COVID-19-related premature ovarian insufficiency: case report and literature review.

OBJECTIVE: The aim of this study is to present the case report of a 36-year-old woman developing premature ovarian insufficiency (POI) after COVID-19 and review the literature referring to the possible impact of SARS-CoV-2 infection on female reproduction. METHODS: A 36-year-old nulligravida with normal menstrual cycles, non-smoker, with a normal body mass index and no pelvic surgery or oncological treatment in her medical history presented to the Infertility Center of the Institute of Mother and Child in Warsaw after a year of unsuccessful attempts to get pregnant. During diagnostic process she was affected by COVID-19 with a mild manifestation and thereafter she presented amenorrhea with intense hot flushes. Further diagnostic confirmed the diagnosis of POI. RESULTS: There is a strong molecular basis for a possible effect of SARS-CoV-2 infection on the female reproductive system; however, the results of available research are conflicting. All of these aspects are discussed in detail. CONCLUSIONS: SARS-CoV-2 infection may cause serious complications that cast a long shadow on a patient's future life and health. Further research is needed to assess the real impact of SARS-CoV-2 infection on female reproductive health, as well as potential preventive and therapeutic strategies for women affected with COVID-19.

The association between serum galectin-3 level and its placental production in patients with preeclampsia.

Galectin-3 is ß-galactoside-binding lectin, used in cardiology as a biomarker of heart failure. Available research suggest galectin-3 may play a role in the development of preeclampsia. Seventy seven women were included in the study: 39 with preeclampsia and 38 with uncomplicated pregnancy. Patients underwent blood sample analysis (galectin-3, N-terminal pro-brain natriuretic peptide (NT-proBNP), soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), cystatin C, creatinine) and echocardiographic examination. After delivery, placental tissue samples were obtained for immunohistochemistry evaluation. In patients with preeclampsia, serum galectin-3 levels (11.8 versus 9.5 ng/ml; p = 0.004) and galectin-3 expression in placental tissue (immunoreactive score (IRS) in extravillous trophoblasts: 9 versus 5; p = 0.002; in syncytiotrophoblasts: 6 versus 2, p < 0.001) were significantly higher than in the control group. Serum NT-proBNP and sFlt-1 levels, sFlt-1/PlGF ratio, serum creatinine and cystatin C levels were significantly higher, whereas serum PlGF levels and estimated glomerular filtration rate (eGFR) were significantly lower in preeclamptic patients than in uncomplicated pregnancy. On echocardiography, preeclamptic women had significantly greater thickness of interventricular septum (IVS) and left ventricle posterior wall (PW) and significantly worse left ventricle diastolic function (higher E/e' values). Serum galectin-3 level did not correlate with any other biochemical parameters, as well as the vast majority of echocardiographic parameters. Significant correlation between serum galectin-3 and its placental expression in syncytiotrophoblasts (STB) was revealed. Renal function parameters and NT-proBNP correlated with antiangiogenic state. This study demonstrated increased serum galectin-3 levels and placental galectin-3 production in preeclamptic patients, in comparison to women with uncomplicated pregnancy. Myocardial dysfunction and worse renal function parameters in patients with preeclampsia were not related to galectin-3. The main source of galectin-3 in maternal blood was its placental production. In the development of preeclampsia, galectin-3 may act as a compensatory mechanism to impaired placentation in early pregnancy.

Serum progesterone concentrations on the day of oocyte retrieval above 9.23 ng/ml may predict ovarian hyperstimulation syndrome risk in in vitro fertilized patients.

The aim of our study was to evaluate serum progesterone levels on the day of oocyte retrieval as a promising biomarker inorder to evaluate the risk of ovarian hyperstimulation syndrome in a group with controlled ovarian hyperstimulation protocols using either gonadotropin antagonists or agonists (GnRH), compare with a natural cycle control group. Patients were divided into 3 groups (148 patients in total): control group in the natural cycle, patients treated with GnRH agonist and patients treated with GnRH antagonist. When we compared both controlled ovarian hyperstimulation (COH) protocol groups with the control group, we found statistically higher levels of progesterone in patients after COH (control versus long protocol group: 1.43 ± 1.28 ng/ml versus 8.95 ± 5.95 ng/ml; P < 0.001; control versus GnRH antagonist group: 1.43 ± 1.28 ng/ml versus 7.18 ± 5.13 ng/ml; P < 0.001). According to receiver operating characteristic (ROC) analysis, the level of serum progesterone on the day of oocyte retrieval, above which the risk of ovarian hyperstimulation syndrome (OHSS) is associated with a more than fourfold higher risk (OR 4.24; 95% CI 2.6 - 6.9) was found to be 9.23 ng/ml, with AUC: 0.896, P = 0.026 (95% CI 0.845 - 0.947). Progesterone level on the day of oocyte retrieval may be used as an additional sensitivity marker in treatment of early forms as well by freezing of embryos in prevention of late forms of OHSS.

High levels of soluble vascular endothelial growth factor receptor 1/sFlt1 and low levels of vascular endothelial growth factor in follicular fluid on the day of oocyte retrieval correlate with ovarian hyperstimulation syndrom regardless of the stimulation protocol.

