A novel de novo mutation in COL2A1 gene associated with fetal skeletal dysplasia.

OBJECTIVE: Skeletal dysplasias, caused by genetic mutations, are a heterogenous group of heritable disorders affecting bone development during fetal life. Stickler syndrome, one of the skeletal dysplasias, is an autosomal dominant connective tissue disorder caused by abnormal collagen synthesis owing to a genetic mutation in COL2A1. CASE REPORT: We present the case of a 38-year-old multipara woman whose first trimester screening showed a normal karyotype. However, the bilateral femur and humerus length symmetrically shortened after 20 weeks. Next-generation sequencing for mutations in potential genes leading to skeletal dysplasia detected a novel de novo mutation (c.1438G > A, p.Gly480Arg) in COL2A1, causing Stickler syndrome type 1. This pathogenic mutation might impair or destabilize the collagen structure, leading to collagen type II, IX, and XI dysfunction. CONCLUSION: We identified a novel de novo mutation in COL2A1 related to the STL1 syndrome and delineated the extent of the skeletal dysplasia disease spectrum.

Association between maternal anemia at admission for delivery and adverse perinatal outcomes.

BACKGROUND: Maternal anemia is a risk factor for poor pregnancy outcomes and threatens maternal or fetal life. Anemia increases the risk of low birth weight and preterm birth. We aimed to determine the cutoff level of hemoglobin and risk factors for maternal anemia at admission for delivery and investigate the association between maternal anemia and adverse perinatal outcomes in contemporary Taiwanese women. METHODS: About 32,234 women admitted to the Taipei Chang Gung Memorial Hospital from 2001 to 2016 were enrolled in this retrospective observational cohort study. The prevalence of pre-delivery maternal anemia in Taiwan and the maternal demographic and perinatal outcomes associated with maternal anemia was assessed. RESULTS: The 10th and 5th percentile hemoglobin levels of the test cohort (2001-2008, n = 15,602) were 10.8 g/dL and 9.9 g/dL, respectively. In the study cohort (2009-2016, n = 13,026), women who were multiparous, who were aged >34 years, with history of cesarean delivery, and with history of uterine fibroids had higher prevalence of anemia. Anemic women were at increased risk of cesarean delivery, primary cesarean delivery, premature rupture of membranes, early preterm birth <34 weeks, having very low birth weight infants (<1,500 g), having large for gestational age infants, and neonatal intensive care center transfer, but at lower risk of having small for gestational age infants. CONCLUSION: Maternal anemia at delivery is a risk factor for primary cesarean delivery and adverse maternal and neonatal outcomes. Furthermore, we hypothesize that maternal anemia might increase fetoplacental vasculogenesis and angiogenesis as an adaptive response.

Clinical Relevance and Treatment Selection of Ureteral Injury After Cesarean Section.

INTRODUCTION: The aim of this case series was to report the clinical relevance and management outcomes of ureteral injuries acquired secondary to cesarean section. METHODS: This was a retrospective case series from January 2007 to September 2014. Description of the patients' characteristics, diagnostic tools for investigation, management, and postoperative follow-up was conducted on postcesarean section patients who developed symptoms of urine leakage after cesarean section and necessitated secondary surgery for ureteral injury. Descriptive statistics was used for demographics and operative data. RESULTS: A total of 5619 cases were managed by cesarean section during the study period. Six (0.107%; 95% confidence interval [CI], 0.1069%-0.1071%) patients had ureteral injury related to the cesarean section. Of 6 cases, 3 (0.053%; 95% CI, 0.0529%-0.0531%) had ureterouterine fistula. Three cases were managed by ureteroneocystostomy, 1 by ureteroneocystostomy with Boari flap, 1 by transureteroureterostomy, and the other one by ureteral stenting via ureterocystoscopy. Three patients had immediate operation because of an acute abdomen and 3 patients had delayed operation. The left ureter was the most common site of ureteral injury (5/6). The postoperative course was uneventful for all cases. CONCLUSIONS: Continuous urinary leakage and acute abdominal distention associated with fluid accumulation after emergency cesarean section should be considered as "red flag" symptoms of ureteral injury and ureterouterine fistulae complications. Delayed management for ureteral repair may not be associated with bad outcomes for management of ureterouterine fistula. Delayed management was associated with less blood loss, less operating time, and acceptable outcome among patients with ureterouterine fistulae when the renal function is not compromised.

