Observational Cohort Study Of Women Research Articles

Hereditary hemorrhagic telangiectasia may be the most morbid inherited bleeding disorder in women

AbstractHereditary hemorrhagic telangiectasia (HHT) is the second-most common inherited bleeding disorder (BD) worldwide and remains without approved therapies. HHT causes serious mucosal bleeding resulting in severe iron-deficiency anemia, major psychosocial complications, and visceral arteriovenous malformations in the brain, lung, and liver, which can cause life-threatening hemorrhagic complications. No study has examined the relative morbidity of HHT and von Willebrand disease (VWD), which is the most common inherited BD in women. We performed an observational cohort study of women with HHT or VWD, comparing a representative sample of 100 randomly selected women with HHT to 100 randomly selected age-matched women with VWD. In HHT vs VWD, recurrent epistaxis and gastrointestinal bleeding were more likely (odds ratio [OR], 32.73 [95% confidence interval, 13.81-71.80]; P < .0001 and 5.69 [2.59-12.89]; P < .0001) and heavy menstrual bleeding was less likely (OR, 0.32 [0.18-0.57]; P < .0001). Iron-deficiency anemia was significantly more likely, and the lowest hemoglobin was significantly lower in HHT than in VWD. The odds of iron infusion dependence, requirement for red cell transfusion, and hemostatic surgical procedures were significantly higher—17-fold, threefold, and eightfold higher, respectively—and hospital admissions to manage disease complications were both ∼14 times more frequent in women with HHT vs those with VWD. In conclusion, much higher disease-related morbidity, mortality, and health care use were observed in women with HHT vs VWD, providing evidence that HHT may be the most clinically significant inherited BD in women. Given the vast gap in research funding for HHT compared with both hemophilia (a disease primarily of men) and VWD, these findings have significant implications for gender equity in hematology.

Hereditary Hemorrhagic Telangiectasia May be the Most Clinically Significant and Morbid Inherited Bleeding Disorder of Women

Background Hereditary hemorrhagic telangiectasia (HHT) is the second most common inherited bleeding disorder (1 in 5000 people) behind von Willebrand disease (VWD) and has no FDA- or EMA-approved therapies. HHT causes serious bleeding resulting in severe iron deficiency anemia, major psychosocial complications, and visceral arteriovenous malformations in brain, lung, and liver that can cause life-threatening hemorrhage, stroke, and other morbid complications. While HHT prevalence is equal in men and women, manifestations may be worse in women (as evidenced by a female predominance in HHT clinical trials). Due to the focus on hemophilia (an X-linked disease nearly exclusive to men) in the hemostasis research community, no study has examined the relative morbidity of the most common inherited bleeding disorders in women: HHT and VWD. Methods We performed an observational cohort study of women with HHT or VWD cared for at our institutional Comprehensive Hemophilia and Von Willebrand Disease Treatment Center or HHT Center of Excellence. Using an electronic patient data registry, a representative sample of 100 randomly selected women with HHT were age-matched to 100 randomly selected women with VWD for analysis. All data was extracted and confirmed using manual chart review; we quantified and compared bleeding and healthcare utilization outcomes. Results Patient Population. The mean (range) age in both groups was 49 (14-87) years. Mean BMI was 27 in both groups, and racial/ethnic breakdown was similar in both groups. Mean follow-up durations were 9.07 years (HHT) and 14.83 years (VWD) per patient. The VWD group included 86 patients with type 1 VWD and 14 with type 2 VWD. Bleeding Outcomes. Bleeding outcomes are detailed in TABLE 1. In women with HHT compared with VWD, recurrent epistaxis and GI bleeding were more likely (odds ratio [OR] [95% CI] = 32.73 [13.81-71.80], P&amp;lt;0.0001 and 5.69 [2.59-12.89], P&amp;lt;0.0001, respectively), and heavy menstrual bleeding was less likely (OR 0.32 [0.18-0.57], P&amp;lt;0.0001). Iron deficiency anemia was significantly more likely, and lowest hemoglobin significantly lower, in HHT versus VWD. Requirements for IV iron and RBC transfusion were significantly more likely in HHT versus VWD. Women with HHT had 17-fold higher odds of iron infusion dependence and 8-fold higher odds of requiring hemostatic surgical procedures than women with VWD. Healthcare Utilization for HHT or VWD Management. Healthcare utilization is detailed in TABLE 2. In women with HHT compared with VWD, emergency department (ED) visits and hospital admissions specifically to manage disease complications were significantly more likely (OR [95% CI] = 3.83 [1.67-8.48], P=0.001 and 7.33 [3.57-14.73], P&amp;lt;0.0001, respectively). Rates of ED visitation, admission, and outpatient encounters specifically for HHT or VWD management were significantly higher in women with HHT vs. women with VWD: ED visits, 10.3 per 100 patient-years (pt-yrs) vs. 0.74 per 100 pt-yrs, P=0.001; admissions, 14.4 per 100 pt-yrs vs. 1.0 per 100 pt-yrs, P&amp;lt;0.0001; outpatient encounters, 386.5 per 100 pt-yrs vs. 43.7 per 100 pt-yrs, P&amp;lt;0.0001. Adjusting these rates for the prevalence of HHT (1 in 5000) and VWD (1 in 1000) at the population level, all rates were still higher in the HHT group. Infusion visits, radiology encounters, and nearly all subspecialty provider visit types were much higher in women with HHT ( TABLE 2). Conclusions Analyzing matched populations of women at a health system that serves as a tertiary referral center for both diseases, HHT, a historically neglected bleeding disorder, was responsible for much higher morbidity and healthcare utilization in women than VWD, certainly at the individual patient level and possibly at the population level (prevalence-adjusted). Overall incidence of disease complications in each group was consistent with the published literature for both HHT and VWD, supporting the generalizability of our findings. These findings are critically important in achieving gender equity in the hemostasis field, given that both government and industry funding for VWD research is many times greater than for HHT research and such funding for hemophilia research, a disease of men, is at least 10-fold greater than for HHT research. Continued neglect of funding for clinical care and research of HHT within the hemostasis academic community and industry will only sustain and exacerbate gender inequities in hematology.

