Clinical utility of fetal autopsy and its impact on genetic counseling.

OBJECTIVES: We aimed to analyze the utility of fetal autopsy in terms of its contribution to establishing a definitive diagnosis and its impact on genetic counseling. SUBJECTS AND METHODS: Detailed fetal autopsy was carried out in fetuses referred for examination. Clinical utility of fetal autopsy and its impact on counseling were measured by adapting previously published parameters. RESULTS: We performed autopsy in 230 fetuses. There were 106 cases with single system and 92 cases with multisystem involvement. We confirmed prenatal findings in 23% of cases and observed additional findings in 37% of cases. In 23% of cases, autopsy findings differed enough to change the diagnosis. However, in 17% of fetuses, no cause of fetal loss was determined. Risk of recurrence became clear in 30.3% of the fetuses, and risk remained the same, but the diagnosis was different in 4.8% of cases after autopsy. Hence, autopsy led to refinement of the risk of recurrence in 36% of cases. Autopsy aided prenatal counseling of couples in 77% of cases by either confirming the prenatal findings (35%) or providing new information/ruling out a diagnosis (42%). CONCLUSION: The present study quantifies the utility of fetal autopsy in reproductive genetic counseling in a large cohort.

A clinical alert: Oral glucose tolerance test triggering diabetic ketoacidosis in pregnancy.

Gestational diabetes mellitus is a common medical disorder of pregnancy. Diabetic ketoacidosis is a complication that may affect both maternal and perinatal wellbeing adversely. It is rare, most often involving women with type 1 or type 2 diabetes, but occasionally can be seen in gestational diabetes mellitus. Here are two cases of ketoacidosis seemingly triggered by glucose ingestion for the oral glucose tolerance test in previously normoglycemic women, posing a diagnostic and therapeutic challenge. Prevention of such complications must be considered when treating high-risk pregnant women> 40 years of age, pregnant as a result of assisted reproductive techniques. Fasting blood glucose checked before ingestion of the glucose in a selected group of women may be one way of avoiding this complication. This suggestion may put women at risk of prolonged fasting and stretching services. Glucose tolerance test is a diagnostic test, and these cases demonstrate a rare complication.

Intrauterine Administration of Autologous Platelet-Derived Growth Factor Concentrate (aka Autologous Blood Cell Derivative) Improves the Endometrial Thickness in 'Thin' Endometrium in the Frozen Embryo Transfer Cycle.

Context: Thin endometrium during the frozen embryo transfer cycles leads to cycle cancellation. The embryo transfer cycle getting deferred is an unpleasant experience for the patients and the fertility specialist. Aims: The purpose of this study is to evaluate the effectiveness of Autologous Blood Cell Derivative (ABCD) growth factor concentrate to obtain an optimal thickness of endometrium for embryo transfer during IVF treatments, where rapid regeneration is crucial for the expected therapeutic outcome. Settings and Design: A retrospective cohort study was conducted in Manipal Assisted Reproduction Center, a referral center in Southern India. Methods and Material: Fifty-six patients with thin endometrium were administered three doses of ABCD growth factor concentrate as per the protocol after informed consent. All of them had a history of embryo transfer (ET) cancellation in frozen-thawed embryo cycles due to inadequate growth of the endometrium despite therapy with estrogens and drugs for improving uterine blood circulation. Results: The endometrium thickness during the implantation window in the patients included in the study averaged 6.48 ± 1.19 mm. After the intervention, 55 out of 56 patients (98.2%) showed a considerable change in the thickness of the endometrium layer with an average thickness of 8.48 ± 1.32 mm (< 0.0001, SE 0.233, 95% CI 1.58-2.5). Out of the 55 patients, 20 got pregnant, i.e., 36.4% pregnancy rate. Till date, thirteen pregnancies had live births (65%), three pregnancies (15%) were biochemical pregnancies, 1 (5%) was ectopic, and three pregnancies (15%) had spontaneous miscarriage before eight weeks. When we compared the endometrial thickness (EMT) in the pregnant and non-pregnant groups pre- and post-ABCD instillation, (6.47 ± 1.31 mm vs 6.48 ± 1.4 mm, p = 0.98 and 8.68 ± 1.32 mm vs 8.48 ± 1.32 mm, p value 0.59) the p value was not statistically significant. Conclusions: The implantation, clinical pregnancy and live birth rates were 36.4, 30 and 65%, respectively. This result is a significant improvement for patients with thin endometrium for whom we would otherwise cancel the frozen transfer. An autologous resource is a safe, readily available and inexpensive treatment modality.

Extrinsic and intrinsic factors influencing metabolic memory in type 2 diabetes.

