Continuous Glucose Monitoring Feedback in the Subsequent Development of Gestational Diabetes: A Pilot, Randomized, Controlled Trial in Pregnant Women.

OBJECTIVE: This study evaluated the effects of receiving glucose feedback from continuous glucose monitoring (CGM) by intermittent scanning (unblinded group), and CGM with masked feedback (blinded group) in the subsequent development of gestational diabetes mellitus (GDM). STUDY DESIGN: This was a prospective, single-center, pilot, randomized controlled trial including n = 206 pregnant women in the first trimester of pregnancy with no prior diagnosis of type 1 or type 2 diabetes. The participants were randomized into the unblinded group or blinded group and wore the CGM in the first trimester of pregnancy (9-13 weeks), the second trimester of pregnancy (18-23 weeks), and late-second to early-third trimester (24-31 weeks). The primary outcome was GDM rate as diagnosed by the 75-g oral glucose tolerance test (OGTT) at 24 to 28 weeks. RESULTS: Over 47 months, 206 pregnant women were enrolled at 9 to 13 weeks. The unblinded group had a higher prevalence of women who developed GDM (21.5 vs. 14.9%; p > 0.05), compared to the blinded group. In the unblinded group compared to the blinded group, plasma glucose values were higher at 1 hour (median 7.7 [interquartile range {IQR}: 6.3-9.2] vs. 7.5 [6.3-8.7]) and 2 hours (6.3 [5.8-7.7] vs. 6.2 [5.3-7.2]), but lower at 0 hour (4.2 [4.0-4.5] vs. 4.3 [4.1-4.6]; p > 0.05). All these differences were not statistically significant. CONCLUSION: Glucose feedback from CGM wear in the first to the third trimester of pregnancy without personalized patient education failed to alter GDM rate. KEY POINTS: · Continuous glucose monitoring (CGM) is feasible for use in pregnant women.. · No significant difference in gestational diabetes rates with or without CGM feedback.. · Future clinical trials should incorporate CGM education and personalized guidance to enhance study outcomes..

Discovery and validation of peritoneal endometriosis biomarkers in peritoneal fluid and serum.

RESEARCH QUESTION: What are the potential biomarkers for peritoneal endometriosis in peritoneal fluid and serum? DESIGN: Case-control studies composed of independent discovery and validation sets were conducted. In the discovery set, untargeted liquid chromatography-mass spectrometry (LC-MS/MS) metabolomics, multivariable and univariable analyses were conducted to generate global metabolomic profiles of peritoneal fluid for endometriosis and to identify potential metabolites that could distinguish peritoneal endometriosis (n = 10) from controls (n = 31). The identified metabolites from the discovery set were validated in independent peritoneal fluid (n =19 peritoneal endometriosis and n = 20 controls) and serum samples (n = 16 peritoneal endometriosis and n = 19 controls) using targeted metabolomics. The area under the receiver-operating characteristics curve (AUC) analysis was used to evaluate the diagnostic performance of peritoneal endometriosis metabolites. RESULTS: In the discovery set, peritoneal fluid phosphatidylcholine (34:3) and phenylalanyl-isoleucine were significantly increased in peritoneal endometriosis groups compared with control groups, with AUC 0.77 (95% CI 0.61 to 0.92; P = 0.018) and AUC 0.98 (95% CI 0.95 to 1.02; P < 0.001), respectively. In the validation set, phenylalanyl-isoleucine retained discriminatory performance to distinguish peritoneal endometriosis from controls in both peritoneal fluid (AUC 0.77, 95% CI 0.61 to 0.92; P = 0.006) and serum samples (AUC 0.81, 95% CI 0.64 to 0.99; P = 0.004), with notably stronger discrimination between peritoneal endometriosis and controls in proliferative phase. CONCLUSION: Our preliminary results propose phenylalanyl-isoleucine as a potential biomarker of peritoneal endometriosis, which may be used as a minimally invasive diagnostic biomarker of peritoneal endometriosis.

Peritoneal Fluid Cytokines Reveal New Insights of Endometriosis Subphenotypes.

