels of coagulation function indexes [prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT)] in the patients in stage I-II were comparable to those in stage III-IV, showing no differences (p>0.05), but the serum FIB level was markedly higher in the patients in stage III-IV than that in in stage I-II (p<0.05). The expression level of serum VEGF was increased distinctly in OC group compared with that in BOD group [(378.15±94.45) pg/mL vs. (164.02±67.38) pg/mL, p<0.05]. Moreover, OC group manifested obviously elevated expression level of serum D-dimer in comparison with BOD group [(4.58±1.48) µg/mL vs. (0.67±0.12) µg/mL, p<0.05]. CONCLUSIONS: TMs, coagulation function indexes and serum VEGF and D-dimer are highly expressed in OC patients, and the combined detection of TMs, coagulation function and serum VEGF can serve as an important method of diagnosing OC.

Retinol-binding protein 4 (RBP4) and high sensitivity C-reactive protein (hs-CRP) levels in patients with diminished ovarian reserve (DOR): a cross-sectional study.

BACKGROUND: Antioxidant/oxidant imbalance has been reported to be related to diminished ovarian reserve (DOR). Vitamin A (retinol), a kind of antioxidant, plays a role in restoring ovarian oxidative damage, while C-reactive protein (CRP) is the classical marker of oxidative stress and has recently been identified as an independent variable that is associated with low anti-Mullerian hormone (AMH) levels in young women with DOR. Additionally, retinol binding protein 4 (RBP4) can be considered a substitute for retinol in healthy, nonobese women. The study aim was to determine the relationship between serum RBP4, high sensitivity C-reactive protein (hs-CRP) concentrations and ovarian reserve in nonobese DOR patients. METHODS: This study included 24 DOR women and 48 normal ovarian reserve (NOR) women from the reproductive medical center of Renmin Hospital of Wuhan University. The serum RBP4 and high-sensitivity CRP (hs-CRP) levels were measured with ELISA kits. RESULTS: RBP4 levels (20,648.36 ± 5475.16 ng/ml vs 23,986.48 ± 5995.64 ng/ml, p = 0.025) were decreased, and hs-CRP levels (695.08 ± 1090.19 ng/ml vs 364.32 ± 786.29 ng/ml, p = 0.012) were increased in the DOR group. Serum RBP4 was positively related to AMH (Pearson r = 0.518, p = 0.000), while hs-CRP was negatively correlated with AMH (Spearman r = - 0.345, p = 0.005). after adjustments were made for the covariables, multiple line regression analysis showed that positive association between RBP4 and AMH still existed (ß = 0.450, p < 0.001). CONCLUSION: Decreased serum RBP4 levels and increased serum hs-CRP were observed in DOR patients in our study, and the strong correlation between RBP4 and AMH supports the notion that oxidative stress plays a role in DOR, and that appropriate levels of antioxidant vitamin A may be protective against ovarian reserve dysfunction.

Delay in IVF treatment up to 180 days does not affect pregnancy outcomes in women with diminished ovarian reserve.

