Zain Al-Safi

Delayed postpartum preeclampsia and eclampsia: Demographics, clinical course, and complications

OBJECTIVE: To estimate and evaluate the demographics, clinical course, and complications of delayed postpartum preeclampsia in patients with and without eclampsia. METHODS: We conducted a retrospective cohort study of patients who were discharged and later readmitted with the diagnosis of delayed postpartum preeclampsia more than 2 days to 6 weeks or less after delivery between January 2003 and August 2009. RESULTS: One hundred fifty-two patients met criteria for the diagnosis of delayed postpartum preeclampsia. Of these, 96 (63.2%) patients had no antecedent diagnosis of hypertensive disease in the current pregnancy, whereas seven (4.6%), 14 (9.2%), 28 (18.4%), and seven (4.6%) patients had gestational hypertension, chronic hypertension, preeclampsia, and preeclampsia superimposed on chronic hypertension, respectively, during the peripartum period. Twenty-two patients (14.5%) developed postpartum eclampsia, and more than 90% of these patients presented within 7 days after discharge from the hospital. The most common presenting symptom was headache in 105 (69.1%) patients. Patients who developed eclampsia were significantly younger than those who did not (mean±standard deviation, 23.2±6.2 compared with 28.3±6.7 years; adjusted odds ratio [OR] 1.13, 95% confidence interval [CI] 1.02–1.26, P=.03), and other demographic variables were no different. A lower readmission hemoglobin was associated with a lower odds of progression to eclampsia (10.7±1.7 compared with 11.6±2.2 g/dL, adjusted OR 0.75, 95% CI 0.57–0.98, P=.04). CONCLUSION: One week after discharge appears to be a critical period for the development of postpartum eclampsia. Education about the possibility of delayed postpartum preeclampsia and eclampsia should occur after delivery, whether or not patients develop hypertensive disease before discharge from the hospital. LEVEL OF EVIDENCE: III

Analysis of adverse events with Essure hysteroscopic sterilization reported to the Manufacturer and User Facility Device Experience database.

STUDY OBJECTIVE The Manufacturer and User Facility Device Experience database may be useful for clinicians using a Food and Drug Administration-approved medical device to identify the occurrence of adverse events and complications. We sought to analyze and investigate reports associated with the Essure hysteroscopic sterilization system (Conceptus Inc., Mountain View, CA) using this database. DESIGN Retrospective review of the Manufacturer and User Facility Device Experience database for events related to Essure hysteroscopic sterilization from November 2002 to February 2012 (Canadian Task Force Classification III). SETTING Online retrospective review. PATIENTS Online reports of patients who underwent Essure tubal sterilization. INTERVENTION Essure tubal sterilization. MEASUREMENTS AND MAIN RESULTS Four hundred fifty-seven adverse events were reported in the study period. Pain was the most frequently reported event (217 events [47.5%]) followed by delivery catheter malfunction (121 events [26.4%]). Poststerilization pregnancy was reported in 61 events (13.3%), of which 29 were ectopic pregnancies. Other reported events included perforation (90 events [19.7%]), abnormal bleeding (44 events [9.6%]), and microinsert malposition (33 events [7.2%]). The evaluation and management of these events resulted in an additional surgical procedure in 270 cases (59.1%), of which 44 were hysterectomies. CONCLUSION Sixty-one unintended poststerilization pregnancies were reported in the study period, of which 29 (47.5%) were ectopic gestations. Thus, ectopic pregnancy must be considered if a woman becomes pregnant after Essure hysteroscopic sterilization. Additionally, 44 women underwent hysterectomy after an adverse event reported to be associated with the use of the device.

Comparative analysis of different laparoscopic hysterectomy procedures.

PurposeTo compare the antecedent gynecological characteristics, indications for, and complications associated with, the different laparoscopic approaches to hysterectomy, in women with benign gynecological conditions.MethodsA retrospective cohort study of 957 patients who underwent laparoscopic supracervical (LSH), total (TLH), and assisted vaginal (LAVH) hysterectomies between January 2003 and December 2009.ResultsAmong 957 LH, 799 (83.5%) were LSH, 62 (6.4%) TLH, and 96 (10.1%) LAVH. Demographic characteristics were not different among the groups. Antecedent gynecologic conditions that were associated with the type of laparoscopic hysterectomy (LH) performed were: postmenopausal bleeding [LAVH vs. LSH, odds ratio (OR) 2.20; 95% confidence interval (CI) 1.04–4.65], previous pelvic surgery (TLH vs. LSH, OR 1.92; CI 1.05–3.52), previous cesarean delivery (LAVH vs. LSH, OR 0.39; CI 0.21–0.76), and prior hysteroscopy (LAVH vs. LSH, OR 0.29; CI 0.16–0.50). Preoperative diagnoses that were associated with the choice of LH were: menometrorrhagia (LAVH vs. LSH, OR 0.23; CI 0.14–0.38; TLH vs. LSH, OR 0.50; CI 0.26–0.98), uterine fibroids (LAVH vs. LSH, OR 0.25; CI 0.15–0.41), endometrial hyperplasia (TLH vs. LSH, OR 5.5; CI 2.04–14.84), and cervical dysplasia (TLH vs. LSH, OR 17.1; CI 6.83–42.79; LAVH vs. LSH, OR 8.05; CI 3.05–22.06). Estimated blood loss, operating time, and length of hospital stay were significantly reduced with LSH.ConclusionAntecedent gynecological history and the indications for surgery were associated with the type of LH performed in our institution. LSH was the most common approach and was associated with significantly less morbidity.

