Transcriptome-wide association analyses identify an association between ARL14EP and polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, which is accompanied by a variety of comorbidities including metabolic, reproductive, and psychiatric disorders. Genome-wide association studies have identified several genetic variants that are associated with PCOS. However, these variants often occur outside of coding regions and require further investigation to understand their contribution to PCOS. A transcriptome-wide association study (TWAS) was performed to uncover heritable gene expression profiles that are associated with PCOS in two independent cohorts. Causal gene prioritization was subsequently performed and expression of genes prioritized through these analyses was examined in 49 PCOS patients and 30 controls. TWAS analyses revealed that increased expression of ARL14EP was significantly associated with PCOS risk in the discovery (P = 1.6 × 10-6) and replication cohorts (P = 2.0 × 10-13). Gene prioritization pipelines provided further evidence that ARL14EP is the most likely causal gene at this locus. ARL14EP gene expression was shown to be significantly different between PCOS cases and controls, after adjusting for body mass index, age and testosterone levels (P = 1.2 × 10-13). This study has provided evidence for the role of ARL14EP in PCOS. Given that ARL14EP has been reported to play an important role in chromatin remodeling, variants affecting the expression of ARL14EP may also affect the expression of other genes that contribute to PCOS pathogenesis.

Fertility-sparing surgery for diffuse adenomyosis: a narrated, stepwise approach to the Osada procedure.

OBJECTIVE: To equip reproductive surgeons with an approach to the Osada procedure and critical prophylactic hemostatic measures that optimize perioperative outcomes. DESIGN: Stepwise demonstration of the Osada procedure with narrated video footage. SETTING: Definitive management of symptomatic adenomyosis requires hysterectomy. However, adenomyomectomy can improve symptoms and restore anatomy while maintaining fertility potential. Limited but comparable perioperative outcomes exist for minimally invasive methods of adenomyomectomy, and most involve resection of focal, not diffuse, adenomyosis. Among the literature involving resection of diffuse adenomyosis using minimally invasive methods, relatively small volumes of resected tissue are reported and none include obstetric outcomes. Most published reports for excision of diffuse adenomyosis involve laparotomic resection, likely because of specific intraoperative challenges curtailed by this approach. In response, a laparoscopic-assisted laparotomic approach was developed in 2011 by Dr. Hisao Osada, a reproductive surgeon in Japan. This procedure involves aggressive excision of adenomyotic tissue with prophylactic hemostatic techniques and subsequent uterine wall reconstruction using a triple-flap method. Compared with other excisional methods for diffuse adenomyomectomy, the Osada procedure has the best reported obstetric outcomes. PATIENT(S): A 37-year-old nulliparous female presented with pelvic pain, bulk symptoms, abnormal uterine bleeding, and infertility. Physical examination demonstrated a 20-week, bulky uterus with limited bimanual mobility. Her endometrial cavity was inaccessible because of marked anatomic distortion. Magnetic resonance imaging revealed marked abnormality of her endometrial contour because of a 15 cm adenomyoma with diffuse adenomyomatous tissue in the posterior uterine compartment. Prior interventions included a trial of combined hormonal contraceptive, leuprolide acetate, and tranexamic acid. She was interested in fertility-sparing adenomyomectomy to address symptoms and fertility potential and chose to proceed with the Osada procedure. She was optimized medically with oral and parenteral iron therapy to bring her hemoglobin from 55-111 g/L preoperatively. Institutional review board approval and informed consent from the patient were obtained. INTERVENTION(S): The Osada procedure was performed using the following 8 surgical steps: Systemic administration of tranexamic acid was also administered intraoperatively. MAIN OUTCOME MEASURE(S): Perioperative blood loss, anatomic normalization, symptom remediation, and maintenance of fertility potential. RESULTS: Perioperative blood loss was minimal, 469 g of adenomyotic tissue was extracted, and discharge was on postoperative day 2 without any complications. Three months later, cyclic pain and bleeding had improved markedly, ultrasound confirmed Doppler flow throughout the uterus, hysterosalpingogram demonstrated a nonobliterated endometrial cavity and tubal patency, and magnetic resonance imaging confirmed normalized uterine dimensions measuring 11 × 7 cm from 19 × 10 cm. Most literature supports waiting at least 6-12 months and until demonstration of normalized uterine blood flow in the operated area before attempting conception. CONCLUSION: Fertility-sparing excision of diffuse adenomyosis can be achieved safely using the Osada procedure, following the 8 discrete steps demonstrated in this video. Reproductive surgeons can reference this video to teach and maintain this important procedure.