STUDY QUESTION: Will a delay in initiating IVF treatment affect pregnancy outcomes in infertile women with diminished ovarian reserve? SUMMARY ANSWER: A delay in IVF treatment up to 180 days does not affect the live birth rate for women with diminished ovarian reserve when compared to women who initiate IVF treatment within 90 days of presentation. WHAT IS KNOWN ALREADY: In clinical practice, treatment delays can occur due to medical, logistical or financial reasons. Over a period of years, a gradual decline in ovarian reserve occurs which can result in declining outcomes in response to IVF treatment over time. There is disagreement among reproductive endocrinologists about whether delaying IVF treatment for a few months can negatively affect patient outcomes. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study of infertile patients in an academic hospital setting with diminished ovarian reserve who started an IVF cycle within 180 days of their initial consultation and underwent an oocyte retrieval with planned fresh embryo transfer between 1 January 2012 and 31 December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Diminished ovarian reserve was defined as an anti-Müllerian hormone (AMH) <1.1 ng/ml. In total, 1790 patients met inclusion criteria (1115 immediate and 675 delayed treatment). Each patient had one included cycle and no subsequent data from additional frozen embryo transfer cycles were included. Since all cycle outcomes evaluated were from fresh embryo transfers, no genetically tested embryos were included. Patients were grouped by whether their cycle started 1-90 days after presentation (immediate) or 91-180 days (delayed). The primary outcome was live birth (≥24 weeks of gestation). A subgroup analysis of more severe forms of diminished ovarian reserve was performed to evaluate outcomes for patients with an AMH <0.5 and for patients >40 years old with an AMH <1.1 ng/ml (Bologna criteria for diminished ovarian reserve). Logistic regression analysis, adjusted a priori for patient age, was used to estimate the odds ratio (OR) with a 95% CI. All pregnancy outcomes were additionally adjusted for the number of embryos transferred. MAIN RESULTS AND THE ROLE OF CHANCE: The mean ± SD number of days from presentation to IVF start was 50.5 ± 21.9 (immediate) and 128.8 ± 25.9 (delayed). After embryo transfer, the live birth rate was similar between groups (immediate: 23.9%; delayed: 25.6%; OR 1.08, 95% CI 0.85-1.38). Additionally, a similar live birth rate was observed in a subgroup analysis of patients with an AMH <0.5 ng/ml (immediate: 18.8%; delayed: 19.1%; OR 0.99, 95% CI 0.65-1.51) and in patients >40 years old with an AMH <1.1 ng/ml (immediate: 12.3%; delayed: 14.7%; OR 1.21, 95% CI 0.77-1.91). LIMITATIONS, REASONS FOR CAUTION: There is the potential for selection bias with regard to the patients who started their IVF cycle within 90 days compared to 91-180 days after initial consultation. In addition, we did not include patients who were seen for initial evaluation but did not progress to IVF treatment with oocyte retrieval; therefore, our results should only be applied to patients with diminished ovarian reserve who complete an IVF cycle. Finally, since we excluded patients who started their IVF cycle greater than 180 days from their first visit, it is not known how such a delay in treatment affects pregnancy outcomes in IVF cycles. WIDER IMPLICATIONS OF THE FINDINGS: A delay in initiating IVF treatment in patients with diminished ovarian reserve up to 180 days from the initial visit does not affect pregnancy outcomes. This observation remains true for patients who are in the high-risk categories for poor response to ovarian stimulation. Providers and patients should be reassured that when a short-term treatment delay is deemed necessary for medical, logistic or financial reasons, treatment outcomes will not be affected. STUDY FUNDING/COMPETING INTEREST(S): No financial support, funding or services were obtained for this study. The authors do not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Plasma levels of polychlorinated biphenyl, genetic polymorphisms, and the risk of advanced stage endometriosis.

Both environmental and genetic factors interact and play a critical role in the pathogenesis of endometriosis. We analyzed the plasma levels of 12 polychlorinated biphenyl (PCB) congeners with genetic polymorphisms of glutathione-S-transferase M1 (GSTM1), glutathione-S-transferase T1 (GSTT1), and aryl hydrocarbon receptor repressor (AhRR) codon 185. Total sum of the 12 congeners was significantly higher in the controls compared with endometriosis group. Women without C/C genotype in AhRR codon 185 had a significantly increased risk of endometriosis compared with those with C/C genotype. Total sum of the 12 congeners was significantly higher in women without C/C genotype compared with those with C/C genotype. Adjusting for age and AhRR codon 185 genotype, there was no significant association between exposure to PCBs and the risk of endometriosis. These findings suggest a possible presence of gene-environment interaction, however, we could not see any clear association between exposure to PCBs and the risk of endometriosis.

Oocyte cryopreservation for fertility preservation in women with ovarian endometriosis.