Nickel hypersensitivity associated with an intratubal microinsert system

BACKGROUND: Although known nickel hypersensitivity is a contraindication to intratubal microinsert placement in the United States, this case demonstrates that nickel hypersensitivity to intratubal microinserts can occur. CASE: A young woman developed an allergic reaction after placement of intratubal microinserts. Nickel hypersensitivity was confirmed with skin patch testing. The microinserts were removed hysteroscopically, and the patient improved. CONCLUSION: If a patient experiences symptoms of an allergic reaction after hysteroscopic sterilization, referral to an allergy specialist is recommended. If nickel hypersensitivity is confirmed, the microinserts should be removed; this may be performed under hysteroscopic guidance.

Joint MiRNA/mRNA Expression Profiling Reveals Changes Consistent with Development of Dysfunctional Corpus Luteum after Weight Gain

Obese women exhibit decreased fertility, high miscarriage rates and dysfunctional corpus luteum (CL), but molecular mechanisms are poorly defined. We hypothesized that weight gain induces alterations in CL gene expression. RNA sequencing was used to identify changes in the CL transcriptome in the vervet monkey (Chlorocebus aethiops) during weight gain. 10 months of high-fat, high-fructose diet (HFHF) resulted in a 20% weight gain for HFHF animals vs. 2% for controls (p = 0.03) and a 66% increase in percent fat mass for HFHF group. Ovulation was confirmed at baseline and after intervention in all animals. CL were collected on luteal day 7–9 based on follicular phase estradiol peak. 432 mRNAs and 9 miRNAs were differentially expressed in response to HFHF diet. Specifically, miR-28, miR-26, and let-7b previously shown to inhibit sex steroid production in human granulosa cells, were up-regulated. Using integrated miRNA and gene expression analysis, we demonstrated changes in 52 coordinately regulated mRNA targets corresponding to opposite changes in miRNA. Specifically, 2 targets of miR-28 and 10 targets of miR-26 were down-regulated, including genes linked to follicular development, steroidogenesis, granulosa cell proliferation and survival. To the best of our knowledge, this is the first report of dietary-induced responses of the ovulating ovary to developing adiposity. The observed HFHF diet-induced changes were consistent with development of a dysfunctional CL and provide new mechanistic insights for decreased sex steroid production characteristic of obese women. MiRNAs may represent novel biomarkers of obesity-related subfertility and potential new avenues for therapeutic intervention.

Omega-3 Fatty Acid Supplementation Lowers Serum FSH in Normal Weight But Not Obese Women

CONTEXT Dietary omega-3 fatty acids delay ovarian aging and promote oocyte quality in mice. OBJECTIVE To test whether dietary supplementation with omega-3 polyunsaturated fatty acids (PUFA) modulates reproductive hormones in reproductive-age women. DESIGN Prospective interventional study. SETTING Academic center. PARTICIPANTS Fifteen obese and 12 normal-weight (NW) eumenorrheic women, ages 28-34 years. INTERVENTION Two frequent blood-sampling studies were performed before and after 1 month of omega-3 PUFA supplementation with 4 g of eicosapentaenoic acid and docosahexaenoic acid daily. MAIN OUTCOME MEASURES Serum LH and FSH (basal and after GnRH stimulation). RESULTS The ratio of omega-6 to omega-3 PUFA was significantly reduced in plasma and red blood cell components for both groups after treatment (both P < .01). Omega-3 PUFA supplementation resulted in reduction of FSH and FSH response to GnRH by 17% on average (P = .06 and P = .03, respectively) in NW but not obese women. Serum levels of IL-1β and TNF-α were reduced after omega-3 PUFA supplementation (-72% for IL-1β; -56% for TNF-α; both, P < .05) in obese but not in NW women. This reduction, however, was not associated with a hormonal change in obese women. CONCLUSIONS Dietary administration with omega-3 PUFA decreased serum FSH levels in NW but not in obese women with normal ovarian reserve. This effect is intriguing and is directionally consistent with murine data whereby higher dietary omega-3 PUFA extends reproductive lifespan. Our results imply that this nutritional intervention should be tested in women with diminished ovarian reserve in an attempt to delay ovarian aging.

New onset delayed postpartum preeclampsia: different disorders?