Suitable timing of surgical intervention for ruptured ovarian endometrioma.

OBJECTIVE: Patients with a rare rupture of endometriomas may require surgery. In this retrospective study, we assessed the outcomes of surgical interventions for ruptured ovarian endometriomas. MATERIALS AND METHODS: Forty-three patients who underwent surgical intervention for ruptured ovarian endometriomas were studied. Depending on the latency to surgery and endometrioma recurrence, patients were divided into two groups, and then compared with respect to patient profiles, intraoperative findings, and outcomes. RESULTS: Thirty-one of the 43 patients had a known ovarian endometrioma with an average diameter of 6.04 cm. Seventeen (39.5%) patients had a recurrent ovarian tumor during the postoperative follow up. Patients who underwent surgery within 72 hours or after 72 hours showed no difference in baseline characteristics and most clinical outcomes, except for the choice of surgery (p = 0.003) and future fertility (p = 0.005). CONCLUSION: Comprehensive and early surgical intervention after endometrioma rupture can assist in excluding ovarian malignancy and can reduce the effects of cyst fluids, prevent adhesions, and preserve fertility.

Twenty-one years of experience with ovarian ectopic pregnancy at one institution in Taiwan.

OBJECTIVE: To review the experience with patients with ovarian ectopic pregnancy (OEP) at Chang Gung Memorial Hospital, Lin-Kou Medical Center, Tao-Yuan, Taiwan, between 1989 and 2009. METHODS: A retrospective review of the presentation, prevalence, diagnosis, and trends in treatment of patients with OEP, and the use of assisted reproductive technology (ART) procedures and intrauterine devices (IUD). The incidence rate ratios (IRR) of ectopic pregnancies (EPs) per live births, OEPs per EPs, and OEPs per live births were analyzed. RESULTS: The 110 OEPs diagnosed comprised 2.0% of all EPs (n=5408) and 1:1543 of all live births, leading to a mean OEP per year of 5.24. Seventy-eight patients were managed with laparoscopy and 32 underwent laparotomy. Twenty-six (23.6%) patients used an IUD and 12 (10.9%) had undergone ART. OEP associated with ART increased in the last 10 years of the study period. The IRR of EPs per live births, OEPs per EPs, and OEPs per live births all increased between 1989 and 2009. Management of OEP tended to favor laparoscopy in the later years. CONCLUSION: There was a trend toward better management of OEP with laparoscopy. ART has become a risk factor for OEP. The IRR of EPs per live births, OEPs per EPs, and OEPs per live births all increased over the 21-year period.

Increased autophagy in placentas of intrauterine growth-restricted pregnancies.

BACKGROUND: Unexplained intrauterine growth restriction (IUGR) may be a consequence of placental insufficiency; however, its etiology is not fully understood. We surmised that defective placentation in IUGR dysregulates cellular bioenergic homeostasis, leading to increased autophagy in the villous trophoblast. The aims of this work were (1) to compare the differences in autophagy, p53 expression, and apoptosis between placentas of women with normal or IUGR pregnancies; (2) to study the effects of hypoxia and the role of p53 in regulating trophoblast autophagy; and (3) to investigate the relationship between autophagy and apoptosis in hypoxic trophoblasts. METHODOLOGY/PRINCIPAL FINDINGS: Compared with normal pregnant women, women with IUGR had higher placental levels of autophagy-related proteins LC3B-II, beclin-1, and damage-regulated autophagy modulator (DRAM), with increased p53 and caspase-cleaved cytokeratin 18 (M30). Furthermore, cytotrophoblasts cultured under hypoxia (2% oxygen) in the presence or absence of nutlin-3 (a p53 activity stimulator) had higher levels of LC3B-II, DRAM, and M30 proteins and increased Bax mRNA expression compared with controls cultured under standard conditions. In contrast, administration of pifithrin-α (a p53 activity inhibitor) during hypoxia resulted in protein levels that were similar to those of the control groups. Moreover, cytotrophoblasts transfected with LC3B, beclin-1, or DRAM siRNA had higher levels of M30 compared with the controls under hypoxia. However, transfection with Bcl-2 or Bax siRNA did not cause any significant change in the levels of LC3B-II in hypoxic cytotrophoblasts. CONCLUSIONS/SIGNIFICANCE: Together, these results suggest that there is a crosstalk between autophagy and apoptosis in IUGR and that p53 plays a pivotal and complex role in regulating trophoblast cell turnover in response to hypoxic stress.