RESEARCH-QUESTION: What is the clinical usefulness of oocyte cryopreservation for fertility preservation in women with ovarian endometriosis? DESIGN: Clinical characteristics were retrospectively analysed in 34 women with endometrioma before a planned ovarian cystectomy. Ovarian stimulation outcomes were compared according to laterality. A one-to-one propensity score-matched analysis was conducted to compare ovarian stimulation outcomes of the first cycle in patients with endometrioma undergoing fertility preservation with those in infertile patients without endometrioma who underwent IVF treatment. The number of oocytes cryopreserved in repeated ovarian stimulation cycles was analysed. RESULTS: The mean endometrioma size at diagnosis was 6.0 ± 2.5 cm. The mean age, serum anti-Mullerian hormone levels and number of oocytes cryopreserved were 30.7 ± 5.9 years, 1.85 ± 1.14 ng/ml, and 4.8 ± 3.2, respectively. The number of oocytes cryopreserved in bilateral endometrioma compared with unilateral endometrioma patients was 4.1 ± 2.9 versus 5.7 ± 3.4 (P = 0.600). In the propensity score-matched cohort (n = 22 per group), the number of oocytes retrieved was significantly lower in the patients with endometrioma undergoing fertility preservation compared with that in infertile patients without endometrioma (5.4 ± 3.8 versus 8.1 ± 4.8; P = 0.045). A total of 13 (38.2%) patients with endometrioma underwent repeated stimulation. The median (interquartile range) number of cryopreserved oocytes at the first and the second cycle were 3.0 (2.5-6.0) and 5.0 (2.5-7.5), respectively. CONCLUSIONS: Women with endometrioma should be counselled about oocyte cryopreservation for fertility preservation before surgery. The number of cryopreserved oocytes can be increased by repeated oocyte retrieval.

The protective effect of platelet-rich plasma administrated on ovarian function in female rats with Cy-induced ovarian damage.

PURPOSE: We evaluated the protective effect of PRP on ovarian function in female rats with cyclophosphamide (Cy)-induced ovarian damage. METHODS: Thirty-two adult female Sprague-Dawley rats were randomly divided into four groups. Group 1 (control-sodium chloride 0.9%; 1 mL/kg, single-dose ip injection), group 2 (Cy); 75 mg/kg, single-dose ip injection and sodium chloride 0.9% (1 mL/kg, single-dose ip injection), group 3 Cy plus PRP, Cy (75 mg/kg, single-dose and PRP (200 µl, single-dose) ip injection), group 4 (PRP, 200 µl, single-dose ip injection). Primordial, antral, and atretic follicle counts; serum anti-Müllerian hormone (AMH) levels; AMH-positive granulosa cells; and gene expression analysis of Ddx4 were assessed. RESULTS: Serum AMH levels were significantly lower in group 2 compared to groups 1, 3, and 4 (p < 0.01, p < 0.01, and p = 0.04, respectively). A significant difference was found in the primordial, primary, secondary, antral, and atretic follicle counts between all groups (p < 0.01). There was a statistically significant difference in AMH-positive staining primary, secondary, and antral follicles count between the groups (p < 0.01). There was a statistically significant difference in primary, secondary, and antral AMH positive staining follicle intensity score between the groups (p < 0.01). Ddx4 expression in group 4 was highest compared to other groups. CONCLUSION: Our study may provide evidence that PRP could protect ovarian function against ovarian damage induced by Cy. It could lead to improved primordial, primary, secondary, and antral follicle numbers.

Can the Need for Invasive Intervention in Tubo-ovarian Abscess Be Predicted? The Implication of C-reactive Protein Measurements.