Endometriosis is a common inflammatory gynecological disorder which causes pelvic scarring, pain, and infertility, characterized by the implantation of endometrial-like lesions outside the uterus. The peritoneum, ovaries, and deep soft tissues are the commonly involved sites, and endometriotic lesions can be classified into three subphenotypes: superficial peritoneal endometriosis (PE), ovarian endometrioma (OE), and deep infiltrating endometriosis (DIE). In 132 women diagnosed laparoscopically with and without endometriosis (n = 73, 59 respectively), and stratified into PE, OE, and DIE, peritoneal fluids (PF) were characterized for 48 cytokines by using multiplex immunoassays. Partial-least-squares-regression analysis revealed distinct subphenotype cytokine signatures-a six-cytokine signature distinguishing PE from OE, a seven-cytokine signature distinguishing OE from DIE, and a six-cytokine-signature distinguishing PE from DIE-each associated with different patterns of biological processes, signaling events, and immunology. These signatures describe endometriosis better than disease stages (p < 0.0001). Pathway analysis revealed the association of ERK1 and 2, AKT, MAPK, and STAT4 linked to angiogenesis, cell proliferation, migration, and inflammation in the subphenotypes. These data shed new insights on the pathophysiology of endometriosis subphenotypes, with the potential to exploit the cytokine signatures to stratify endometriosis patients for targeted therapies and biomarker discovery.

Are women in Singapore gaining weight appropriately during pregnancy: a prospective cohort study.

BACKGROUND: We aimed to study gestational weight gain (GWG) in a Singaporean population and compare it with Institute of Medicine (IOM) 2009 GWG guidelines. METHODS: Nine hundred twenty-six women with low-risk singleton pregnancy were enrolled in a prospective cohort study from 2010 to 2014 in a Singapore tertiary maternity hospital. Seven hundred twenty-four patients had maternal weight information till term pregnancy and were included in analysis. Participants were categorized according to their first antenatal visit body mass index (BMI) as underweight, normal weight, overweight and obese. Total GWG for each BMI group was calculated. Multivariate logistic regression was performed to determine the predictors of total GWG above and below IOM guidelines. RESULTS: Obese women had a mean total GWG (9.1 kg) that exceeded the upper limit IOM guidelines (9 kg). In multivariate analysis of predictors of total GWG above IOM guidelines, being overweight (adjusted OR: 3.91 [95% CI, 2.60-5.88]; p < .0001) and obese (adjusted OR: 4.78 [95% CI, 2.80, 8.15]; p < .0001) significantly increased the risks of gaining weight above IOM guidelines during pregnancy, compared to being normal weight. CONCLUSIONS: Overweight and obesity are independent significant risk factors for gaining excessive gestational weight. Appropriate weight management for overweight and obese Singaporean women prior to and during pregnancy is important.

Uterine Manipulation May Not Influence Ongoing Pregnancy: Case Report and Literature Review.

Abdominal pain is a very common presentation in early pregnancy. Its cause may be gynecological or totally nonpregnancy related. While acute appendicitis is the most common nonobstetric cause of pain in pregnant women, diagnosis and differentiation from other causes, including ectopic pregnancy, remain challenging. In clinical situations of uncertainty, laparoscopy is a useful diagnostic tool, but uterine manipulation should be avoided if an intrauterine pregnancy is a possibility. In this report, we describe a case of complicated appendicitis in very early pregnancy where the patient ended with a full-term healthy pregnancy despite undergoing a diagnostic laparoscopy with inadvertent uterine manipulation.

Scope and Suction: Hysteroscopic-guided Suction Evacuation of Cesarean Scar Pregnancy - A Safe and Efficacious Treatment for Selected Patients.

Objectives: This study aimed to evaluate hysteroscopic-guided suction evacuation for the treatment of cesarean scar pregnancy (CSP). Materials and Methods: This was a retrospective analysis of CSP over 2 years. This study was conducted at KK Women's and Children's Hospital (KKH), Singapore, thirty-seven patients with a CSP. Hysteroscopic-guided suction evacuation to treat CSP used alone or in combination with laparoscopy depending on residual myometrial thickness (RMT) and future fertility requirements. Results: The majority of women (29) were diagnosed under 9-week gestation. Just over a third (13) had an RMT of more than 3 mm. Women with an RMT <3 mm had added laparoscopy. In total, 22 women had hysteroscopic-guided suction evacuation with 9 having it performed under laparoscopic guidance because the RMT was under 3 mm. The remaining patients underwent either laparoscopic repair (5 cases) or vaginal repair (1 case) done under laparoscopic guidance. Conclusion: Hysteroscopic-guided suction evacuation of CSP has the potential to become part of the routine management for uncomplicated cases of CSP in women with an RMT of greater than 3 mm who do not wish for future pregnancy. Its use, in combination with other minimally invasive techniques, can be extended to more complex cases where the RMT is <3 mm and future fertility is desired.

Cesarean Scar Pregnancy: Current Understanding and Treatment Including Role of Minimally Invasive Surgical Techniques.