Adnexal torsion in a woman undergoing ovarian hyperstimulation with clomiphene citrate therapy: a case report and review of the literature.

Ovarian stimulation is a unique aid for patients treated for anovulation and an important tool in various assisted reproduction treatments. Clomiphene citrate, an orally active, non-steroidal triphenylethylene derivate, is a commonly prescribed agent for ovulation induction. Clomiphene citrate is considered a safe agent and has rarely been associated with significant side effects. This report describes a case of unilateral adnexal torsion after ovulation induction with clomiphene citrate; we performed unwinding of the adnexum, which appeared ischemic via laparoscopy. Unfortunately, the affected adnexum became hemorrhagic after this approach, which invariably led to its resection.

Long-term follow-up of patients surgically treated for ruptured ovarian endometriotic cysts.

OBJECTIVE: Approximately 4% of women are admitted to hospitals because of ovarian cyst rupture, hemorrhage, or torsion. Endometriotic cyst rupture is a rare surgical emergency associated with severe peritonitis and pelvic adhesion, and we aimed to determine its prognosis and long-term outcome. MATERIALS AND METHODS: We reviewed and analyzed the medical records of 11 patients (mean age, 31.8 ± 7.2 years) with ruptured endometrioma and a history of dysmenorrhea (4.9 ± 2.3 of maximum 10) who were surgically treated, and then regularly followed-up for more than 3 years (range, 35-261 months). RESULTS: Previous ultrasound examinations revealed pelvic cysts in seven patients. Three patients had a history of endometrioma surgery. In the emergency room, eight patients complained of uterine motion tenderness. Sonography revealed residual ovarian tumors (size range, 4.2-10.4 cm), with or without fluid accumulation in the cul-de-sac. Surgical enucleation by laparoscopy or laparotomy revealed high revised American Fertility Society endometriosis scores (78 ± 20.1) as well as high adhesion scores (48.7 ± 11.3). In the postoperative period, four patients had recurrent ovarian tumors that were related to elevated serum cancer antigen 125 levels and high postoperative pain scores. In contrast, three patients who became pregnant during the postoperative period had low serum cancer antigen 125 levels and pain scores. CONCLUSION: Endometrioma rupture should be considered in females presenting with sudden lower abdominal pain, associated with a history of dysmenorrhea and preexisting pelvic cysts. Emergency surgical intervention may lead to a better prognosis, particularly in patients without a history of previous endometrioma surgery.

Clinical manifestations in women with isolated fallopian tubal torsion; a rare but important entity.

BACKGROUND: The diagnosis of adnexal torsion can be difficult to make, especially in isolated fallopian tube torsion (FTT). Only small series and several case reports on isolated FTT have been published in the literature. AIMS: To demonstrate symptom presentations, objective findings and surgical outcomes in women with isolated FTT over a 12-year period at a tertiary hospital. METHODS: Using the International Classification of Disease, Ninth Revision, and Clinical Modification, we reviewed the clinical records of women with isolated FTT during 1996 and 2008 at our institute. RESULTS: Seventeen women, age 13-50 (mean 32) with surgically proven isolated FTT, were included. Five women (29.4%) had tubal ligation history. None of these cases were diagnosed before operation. Pain characteristics were variable; the onset was sudden in 10 (58.8%) and 17 (100%) complained of lower abdominal pain, but only six (35.3%) had peritoneal signs. Other clinical manifestations were as follows: nausea or vomiting in seven women (41.2%), lower urinary tract symptoms in four (23.5%) and fever in three (17.6%). All the women had a cystic adnexal mass on ultrasound. An enlarged tubal mass (5-14 cm) was found in all the cases at surgery. Eleven women (64.7%) underwent laparoscopy, and six (35.3%) laparotomy for salpingectomy. CONCLUSIONS: The diagnosis of isolated FTT is often not made before surgical intervention because clinical features are non-specific. However, it needs to be considered in women with acute lower abdominal pain with a unilateral cystic adnexal mass.