1182-P: Low Socioeconomic Status and Pregnancy Outcomes in Women with Type 2 Diabetes

Aims: Pregnant women with pre-existing type 2 diabetes have a high rate of social deprivation. Low socioeconomic status (SES) is associated with adverse pregnancy outcomes. Our objective was to assess the association of low SES with adverse pregnancy outcomes in women with type 2 diabetes. Materials and Methods: We conducted an observational cohort study of women in the MiTy trial. Maternal and neonatal outcomes were compared in women with and without low SES. Low SES was described as recent immigration within the previous 5 years, low maternal education or single-parent households. Results: A total of 502 women were included in the MiTy trial. Of the eligible women, 192 (41.60%) met criteria for low SES. Women with low SES had significantly higher HbA1c at 34 weeks gestation (6.18% vs 5.89%, p=&amp;lt;0.01). Low SES was associated with an increase in preterm birth (28.1% vs 19.7%, p=0.05), neonatal hypoglycemia (19% vs 9.8%, p=0.007), and NICU admission &amp;gt;24 hrs (27.2% vs 16.8%, p=0.01). After adjustment for confounders, low SES was associated with an increased risk of an adverse neonatal composite outcome (44.7% vs 31.8%, p=0.007; OR 1.83 (95% CI 1.16-2.92). Of the components of the low SES composite, low maternal education was most strongly associated with the composite neonatal outcome OR 1.71 (95% CI 1.03 - 2.82, p=0.04). Conclusions: In women with type 2 diabetes, low SES was associated with poorer glycemic control and an increased risk of adverse neonatal outcomes. Special attention should be paid to low maternal education as a predictor of adverse outcomes. Disclosure S.Campbell: Speaker's Bureau; Novo Nordisk Canada Inc., HLS Therapeutics Inc. G.Tomlinson: None. D.Feig: Advisory Panel; Novo Nordisk Canada Inc., Speaker's Bureau; Sanofi, Novo Nordisk Canada Inc. Funding Canadian Institutes of Health Research

Long-term health-related quality of life and symptom severity following hysterectomy, myomectomy, or uterine artery embolization for the treatment of symptomatic uterine fibroids

