Systematic Review and Meta-Analysis of Perioperative Administration of Acetazolamide for Management of Postoperative Pain after Laparoscopy.

Background and Objective: To perform a systematic review and meta-analysis to evaluate the efficacy of perioperative acetazolamide (ACTZ) administration with laparoscopy for reducing postoperative referred pain. Methods: The following databases were searched from inception to March 1, 2020: Cochrane, PubMed, PubMed Central, Ovid, and Embase. Electronic search used: Acetazolamide AND (laparoscopy OR laparoscopic OR Celioscopy OR Celioscopies OR Peritoneoscopy OR Peritoneoscopies). No limits or filters were used. We included only studies of patients who underwent abdominal laparoscopy (LSC), had a pain assessment at approximately 24 hours postoperatively, and included a treatment with ACTZ group and a no-treatment or minimal-treatment comparison group. Results: Five studies met inclusion criteria, with a combined total of 253 participants, 116 in the ACTZ group and 137 in the control group. A Bayesian hierarchical model was assumed for the study specific treatment effects. Posterior sampling was conducted via Markov Chain Monte Carlo methods, and posterior inference carried out on the hierarchical treatment effect. ACTZ significantly decreased average pain scores compared to control group by -0.726 points (95% confidence interval -1.175-0.264). The posterior probability that ACTZ decreases mean pain scores by ≥ 0.5 was 0.846. Conclusion: Current available evidence demonstrates that perioperative ACTZ may provide a modest improvement in postoperative referred pain following LSC.

Pathology of hyperandrogenemia in the oocyte of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common ovulatory disorder in the world and is associated with multiple adverse outcomes. The phenotype is widely varied, with several pathologies contributing to the spectrum of the disease including insulin resistance, obesity and hyperandrogenemia. Of these, the role of hyperandrogenemia and the mechanism by which it causes dysfunction remains poorly understood. Early studies have shown that androgens may affect the metabolic pathways of a cell, and this may pose hazards at the level of the mitochondria. As mitochondria are strictly maternally inherited, this would provide an exciting explanation not only to the pathophysiology of PCOS as a disease, but also to the inheritance pattern. This review seeks to summarize what is known about PCOS and associated adverse outcomes with focus on the role of hyperandrogenemia and specific emphasis on the oocyte.

Hyperandrogenemia alters mitochondrial structure and function in the oocytes of obese mouse with polycystic ovary syndrome.

CAPSULE: Hyperandrogenemia in an obese PCOS mouse model results in altered glucose/insulin metabolism and mitochondrial structure and function in the oocytes, in part explaining adverse outcomes and inheritance patterns seen in PCOS. OBJECTIVE: To study the oocyte quality by means of mitochondrial structure and function in a well-established classic PCOS mouse model. DESIGN: Animal study using an obese PCOS mouse model compared with control. SETTING: Animal research facility in a tertiary care university hospital setting. ANIMALS: C57/B6J mice. INTERVENTION: Three week old mice had subdermal implants of DHT controlled release pellet or placebo for 90 days. MAIN OUTCOME MEASURES: The mouse model was validated by performing glucose tolerance test, HbA1c levels, body weight and estrous cycle analyses. Oocytes were subsequently isolated and were used to investigate mitochondrial membrane potential, oxidative stress, lipid peroxidation, ATP production, mtDNA copy number, transcript abundance, histology and electron microscopy. RESULTS: Results showed glucose intolerance and hyperinsulinemia along with dysregulated estrus cycle. Analysis of the oocytes demonstrated impaired inner mitochondrial membrane function, increased ATP production and mtDNA copy number, altered RNA transcript abundance and aberrant ovarian histology. Electron microscopy of the oocytes showed severely impaired mitochondrial ultrastructure. CONCLUSION: The obese PCOS mouse model shows a decreased oocyte quality related to impaired mitochondrial function.

Prenatal androgen induced lean PCOS impairs mitochondria and mRNA profiles in oocytes.

Polycystic ovary syndrome (PCOS) is the most common ovulatory defect in women. Although most PCOS patients are obese, a subset of PCOS women are lean but show similar risks for adverse fertility outcomes. A lean PCOS mouse model was created using prenatal androgen administration. This developmentally programmed mouse model was used for this study. Our objective was to investigate if mitochondrial structure and functions were compromised in oocytes obtained from lean PCOS mouse. The lean PCOS mouse model was validated by performing glucose tolerance test, HbA1c levels, body weight and estrous cycle analyses. Oocytes were isolated and were used to investigate inner mitochondrial membrane potential, oxidative stress, lipid peroxidation, ATP production, mtDNA copy number, transcript abundance, histology and electron microscopy. Our results demonstrate that lean PCOS mice has similar weight to that of the controls but exhibited glucose intolerance and hyperinsulinemia along with dysregulated estrus cycle. Analysis of their oocytes show impaired inner mitochondrial membrane function, elevated reactive oxygen species (ROS), increased RNA transcript abundance and aberrant ovarian histology. Electron microscopy of the oocytes showed impaired mitochondrial ultrastructure. In conclusion, the lean PCOS mouse model shows a decreased oocyte quality related to impaired mitochondrial ultrastructure and function.