Surgical intervention for maternal ovarian torsion in pregnancy.

OBJECTIVE: Maternal ovarian torsion in pregnancy is a rare complication. This study was conducted to review the clinical manifestations, and to compare the outcome between laparoscopy and laparotomy in women undergoing surgery for ovarian torsion (OT) during pregnancy. MATERIALS AND METHODS: Using the International Classification of Disease, Ninth Revision, and Clinical Modification, we reviewed the clinical records of patients with OT during pregnancy between 1997 and 2008 at a university hospital. RESULTS: Twenty pregnant women were identified with surgically proven OT, 10 in the first trimester, eight in the second, and two in the third. Thirteen (65%) cases were suspected before operation to be adnexal torsion. The most common symptom and sign were pelvic pain (95%) and an adnexal or pelvic mass (95%), followed by nausea and vomiting (65%), elevated white blood cell count >12×10(9)/L (45%), and fever (10%). Most patients in the first trimester (75%) and a minority in the second and third trimesters (37.5%) received management via laparoscopy. Patients undergoing laparoscopy treatment had smaller ovarian masses and a shorter postoperative hospital stay than those receiving laparotomy. None of these patients had significant complications during or after surgery. However, the outcomes of pregnancy varied: 12 (60%) term deliveries, three (15%) preterm deliveries at over 31 gestational weeks, one missed abortion and four elective abortions in the first trimester. CONCLUSION: The diagnosis of OT during pregnancy is often missed due to nonspecific clinical features and uncommon objective findings. Detorsion only or detorsion plus ancillary procedures via laparoscopy is recommended to treat pregnant women suffering from OT, owing to the advantages of a shorter hospital stay and favorable surgical and pregnancy outcomes.

Effectiveness of ultrasound-guided aspiration and sclerotherapy with 95% ethanol for treatment of recurrent ovarian endometriomas.

OBJECTIVE: To evaluate the effectiveness of transvaginal ultrasound aspiration and ethanol sclerotherapy in patients with recurrent ovarian endometriomas. DESIGN: Retrospective study. SETTING: Teaching hospital affiliated with Chang Gung University, Taipei. PATIENT(S): Patients (n = 108) with recurrent ovarian endometriomas >or=3 cm. INTERVENTION(S): Preoperative evaluation of previous pathology, midcycle serum CA-125 level, and color Doppler ultrasonography to exclude possibility of malignancies. After aspiration, sclerotherapy with 95% ethanol irrigation of the cystic cavity was performed (group 1, n = 78, 0-10 minutes of retention; group 2, n = 30, ethanol left in situ [retention]). MAIN OUTCOME MEASURE(S): Ultrasonography was performed at 3, 6, 9, and 12 months to determine persistence and size of cysts and the number of antral follicles. Pelvic pain score was also determined at those time points. RESULT(S): The 1-year recurrence rate for group 2 patients was significantly lower than for group 1 patients (13.3% vs. 32.1%). Antral follicle count was increased and pain score was decreased in both groups to a similar level. No significant change in CA-125 was observed. CONCLUSION(S): Ultrasound-guided sclerotherapy with 95% ethanol is an effective therapy for ovarian endometriomas. Retention of ethanol is more effective than irrigation only.

Laparoscopy versus laparotomy for surgical intervention of ovarian torsion.

