Deepika Garg

The role of AMH in the pathophysiology of polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) affects 5 - 10% of reproductive age women, but its pathogenesis is still poorly understood. The aim of this review is to collate evidence and summarize our current knowledge of the role of anti-Müllerian hormone (AMH) in PCOS pathogenesis. AMH is increased and correlated with the various reproductive and metabolic/endocrine alterations in PCOS. AMH plays an inhibitory role in follicular development and recruitment, contributing to follicular arrest. AMH inhibitory action on FSH-induced aromatase production likely contributes to hyperandrogenism in PCOS, which further enhances insulin resistance in these women. Elevated serum AMH concentrations are predictive of poor response to various treatments of PCOS including weight loss, ovulation induction and laparoscopic ovarian drilling, while improvement in various clinical parameters following treatment is associated with serum AMH decline, further supporting an important role for AMH in the pathophysiology of this syndrome. This review emphasizes the need for understanding the exact mechanism of action of AMH in the pathophysiology of PCOS. This may lead to the development of new treatment modalities targeting AMH to treat PCOS, as well as help clinicians in prognostication and better tailoring existing treatments for this disease.

Progesterone-Mediated Non-Classical Signaling

Progesterone is essential for pregnancy maintenance and menstrual cycle regulation. Hormone action has been primarily ascribed to the well-characterized classical signaling pathway involving ligand binding, activation of nuclear progesterone receptors (PRs), and subsequent activation of genes containing progesterone response elements (PREs). Recent studies have revealed progesterone actions via non-classical signaling pathways, often mediated by non-genomic signaling. Progesterone signaling, in conjunction with growth factor signaling, impacts on the function of growth factors and regulates important physiological actions such as cell growth and remodeling, as well as apoptosis. This review focuses on non-classical progesterone signaling pathways, both including and excluding PR, and highlights how research in this area will provide a better understanding of progesterone actions and may inform novel therapeutic strategies.

Relationship between Advanced Glycation End Products and Steroidogenesis in PCOS

BackgroundWomen with PCOS have elevated levels of the harmful Advanced Glycation End Products (AGEs), which are highly reactive molecules formed after glycation of lipids and proteins. Additionally, AGEs accumulate in the ovaries of women with PCOS potentially contributing to the well-documented abnormal steroidogenesis and folliculogenesis.Main bodyA systematic review of articles and abstracts available in PubMed was conducted and presented in a systemic manner. This article reports changes in steroidogenic enzyme activity in granulosa and theca cells in PCOS and PCOS-models. It also described the changes in AGEs and their receptors in the ovaries of women with PCOS and presents the underlying mechanism(s) whereby AGEs could be responsible for the PCOS-related changes in granulosa and theca cell function thus adversely impacting steroidogenesis and follicular development. AGEs are associated with hyperandrogenism in PCOS possibly by altering the activity of various enzymes such as cholesterol side-chain cleavage enzyme cytochrome P450, steroidogenic acute regulatory protein, 17α-hydroxylase, and 3β-hydroxysteroid dehydrogenase. AGEs also affect luteinizing hormone receptor and anti-Mullerian hormone receptor expression as well as their signaling pathways in granulosa cells.ConclusionsA better understanding of how AGEs alter granulosa and theca cell function is likely to contribute meaningfully to a conceptual framework whereby new interventions to prevent and/or treat ovarian dysfunction in PCOS can ultimately be developed.

Advanced Glycation End Products: Link between Diet and Ovulatory Dysfunction in PCOS?

PCOS is the most common cause of anovulation in reproductive-aged women with 70% experiencing ovulatory problems. Advanced glycation end products are highly reactive molecules that are formed by non-enzymatic reactions of sugars with proteins, nucleic acids and lipids. AGEs are also present in a variety of diet where substantial increase in AGEs can result due to thermal processing and modifications of food. Elevation in bodily AGEs, produced endogenously or absorbed exogenously from high-AGE diets, is further exaggerated in women with PCOS and is associated with ovulatory dysfunction. Additionally, increased expression of AGEs as pro-inflammatory receptors in the ovarian tissue has been observed in women with PCOS. In this review, we summarize the role of dietary AGEs as mediators of metabolic and reproductive alterations in PCOS. Once a mechanistic understanding of the relationship between AGEs and anovulation is established, there is a promise that such knowledge will contribute to the subsequent development of targeted pharmacological therapies that will treat anovulation and improve ovarian health in women with PCOS.

Inositol Treatment and ART Outcomes in Women with PCOS.

Polycystic ovary syndrome (PCOS) affects 5–10% of women in reproductive age and is characterized by oligo/amenorrhea, androgen excess, insulin resistance, and typical polycystic ovarian morphology. It is the most common cause of infertility secondary to ovulatory dysfunction. The underlying etiology is still unknown but is believed to be multifactorial. Insulin-sensitizing compounds such as inositol, a B-complex vitamin, and its stereoisomers (myo-inositol and D-chiro-inositol) have been studied as an effective treatment of PCOS. Administration of inositol in PCOS has been shown to improve not only the metabolic and hormonal parameters but also ovarian function and the response to assisted-reproductive technology (ART). Accumulating evidence suggests that it is also capable of improving folliculogenesis and embryo quality and increasing the mature oocyte yield following ovarian stimulation for ART in women with PCOS. In the current review, we collate the evidence and summarize our current knowledge on ovarian stimulation and ART outcomes following inositol treatment in women with PCOS undergoing in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI).

