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Concept: Uterus

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BACKGROUND: Noninvasive prenatal detection of common fetal aneuploidies with cell-free DNA from maternal plasma has been achieved with high-throughput next-generation sequencing platforms. Turnaround times for previously tested platforms are still unsatisfactory for clinical applications, however, because of the time spent on sequencing. The development of semiconductor sequencing technology has provided a way to shorten overall run times. We studied the feasibility of using semiconductor sequencing technology for the noninvasive detection of fetal aneuploidy.METHODS: Maternal plasma DNA from 13 pregnant women, corresponding to 4 euploid, 6 trisomy 21 (T21), 2 trisomy 18 (T18), and 1 trisomy 13 (T13) pregnancies, were sequenced on the Ion Torrent Personal Genome Machine sequencer platform with 318 chips. The data were analyzed with the T statistic method after correcting for GC bias, and the T value was calculated as an indicator of fetal aneuploidy.RESULTS: We obtained a mean of 3 524 401 high-quality reads per sample, with an efficiency rate of 77.9%. All of the T21, T13, and T18 fetuses could be clearly distinguished from euploid fetuses, and the time spent on library preparation and sequencing was 24 h.CONCLUSIONS: Semiconductor sequencing represents a suitable technology for the noninvasive prenatal detection of fetal aneuploidy. With this platform, sequencing times can be substantially reduced; however, a further larger-scale study is needed to determine the imprecision of noninvasive fetal aneuploidy detection with this system.

Concepts: Pregnancy, Infant, Embryo, Fetus, Uterus, Fertility, Abortion, Aneuploidy

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BACKGROUND: Postpartum depression is a serious problem for women and their offspring. Micronutrient supplements are recommended for pregnant women because of their documented protective effects for the offspring, but their potential beneficial effects on maternal mental health are unknown. This study investigated the association between prenatal micronutrient supplementation and the risk for symptoms of postpartum depression in a longitudinal pregnancy cohort from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. METHODS: Participants came from a cohort of the first 600 APrON women. Supplemental nutrient intake and symptoms of depression (measured with the Edinburgh Postnatal Depression Scale (EPDS)) were collected at each trimester and 12 weeks postpartum. RESULTS: Of the 475 participants who completed the EPDS at least twice in pregnancy and at 12 weeks postpartum, 416 (88%) scored <10 and 59 (12%) scored >=10, where an EPDS >=10 is considered to be “at least probable minor depression”. Mean nutrient intakes from supplements were higher in women with lower EPDS scores, particularly selenium (p = 0.0015) and omega-3s (p = 0.01). Bivariate analyses showed that several demographic and social/lifestyle variables were associated with EPDS >=10: not having been born in Canada (p = 0.01), greater number of chronic conditions (p = 0.05), greater number of stressful life events during this pregnancy (p = 0.02), and lower prenatal and postnatal support (p = 0.0043 and p = 0.0001, respectively). Adjusting for covariates and nutrients known to be associated with postpartum depression, logistic regression showed that having a prenatal EPDS >= 10 increased the odds of postpartum depressive symptoms (second and third trimester OR = 3.29, 95% CI = 1.55 - 7.01, p = 0.004 and OR = 4.26, 95% CI = 2.05 - 8.85, p < 0.0001, respectively), while prenatal supplemental selenium (per 10 mg, OR = 0.76, 95% CI = 0.74 - 0.78, p = 0.0019) and postnatal social support (OR = 0.87, 95% CI = 0.78 - 0.97, p = 0.0015) were protective. CONCLUSIONS: Multiple factors, including supplementary selenium intake, are associated with the risk of postpartum depressive symptoms. Future research on dietary supplementation in pregnancy with special attention to selenium intake is warranted.

Concepts: Pregnancy, Childbirth, Uterus, Obstetrics, Abortion, Bipolar disorder, Postpartum depression, Trimester

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Purpose: Imaging features and clinical characteristics of degenerated leiomyoma in patients referred for uterine fibroid embolization (UFE) were analyzed to assess the incidence of degenerated leiomyoma. Materials and Methods: Patients referred for UFE between 2008 and 2009 were retrospectively analyzed (n=276). Patients ranged in age from 27 to 51 years (mean 38.0 years). All patients underwent screening MRI with contrast enhancement. Medical histories and clinical symptoms were evaluated. Results: Among the 276 patients who underwent MRI, 14 (5.1%) showed degenerated leiomyomas. Symptoms were abdominal pain (n=4, 26.7%), menorrhagia (n=5, 35.7%) and bulk-related symptoms (n=5, 35.7%) and no symptoms (n=5, 35.7%). Of the 14 patients with degenerated leiomyomas, 5 (42.9%) had a history of pregnancy in the past two years. For T1-weighted imaging (T1WI), a high signal intensity (SI) of the leiomyoma was the most common finding (n=9, 64.3%) and a hyperintense rim (n=4, 28.6%) was the second most common. On T2-weighted imaging (T2WI), a low SI of the leiomyoma was found in six patients (42.9%), a high SI in four (28.6%) and a heterogeneous SI in four (28.6%) patients. Conservative management was performed in 11 (78.6%) patients, surgery in 3 (21.4%) and uterine artery embolization in one (7.1%) patient. Conclusion: The incidence of degeneration of leiomyoma in patients referred for UFE was 5.1%. Patients presented with variable clinical symptoms with or without a history of pregnancy. MR imaging showed a high SI on T1WI and various SIs on T2WI without contrast enhancement. An understanding of the degeneration of leiomyomata is essential when considering UFE.

