History Of Multiple Miscarriages Research Articles

O-130 The influence of vaginal microbiota on frozen blastocyst implantation after transfer: a prospective study through next-generation 16S rRNA sequencing

Abstract Study question A prospective study to investigate the relationship between the composition of vaginal microbiota through next-generation sequencing and the efficacy of single frozen blastocyst transfer in the same cycle. Summary answer Dominant presence of lactobacillus and other lactate producing microbes in the upper vagina was highly correlated with implantation of transferred blastocyst in this pilot study. What is known already Next-generation sequencing of 16S rRNA detected microbes in the uterine cavity and recent studies indicated that dominant presence of Lactobacillus correlated highly with successful implantation of the transferred embryos. Aberrant vaginal microbiota has been known to cause poor obstetrical outcomes, however little is known for its effect on embryo implantation in assisted reproduction. Study design, size, duration A prospective study with 25 female subjects transferring a frozen blastocyst using autologous oocyte, over 14 months period in 2019-2020. Participants/materials, setting, methods 25 female patients without tubal and uterine pathology and no history of multiple miscarriages and implantation failures were recruited with consent at a private ART clinic. Transdermal estrogen was used to prepare endometrium. Upper vaginal fluid was obtained in follicular phase of the the same cycle and analyzed through next-generation sequencing, but the result was reported after pregnancy confirmation. Single frozen blastocyst transfer and standard luteal phase support were performed. Institutional IRB approved the protocol. Main results and the role of chance The mean age was 36.2 y.o.(range 29-41 y.o.), and 14 gestational sacs (implantation rate 56%), and 3 miscarriage (21.4%) were observed. Next-generation sequencing for 16S rRNA revealed average 69.2% presence of Lactobacillus (0-100%) and average 78.0% (0.2-100%) lactate producing microbes (LPM: Lactobacillus, Bifidobacterium, Streptococcus, and Enterococcus) in the vaginal fluid. Using 90% as cut-off, implantation rates were 11/15 (73.3%) and 3/10 (30%) with Lactobacillus dominant and non-dominant, 12/16 (75%) and 2/9 (22.2%) with LPM dominant and non-dominant microbiota, respectively. The difference in each group were not statistically significant. The relative risks for pregnancy were 2.63 (95%CI 1.03-6.67, P=0.04) for Lactobacillus and 3.11 (95%CI 1.24-7.79, P=0.02) for LPM. As for ROC analysis for embryo implantation and dominant microbes, AUC and associated criterion were 0.62 and 90.7% (sensitivity 78.6%, specificity 72.7%) for Lactobacillus, 0.69 and 96.6% (sensitivity 85.7%, specificity 72.7%) for LPM, respectively. The difference of AUC was not significant (P=0.24). Limitations, reasons for caution Despite prospective nature of the study, small sample size limited the analytical power of the study. Aneuploidy screening was not performed to remove confounding factor. Wider implications of the findings Our pilot study revealed possible relationship between vaginal microbiota and embryo implantation. Dominance of Lactobacillus or other lactate producing microbes may be advantageous for successful ART. Sampling vaginal fluid for microbe analysis is less invasive than endometrial sampling and can obtain more abundant RNA with possible higher accuracy of analysis. Trial registration number not applicable

Extended spectrum penicillins reduce the risk of omphalocele: A population-based case-control study

BackgroundOmphalocele is a major congenital anomaly associated with significant morbidity and mortality. Regardless, the influence of maternal use of prescription drugs on the risk of omphalocele has only been addressed in a handful of studies. The aim of this study was to assess the influence of maternal risk factors and prescription drugs in early pregnancy on the risk of omphalocele. MethodsWe performed a nationwide register-based case-control study in Finland. The analysis is based on the Finnish Register of Congenital Malformations and Drugs and Pregnancy databases, both upheld by the Finnish Institute for Health and Welfare. All omphalocele cases were identified between Jan 1, 2004, and Dec 31, 2014. Five age-matched controls from the same geographical region were randomly selected for each case. The main outcome measures were maternal risk factors for omphalocele. Our analysis compared the maternal characteristics and the use of prescription drugs during the first trimester of pregnancy between case and control mothers. ResultsMothers of 359 omphalocele cases were compared with 1738 randomly selected age and area-matched mothers of healthy infants between 1 January 2014 and 31 December 2014. Both maternal obesity (BMI ≥30) and diabetes increased the risk for omphalocele, and their co-occurrence accumulated this risk (aOR 5.06, 95% Cl 1.19–21.4). Similarly, history of multiple miscarriages was an independent risk factor (2.51, 1.16–5.43). The oral use of extended spectrum penicillins during the first trimester of pregnancy had a significant, protective influence (0.17, 0.04–0.71). These analyses were adjusted for sex, parity, and risk factors reported above. No significant changes in risk were observed with any other medication used during the first trimester. ConclusionIn conclusion, these findings may suggest that extended spectrum penicillins in the first trimester reduces the risk of omphalocle formation. Additionally, consistent with earlier studies, previous repeated miscarriages, maternal obesity, and diabetes were significant risk factors for omphalocele.

