Biochemical Pathways and Modeling.

The precise etiology of the biochemical changes and the resulting constellation of symptoms seen in polycystic ovary syndrome (PCOS) has remained a mystery. Despite advances in our knowledge, the pathogenesis and alterations in the biochemical pathways underlying this disease are still not fully understood. PCOS is a multifactorial syndrome where a combination of genetics, lifestyle, and hormone abnormalities all play an intertwining role. This article will provide an in-depth look at the multitude of biochemical pathways that are dysregulated in PCOS and their relation to alterations in female physiology.

Polycystic Ovary Syndrome and Medical Conditions.

Polycystic ovary syndrome is a common endocrinopathy that has been associated with many medical conditions across nearly every specialty. This chapter reviews the current understanding of polycystic ovary syndrome and associated medical conditions.

Urinary symptoms after bladder flap at the time of primary cesarean delivery: a randomized controlled trial (RTC).

INTRODUCTION AND HYPOTHESIS: The aim of this study was to evaluate urinary symptoms in the postpartum period after omission of the bladder flap at the time of primary cesarean delivery. METHODS: This was a single-blind parallel-group randomized comparison (bladder flap, no bladder flap) in women scheduled for a primary cesarean delivery at 37 weeks gestation or later. The primary outcome was urinary symptom scores at 6-8 weeks postpartum. Secondary outcomes included comparisons of preoperative and postoperative pelvic floor symptom scores and the proportions of symptom bother responses between the study groups. RESULTS: A total 43 women were available for analysis. Randomization was as follows: omission of the bladder flap (n = 22) and bladder flap (n = 21). Demographic characteristics and baseline pelvic floor symptom scores were similar between the groups. The primary outcome, urinary symptom scores at 6-8 weeks postpartum, did not differ significantly between the groups, but urinary symptom bother was significantly higher in women who received a bladder flap. Pelvic floor symptom scores improved significantly following delivery. CONCLUSIONS: Urinary symptom scores as measured by the UDI-6 did not differ between women randomized to bladder flap or omission of the bladder flap, but the proportion of women with urinary symptom bother was significantly higher among those who received a bladder flap.

Follicle flushing does not improve live birth and increases procedure time: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To determine whether follicle flushing during oocyte retrieval improves live birth or secondary outcomes in assisted reproductive technology (ART). DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women undergoing ART using autologous gametes. INTERVENTION(S): A systematic search of PubMed, EMBASE, Cochrane Database, and Web of Science for randomized controlled trials comparing follicle flushing to direct aspiration during oocyte retrieval published in English between 1989 to 2020. MAIN OUTCOME MEASURE(S): Live birth as primary outcome, and clinical and ongoing pregnancy, total and mature metaphase II (MII) oocytes retrieved, and operating time as secondary outcomes. RESULT(S): Eleven studies were included totaling 1,178 cases. No difference in live birth was demonstrated between follicle flushing and direct aspiration. Clinical pregnancy and ongoing pregnancy were not improved with flushing. Total oocyte and MII yield were lower with flushing compared with direct aspiration. Procedure time was increased with flushing by 2 minutes in poor responders and 9 minutes in normal responders. Other sensitivity analyses did not demonstrate any changes, except the difference in MII yield was no longer statistically significant. CONCLUSION(S): Follicle flushing during oocyte retrieval increases procedure time and does not improve live birth or secondary ART outcomes. Randomized data do not support the use of follicle flushing as an intervention in ART.

Recurrent ovarian torsion in a premenarchal adolescent girl: contemporary surgical management.

BACKGROUND: Recurrent ovarian torsion in a premenarchal adolescent girl is a rare event. Several methods of prevention using surgical plication have been proposed, which require varying degrees of technical expertise and can result in altered reproductive anatomy. CASE: A premenarchal adolescent girl presented with a history of salpingo-oophorectomy for torsion and recurrence treated by detorsion. She was evaluated for preventive strategies and underwent a laparoscopic oophoropexy, performed using transvaginal ultrasound guidance, to facilitate access should oocyte retrieval be indicated for future fertility. CONCLUSION: Recurrent ovarian torsion is an uncommon event, but given the possibility of permanent sterility, oophoropexy should be discussed. As assisted reproductive technology procedures become more common, oophoropexy designed to aid ovarian access should be considered before surgical intervention.

Genital Autoinoculation with Vaccinia: A Look at Two Cases.

Introduction: Smallpox, or vaccinia, has been eradicated worldwide as a disease; however, it may be weaponized and is thus a required immunization when military members deploy to certain parts of the world. Materials and Methods: We report two unusual cases of genital autoinoculation following smallpox vaccination. Results: Both patients' lesions resolved without sequelae within 20 d. Conclusions: We advocate for thorough education on this potential vaccination adverse event. These cases highlight the importance of a broad differential diagnosis when dealing with vulvar lesions, particularly in our military population.

Estradiol regulates GH-releasing peptide's interactions with GH-releasing hormone and somatostatin in postmenopausal women.