The aim of the study was to assess the predictive value of vascular endothelial growth factor (VEGF), its soluble receptor - sVEGF-R1/sFlt1 and endocrine gland-derived vascular endothelial growth factor (EG-VEGF) concentrations in serum and follicular fluid (FF) for ovarian hyperstimulation syndrome (OHSS) in women undergoing controlled ovarian hyperstimulation (COH) protocols. Patients have been divided into 3 groups: control group on natural cycle, patients stimulated with GnRH agonist and patients stimulated with GnRH antagonist. The FF and serum concentrations of VEGF, EG-VEGF, sVEGF R1 and the expression of VEGF and EG-VEGF mRNA in GC in small and large follicles collected from patients were investigated. When we compared all patients in a trial, OHSS occurrence was correlated with higher level of sVEGF R1 and a lower level of VEGF in a follicular fluid from large follicles in a day of oocyte retrieval. The VEGF/sVEGF-R1 ratio for patients in COH groups, above which the risk of developing OHSS is very low (OR 0.1 (95% CI 0.01 - 0.29, P = 0.0006) was found to be 0.281 pg/ml, with AUC - 0.738, P = 0.042, (95% CI 0.656 - 0.82). High levels of sVEGF-R1 and low level of VEGF in FF on the day of oocyte retrieval correlate with OHSS regardless of the stimulation protocol.

Pain assessment during outpatient hysteroscopy using room temperature versus warm normal saline solution as a distention medium - a prospective randomized study.

OBJECTIVE: To assess the efficacy of warm normal saline distention solution versus a standard, room-temperature normal saline as distention medium for pain relief during outpatient hysteroscopy. MATERIALS AND METHODS: A prospective randomized case-placebo controlled study was conducted in tertiary care centre - Central Clinical Hospital of Ministry of Interior and Administration. Study group consisted of 100 women referred for outpatient hysteroscopy between January 2015 and July 2015. Every patient, who was referred for an office hysteroscopy, was offered to participate in the study to receive a sterile, 0.9% normal saline warmed up to 36°C as distention medium. Control group were women receiving sterile, room temperature of 25°C, 0.9% normal saline solution as a distention medium. No pre-medication nor analgesia were used. A visual analogue scale (VAS) was used for one-dimensional pain assessment. Women were asked to mark a VAS score before, during, and five and 15 minutes following the procedure. RESULTS: Median VAS scores during and directly after the anaesthesia-free hysteroscopy were no different between two groups. (p = 0.554 and p = 0.121, respectively). There were also no differences in the procedure time between groups (p = 0.845). CONCLUSIONS: Warm normal saline distention solution does not reduce the pain during and at the end of the outpatient hysteroscopy. The effect does not depend on the age of women, menopausal status, parity or type of outpatient hysteroscopy (operative or diagnostic).

Accuracy and diagnostic value of outpatient hysteroscopy for malign and benign disease.

BACKGROUND: The aim of the study was to evaluate accuracy of the outpatient hysteroscopy. MATERIALS AND METHODS: This was a retrospective cohort study of 494 women who underwent outpatient hysteroscopy after administration ofnon-steroidal anti-inflammatory agents with the 3.2 mm hysteroscope. Normal saline solution was used as the distension medium. All women were discharged in good general condition afterwards. RESULTS: In cases of abnormal uterine bleeding, there was no apparent pathology found in 112 cases (83.6%). Detection rate (DR) of endometrial polyps was 88.7% with false positive rate (FPR) of 4.6%. Positive predictive value (PPV) was 82.7% with negative predictive value (NPV) of 93.1%. Detection rate (DR) of the submucosal fibroids was 57.7%. Positive predictive value (PPV) was 57.7% with negative predictive value (NPV) of 95.0%. Endometrial cancer was confirmed in ten cases (2.0%), being suspected in eight cases during the procedure. DR in case of the endometrial cancer was 80.0% with FPR of 0.4%. PPV was 66.7% with NPV) of 99.6%. CONCLUSIONS: Outpatient hysteroscopy seems to be an effective and accurate diagnostic tool.

Heme oxygenase-1 protects tumor cells against photodynamic therapy-mediated cytotoxicity.

Photodynamic therapy is a promising antitumor treatment modality approved for the management of both early and advanced tumors. The mechanisms of its antitumor action include generation of singlet oxygen and reactive oxygen species that directly damage tumor cells and tumor vasculature. A number of mechanisms seem to be involved in the protective responses to PDT that include activation of transcription factors, heat shock proteins, antioxidant enzymes and antiapoptotic pathways. Elucidation of these mechanisms might result in the design of more effective combination strategies to improve the antitumor efficacy of PDT. Using DNA microarray analysis to identify stress-related genes induced by Photofrin-mediated PDT in colon adenocarcinoma C-26 cells, we observed a marked induction of heme oxygenase-1 (HO-1). Induction of HO-1 with hemin or stable transfection of C-26 with a plasmid vector encoding HO-1 increased resistance of tumor cells to PDT-mediated cytotoxicity. On the other hand, zinc (II) protoporphyrin IX, an HO-1 inhibitor, markedly augmented PDT-mediated cytotoxicity towards C-26 and human ovarian carcinoma MDAH2774 cells. Neither bilirubin, biliverdin nor carbon monoxide, direct products of HO-1 catalysed heme degradation, was responsible for cytoprotection. Importantly, desferrioxamine, a potent iron chelator significantly potentiated cytotoxic effects of PDT. Altogether our results indicate that HO-1 is involved in an important protective mechanism against PDT-mediated phototoxicity and administration of HO-1 inhibitors might be an effective way to potentiate antitumor effectiveness of PDT.