Concepts: Uterus, Anatomical pathology, Radiology, Gynecology, Uterine fibroids, Leiomyoma, Myometrium, Uterine artery embolization

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BACKGROUND: Hypertensive disorders in pregnancy are associated with systemic endothelial dysfunction leading to impaired physiological vasodilation. Recent evidence has shown central aortic pressures obtained through pulse wave analysis, at less than 14 weeks of gestation, to be predictive of pre-eclampsia. In light of this, we aimed to evaluate the role of central aortic stiffness in the prediction and discrimination of hypertensive disorders in pregnancy. METHODS: A cohort study of women with viable, singleton pregnancies at less than 14 weeks of amenorrhoea, and without multiple pregnancies, autoimmune or renal disease, diagnosed with aneuploidy or fetal anomaly will be recruited from a single maternity hospital and followed up till delivery and puerperium. A targeted sample size of 1000 eligible pregnant women will be enrolled into the study from antenatal clinics. Main exposure under study is central aortic pulse pressure using radial pulse wave recording, and the outcomes under follow-up are gestational hypertension and pre-eclampsia. Other measures include lifestyle factors such as smoking, physical exercise, psychometric evaluations, vasoactive factors, uterine artery pulsatility index, height and weight measurements. These measures will be repeated over 4 antenatal visits at 11-14, 18-22, 28-32 and above 34 weeks of gestation. Double data entry will be performed on Microsoft Access, and analysis of data will include the use of random effect models and receiver operating characteristic curves on Stata 11.2. DISCUSSION: The proposed study design will enable a longitudinal evaluation of the central aortic pressure changes as a marker for vascular compliance during pregnancy. As measures are repeated over time, the timing and severity of changes are detectable, and findings may yield important information on how aberrant vascular responses occur and its role in the early detection and prediction of hypertensive disorders.

Concepts: Pregnancy, Childbirth, Hypertension, Embryo, Fetus, Uterus, Blood pressure, Obstetrics

168

BACKGROUND: Perinatal mortality reflects maternal health as well as antenatal, intrapartum and newborn care, and is an important health indicator. This study aimed at classifying causes of perinatal death in order to identify categories of potentially preventable deaths. METHODS: We studied a total of 1958 stillbirths and early neonatal deaths above 500 g between July 2000 and October 2010 registered in the Medical Birth Registry and neonatal registry at Kilimanjaro Christian Medical Centre (KCMC) in Northern Tanzania. The deaths were classified according to the Neonatal and Intrauterine deaths Classification according to Etiology (NICE). RESULTS: Overall perinatal mortality was 57.7/1000 (1958 out of 33 929), of which 1219 (35.9/1000) were stillbirths and 739 (21.8/1000) were early neonatal deaths. Major causes of perinatal mortality were unexplained asphyxia (n=425, 12.5/1000), obstetric complications (n=303, 8.9/1000), maternal disease (n=287, 8.5/1000), unexplained antepartum stillbirths after 37 weeks of gestation (n= 219, 6.5/1000), and unexplained antepartum stillbirths before 37 weeks of gestation (n=184, 5.4/1000). Obstructed/prolonged labour was the leading condition (251/303, 82.8%) among the obstetric complications. Preeclampsia/eclampsia was the leading cause (253/287, 88.2%) among the maternal conditions. When we excluded women who were referred for delivery at KCMC due to medical reasons (19.1% of all births and 36.0% of all deaths), perinatal mortality was reduced to 45.6/1000. This reduction was mainly due to fewer deaths from obstetric complications (from 8.9 to 2.1/1000) and maternal conditions (from 8.5 to 5.5/1000). CONCLUSION: The distribution of causes of death in this population suggests a great potential for prevention. Early identification of mothers at risk of pregnancy complications through antenatal care screening, teaching pregnant women to recognize signs of pregnancy complications, timely access to obstetric care, monitoring of labour for fetal distress, and proper newborn resuscitation may reduce some of the categories of deaths.