The incidence of cesarean scar pregnancy (CSP) is increasing reflecting the global increase in cesarean section (CS) rate which has almost doubled since 2000. CSP differs from other types of ectopic pregnancy in its ability to progress while still carrying a significant risk of maternal morbidity. Little is known about precise etiology or natural history although current interest in the pathology of placenta accretes spectrum disorders might be enlightening. Early detection and treatment of CSP are challenging. Once diagnosed, the recommendation is to offer early termination of pregnancy because of the potential risks of continuing the pregnancy. However, as the likelihood of future pregnancy complications for any CSP varies depending on its individual characteristics, this might not always be necessary nor might it be the patient's preferred choice if she is asymptomatic, hemodynamically stable, and wants a baby. The literature supports an interventional rather than a medical approach but the safest and most efficient clinical approach to CSP in terms of treatment modality and service delivery has yet to be determined. This review aims to provide an overview of CSP etiology, natural history, and clinical implications. Treatment options and methods of CSP repair are discussed. We describe our experience in a large tertiary center in Singapore with around 16 cases/year where most treatment modalities are available as well as an "accreta service" for continuing pregnancies. We present a simple algorithm for approach to management including a method of triaging for those CSPs suitable for minimally invasive surgery.

Association between gestational weight gain and pregnancy outcomes in a Singaporean population: A prospective cohort study.

OBJECTIVES: Inadequate or excessive gestational weight gain (GWG) is associated with adverse pregnancy outcomes. We aimed to study GWG in a Singaporean population and its association with pregnancy outcomes, including small for gestational age (SGA), macrosomia, and caesarean section secondary to failure to progress (FTP) or cephalopelvic disproportion (CPD). STUDY DESIGN: 926 women with low-risk singleton pregnancy were enrolled in a prospective cohort study from 2010 to 2014 in a Singapore tertiary maternity hospital. 704 patients without pre-existing diabetes or hypertension and had maternal weight information till term pregnancy were included in analyses. Participants were categorized according to their first antenatal visit body mass index (BMI) as underweight, normal weight, overweight and obese. Total GWG for each BMI group was calculated and compared to Institute of Medicine (IOM) 2009 GWG guidelines. Logistic regression analyses were performed to assess the association of GWG below or above IOM guidelines with pregnancy outcomes. RESULTS: GWG below IOM guidelines was associated with an increased risk of SGA (adjusted OR: 2.97 [1.71, 5.15]; p < 0.0001). GWG above IOM guidelines significantly increased the risk of caesarean section due to FTP or CPD (adjusted OR: 2.10 [1.09, 4.01]; p = 0.0275). GWG above IOM guidelines was associated with an increased risk of macrosomia (adjusted odds ratio: 2.27 [1.43, 3.63]; p = 0.0006), while GWG below IOM guidelines was associated with a reduced risk of macrosomia (adjusted odds ratio: 0.18 [0.08, 0.39]; p < 0.0001). CONCLUSIONS: GWG not achieving the IOM recommendations has been found to be associated with adverse pregnancy outcomes in Singaporean women. Inadequate GWG is associated with an increased risk of SGA whereas excessive GWG is associated with increased risks of macrosomia and caesarean section due to failure to progress or CPD. Results of the current study add to our understanding on the association of GWG with pregnancy outcomes in the South-East Asia and suggest that appropriate weight management during pregnancy is important.

Laparoscopic management of primary hepatic pregnancy.

A 30-year-old woman presented with epigastric pain with elevated serum human chorionic gonadotropin level (hCG), absence of intrauterine gestational sac and absence of an abnormal adnexal mass on pelvic ultrasonography. Laparoscopy revealed a ruptured hepatic ectopic pregnancy. This was removed by laparoscopic suctioning and haemostasis secured with Surgicel((R)) Fribrilla Absorbable Hemostat. Intramuscular methotrexate was administered post-operatively. Patient recovered uneventfully and serum hCG returned to normal.

Interstitial Ectopic Pregnancy and Laparoscopic Removal of the Interstitial Portion of the Tube: the New Frontier?

We present a case of a 40-year-old lady with 9 weeks of amenorrhea diagnosed with an interstitial pregnancy and multiple uterine fibroids. She underwent laparoscopic salpingectomy including the interstitial part of fallopian tube with products of conception without myomectomy and cornuostomy. Intra-operative blood loss was minimal. She was followed up post-operatively with weekly serum beta human chorionic gonadotropin (serum ß-hCG), which down-trended optimally at day 23 of surgery. Histopathology confirmed ectopic pregnancy with underlying salpingitis isthmica nodosa. Patient recovered well.