STUDY OBJECTIVE: To evaluate the clinical parameters of hospitalized patients with pelvic inflammatory disease (PID) for the presence of tubo-ovarian abscess (TOA) and predict the need for intervention. DESIGN: A prospective cohort study. SETTING: A tertiary care university medical center. PATIENTS: Ninety-four patients were diagnosed with complicated PID and hospitalized between 2015 and 2017. INTERVENTIONS: Patients with PID were treated with parenteral antibiotics according to Centers for Disease Control guidelines. Demographic, clinical, sonographic, and laboratory data for patients with PID were analyzed. Inflammatory markers including C-reactive protein (CRP), white blood cells (WBCs), erythrocyte sedimentation rate (ESR), and clinical parameters were collected at admission and during hospitalization. MEASUREMENTS AND MAIN RESULTS: Forty-eight of 94 patients (51.1%) hospitalized with complicated PID were diagnosed with TOA sonographically. CRP levels were the strongest predictor of TOA, followed by WBC count, ESR, and fever on admission. The areas under the receiver operating characteristic (ROC) curve for CRP, WBC, ESR, and fever were .92, .75, .73 and .62, respectively. CRP specificity was 93.4% and sensitivity was 85.4% for predicting TOA, with cutoff value of 49.3 mg/L. Twelve patients (25%) failed conservative management and underwent surgical intervention including laparoscopy (n = 7), computed tomography (CT)-guided drainage (n = 4), and laparotomy (n = 1). In this group, CRP levels significantly increased from admission to day 1 and day 2 during hospitalization (128.26, 173.75, and 214.66 mg/L, respectively; p < .05 for both). In the conservative management group, CRP levels showed a plateau from admission to day 1 and then a decrease until day 3 (110, 120.49, 97.52, and 78.45 mg/L, respectively). CONCLUSION: CRP is a sensitive, specific inflammatory marker for predicting TOA in patients with complicated PID, and levels >49.3 mg/L suggest the presence of TOA. In the TOA group, CRP level trends correlated well with success or failure of conservative management. Increasing CRP levels during treatment may be used as an indicator of the need for invasive intervention, and daily CRP measurements can help predict the need for invasive intervention.

AMH: Could It Be Used as A Biomarker for Fertility and Superovulation in Domestic Animals?

Anti-Müllerian hormone (AMH) is a reliable and easily detectable reproductive marker for the fertility competence of many farm animal species. AMH is also a good predictor of superovulation in cattle, sheep, and mares. In this review, we have summarized the recent findings related to AMH and its predictive reliability related to fertility and superovulation in domestic animals, especially in cattle. We focused on: (1) the dynamics of AMH level from infancy to prepubescence as well as during puberty and adulthood; (2) AMH as a predictor of fertility; (3) the association between antral follicle count (AFC) and plasma AMH level; (4) AMH as a predictor of superovulation; and (5) factors affecting AMH levels in domestic animals, especially cattle. Many factors affect the circulatory levels of AMH when considering the plasma, like nutrition, activity of granulosa cells, disease state and endocrine disruptions during fetal life. Briefly, we concluded that AMH concentrations are static within individuals, and collection of a single dose of blood has become more popular in the field of assisted reproductive technologies (ART). It may act as a potential predictor of fertility, superovulation, and ovarian disorders in domestic animals. However, due to the limited research in domestic animals, this potential of AMH remains underutilized.

An investigation of the effects of metformin on ovarian ischemia-reperfusion injury in rats.

Damage to the ovaries or tissue torsion can significantly reduce the ovarian reserve and thus cause severe gynecological and hormonal deficiencies. The discovery of new agents is always needed in the treatment of this condition. Metformin (MET) has been shown to be beneficial in attenuating ovarian ischemia-reperfusion injury. Fifty-six female Sprague Dawley rats were divided into seven groups. Group 1 represented the control group (C), Group 2, the ischemia group (I), and Group 3, the ischemia/reperfusion group (I/R). Group 4, the ischemia (I)+250 group, and Group 5, the ischemia (I)+500 group, received 250 mg/kg and 500 mg/kg MET, respectively. Group 6, the ischemia/reperfusion (I/R)+250 group, and Group 7, the ischemia/reperfusion (I/R)+500 group, received 250 mg/kg and 500 mg/kg MET, respectively. Tissue malondialdehyde (MDA), glutathione (GSH), and tumor necrosis factor-alpha (TNF-α) levels in ovarian tissue increased following I/R, while estradiol (E2) levels decreased. Moreover, infiltration and diffuse edematous areas were observed in addition to diffuse vascular congestion and hemorrhage findings. Caspase-3 and nuclear factor kappa B (NF-κß) expression levels also increased. MDA and TNF-α concentrations decreased in the MET treatment groups, while GSH and E2 levels increased. The findings showed that I/R causes ovarian damage through the induction of oxidative stress, inflammation, and apoptosis. However, MET application was effective in preventing damage in ovarian tissue by reducing levels of reactive oxygen species, proinflammatory cytokines, caspase-3 and NF-κß.