Concepts: Pregnancy, Childbirth, Infant, Embryo, Fetus, Uterus, Obstetrics, Gestational age

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OBJECTIVE: To analyze the outcomes of second round of fertility-sparing management using progestin in patients with recurrent endometrial cancer after successful fertility-sparing management using progestin. METHODS: We reviewed 45 patients who had recurrence after achieving complete remission by fertility-sparing management using progestin for presumed stage IA, grade 1, endometrioid adenocarcinoma of the uterus. Of 45 patients, 33 tried progestin re-treatment at recurrence and were included in this study. RESULTS: Recurrent disease was atypical hyperplasia in 13 patients (39%) and grade 1 endometrioid adenocarcinoma in 20 patients (61%) which were confined to the endometrium. Thirty patients (91%) received medroxyprogesterone acetate (dose range, 80-500 mg/day) and three patients (9%) received megestrol acetate (dose range, 80-160 mg/day), with 29 patients receiving a dose of 500 mg/day of medroxyprogesterone acetate. The median duration of treatment was 6 months (range, 3-19 months). Five patients failed to respond to progestin re-treatment and underwent definitive surgical treatment including hysterectomy. Twenty eight patients (85%) showed complete response to progestin re-treatment. The median follow-up time after progestin re-treatment in 28 patients who achieved complete remission was 51 months (range, 24-160 months). During follow-up, five patients had second recurrence after median time interval of 14 months (range, 4-82 months). All patients who tried progestin re-treatment are alive without evidence of disease. CONCLUSION: Progestin re-treatment in patients with recurrent endometrial cancer was effective and safe. Therefore, this can be recommended for young women who still want to preserve fertility at recurrence after complete response to progestin.

Concepts: Cancer, Uterus, Menopause, Estrogen, Endometrium, Endometrial cancer, Endometrial hyperplasia, Medroxyprogesterone

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Zika virus (ZIKV), an emerging flavivirus, has recently spread explosively through the Western hemisphere. In addition to symptoms including fever, rash, arthralgia, and conjunctivitis, ZIKV infection of pregnant women can cause microcephaly and other developmental abnormalities in the fetus. We report herein the results of ZIKV infection of adult rhesus macaques. Following subcutaneous infection, animals developed transient plasma viremia and viruria from 1-7 days post infection (dpi) that was accompanied by the development of a rash, fever and conjunctivitis. Animals produced a robust adaptive immune response to ZIKV, although systemic cytokine response was minimal. At 7 dpi, virus was detected in peripheral nervous tissue, multiple lymphoid tissues, joints, and the uterus of the necropsied animals. Notably, viral RNA persisted in neuronal, lymphoid and joint/muscle tissues and the male and female reproductive tissues through 28 to 35 dpi. The tropism and persistence of ZIKV in the peripheral nerves and reproductive tract may provide a mechanism of subsequent neuropathogenesis and sexual transmission.

Concepts: Immune system, Nervous system, Pregnancy, Reproduction, Embryo, Organism, Uterus, Infection

148

Intrauterine contraceptive device is the most common method of reversible contraception in women. The intrauterine contraceptive device can perforate the uterus and can also migrate into pelvic or abdominal organs. Perforation of the urinary bladder by an intrauterine contraceptive device is not common. In West Africa, intravesical migration of an intrauterine contraceptive device has been rarely reported. In this report, we present a case of an intrauterine contraceptive device migration into the urinary bladder of a 33 year old African woman at the Komfo Anokye Teaching Hospital, Kumasi, Ghana.

Concepts: Kidney, Birth control, Africa, Uterus, Intrauterine device, Urinary bladder, Pelvis, Peritoneum

147

Pregnancy is a period involving important metabolic changes that enable the maintenance of the mother’s health and development of the fetus. This study aimed to assess the relationship among periodontal disease, insulin resistance, salivary cortisol concentration and level of perceived stress in pregnant women. This was a cross-sectional study. The sample comprised 96 pregnant women between the fifth and seventh month of pregnancy registered at the Basic Health Units of the Unified Health System (SUS). The periodontal condition was assessed after obtainment free and informed consent from the participants. Participants were divided into three groups: control subjects with a healthy periodontal condition (CN; n=46), patients with gingivitis (GI; n=26), and patients with periodontitis (PI; n=24). Saliva and blood samples were collected for evaluation of salivary cortisol concentration, glycemia, insulinemia and Homeostasis Model Assessment-Insulin Resistance index. A validated survey for the assessment of perceived stress levels was also performed. PI group showed significantly higher (p<0.05) blood glucose levels (CN: 4.43±0.05; GI: 4.46±0.04; PI: 4.68±0.08), insulinemy (CN: 6.93±0.45; GI: 8.87±0.79; PI: 12.77±1.30), insulin resistance (CN: 1.40±0.10; GI: 1.81±0.18; PI: 2.66±0.29) compared with the CN and GI groups. The levels of perceived stress were higher (p<0.05) in PI and GI groups when compared to CN group (CN: 20.5±1.26; GI: 25.8±1.95; PI: 26.6±1.36). There was no significant difference in the concentration of salivary cortisol between the groups (CN: 11.13±0.58; GI: 11.96±0.74; PI: 11.47±0.74). It was concluded that there is a relationship between higher levels of perceived stress, insulin resistance and the occurrence of periodontal disease during pregnancy. This study emphasizes the importance of preventing periodontitis in order to avoid insulin resistance and stress during pregnancy since these can cause systemic complications for the mother and the fetus.

Concepts: Pregnancy, Embryo, Fetus, Uterus, Blood sugar, Abortion, Periodontitis, Periodontal disease