OBJECTIVE: Estrogen stimulates pulsatile secretion of GH, via mechanisms that are largely unknown. An untested hypothesis is that estradiol (E2) drives GH secretion by amplifying interactions among GH-releasing hormone (GHRH), somatostatin (SS), and GH-releasing peptide (GHRP). DESIGN: The design comprised double-blind randomized prospective administration of transdermal E2 vs placebo to healthy postmenopausal women (n=24) followed by pulsatile GHRH or SS infusions for 13 h overnight with or without continuous GHRP2 stimulation. METHODS: End points were mean concentrations, deconvolved secretion, and approximate entropy (ApEn; a regularity measure) of GH. RESULTS: By generalized ANOVA models, it was observed that E2 vs placebo supplementation: i) augmented mean (13-h) GH concentrations (P=0.023), GHRH-induced pulsatile GH secretion over the first 3 h (P=0.0085) and pulsatile GH secretion over the next 10 h (P=0.054); ii) increased GHRP-modulated (P=0.022) and SS-modulated (P<0.001) GH ApEn; and iii) did not amplify GHRH/GHRP synergy during pulsatile GH secretion. By linear regression, E2 concentrations were found to be positively correlated with GH secretion during GHRP2 infusion (P=0.022), whereas BMI was found to be negatively correlated with GH secretion during GHRH (P=0.006) and combined GHRH/GHRP (P=0.015) stimulation. E2 and BMI jointly determined triple (combined l-arginine, GHRH, and GHRP2) stimulation of GH secretion after saline (R²=0.44 and P=0.003) and pulsatile GHRH (R²=0.39 and P=0.013) infusions. CONCLUSION: In summary, in postmenopausal women, E2 supplementation augments the amount (mass) and alters the pattern (regularity) of GH secretion via interactions among GHRH, SS, GHRP, and BMI. These outcomes introduce a more complex model of E2 supplementation in coordinating GH secretion in aging women.

Short-term estradiol supplementation potentiates low-dose ghrelin action in the presence of GHRH or somatostatin in older women.

CONTEXT: Ghrelin is a potent gastric-derived GH-releasing peptide. How ghrelin interacts with sex steroids, GHRH, and somatostatin (SS) is not known. OBJECTIVE: Our objective was to test the hypotheses that ghrelin's interactions with GHRH (synergistic) and SS (disinhibitory) are ghrelin dose-dependent and amplified by estrogen. SUBJECTS, SETTING, AND DESIGN: Healthy postmenopausal women were treated with placebo (n=12) or 17ß-estradiol (E2) (n=12) at the Center for Translational Science Activities in a randomized double-blind prospective study. METHODS: Ghrelin dose-dependence was assessed by nonlinear curve fitting of the relationship between deconvolved GH secretory-burst mass and 5 randomly ordered ghrelin doses (0, 0.03, 0.135, 0.6, and 2.7 µg/kg bolus iv) during saline, GHRH, and SS infusion. RESULTS: Under placebo, neither GHRH nor SS altered the ED50 of ghrelin (range 0.64-0.67 µg/kg). Under E2 (median E2 88 pg/mL), the ED50 of ghrelin declined in the presence of GHRH to 0.52 µg/kg. In contrast, the efficacy of ghrelin rose markedly during GHRH vs saline exposure with and without E2: placebo and saline 52±1.0 vs GHRH 173±3.8 µg/L; and E2 and saline 56±0.90 vs GHRH 174±3.7 µg/L. Sensitivity to ghrelin was similar under all conditions. SUMMARY: Short-term E2 supplementation in postmenopausal women reduces the ED50 (increases the potency) of ghrelin when GHRH is present, without altering ghrelin efficacy (maximal effect) or hypothalamo-pituitary sensitivity (slope of dose response) to ghrelin. The data suggest possible physiological interactions among sex steroids (endogenous), ghrelin, and GHRH during E2 replacement in postmenopausal women.

Migraines and ovarian hyperstimulation syndrome: a dopamine connection.

This case-control study shows a strong association between migraine history and development of ovarian hyperstimulation syndrome (OHSS). We hypothesize there may be a similar gene variant that predisposes women to both migraines and OHSS and identification will lead to optimal therapy, not only for OHSS, but also for women who suffer from migraines.

Treatment of ovarian hyperstimulation syndrome using a dopamine agonist and gonadotropin releasing hormone antagonist: a case series.

OBJECTIVE: To describe an outpatient treatment protocol for ovarian hyperstimulation syndrome (OHSS) that results in rapid normalization of symptoms with minimal side effects. DESIGN: Case series. SETTING: Midwestern academic reproductive endocrinology division. PATIENT(S): Four consecutive patients, diagnosed with OHSS, who presented after oocyte retrieval but before embryo transfer. INTERVENTION(S): All embryos were frozen and each patient was treated with the same dopamine agonist and GnRH antagonist protocol. MAIN OUTCOME MEASURE(S): Daily weights, days to resolution of clinical symptoms, side effects of the treatment protocol, and whether or not acute care or hospitalization was necessary. RESULT(S): The most rapid weight loss was within the first 5 days of treatment. The average time to resolution of clinical symptoms was 5.75 days. No side effects were reported and no patients required acute care or hospitalization. CONCLUSION(S): Dopamine agonists and GnRH antagonists, when given together at the time of diagnosis of OHSS, appear to work rapidly and effectively to diminish the clinical symptoms of the disease. The potential benefit of finding an outpatient treatment for OHSS with rapid onset and minimal side effects warrants further investigation into this protocol.