Few studies have directly compared different surgical procedures for uterine fibroids with respect to long-term health-related quality of life outcomes and symptom improvement. We examined differences in change from baseline to 1, 2 or 3-year follow-up in health-related quality of life and symptom severity among patients who underwent abdominal myomectomy, laparoscopic or robotic myomectomy, abdominal hysterectomy, laparoscopic or robotic hysterectomy, or uterine artery embolization. The COMPARE-UF Registry is a multi-institutional prospective observational cohort study of women undergoing treatment for uterine fibroids. A subset of 1,384 women ages 31-45 years who underwent either abdominal myomectomy (n=237), laparoscopic myomectomy (n=272), abdominal hysterectomy (n=177), laparoscopic hysterectomy(n=522), or uterine artery embolization (n=176) were included in this analysis. We obtained demographics, fibroid history, and symptoms by questionnaires at enrollment and at 1-, 2-, and 3-years post-treatment. We used the Uterine Fibroids Symptom and Quality of Life (UFS-QoL) questionnaire to ascertain symptom severity and health-related quality of life scores among participants To account for potential baseline differences across treatment groups, a propensity score model was used to derive overlap weights and compare total HR-QoL and symptom severity (SS) scores post-enrollment with a repeated measures model. For this HRQOL tool, a specific minimal clinically important difference (MCID) has not been determined, but based on previous research, a difference of 10 points was considered a reasonable estimate of MCID. Use of this difference was agreed upon by the Steering Committee at the time the analysis was planned. At baseline, women undergoing hysterectomy and uterine artery embolization reported the lowest health-related quality of life scores and highest symptom severity scores compared to those undergoing abdominal myomectomy or laparoscopic myomectomy (p<0.001). Those undergoing hysterectomy and uterine artery embolization reported the longest duration of fibroid symptoms with a mean of 6.3 years (SD: 6.7, p<0.001). The most common fibroid symptoms were menorrhagia (75.3%), bulk symptoms (74.2%), and bloating (73.2%). More than half (54.9%) of participants reported anemia, and 9.4% women reported a history of blood transfusion. Across all modalities, total health-related quality of life and symptom severity score markedly improved from baseline to 1-year with the largest improvement in the laparoscopic hysterectomy group (UFS-QoL: delta= (+) 49.2; symptom severity: delta= (-)51.3). Those undergoing abdominal myomectomy, laparoscopic myomectomy, and uterine artery embolization also demonstrated significant improvement in health-related quality of life ( delta= (+)43.9, (+)32.9, (+)40.7, respectively) and symptom severity (delta= (-)41.4, (-) 31.5, (-) 38.5, respectively) at 1 year, and the improvement persisted from baseline for uterine sparing procedures during 2nd (UFS-QOL: delta= (+)40.7, (+)37.4, (+)39.3 SS: delta= (-) 38.5, (-) 32.0, (-) 37.7 and 3rd year (UFS-QOL: delta= (+) 40.9, (+)39.9, (+)41.1and SS: delta= (-) 33.9 , (-)36.5, (-) 33.0, respectively), post-treatment intervals, however with a trend towards decline in degree of improvement from years 1 and 2. Differences from baseline were greatest for hysterectomy; however, this may reflect the relative importance of bleeding in the UFS-QoL, rather than clinically meaningful symptom recurrence among women undergoing uterus-sparing treatments. All treatment modalities were associated with significant improvement in health-related quality of life and symptom severity reduction 1-year post-treatment. However, abdominal myomectomy, laparoscopic myomectomy and uterine artery embolization indicated an a gradual decline in symptom improvement and health-related quality of life by 3rd year post-procedure.

Transvaginal Photobiomodulation Improves Pain in Women with Pelvic Muscle Tenderness and Interstitial Cystitis/Bladder Pain Syndrome: A Preliminary Observational Study