Ovarian Hyperstimulation Syndrome Complicating Spontaneous Molar Pregnancy: A Case Report and Review of the Literature.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is traditionally associated with fertility treatments and results in elevated human chorionic gonadotropin (ßhCG) levels and fluid shifts to extravascular compartments. Rarely, spontaneous pregnancies with significant ßhCG elevations, such as molar pregnancies, can give rise to OHSS. CASE: A 24-year-old woman was diagnosed as having a molar pregnancy at approximately 12 weeks gestation following spontaneous conception. Her initial ßhCG was over 1 million IU/L. There was no evidence of metastatic disease. She underwent an uncomplicated dilation and curettage. Three days later, she presented with chest pain, shortness of breath, and abdominal discomfort. Massively enlarged ovaries were identified with bilateral pleural effusions requiring repeated thoracentesis. CONCLUSION: This case demonstrates rare sequelae of molar pregnancy. Treatment is mainly supportive, and close observation is required to manage complications. In patients with extremely elevated ßhCG levels, clinicians must remain vigilant for signs suggesting OHSS, even following evacuation of the uterus.

Cardiovascular magnetic resonance in pregnancy: insights from the cardiac hemodynamic imaging and remodeling in pregnancy (CHIRP) study.

BACKGROUND: Cardiovascular disease in pregnancy is the leading cause of maternal mortality in North America. Although transthoracic echocardiography (TTE) is the most widely used imaging modality for the assessment of cardiovascular function during pregnancy, little is known on the role of cardiovascular magnetic resonance (CMR). The objective of the Cardiac Hemodynamic Imaging and Remodeling in Pregnancy (CHIRP) study was to compare TTE and CMR in the non-invasive assessment of maternal cardiac remodeling during the peripartum period. METHODS: Between 2010-2012, healthy pregnant women aged 18 to 35 years were prospectively enrolled. All women underwent TTE and CMR during the third trimester and at least 3 months postpartum (surrogate for non-pregnant state). RESULTS: The study population included a total of 34 women (mean age 29 ± 3 years). During the third trimester, TTE and CMR demonstrated an increase in left ventricular end-diastolic volume from 95 ± 11 mL to 115 ± 14 mL and 98 ± 6 mL to 125 ± 5 mL, respectively (p<0.05). By TTE and CMR, there was also an increase in left ventricular (LV) mass during pregnancy from 111 ± 10 g to 163 ± 11 g and 121 ± 5 g to 179 ± 5 g, respectively (p<0.05). Although there was good correlation between both imaging modalities for LV mass, stroke volume, and cardiac output, the values were consistently underestimated by TTE. CONCLUSION: This CMR study provides reference values for cardiac indices during normal pregnancy and the postpartum state.

Remote discovery of an asymptomatic bowel perforation by a mid-urethral sling.

Bowel perforation is a rare complication of mid-urethral sling procedures and is usually reported shortly after the surgery. We report a remotely discovered asymptomatic bowel injury found at the time of subsequent surgery. The patient with a history of several prior pelvic surgeries underwent an uneventful retropubic mid-urethral sling placement. Five years later, during an abdominal sacrocolpopexy procedure, mesh from the mid-urethral sling was found perforating the wall of the cecum and fixating it to the right pelvic sidewall. Cecal wedge resection was performed to excise the sling mesh. Asymptomatic bowel perforation by mid-urethral sling mesh has not been previously reported. Pelvic and abdominal surgeons should be aware of the possibility of finding this injury in patients with prior sling surgeries.