Direct and indirect influence of pathological conditions in Type 2 Diabetes (T2D) on vasculature manifests in micro and/or macro vascular complications that act as a major source of morbidity and mortality. Although preventive therapies exist to control hyperglycemia, diabetic subjects are always at risk to accrue vascular complications. One of the hypotheses explained is 'glycemic' or 'metabolic' memory, a process of permanent epigenetic change in different cell types whereby diabetes associated vascular complications continue despite glycemic control by antidiabetic drugs. Epigenetic mechanisms including DNA methylation possess a strong influence on the association between environment and gene expression, thus indicating its importance in the pathogenesis of a complex disease such as T2D. The vascular system is more prone to environmental influences and present high flexibility in response to physiological and pathological challenges. DNA methylation based epigenetic changes during metabolic memory are influenced by sustained hyperglycemia, inflammatory mediators, gut microbiome composition, lifestyle modifications and gene-nutrient interactions. Hence, understanding underlying mechanisms in manifesting vascular complications regulated by DNA methylation is of high clinical importance. The review provides an insight into various extrinsic and intrinsic factors influencing the regulation of DNA methyltransferases contributing to the pathogenesis of vascular complications during T2D.

Crossing the Hurdle of a Low Oocyte Yield in an in vitro Fertilization Cycle to Obtain Mature Oocytes.

The complex process of oocyte maturation involves a coordinated set of events to take place so that an adequate number of oocytes can be obtained during an oocyte pickup procedure following controlled ovarian stimulation. A weak link in any of the steps can yield a sparse number of oocytes which can be a setback in the process.

Random Start Ovarian Stimulation.

Fertility preservation is emerging in recent years as an important option for various indications many of which being for cancer patients and for certain benign conditions as well. In the present case report, we set out to utilise the same protocol, however, for different indications.

Sperm characteristics in normal and abnormal ejaculates are differently influenced by the length of ejaculatory abstinence.

BACKGROUND: No association between the length of ejaculatory abstinence (LEA) and semen characteristics has been confirmed. A short LEA has been linked to improved sperm characteristics and a higher pregnancy rate, but its negative influence on sperm chromatin maturity and longevity may adversely affect reproductive outcomes. OBJECTIVES: We sought to determine the influence of LEA on (i) semen parameters in normozoospermic and abnormal ejaculates; and (ii) the outcomes of sperm-preparation methods in a large number of subfertile men undergoing infertility workups. MATERIALS AND METHODS: This retrospective registry-based cohort study analyzed the data of 10,674 ejaculates from 7972 subfertile men, who were then segregated into normozoospermic, oligozoospermic, asthenozoospermic, and oligo-asthenozoospermic cohorts. Variations in semen characteristics and post-wash outcomes were studied between four LEA intervals across 0-15 days. RESULTS: An age-adjusted analysis of covariance (ANCOVA) model linked significant increases in ejaculate volume, sperm concentration (except in the oligozoospermic cohort), and total sperm count to an increased LEA (p < 0.05). LEA was negatively associated with motility (except in the asthenozoospermic cohort) and vitality (p < 0.05). Large-headed spermatozoa were less common with an increased LEA only in the oligo-asthenozoospermic cohort (p < 0.05). In the normozoospermic cohort, a longer LEA led to fewer spermatozoa with amorphous heads but more spermatozoa with tapered heads and cytoplasmic droplets (p < 0.05). LEA extension resulted in greater sperm DNA fragmentation in the abnormal cohort (p < 0.01). The post-wash sperm concentration and total motile sperm count were significantly improved with a longer LEA in the normozoospermic cohort (p < 0.05). DISCUSSION AND CONCLUSION: Considering the findings in this study and existing literature, a generalized recommendation for long LEA has no clinical value. The LEA should be individualized based on the ejaculate profile and the need for specific clinical intervention.

Clear cell variant, urothelial carcinoma of ureter: A rare entity.

Clear cell variants of transitional cell carcinoma of upper urinary tract is extremely rare. Although clear cell of urinary bladder has been reported, its occurrence in the upper tract has not been reported readily in literature. We present a case of 77 year old female who was suspected with TCC of the ureter, but was found to have clear cell variant on histology post radical nephroureterectomy. This was the first such case in our institution.

Fetal Adrenal Gland Volume a Novel Predictor of Onset of Labor.