Interstitial Cystitis/ Bladder Pain Syndrome (IC/BPS) is characterized by pelvic/bladder pain, associated with pelvic muscle tenderness, urgency, frequency, and dysuria. Prior studies show that transvaginal photobiomodulation (TV-PBM) reduces pain in women with chronic pelvic pain (CPP). Our objective was to obtain preliminary data on treatment effect and adherence, in women with IC/BPS who selected TV-PBM therapy for management of pelvic pain. Before-and-after observational cohort study of women with IC/BPS who received TV-PBM in 17 US practices. Pain was measured using a 0-10 numeric rating scale (NRS). The primary outcome was a minimal clinical important difference (MCID); reduction of overall pelvic pain severity by ≥2 NRS points from baseline compared to after 8 treatments. Cohen d coefficient measured effect size (low effect size d<0.2, medium 0.2<d<0.8, and high d>0.8). Of 140 patients with IC/BPS who self-selected to start TV-PBM therapy, 89.3% (n=125) completed 4 treatments and 59.3% (n=83) completed 8. Improvement ≥1 NRS point was reported by 73.5% (n=61) and meaningful improvement (≥2 points) was reported by 63.9% (n=53) after 8 treatments. In this group, patients with severe / moderate pain decreased from 83.1% (n=44) to 38.5% (n=20); p<0.001. Pain levels decreased as follows: overall pelvic pain MCID=-2.7, d=1.07, pain with urination MCID=-2.6, d=1.0; pain with exercise MCID=-2.6, d=0.91, pain with intercourse MCID=-2.5, d=0.82. In real-world clinical settings, 2/3 women with IC/BPS who opted to undergo TV-PBM therapy reported significant decrease in pelvic pain and dysuria. These findings are promising; however, controlled studies are needed.

Body composition and chemotherapy toxicity in women with early breast cancer (CANDO-3): protocol for an observational cohort study

IntroductionSystemic anticancer therapy is given to selected patients with early breast cancer (EBC) before or after surgery with the aim of eradicating micrometastatic spread and reducing the risk of cancer...

Prospective cohort study of induction of labor: Indications, outcome and postpartum hemorrhage.

INTRODUCTIONThis study was undertaken because of the increasing rate of induction of labor (IOL) in our hospital and its associated higher caesarean section (CS) rates. The objective was to ascertain the incidence, indications, methods, outcome, and complications of IOL, in particular postpartum hemorrhage.METHODSThis was a prospective observational cohort study of women who underwent IOL in a medium-sized district general hospital. Blood loss was measured by the gravimetric method and correlated to postpartum hemoglobin level within 48 hours of birth.RESULTSA total of 445 women needed IOL (incidence 33%). Common indications were: small for gestational age (SGA) or fetal growth restriction (FGR) (18%), spontaneous rupture of membrane (17%), reduced fetal movement (16%), prolonged pregnancy (15%), and diabetes (13%). In all, 67% women achieved spontaneous vaginal delivery and 18% underwent caesarean section. With regard to blood loss, 62 women (14%) had postpartum hemorrhage (PPH) of >1000 mL and 22 women (4.9%) had a blood loss >1500 mL. The caesarean section rate was higher than the overall emergency caesarean section rate in that year. Incidence of PPH in this cohort was higher than the normal incidence.CONCLUSIONSIncreasing trend of induction of labor (IOL) is due to the changing clinical policy on management of small for gestational age babies, spontaneous rupture of membrane, reduced fetal movement and other complications of pregnancy. There is conflicting evidence on the effect of IOL on caesarean section rates. IOL is a risk factor for PPH. Accurate measurement of blood loss is essential in detecting a fall in hemoglobin which in turn helps in the appropriate management of PPH.

Impact of past obstetric history and cervical excision on preterm birth rate.