Presurgical management of dysmenorrhea and endometriosis in a patient with Mayer-Rokitansky-Kuster-Hauser syndrome.

OBJECTIVE: To report a patient with Mayer-Rokitansky-Kuster-Hauser syndrome with functional endometrium treated with preoperative continuous combined low-dose monophasic oral contraceptives. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 12-year-old nulligravid adolescent girl. INTERVENTION(S): Preoperative continuous combined low-dose monophasic oral contraceptives for 7 months, and laparoscopic resection of the rudimentary uterus and uterine horns with unilateral salpingo-oophorectomy. MAIN OUTCOME MEASURE(S): Relief of pain after hormonal treatment and the operative procedure. RESULT(S): Successful preoperative treatment of endometriosis and pain before definitive diagnosis and removal of müllerian remnants in a patient with Mayer-Rokitansky-Kuster-Hauser syndrome. CONCLUSION(S): Patients with obstructive müllerian malformations with functional endometrium can be preoperatively managed with continuous combined low-dose monophasic oral contraceptives to control pain and treat endometriosis. This may permit a delay in surgical intervention to facilitate other investigations and to allow thorough counselling of the patient and her family about the implications of the diagnosis.

Primary testicular mucinous neoplasms: case report and literature review.

Testicular epithelial mucinous tumours are an extremely rare, but interesting form of testicular neoplasm. We reviewed the medical literature using PubMed search terms: testis, mucinous cystadenoma, mucinous cystadenocarcinoma, neoplasms and testicular neoplasms. We describe a case from our institution and provide a review of the literature. Only 11 previously reported cases of mucinous testicular tumours have been reported in the English literature. The natural history of these tumours is poorly understood, due to their rarity, but it appears that, like their ovarian counterparts, they have an excellent prognosis. Exclusion of metastasis is an important point for the urologist when encountering a mucinous testicular tumour, as metastatic cystic lesions may mimic a primary mucinous tumour. We describe a case of ossified testicular mucinous tumour of low malignant potential. Such tumours are common in the ovary, but arise very rarely in the testicle. The clinical and histological features of this tumour are presented, and previously reported cases are reviewed to highlight important clinical features.

Inhibition of acetyl-CoA carboxylase isoforms by pyridoxal phosphate.

Mammalian isoforms of acetyl-CoA carboxylase (ACC-1 and ACC-2) play important roles in synthesis, elongation, and oxidation of long-chain fatty acids, and the possible significance of ACC in the development of obesity has led to interest in the development of inhibitors. Here, we demonstrate that pyridoxal phosphate (PLP) is a linear and reversible inhibitor of ACC-1 and ACC-2. ACC from rat liver and white adipose tissue (largely ACC-1) exhibited an IC50 of approximately 200 microm, whereas ACC-2 from heart or skeletal muscle exhibited an IC50 exceeding 500 microm. ACC from rat liver was equally sensitive to PLP following extensive purification by avidin affinity chromatography. When added before citrate, PLP inhibited ACC with a Ki of approximately 100 microm, reducing maximal activity >90% and increasing the Ka for citrate approximately 5-fold but having little effect on substrate Km values. Pre-treatment with citrate increased the apparent Ki for ACC inhibition by PLP by approximately 4-fold. Inhibition of ACC was reversed by removal of PLP, either by washing or by reaction with hydroxylamine or amino-oxyacetate. ACC was irreversibly inhibited and radiolabeled, to a stoichiometry of approximately 0.4 mol[H]/mol subunit, in the presence of PLP plus [3H]borohydride. Studies with structurally related compounds demonstrated that the reactive aldehyde and negatively charged substituents of PLP contribute importantly to ACC inhibition. The studies reported here suggest a rationale to develop ACC inhibitors that are not structurally related to the substrates or products of the reaction and an approach to probe the citrate-binding site of the enzyme.