INTRODUCTION: There is a definite need to find a highly sensitive and specific, noninvasive, and cost-effective marker for prediction of preterm labor. We hypothesize that a measurement of adrenal gland volume can predict a preterm as well as a term labor. MATERIALS AND METHODS: Two hundred and sixty-eight pregnant women were enrolled in the study at 28-34 weeks' antenatal visit. Final analysis was done in 204. All of them were subjected to 2D ultrasonographic measurement of the corrected fetal adrenal gland volume (cFAGV) and fetal adrenal zone parameters including the width ratio and depth ratio. The cohort was followed up to term, and a reassessment of cFAGV and fetal adrenal zone parameters was repeated between 37 and 39 weeks. Women who presented with features of preterm labor had a scan at the time of presentation to record cFAGV and fetal adrenal zone parameters. RESULTS: Women, who developed features of preterm labor eventually, had a significantly high cFAGV (404.70 mm3/kg body weight) during the first scan compared to those who reached term asymptomatically (241.35 mm3/kg body weight). A cutoff value of 271.16 mm3/kg body weight showed 90% sensitivity and 81.9% specificity. Fetal adrenal gland width ratio had the best efficacy (sensitivity 96.67%, specificity 86.2%) followed by cFAGV (sensitivity 96.67%, specificity 83%) for predicting preterm delivery. CONCLUSION: 2D ultrasound measurement of fetal adrenal gland parameters can be used as a marker for prediction of preterm delivery. cFAGV at term can also be used to predict the possibility of spontaneous onset of labor.

What does fetal autopsy unmask in oligohydramnios?

OBJECTIVE: We aimed to determine the value of autopsy in fetuses with antenatally diagnosed oligohydramnios. PATIENTS AND METHODS: We evaluated all fetal losses over a period of 6.5 years. Those with oligohydramnios on antenatal scan were critically analyzed. Oligohydramnios was defined as amniotic fluid index of less than five objectively or as an obvious lack of liquor at subjective assessment. A detailed postmortem examination was carried out in all the fetuses after obtaining an informed consent. RESULTS: Fetal autopsy was conducted in 255 cases. Fifty-five (21.5%) fetuses were diagnosed to have oligohydramnios on antenatal ultrasonography. On analysis of antenatal causes of oligohydramnios, maternal/placental factors were noted in 18%, ultrasound findings known to affect amniotic fluid in 27% while cause remained unidentified in 54.5% of cases. On autopsy, fetal malformations were noted in 61.8% cases, intrauterine growth retardation in 21.8% fetuses and no obvious malformations in 16.3% fetuses. Renal anomalies were noted in 40% cases and non-renal malformations in 21.8% cases. CONCLUSION: The postmortem examination helped us to identify the cause of fetal loss in 46 (83.6%) fetuses with antenatal oligohydramnios. A working diagnosis could not have been established without autopsy in 19 (34.5%) cases.

Fallopian tube choriocarcinoma presenting as ovarian tumour: a case report.

Choriocarcinoma of the fallopian tube is a rare form of gestational trophoblastic disease. It can be gestational or non gestational choriocarcinoma, based on the origin. Fallopian tube choriocarcinoma has been reported commonly after ectopic pregnancy. Choriocarcinomas are germ cell tumours formed by trophoblastic elements. A 26-year-old lady presented with pain and mass abdomen of 15 days duration. Clinical examination revealed a ovarian tumour with elevated beta HCG. The working diagnosis was ovarian choriocarcinoma. Patient was also found to be having pulmonary artery hypertension due to the metastasis to lungs. Staging laparotomy was done. Histopathology revealed it to be metastatic gestational choriocarcinoma of fallopian tube with vascular emboli. The stage was stage III and WHO scoring of 15. She received Etoposide, Methotrexate, Actinomicin, Cyclophosphamide and Oncovin therapy. Following treatment there was a significant drop in the beta HCG. Patient tolerated the chemotherapy well. This is a rare presentation of choriocarcinoma with good prognosis.

Predictive value of middle cerebral artery to uterine artery pulsatility index ratio in hypertensive disorders of pregnancy.

Aims and Objectives. (i) To determine the predictive value of cerebrouterine (CU) ratio (middle cerebral artery to uterine artery pulsatility index, MCA/UT PI) in assessing perinatal outcome among hypertensive disorders of pregnancy. (ii) To compare between CU ratio and CP ratio (MCA/Umbilical artery PI) as a predictor of adverse perinatal outcome. Methods. A prospective observational study was done in a tertiary medical college hospital, from September 2012 to August 2013. One hundred singleton pregnancies complicated by hypertension peculiar to pregnancy were enrolled. Both CU and CP ratios were estimated. The perinatal outcomes were studied. Results. Both cerebrouterine and cerebroplacental ratios had a better negative predictive value in predicting adverse perinatal outcome. However, both CU and CP ratios when applied together were able to predict adverse outcomes better than individual ratios. The sensitivity, specificity, positive predictive value, and the negative predictive values for an adverse neonatal outcome with CU ratio were 61.3%, 70.3%, 56%, and 78.9%, respectively, compared to 42%, 57.5%, 62%, and 76% as with CP ratio. Conclusion. Cerebrouterine ratio and cerebroplacental ratio were complementary to each other in predicting the adverse perinatal outcomes. Individually, both ratios were reassuring for favorable perinatal outcome with high negative predictive value.