Longitudinal circulating placental growth factor (PlGF) and soluble FMS-like tyrosine kinase-1 (sFlt-1) concentrations during pregnancy in Asian women: a prospective cohort study.

OBJECTIVES: To analyse the placental growth factor (PlGF) and soluble FMS-like tyrosine kinase-1 (sFlt-1) trends in the normal pregnant Asian population in Singapore. DESIGN: A prospective study was conducted. SETTING: The largest tertiary hospital in Singapore. METHODS: Women with single viable pregnancies, less than 14 weeks of gestation, were recruited between September 2010 and November 2013 in KK Women's and Children's Hospital. They were followed up from recruitment till their postnatal discharge from the hospital. There were four antenatal visits: gestational age (GA) less than 14+0 weeks of gestation (V1), GA 18+0 to 22+0 weeks (V2), GA 28+0 to 32+0 weeks (V3) and GA 34+0 and above (V4). Serum biochemical markers (sFlt-1, PlGF) were measured at each visit. RESULTS: There were 934 participants in the study, of which 674 had normal pregnancy outcomes. The sFlt-1 remained relatively constant till GA 28-32 weeks before it increased (p<0.001). The sFlt-1 levels increased earlier before 30 weeks' of gestation among the Malay participants and the other ethnicities. For PlGF, the levels increased from the first to the third trimester, peaking at 30-32 weeks before decreasing (p<0.001). Its serum levels significantly differed among the Indian participants and other ethnicities as compared with the Malay and Chinese participants at V3 and V4, (p=0.04 and p<0.001, respectively). CONCLUSION: There are significant differences in the PlGF and sFlt-1 concentrations during pregnancy between different ethnicities, which should be taken into consideration when using these references values for further research.

Elevated peritoneal fluid ceramides in human endometriosis-associated infertility and their effects on mouse oocyte maturation.

OBJECTIVE: To characterize the peritoneal fluid (PF) sphingolipid profile in endometriosis-associated infertility (EAI), and to assess the plausible functional role(s) of ceramides in oocyte maturation potential. DESIGN: Retrospective case-control study and in vitro mouse oocyte study. SETTING: University-affiliated hospital and university laboratory. SUBJECTS: Twenty-seven infertile patients diagnosed with endometriosis and 20 infertile patients who did not have endometriosis; BALB/c female mice. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): PF sphingolipid concentrations. Number of metaphase II (MII) mouse oocytes. RESULT(S): Liquid chromatography-tandem mass spectrometry revealed 11 significantly elevated PF sphingolipids in infertile women with severe endometriosis compared with infertile women without endometriosis (change >50%, false discovery rate ≤10%). Logistic regression analysis identified three very-long-chain ceramides potentially associated with EAI. Functional studies revealed that very-long-chain ceramides may compromise or induce murine MII oocyte maturation. The oocyte maturation effects induced by the very long-chain ceramides were triggered by alterations in mitochondrial superoxide production in a concentration-dependent manner. Scavenging of mitochondrial superoxide reversed the maturation effects of C24:0 ceramide. CONCLUSION(S): EAI is associated with accumulation of PF very-long-chain ceramides. Mouse studies demonstrated how ceramides affect MII oocyte maturation, mediating through mitochondrial superoxide. These results provide an opportunity for direct functional readout of pathophysiology in EAI, and future therapies targeted at this sphingolipid metabolism may be harnessed for improved oocyte maturation.

Limited value of pro-inflammatory oxylipins and cytokines as circulating biomarkers in endometriosis - a targeted 'omics study.

Endometriosis is a common, complex gynecologic disorder characterized by the presence of endometrial-like tissues at extrauterine sites. Elevation in protein and lipid mediators of inflammation including oxylipins and cytokines within the peritoneum characterize the inflamed pelvic region and may contribute to the survival and growth of displaced endometrial tissues. The presence of a clinically silent but molecularly detectable systemic inflammation in endometriosis has been proposed. Thus, we examined serum oxylipin and immunomodulatory protein levels in 103 women undergoing laparoscopy to evaluate systematically any involvement in systemic pathophysiological inflammation in endometriosis. Oxylipin levels were similar between women with and without endometriosis. Stratification by menstrual phase or severity did not offer any difference. Women with ovarian endometriosis had significantly lower 12-HETE relative to peritoneal endometriosis (-50.7%). Serum oxylipin levels were not associated with pre-operative pain symptoms. Changes to immunomodulatory proteins were minimal, with IL-12(p70), IL-13 and VEGF significantly lower in mild endometriotic women compared to non-endometriotic women (-39%, -54% and -76% respectively). Verification using C-reactive protein as a non-specific marker of inflammation further showed similar levels between groups. The implications of our work suggest pro-inflammatory mediators in the classes studied may have potentially limited value as circulating biomarkers for endometriosis, suggesting of potentially tenuous systemic inflammation in endometriosis.

