Endoplasmic reticulum stress response and the regulation of endometrial interferon-beta production.

OBJECTIVE: To gain an understanding of the potential role of endoplasmic reticulum (ER) stress in the endometrial compartment during early pregnancy, a highly understudied area. DESIGN: This study examined the regulation of interferon-ß (IFNß) in response to ER stress in human decidualized and nondecidualized endometrial cells (human endometrial stromal cells [HESCs]) in vitro. In vivo, we examined ER stress and the IFNß levels locally in the mouse endometrium before and after implantation at embryonic day (E)1, E3, and E6. SETTING: The study was performed in a reproductive sciences laboratory for Human Growth and Development. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Quantitative polymerase chain reaction, Western blotting, and immunohistochemical analysis allowed us to test the action of endogenous ER stress activation in the endometrial compartment likely triggered by implantation and its ability to increase the endometrial IFNß levels. RESULT(S): In vitro, we observed a significant difference in the IFNß levels in HESCs, in response to ER stress activation, where decidualized HESCs exhibited a threefold increase in the IFNß levels compared with nondecidualized HESCs. Apoptotic caspase-3 activation was also isolated to the decidualized cells as a result of ER stress-dependent suppression of nuclear factor-kappa beta-regulated antiapoptotic factors, XIAP and MCL-1. In vivo, mouse endometrial IFNß was present in F4/80-positive macrophages at all time points examined. After implantation (E6), the mouse luminal epithelial cells robustly coexpressed both IFNß and the ER stress marker immunoglobulin heavy chain binding protein (BiP). CONCLUSION(S): These analyses demonstrate that both in vivo and in vitro, differentiated and decidualized endometrial cells undergoing ER stress have the capacity to produce increased IFNß levels; therefore, ER stress activation in the endometrial compartment may play a vital role in promoting successful implantation events.

Potential Role of Zinc in the COVID-19 Disease Process and its Probable Impact on Reproduction.

COVID-19 (coronavirus disease 2019) is the current world health crisis, producing extensive morbidity and mortality across all age groups. Given the established roles of zinc in combating oxidative damage and viral infections, zinc is being trialed as a treatment modality against COVID-19. Zinc also has confirmed roles in both male and female reproduction. The possible depletion of zinc with the oxidative events of COVID-19 is especially relevant to the fertility of affected couples. This review aims to present the pathophysiology of COVID-19, especially in relation to reproductive function; the role of zinc in the COVID-19 disease process; and how zinc depletion in concert with cytokine storm and reactive oxygen species production could affect reproduction. It also highlights research areas to better the understanding of COVID-19 and its impact on fertility and potential ways to mitigate the impact.

Massive ovarian edema masquerading as an androgen-secreting tumor.

OBJECTIVE: To highlight the management of massive ovarian edema in young reproductive-age women. DESIGN: A case report of a healthy female with clitoromegaly and elevated androgen levels secondary to massive ovarian edema. SETTING: Reproductive Endocrinology and Infertility Department of an academic hospital. PATIENT: A healthy 20-year-old woman who presented for routine gynecological care and was found to have a 2-cm clitoromegaly and elevated androgen levels. INTERVENTIONS: The patient underwent a diagnostic laparoscopy and right oophorectomy. MAIN OUTCOME MEASURES: Measurement of androgen levels. RESULTS: Final pathology showed massive edema of the ovary with no evidence of malignancy or androgen-secreting tumor cells. In addition, resolution of the elevated androgen levels was observed. CONCLUSIONS: Massive ovarian edema due to asymptomatic subacute torsion should be included in the differential diagnosis of reproductive-age patients who present with ovarian mass and hyperandrogenemia within the tumor range. Although not performed in our case, conservative management that involves detorsion, ovarian biopsy, and oophoropexy to prevent a recurrence should be the treatment of choice.

Sheehan Syndrome: An Unusual Presentation Without Inciting Factors.

Background: Sheehan syndrome (SS) is a rare complication of severe postpartum hemorrhage or hypotension during the processes of labor and delivery that results in ischemic pituitary infarction and necrosis. In this case report, we describe an unusual presentation of SS without inciting factors. Case Presentation: A 30-year-old multiparous woman presented 2 hours after a normal spontaneous vaginal delivery with a profound severe headache, and subsequent agalactia, dry skin, and mood changes. She was managed conservatively until 10 months postdelivery when she complained of persistent symptoms including amenorrhea. A brain magnetic resonance (MR) with pituitary imaging revealed findings consistent with SS. The patient's symptoms improved and ultimately resolved after levothyroxine, estrogen replacement therapy, and hydrocortisone were instituted. Conclusions: SS can present without recognized inciting factors. During the initial phase, women may present with profound headache and/or visual disturbances warranting neurological evaluation. A high index of suspicion and a brain MR with pituitary imaging should prompt early consideration of SS to aid in the diagnosis.

Patient-Reported Outcomes After Extensive (Ultraradical) Surgery for Ovarian Cancer: Results From a Prospective Longitudinal Feasibility Study.

BACKGROUND: Extensive (ultraradical) surgery may facilitate complete cytoreduction in ovarian cancer with potential survival benefit but with greater morbidity. Currently, patient-reported outcomes (PROs) from such surgery are unknown. We conducted the Surgery in Ovarian Cancer Quality of life Evaluation Research study (SOCQER 1), a prospective study investigating the feasibility of collection of serial PROs in patients who had extensive surgery and standard surgery for ovarian cancer. METHODS: Ninety-three patients were recruited for 33 months to complete serial PRO assessments using the validated EORTC QLQ-C30 and the ovarian cancer-specific QLQ-OV28 questionnaires preoperatively, at 6 weeks, and at 3, 6, and 9 months postoperatively. Aletti Surgical Complexity Score of 3 or lower was considered standard surgery; a Surgical Complexity Score of 4 or higher was considered extensive surgery. Prospective data collection was obtained from the hospital electronic database, including patient demographics, American Society of Anaesthesiologists grade, preoperative serum CA125 and albumin levels, chemotherapy regimen, and surgical morbidity. RESULTS: Three cohorts of patients--32 benign, 32 undergoing standard surgery, and 24 undergoing extensive surgery--completed the questionnaires. Median questionnaire completion rate in this study was 64%, demonstrating the feasibility of longitudinal quality of life (QoL) assessment after surgery. Patient-reported outcomes revealed a falling trend in QoL in the short-term (6 weeks-3 months) after surgery, which gradually returned to baseline at 6 to 9 months; this trend was more marked after extensive surgery. CONCLUSIONS: This study provides useful insight into the impact of extensive surgery on patients. Further multicenter studies are needed to evaluate the impact of extensive surgery on patient's QoL and survival.