Fetal Head Position during the First Stage of Labor: Comparison between Vaginal Examination and Transabdominal Ultrasound.

Introduction. Recent evidence indicates that clinical examination, for determination of fetal head position, is subjective and inaccurate. Present study was aimed to compare transabdominal ultrasound for fetal head position with vaginal examination during first stage of labor. Material and Methods. This prospective study was performed at a tertiary center during a two-year period. Before or after clinically indicated vaginal examinations, transverse suprapubic transabdominal real-time ultrasound fetal head position assessment was done. Frequencies of various ultrasound depicted fetal head positions were compared with position determined at vaginal examination. Results. In only 31.5% of patients, fetal head position determinations by vaginal examinations were consistent with those obtained by ultrasound. Cohen's Kappa test of concordance indicated a poor concordance of 0.15. Accuracy of vaginal examination increased to 66% when fetal head position at vaginal examination was recorded correct if reported within +45° of the ultrasound assessment. Rate of agreement between the two assessment methods for consultants versus residents was 36% and 26%, respectively (P = 0.17). Conclusion. We found that vaginal examination was associated with a high error rate in fetal head position determination. Data supports the idea that intrapartum transabdominal ultrasound enhances correct determination of fetal head position during first stage of labor.

Correlation of fetal abdominal subcutaneous tissue thickness by ultrasound to predict birth weight.

INTRODUCTION: Fetal growth abnormality is associated with changes in the soft tissue mass, which is decreased in growth restricted fetuses and increased in macrosomia. OBJECTIVE: To correlate fetal abdominal subcutaneous tissue thickness (FASTT) measured by ultrasound at term and birth weight and to obtain a cut-off value of FASTT to predict large and small for gestational age babies in our population. METHODS: FASTT was measured at the anterior 1/3(rd) of abdominal circumference by ultrasound after 36 weeks and weight of the baby measured after birth. RESULTS: There was positive correlation between FASTT and birth weight. FASTT of 6.25 mm was sensitive to predict large for gestational age (LGA) babies and had a high negative predictive value; FASTT measurement for prediction of small babies with birth weight < 2500 g was not sensitive. CONCLUSION: FASTT can be used as an additional indicator to predict large for gestational age babies along with other known birth weight indicators.

A 31-year-old female with fever and back pain.

Primary pyomyositis is a suppurative infection of striated muscle, the diagnosis of which is overlooked or delayed due to its rarity and vague clinical presentation. Though rare in the United States and temperate zones, pyomyositis is more frequently reported from tropical countries. The exact pathogenesis of pyomyositis is uncertain in most cases. The disease progresses through three stages with characteristic features and require a high index of suspicion to institute stage-wise treatment. Newer imaging methods, particularly magnetic resonance imaging, have facilitated the accurate diagnosis of the infection and of the extent of involvement. Early recognition with appropriate antibiotics in the pre-suppurative stage and prompt surgical intervention in the late stages form the corner stone of treatment. Delay in diagnosis can result in increased morbidity and mortality, especially in diabetics and immunocompromised state. Here, we report a case of primary paraspinal pyomyositis in a middle-aged female and emphasize the importance of early diagnosis and treatment.

Twin pregnancy with Hydatidiform Mole and Co-existent Live Fetus: Lessons Learnt

This is a case report of a twin pregnancy with one fetus and a coexistent mole diagnosed at 13 weeks. After thorough counseling, the pregnancy was continued as per the patient’s desire. The pregnancy was closely monitored with serial S β hCG, ultrasound for fetal growth, size of molar sac, and theca lutein cysts, which gradually decreased in size during the second trimester of pregnancy. An emergency caesarean delivery was done at 36 weeks due to breech in early labour. A live baby weighing 1.8 kg was delivered in good condition. Her S β hCG reached normal levels at the end of three weeks, and she is now on post-molar surveillance. Though the general trend is to terminate pregnancy in twins with coexistent mole in anticipation of complications, under close surveillance, optimal outcomes can be achieved. Monitoring of S β hCG, serial ultrasound for fetal growth, size of molar component, and theca lutein cysts can help to predict good patient outcomes.