Struma ovarii: management and follow-up of a rare ovarian tumour.

INTRODUCTION: Struma ovarii represents about 1.0% of all ovarian tumours. While management involves surgery, there is a paucity of data regarding the extent and approach of surgery, and postoperative management. This study aimed to delineate the management of struma ovarii, its associated complications, and postoperative follow-up and investigations. METHODS: We retrospectively reviewed cases of benign struma ovarii treated at KK Women's and Children's Hospital, Singapore, between January 2000 and May 2011. RESULTS: A total of 68 patients underwent surgical removal of ovarian cyst or mass (24 cystectomy, 20 salpingo-oopherectomy and 24 total hysterectomy and bilateral salpingo-oopherectomy). Of the 68 surgeries, 39 (57.4%) included intraoperative frozen section sampling or procedures for staging of ovarian malignancy. The majority (73.5%) of surgeries were laparotomies. Histology revealed benign struma ovarii in all (98.5%) but one patient. Only 7 (10.3%) patients had postoperative complications - 3 wound-related, 2 thyroid-related, 1 incisional hernia and 1 nonspecific. The mean length of hospital stay was 4.2 days. During follow-up, 45 (66.2%) patients required no additional investigations. The most common investigation done was ultrasonography (n = 18, 26.5%). While no recurrences were diagnosed histologically, two patients were subsequently found to have complex/dermoid ovarian cysts on the ipsilateral side of the previous struma ovarii on ultrasonography. CONCLUSION: Simple surgery is recommended for patients with struma ovarii, especially if they have fertility potential. Laparoscopic surgery is the recommended approach due to its shorter recovery time and lower morbidity. Most patients do not require extended periods of follow-up or postoperative investigations.

Extrauterine fibroids: a diagnostic challenge and a long-term battle.

Extrauterine fibroids often present a diagnostic challenge due to the unusual locations they arise from. We present a series of rare extrauterine fibroids. In recent years, these fibroids have been associated with previous morcellated hysterectomies or myomectomies. Our series of six patients were found to have extrauterine fibroids (confirmed through histology) and underwent open hysterectomy and open or laparoscopic myomectomy. Four had undergone previous laparoscopic myomectomies while the other two had no previous intra-abdominal surgeries. Postsurgical occurrence may be caused by incomplete removal of morcellated fibroid tissue. Spontaneous occurrence can be associated with congenital Müllerian system defects. Extrapolating from this hypothesis, we recommend physicians to make sure that counselling for extrauterine seeding and dissemination of unexpected malignancy is undertaken in cases of minimally invasive surgeries where morcellation is expected. Long-term tumour surveillance is thus essential in such instances.

Total laparoscopic hysterectomy: a 5-year experience.

AIM: To evaluate our surgical technique with regards to the success of total laparoscopic hysterectomy (TLH) for the removal of the uterus by analysing its intra-operative and post-operative outcomes and complications in the hope of reducing their occurrence. METHODS: Retrospective study based on TLH operations performed from January 2001 to December 2005. The KOH Colpotomizer System and the RUMI Uterine Manipulator were used. RESULTS: Five hundred and twelve women consented for TLH. Five hundred and three women (98.2%) had successful TLH with three mini-laparotomy and six laparotomy conversions (1.8% failure rate). Mean uterine size was 11 cm (5-17). Mean operating time was 133 min (40-257). Mean blood loss was 309 ml (50-1,500). Twenty patients (4%) required blood transfusion (five excessive bleeding). Injuries include bowel injury (5), bladder (2), uterine perforation (1), ureterovaginal fistula (1) and vaginal laceration (5). Post-operative complications include pyrexia (36), umbilical wound infection (5), urinary tract infection (UTI) (4) and vault haematoma (3). Mean hospital stay was 2.7 days (1-10). Eighteen patients (3.6%) were readmitted for vaginal bleeding (10), vault haematoma (2), UTI (1), anxiety (3), giddiness (1) and ureterovaginal fistula (1). Twenty-three women (4.5%) encountered major complications (laparotomy conversion, excessive bleeding requiring blood transfusion, hemorrhage > or =1,000 ml, ureteric injury, bowel injury and pulmonary embolus) which compares favourably with other centres (4-11%). Our mean operating time, mean estimated blood loss, mean hospital stay and readmission rate are comparable. CONCLUSION: TLH with adequate training is associated with low morbidity, few complications and a high success rate.