To determine the impact on preterm birth (PTB) of a history of large loop excision of the transformation zone (LLETZ)-alone compared with a history of previous preterm birth-alone (PPTB) or a history of both (LLETZ+PPTB). Secondary analyses were performed to evaluate the impact of antenatal interventions, depth of cervical excision, and patient risk factors on PTB rate in each cohort. A retrospective observational cohort study of women referred to a tertiary Antenatal Prematurity Prevention Clinic with a history of LLETZ, PPTB, or LLETZ+PPTB. Information was collated from routinely collected clinical data on patient demographics, previous obstetric history, LLETZ dimensions, antenatal investigations/interventions, and gestation at delivery. A total of 1231 women with singleton pregnancies were included, 543 with history of LLETZ-alone, 607 with a history of PPTB-alone and 81 with a history of LLETZ+PPTB. PTB rates were 8.8% in the LLETZ-alone group, which mirrored the PTB rate in the local background obstetric population (8.9%) compared with 28.7% in the PPTB-alone and 37.0% in the LLETZ+PPTB cohorts. PTB rates were higher in LLETZ cohorts treated with antenatal intervention (cervical cerclage or progesterone pessary) and there was no evidence of an effect of intervention on risk of PTB in post-excision patients with identified shortened mid-trimester cervical length. Logistic regression modeling identified PPTB as a strong predictor of recurrent PTB. Excision depth was correlated with gestation at delivery in the LLETZ-alone group (r=-0.183, p<0.01) although this only reached statistical significance at depths of 20mm or more (odds ratio [OR] 3.40, 95% CI 1.04-1.11, p=0.04). Depth of excision was not correlated with delivery gestation in the LLETZ+PPTB group (r=-0.031, p=0.82). PPTB has a greater impact on subsequent PTB risk compared with depth of cervical excisional treatment. The value and nature of antenatal interventions should be investigated in the post-excision population.

Endometriosis increases the rate of spontaneous early miscarriage in women who have adenomyosis lesions

Research questionIn women with radiologically diagnosed adenomyosis, is the presence of endometriosis associated with a higher rate of miscarriage? DesignAn observational cohort study of women who received medical care for benign gynaecological conditions between May 2005 and May 2018. Women who had adenomyosis lesions visualized by uterine magnetic resonance imaging (MRI) were included. Women who had never been pregnant were excluded. Women with adenomyosis identified by MRI but who did not have endometriosis lesions (control group) were compared with women with adenomyosis and endometriosis lesions (study group). Primary outcome was rate of a previous history of early miscarriage. ResultsA total of 214 pregnancies in the study group and 53 pregnancies in the control group were analysed. The rate of a previous miscarriage was significantly higher among women with adenomyosis and endometriosis lesions compared with women in the control group (61/214 [28.5%] versus 6/53 [11.3%], respectively, P = 0.009). A multivariable generalized estimating equation logistic regression model, adjusted for adenomyosis and endometriosis phenotypes, found that the association between endometriosis and adenomyosis significantly increased the risk of miscarriage (OR 3.2, 95% CI 1.1 to 9.65). The risk was significantly higher with deep infiltrating endometriosis (OR 4.37, 95% CI 1.32 to 14.53). ConclusionsWomen affected by endometriosis had a significantly higher rate of previous spontaneous miscarriage than women without endometriosis with adenomyosis lesions identified by MRI. Mechanistic studies are needed to establish the complex link between the presence of endometriosis and adenomyosis and the rate of spontaneous miscarriage.

Incidence and predictors of persistent pelvic pain following hysterectomy in women with chronic pelvic pain

Chronic pelvic pain is a debilitating problem that afflicts 15% to 20% of women in the United States. Although more than 200,000 hysterectomies are performed annually for the treatment of chronic pelvic pain, previous studies indicate that 1 in 4 women undergo the discomfort and morbidity of hysterectomy without the relief of pain. The factors that predict treatment failure remain poorly characterized. To describe the incidence of persistent pelvic pain 6 months following hysterectomy in women with chronic pelvic pain and determine whether a simple, self-reported measure of central sensitization is associated with a greater risk of persistent pelvic pain following hysterectomy. We conducted a prospective, observational cohort study of women undergoing hysterectomy at an academic tertiary care center for a benign indication. Patients with preoperative chronic pelvic pain, defined as average pelvic pain ≥3 on a 0 to 10 numeric rating scale for >3 months before hysterectomy, were included in this analysis. The patients completed validated assessments of pain, anxiety, depression, and centralized pain (using the 2011 Fibromyalgia Survey Criteria, 0-31 points) preoperatively and 6 months after hysterectomy. The demographic information, surgical history, intraoperative findings, and surgical pathology were abstracted from the electronic medical records. Multivariate logistic regression was used to identify the independent predictors of persistent pelvic pain 6 months following hysterectomy, defined as <50% improvement in pelvic pain severity. Among 176 participants with pelvic pain before hysterectomy, 126 (71.6%) were retained at 6 months, and 15 (11.9%) reported persistent pelvic pain. There was no difference in age (P=.46), race (P=.55), average pain severity during menses (P=.68), average overall pelvic pain (P=.10), or pain duration (P=.80) in those with and without persistent pelvic pain. Whereas intraoperative findings of endometriosis (P=.05) and uterine fibroids (P=.03) were associated with a higher incidence of persistent pain on univariate analysis, the surgical route (P=.46), pelvic adhesions (0.51), uterine weight (P=.66), and adenomyosis on histopathology (P=.27) were not related to the risk of persistent pain. Higher preoperative centralized pain scores (P=.01) but not depression (P=.64) or anxiety (P=.45) were more common in women with persistent pelvic pain. Multivariate logistic regression adjusting for age, preoperative pain severity, anxiety, depression, and operative findings of endometriosis and fibroids indicated that every 1-point increase in centralized pain before hysterectomy was associated with a 27% increase in the odds of persistent pelvic pain (odds ratio, 1.27; 95% confidence interval, 1.03-1.57) 6 months after surgery. Although the majority of women with chronic pelvic pain report considerable improvement in pain following hysterectomy, higher degrees of centralized pain before hysterectomy is a robust predictor of persistent pelvic pain.