SAT-211 Is Doxazosin the Right Choice for Preoperative Management of Pheochromocytoma in Pregnancy?

Pheochromocytoma (PCC) in pregnancy is a very rare condition, with a reported incidence of less than 0.2 per 10.000 pregnancies (1), having fetal and maternal mortality of 50% if untreated (2). Choosing between selective vs. nonselective alpha blockers as preoperative management in pregnancy is controversial.We report a case of a 39-year-old female having episodes of nervousness, hand tremors, palpitations, diaphoresis, and headaches since 2012; she also had a history of multiple miscarriages and uncontrolled hypertension(HTN) since 2018. In 2019, she was found to have plasma metanephrines 690pg/mL (0-62) and plasma normetanephrine of 3803pg/mL(0-145). Repeat labs showed: plasma metanephrines 2.071pg/mL(0-62), normetanephrine 6.289pg/mL(0-145), norepinephrine 4.268pg/mL(0-874), epinephrine 555pg/mL(0-62). CT abdomen showed a 6.2x5.1x6.4cm left adrenal mass, with 44 Hounsfield units and less than 50% of washout. She was started on Doxazosin 2mg/d, which eventually was increased to 6mg/d with optimal blood pressure (BP) control. After her preoperative workup, she was found to be 7 weeks pregnant. OB-GYN recommended left adrenalectomy before 14 weeks gestation. She had left open adrenalectomy, with normal range postoperative BP, off of antihypertensive medications.The diagnosis of PCC in pregnancy should be considered in the setting of paroxysmal HTN, with no proteinuria, episodic palpitations, diaphoresis, facial flushing, and orthostatic hypotension. Anterior adrenalectomy early in pregnancy is recommended. The increased intraabdominal pressure, fetal movements, uterine contractions, delivery process, and abdominal surgical intervention can trigger the catecholamine release by the PCC, which could lead to placental abruption and miscarriage; and the rebound hypotension may lead to severe hypoxia, causing fetal demise (2). Definitive preoperative treatment between selective vs non-selective alpha-blockers remains controversial. Phenoxybenzamine, appeared to produce better attenuation of intraoperative HTN, however, it is associated with more maternal intraoperative/postoperative hypotension, and reflexive tachycardia. It crosses the placenta and accumulates in the fetus, increasing the risk of neonatal hypotension and respiratory depression (3,4,5). On the other hand, Doxazosin, can be displaced by high levels of catecholamines, but it is less associated with intraoperative/postoperative hypotension (6,7), with no reports of neonatal hypotension, and respiratory depression. Due to the lack of presynaptic a2-adrenoceptor blockade there is less reflex tachycardia, reducing the use of Beta-blockers (8). Doxazosin seems to be a safe, affordable alternative for preoperative management of PCC in pregnant patients.

Abstract #805701: Challenging Case of Gitelman Syndrome in Pregnancy, With a Prior History of Multiple Miscarriages

Abstract #805701: Challenging Case of Gitelman Syndrome in Pregnancy, With a Prior History of Multiple Miscarriages

Perceived Subfecundity and Contraceptive Use Among Young Adult U.S. Women.

Women who view themselves as having difficulty becoming pregnant (i.e., being subfecund) may feel that they do not need to use contraceptives to prevent unintended pregnancy. However, subfecundity perceptions are not always medically accurate and may therefore confer a false sense of protection. The extent to which perceived fecundity is related to contraceptive use is not well understood. Multinomial logistic regression was used to investigate the relationship between perceived fecundity at age 25-30 and contraceptive use among 2,091 women from the National Longitudinal Survey of Youth 1997 cohort. Compared with women who considered themselves very likely to become pregnant, those who thought that they were only somewhat likely and those who viewed themselves as not very likely to do so had significantly higher risks of not using contraceptives within the next year (risk ratios, 1.9 and 2.4, respectively). Results were similar in analyses controlling for either a medical diagnosis of infertility, a history of multiple miscarriages or stillbirths, or absence of pregnancy following at least six months of unprotected sex, suggesting that perceived subfecundity operates independently of experienced subfecundity. Because few studies have investigated fecundity perceptions in their own right, more research is needed to understand how women evaluate their fecundity and to integrate these perceptions into broader frameworks describing women's perception of pregnancy risk. Such work may help identify potential levers to improve contraceptive use.