Objective: Delayed postpartum preeclampsia is a poorly studied disorder. We compared new onset delayed postpartum preeclampsia (NOPP) to recurrent/persistent, delayed onset postpartum preeclampsia (RPP) to see whether these were different disorders. Methods: Delayed onset preeclampsia was defined as readmission >2 days to ≤6 weeks postpartum for preeclampsia. The NOPP group had no antecedent diagnosis of hypertensive disorders in the current pregnancy, and was compared to the RPP defined as a prior hypertensive disorder in the current pregnancy in terms of maternal demographics, obstetric and medical history, intrapartum and early postpartum course and clinical signs and symptoms and outcomes on postpartum readmission. Results: There were a total of 56 (36.8%) patients in the RPP and 96 (63.2%) patients in the NOPP groups. NOPP cases delivered significantly later 39.0 ± 2 weeks vs. 37 ± 3.0 weeks p < 0.001, and had significantly lower blood pressure during the antepartum, early postpartum and readmission periods. In addition the NOPP group had significantly higher average number of symptoms 2 vs. 1.5 p = 0.013 on postpartum readmission. There were no statistically significant differences in the rates of major complications. Conclusions: In this comprehensive study of delayed postpartum preeclampsia, there were few significant differences in the clinical course and no differences in complications in the NOPP subgroup compared to cases with preeclampsia recurring in the late postpartum period.

Estradiol Priming Improves Gonadotrope Sensitivity and Pro-Inflammatory Cytokines in Obese Women.

CONTEXT Obesity is associated with a pro-inflammatory state and relative hypogonadotropic hypogonadism. Estrogen (E2) is a potential link between these phenomena because it exhibits negative feedback on gonadotropin secretion and also inhibits production of pro-inflammatory cytokines. OBJECTIVE We sought to examine the effect of estrogen priming on the hypothalamic-pituitary-ovarian axis in obesity. DESIGN, SETTING, AND PARTICIPANTS This was an interventional study at an academic center of 11 obese and 10 normal-weight (NW) women. INTERVENTION A frequent blood-sampling study and one month of daily urinary collection were performed before and after administration of transdermal estradiol 0.1 mg/d for one entire menstrual cycle. MAIN OUTCOME MEASURES Serum LH and FSH before and after GnRH stimulation, and urinary estrogen and progesterone metabolites were measured. RESULTS E2 increased LH pulse amplitude and FSH response to GnRH (P = .048, and P < .03, respectively) in obese but not NW women. After E2 priming, ovulatory obese but not NW women had a 25% increase in luteal progesterone (P = .01). Obese women had significantly higher baseline IL-6, IL-10, TGF-β, and IL-12 compared with NW (all P < .05); these levels were reduced after E2 (-6% for IL-1β, -21% for IL-8, -5% for TGF-β, -5% for IL-12; all P < .05) in obese but not in NW women. CONCLUSIONS E2 priming seems to improve hypothalamic-pituitary-ovarian axis function and systemic inflammation in ovulatory, obese women. Reducing chronic inflammation at the pituitary level may decrease the burden of obesity on fertility.

Elevated Insulin in Obese Women Relates to Low Endogenous Luteinizing Hormone

INTRODUCTION: Obesity is a state of insulin resistance as it is also a state of relative hypogonadotropic hypogonadism. The physiology behind this is still unclear and may be the result of hypothalamic or pituitary factors or pharmacokinetics of gonadotropins. We sought to investigate if insulin, directly or indirectly, suppresses pituitary luteinizing hormone (LH) secretion. METHODS: A luteal phase frequent blood sampling study was undertaken in regularly menstruating obese (n=10) and normal-weight women (n=10). The study included 12 hours of unstimulated monitoring (to evaluate endogenous hypothalamic–pituitary function) with subsequent administration of intravenous bolus of gonadotropin-releasing hormone (to evaluate pituitary sensitivity). Luteinizing hormone was measured with an immunofluorometric assay. Luteinizing hormone pulsatility was evaluated using an objective, widely accepted method. RESULTS: All women were ovulatory. The obese group was significantly older than the normal weight group (32.5±4.7 compared with 27.3±2.6 years, P=.006). Insulin was significantly higher in the obese group than the normal-weight group (21.5 [14.3–28.7] compared with 11.7 [8.9–14.5] mU/L, P=.01). In the 2-hour postprandial period, there was a rise in insulin that was significantly higher (35.6 [17.1–54.1] compared with 16.5 [8.4–24.7] mU/L, P=.04) and LH that trended lower in the obese women (8.1 [3.5–12.7] compared with 4.2 [2.8–5.6] IU/L) (Figure 1). Composite of mean endogenous luteinizing hormone (LH) (±standard error of mean). CONCLUSIONS: Higher insulin in obese women may be associated with lower endogenous LH output. A direct role of insulin in suppressing pituitary LH secretion should be further investigated.

Fertility preservation in a patient with benign multicystic peritoneal mesothelioma

Benign multicystic peritoneal mesothelioma (BMPM) is a rare peritoneal tumor. Surgery is the only effective treatment for BMPM, and affected tissues occasionally must be sacrificed to achieve adequate debulking. A 25‐year‐old female was diagnosed with BMPM. She was counseled on fertility preservation and had oocyte cryopreservation prior to her debulking. Fertility preservation through embryo or oocyte cryopreservation is a valuable option for patients at risk of losing reproductive tissues during extensive surgery and chemotherapy. J. Surg. Oncol. 2014; 110:372–374.