Endometrial osseous metaplasia: an unusual cause of infertility

Osseous metaplasia of the endometrium is a rare disorder associated with the presence of bone in the uterine endometrium. Most patients with this condition presenting with infertility do so owing to the presence of a foreign body in the endometrium. We report a case of a 38-year-old woman who presented with secondary infertility due to osseous metaplasia in the endometrial cavity. She conceived spontaneously after hysteroscopic removal of the bony fragments from the uterus. Uterine osseous metaplasia is a rare cause of infertility that can be easily managed by hysteroscopic removal of the bony fragments, which results in return of fertility.

Late Postpartum Eclampsia with Postpartum Angiopathy: An Uncommon Diagnosis in the Emergency Department.

BACKGROUND Late postpartum eclampsia is defined as occurrence of eclampsia >48 h after delivery and is a rare clinical entity. The delayed onset and nonspecific symptoms at presentation make this entity a challenge to diagnose in patients presenting to the emergency department (ED); however, early recognition and timely interventions are the keys to reducing morbidity and mortality in patients with late postpartum eclampsia. CASE REPORT A 28-year-old woman presented to our ED with a chief complaint of headache of 4 days duration, 8 days after an uncomplicated, normal vaginal delivery. Her past medical history was unremarkable and her entire pregnancy was without medical incident. The patients examination was within normal limits other than a blood pressure of 152/111 mm Hg and pulse of 54 beats/min. Given her undifferentiated headache and the possibility of preeclampsia, the patient was treated with magnesium sulfate, which was subsequently stopped due to worsening bradycardia. Hydralazine was administered for blood pressure control. Three hours after the magnesium was stopped, the patient reported blurry vision, which was immediately followed by a generalized tonic-clonic seizure. After the seizure, lorazepam was given for control of seizures, and the patient was admitted to the medical intensive care unit. The patient was transferred to the postpartum floor 6 days later in stable condition and without any further seizure activity. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Patients with late postpartum eclampsia are infrequently encountered in the ED due to the rarity of this condition. Increased awareness of this entity among emergency physicians will lead to early interventions, which are crucial in decreasing morbidity and mortality in these patients.

A rare case of fatal stroke after ethylene glycol toxicity

A 58-year-old man presented to the emergency department with acute left-sided weakness and left visual field defect. His examination was significant for confusion, acetone odour, tachycardia and tachypnoea. Further blood tests revealed an anion gap of 31 mEq/L, serum osmolal gap of 34 mOsm/kg, and creatinine 3.6 mg/dL. Brain MRI revealed acute infarctions scattered throughout the brain along with generalised oedema. The patient deteriorated rapidly and soon thereafter it was reported that a bottle of antifreeze was found near him at home. Haemodialysis was initiated and the patient received fomepizole and bicarbonate. Three days later the patient did not show any neurological improvement and expired later that day. Ethylene glycol toxicity can rarely present with stroke which can be life-threatening when not diagnosed and managed in a timely fashion.

Treatment Modalities for Fibroids, Indications, Risks, and Benefits

Uterine fibroids are the most common benign neoplasm of the uterus in women of reproductive age. Although they are often asymptomatic, uterine fibroids may present abnormal uterine bleeding, pressure symptoms such as urinary frequency and constipation, abdominal pain or increasing abdominal girth, dyspareunia, and infertility. Various management options are available for the treatment of fibroids, which include medical management, such as hormonal therapies, and the use of gonadotropin-releasing hormone agonists. Surgical management includes uterine-sparing interventions, minimally invasive surgery, interventional radiological approaches, myomectomy, and hysterectomy. The choice of management approach for fibroids is dictated by size, number, location, nature of clinical manifestations, and future desire for fertility. No routine single management strategy is optimal because of the variable location and size of fibroids. Treatment should be tailored to the patient’s symptoms, disease location, and disease severity. With recent advancements in the minimally invasive surgeries and interventional radiological procedures, new treatment options for fibroid management have been proven successful and demonstrated efficacy and safety, along with reduced long-term reoccurrence. The purpose of this chapter is to summarize the various treatment modalities and available evidence for the management of fibroids with the focus on procedural indications, risk, and benefits.

Fetal proximal humeral epiphysis as an indicator of term gestation in different ethnic groups

Abstract Objectives: Accurate pregnancy dating is critical for appropriate clinical management. Our aim was to determine the time of appearance of proximal humeral epiphysis (PHE), consistency of its appearance among ethnic groups and whether 3D imaging helps with its visualization. Methods: A cross-sectional study was done on 360 patients with 563 scans in different ethnic groups between August 2013 and July 2015. Inclusion criteria were singleton pregnancies (34–40+  weeks of gestation), well dated by <20 weeks sonogram. Results: PHE was not seen at 34 (n = 44) or 35 weeks (n = 36) and was present at gestational ages 36 (n = 3), 37 (n = 126), 38 (n = 96), 39 (n = 100) and 40 weeks (n = 28) in 2%, 12%, 51%, 75% and 100%, respectively. PHE was seen in 20 of 50 (60%) African–Americans, 22 of 61 (64%) south Asians, 41 of 72 (57%) Caucasians, 45 of 86 (48%) Hispanics and 41 of 80 (49%) Asians. Conclusion: Appearance of PHE did increase with gestational age, prior to 40 weeks, it was not uniformly present and was seen as early as 36 weeks independent of ethnic group.