AIM: To review the clinical manifestations of ovarian torsion (OT) and to compare the surgical results between laparoscopy and laparotomy. METHODS: From 1997 to 2006, data on 179 patients admitted to a medical center with surgically proven OT were collected. We compared patients' symptom presentations, objective findings and surgical outcomes between patients who underwent laparotomy and those who received laparoscopy, and between patients admitted via the emergency room and those via the outpatient department. RESULTS: The most common symptom and sign was pelvic pain (82.1%), followed by nausea and vomiting (49.7%), elevated white blood count (20.1%), lower urinary tract symptoms (14.5%) and fever (7.8%). An adnexal or pelvic mass could be detected using gynecological ultrasound in almost all of the patients (98.3%). Ovarian torsion was considered among the admission differential diagnoses in 51.4% of patients. One hundred and five patients (58.7%) seen in the emergency room were more likely to present with nausea and vomiting, sudden pain onset and peritoneal signs than those seen in the outpatient department. Patients undergoing laparoscopy had a smaller sized ovarian mass; they were less likely to require oophorectomy; they had a shorter hospital stay; and fewer of them suffered from postoperative fever compared to patients undergoing laparotomy. Discriminant analysis showed that mass size was the single determining factor for choice of operating methods. CONCLUSION: The diagnosis of OT is missed in half of the patients because clinical features are unspecific and objective findings are uncommon. The laparoscopy procedure for ovarian conservation is recommended to treat patients suffering from OT owing to its shorter hospital stay, fewer postoperative complications and ovarian preservation.

Risk factors for placenta previa in an Asian population.

OBJECTIVE: To identify the risk factors for placenta previa in an Asian population. METHODS: This retrospective cohort study involved Taiwanese women delivered between July 1990 and December 2003 at Chang Gung Memorial Hospital, Taipei, Taiwan. Pregnancies complicated by multiple gestation and fetal anomalies were excluded. RESULTS: There were 457 cases of placenta previa (1.2%) among the 37,702 pregnancies analyzed. Risk factors for placenta previa included a prior preterm birth (OR, 6.6; 95% confidence interval [CI], 4.1-10.6); technology-assisted conception (OR, 4.8; 95% CI, 2.9-7.8); smoking (OR, 3.3; 95% CI, 1.2-9.1) or working (OR, 3.8; 95% CI, 2.8-5.3) during pregnancy; maternal age of, or greater than 35 years (OR, 2.0 to 2.2; 95% CI, 1.3-3.7); and previous induced abortions (OR, 1.3-3.0; 95% CI, 1.1-7.1). CONCLUSION: The risk factors for placenta previa were found to be the same for Asian women as those previously recorded for American and European women, but additional factors were detected.

Real-time and power Doppler imaging of fetal adrenal hemorrhage.

Adrenal hemorrhages are not uncommon in newborns, but they may occur before birth. The incidence of adrenal hemorrhages based on extensive necropsy has been estimated as about 1.7 per 1000 births. With the increasing use of ultrasonography, prenatal recognition of fetal adrenal hemorrhages has become more common in recent years. We report an echogenic abdominal mass, which was found at 36 weeks of gestation using real-time ultrasound, and was enlarged during the 2-week follow-up period. No trauma history was noted during the pregnancy. Since the mass was close to the kidney, we performed power Doppler imaging to localize the lesion and tried to make a differential diagnosis. The left adrenal mass was posterior to the stomach and was without pulsatile blood flow inside. After birth, sonography confirmed a solid homogenous adrenal mass in the newborn. Seven days after birth, the persistent adrenal echogenic mass without resolution by computerized tomography led to a diagnosis of neuroblastoma. The mass was removed by surgery and adrenal hemorrhage diagnosed. The outcome of the adrenal hemorrhage was excellent. The differential diagnosis in unilateral adrenal mass is difficult from the images of 2-D ultrasound since similar pictures may occur among them. In this case, accurate localization of an adrenal mass is feasible using power Doppler imaging (PDI) before birth by determining its blood supply from the middle suprarenal artery. At the same time, fetal adrenal hemorrhages can be demonstrated as an avascular mass, which is the major difference from adrenal tumors. In conclusion, PDI offered more information to localize the adrenal glands from other lesions by separating the blood supply. In addition, the avascular adrenal mass favors the prenatal diagnosis of adrenal hemorrhage.