Relation of Stress during Pregnancy with Congenital Malformations in Children Admitted in Various Clinical Settings in Lahore

<p><strong>Objectives:</strong><strong> </strong>To study relation of stress in pregnancy and congenital malformations in newborns delivered at various hospitals of public sector in Lahore.<strong></strong></p><p><strong>Materials and Methodology:</strong><strong> </strong>Descriptive cross sectional study design was used. The study was conducted at various clinical settings of Lahore for one month. Mothers of 40 malformed neonates were taken as sample. A data collection tool (a questionnaire) was developed and the mothers were interviewed regarding various type of stress such as poor socio-economic conditions, divorce and separation, death of a close relative, post dramatic stress disorders, serious illness, catastrophic events and pregnancy related stress including history of multiple miscarriages. Questionnaire was pretested before the data. SPSS computer software was used for entry, compilation and analysis of data.<strong></strong></p><p><strong>Results:</strong><strong> </strong>Out of 40 subjects, 14 (35%) of mothers suffered from stress while 26 (65%) did not suffer from stress during pregnancy. Out of 14, 12.5% were having facial defects (cleft lip, cleft palate), 10% had neural tube defects while those with cvs, git, and urogenital defects were 7.5%. 2.5% and 2.5% respectively.</p><p><strong>Conclusion:</strong><strong> </strong>This study suggests that prevalence of congenital malformations has a significant association with the events causing stress in life during pregnancy. Therefore it is one of the overlooked but important aggravating factor in the development of malfunctions. Out of 40 subjects 35% of mothers suffered from stresses like poor socioeconomic conditions, separation and deaths in the family. The number of conotruncal, or facial and neural tube defects was significantly higher in our subjects having stress.<strong></strong></p>

Effect of Multiple Previous Miscarriages on Health Behaviors and Health Care Utilization During Subsequent Pregnancy

BackgroundWomen with a history of miscarriage report feeling emotionally guarded during a subsequent pregnancy and may be at increased risk for pregnancy-related anxiety and greater health care utilization compared with women without a history of miscarriage. However, these behaviors have not been studied in women with a history of multiple miscarriages. MethodsWe examined the effect of a history of multiple miscarriages on health behaviors and health care utilization in 2,854 women ages 18 to 36 years expecting their first live-born baby. Self-reported health behaviors and use of health care resources during pregnancy were compared for women with a history of two or more miscarriages and women with one or no miscarriages. FindingsWomen with a history of multiple miscarriages were more than four times as likely to smoke during pregnancy (adjusted odds ratio [aOR], 4.69; 95% CI, 2.63–8.38) compared with women without a history of multiple miscarriages. They initiated prenatal care earlier (7.0 vs. 8.2 weeks gestation), had higher odds of third trimester emergency department visit (aOR, 2.21; 95% CI, 1.24–3.94), higher odds of hospitalization during pregnancy (aOR, 1.66; 95% CI, 1.01–2.73), and twice the mean number of third trimester emergency department visits and hospitalizations during pregnancy. ConclusionsWomen with a history of multiple miscarriages may be more likely to smoke and may demonstrate increased health care utilization during a subsequent pregnancy. Compassionate, individualized, and supportive counseling by providers may address smoking and other health behaviors as well as increased health care utilization.

A Serpiginous Eruption —Quiz Case

A75-year-oldwomanpresentedwitha2-yearhistoryofexquisitely tender ulcerations on her bilateral ankles, which caused pain with ambulation. She had a history of multiple miscarriages, a myocardial infarction at age 60 years, and hypertension. Physical examination revealed stellate purpuric macules, 2 areas of punched-out ulcerations, and 3 white stellate atrophic scars on the left lateral ankle (Figure 1). A 4-mm punch biopsy was obtained from the left lateral ankle (Figure 2 and Figure 3). What is your diagnosis?

Ulceration of Abdominal Striae Distensae (Stretch Marks) in a Cancer Patient —Quiz Case

A75-year-oldwomanpresentedwitha2-yearhistoryofexquisitely tender ulcerations on her bilateral ankles, which caused pain with ambulation. She had a history of multiple miscarriages, a myocardial infarction at age 60 years, and hypertension. Physical examination revealed stellate purpuric macules, 2 areas of punched-out ulcerations, and 3 white stellate atrophic scars on the left lateral ankle (Figure 1). A 4-mm punch biopsy was obtained from the left lateral ankle (Figure 2 and Figure 3). What is your diagnosis?

Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies

Chromosomal microarray (CMA) is increasingly utilized for genetic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA). Performing CMA and G-banded karyotyping on every patient substantially increases the total cost of genetic testing. The International Standard Cytogenomic Array (ISCA) Consortium held two international workshops and conducted a literature review of 33 studies, including 21,698 patients tested by CMA. We provide an evidence-based summary of clinical cytogenetic testing comparing CMA to G-banded karyotyping with respect to technical advantages and limitations, diagnostic yield for various types of chromosomal aberrations, and issues that affect test interpretation. CMA offers a much higher diagnostic yield (15%-20%) for genetic testing of individuals with unexplained DD/ID, ASD, or MCA than a G-banded karyotype ( approximately 3%, excluding Down syndrome and other recognizable chromosomal syndromes), primarily because of its higher sensitivity for submicroscopic deletions and duplications. Truly balanced rearrangements and low-level mosaicism are generally not detectable by arrays, but these are relatively infrequent causes of abnormal phenotypes in this population (<1%). Available evidence strongly supports the use of CMA in place of G-banded karyotyping as the first-tier cytogenetic diagnostic test for patients with DD/ID, ASD, or MCA. G-banded karyotype analysis should be reserved for patients with obvious chromosomal syndromes (e.g., Down syndrome), a family history of chromosomal rearrangement, or a history of multiple miscarriages.

Application of Multicolor Banding for Identification of Complex Chromosome 18 Rearrangements

Multicolor chromosome banding (mBAND) is a recently developed technique that allows the delineation of chromosomal regions with a resolution of a few megabase pairs. The resolution of mBAND is slightly below that of conventional chromosome banding; however, the color bands have a great value in identifying chromosomal abnormalities, particularly complex chromosome rearrangements, and intrachromosome exchanges (ie, inversions, deletions, duplications, and insertions). These abnormalities cannot be defined easily by conventional cytogenetic analysis or chromosome paint. In this report, we present the application of the mBAND analysis for identification of complex intrachromosome rearrangements of chromosome 18 in a child with dysmorphic features.

Epidemiology of hysterectomy in the United States: demographic and reproductive factors in a nationally representative sample.

We describe the epidemiology of hysterectomy, overall as well as for specific indications. Data were obtained from the Epidemiologic Follow-up to the First National Health and Nutrition Examination Survey, a nationally representative cohort followed prospectively from the mid-1970s through 1992. Black and white women 25-49 years of age, interviewed during follow-up, were included in the analyses. The probability of undergoing a hysterectomy was estimated by demographic and reproductive factors. Hysterectomy as confirmed by hospital records was our main outcome measure. We found that women who had completed 9-11 years of education were more likely to have undergone a hysterectomy than were women with either more or less education. Women who had completed 9-11 years of education were also more likely to have had a hysterectomy because of menstrual problems. Three or more miscarriages, especially if caused by uterine prolapse, increased the probability of hysterectomy. Having had no live births decreased the probability of hysterectomy for menstrual disorders and uterine prolapse, but women who had their first child before age 20 were at increased risk of hysterectomy because of endometriosis. Hysterectomy appears to be associated with low education, high parity, and a history of multiple miscarriages. The influence of these factors varies depending on the primary indication for the hysterectomy.

Apparent Smith‐Lemli‐Opitz syndrome and Miller‐Dieker syndrome in a family with segregating translocation t(7;17)(q34;p13.1)

We describe a family in which one male infant presented with Miller-Dieker syndrome and four male relatives had a phenotype similar to the Smith-Lemli-Opitz (SLO) syndrome. High resolution cytogenetic analysis on the child with Miller-Dieker syndrome showed 46,XY,-17,+der17t(7;17)(q34:p13.1). Paternal chromosomes showed a balanced translocation: 46,XY,t(7;17)(q34:p13.1). The paternal grandmother had a history of multiple miscarriages, and a paternal uncle had two sons who died neonatally. Chromosomes on these children and their father had originally been reported as normal. There was also a paternal cousin to the father of the propositus who had had two sons with similar clinical findings. A diagnosis of SLO syndrome was considered. Image enhancement techniques on previous suboptimal preparations on these four children documented the subtle unbalanced translocation 46,XY,-7,+der7t(7;17)(q34:p13.1). Subsequent high resolution analysis on one of these four children who was still living confirmed this chromosome constitution. It is postulated that these apparent SLO cases may represent a contiguous gene syndrome in which SLO or a separate entity closely mimicking the syndrome in included.