Ultrasonographic and hormonal characterization of reproductive health and disease in wild, semiwild, and aquarium-housed southern stingrays (Hypanus americanus).

OBJECTIVE: To characterize physical examination, plasma biochemical, and ultrasonographic findings in aquarium-housed, managed semiwild, and wild southern stingrays (Hypanus americanus) with and without reproductive disease. ANIMALS: Southern stingrays from aquarium (n = 48), lagoon (managed semiwild; 34), and wild (12) habitats. PROCEDURES: Limited, opportunistic prosections were performed of presumed anatomically normal wild southern stingrays and compared with findings for aquarium-housed stingrays with reproductive disease. Ultrasonographic video data from both groups were used to assign a score (1 to 5) indicating increasing severity of ovarian and uterine reproductive disease. Plasma total 17ß-estradiol, estrone, progesterone, and testosterone concentrations were measured with enzyme immunoassays validated for use in southern stingrays. RESULTS: Ultrasonographic ovarian scores were significantly correlated with uterine scores. No reproductive disease was detected in semiwild or wild stingrays, but 65% (31/48) of aquarium-housed stingrays had developing or advanced reproductive disease (ie, ultrasonographic ovarian or uterine score of 4 or 5). Significant correlations were identified between ovarian and uterine disease status and plasma concentrations of all steroid hormones except testosterone. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggested that ultrasonography and plasma hormone concentrations may be useful in the identification of reproductive disease and determination of disease severity in southern stingrays.

Preoperative serum anti-Müllerian hormone level is a potential predictor of ovarian endometrioma severity and postoperative fertility.

OBJECTIVE: To establish a model for predicting revised American Society of Reproductive Medicine (rASRM) scores before endometrioma surgery based on serum anti-Müllerian hormone (AMH) level and to identify factors that might reliably predict postoperative fertility of women diagnosed with endometrioma. STUDY DESIGN: The study population was composed of 134 women with endometrioma, 58 with benign cyst, and 115 with non-ovarian lesion. Preoperative serum AMH level and clinical parameters were compared among three groups. Univariate correlation analyses and multivariate linear regression modeling with a stepwise method were performed for constructing an rASRM scores prediction model. Cox regression analysis was then used to identify predictive variables of spontaneous pregnancy following surgical treatment of endometrioma. RESULTS: Preoperative AMH level were significantly lower in the endometrioma group than in the other two groups (p < 0.001). Multivariate linear regression analysis revealed that age (ß=-0.324, p < 0.001), rASRM scores (ß=-0.298, p < 0.001) and serum CA125 level (ß=-0.176, p = 0.026) independently and negatively correlated with serum AMH level. Cox regression analysis of women with endometrioma who underwent surgical resection indicated that older age (per five-year increase, HR: 0.517; 95% CI, 0.299-0.896) and higher serum AMH level (cut-off value: >3.68 ng/ml, HR: 2.383; 95% CI, 1.093-5.197) were independent predictors for postoperative fertility. CONCLUSION: Patients with advanced staged endometriosis tended to have a lower serum AMH level while postoperative infertility was more likely to occur in older patients with a lower level of serum AMH. Thus, timely detection of AMH levels to assess the severity of ovarian endometriosis and possibility for postoperative pregnancy success is necessary to ensure that optimal medical treatment can be provided.