P–600 Ovarian function following intraovarian injection of autologous platelet rich plasma (APRP) in women with low functional ovarian reserve

Abstract Study question Does exposure of ovaries to autologous growth factors in platelet rich plasma (APRP) affect the pituitary ovarian axis? Summary answer Within 60 days after injection, growing follicle numbers and estrogen levels increased, though FSH did not change, with effects most pronounced in still menstruating women. What is known already APRP is extracted from a patient’s autologous blood and delivers growth factors. It is widely used in several medical specialties and has in infertility practice been reported to increase folicle/egg numbers if injected into ovaries and improve endometrial thickness/implantation if used for perfusion of the endometrium. Study design, size, duration Prospective observational cohort study of women with low functional ovarian reserve, followed for 60 days after subcortical injection of ovaries. Participants/materials, setting, methods 44 women with prior poor response to ovulation induction, FSH &amp;gt; 12 mIU/mL and AMH &amp;lt; 1.0 ng/mL. APRP was prepared using Regen Lab PRP Kit which is approved by the US-FDA. 1.0–1.5 ml of PRP was injected into the cortex of each ovary divided among 7 to 10 injection sites. Participants were followed every three days with monitoring for estradiol, FSH and follicle growth for the first two weeks after PRP and then weekly. Main results and the role of chance 21/43 patients still regularly menstruated (subgroup A, age 43.9 ± 5.1 years); 23/43 (subgroup B, age 42.6 ± 6.2 years) were amenorrheic for a median of 6 months. In A, AMH, FSH and estradiol were 0.18 ± 0.20 ng/mL, 37.5 ± 47.6 mIU/mL, and 100.2 ± 73.4 pg/mL, while in B they were 0.06 ± 0.11 ng/mL, 73.0 ± 44.8 mIU/mL and 66.7 ± 57.6 pg/mL. Following APRP, A-patients demonstrated increased estradiol to 211 ± 193.7 pg/mL (P = 0.029) while B-patients only demonstrated a trend to 98.1 ± 86.5 (P = 0.09). Among A patients, 14/21 (66.7%) entered IVF cycles and 5/21 (23.8%) reached retrieval. So-far 1 patients established an ongoing clinical pregnancy. Among B patients 8/23 (34.8%) entered IVF cycles and only 2/23 (8.7%) reached retrieval and none achieved pregnancy. Limitations, reasons for caution This observational study was only carried out to estimate possible effects of APRP treatments. Based on these observations, we are now conducting a randomized controlled trial, limited to cycling women under age 45 years [registration # NCT04278313]. Wider implications of the findings: PRP appears to have limited ability to affect ovarian reserve of older, and especially amenorrheic women. It may, however, exert more favorable effects on still menstruating women. Promotion of APRP treatment as “ovarian rejuvenation,” however, appears to be an inappropriate choice of words. Trial registration number N/A

P–266 Morphometric assessment of Ratio of inner-cell-mass diameter to blastocyst diameter is an effective criterion to select best embryo for successful outcomes in single blastocyst transfer-cycles

Abstract Study question Can semi-quantitative measurement of ICM diameter vis-à-vis blastocyst diameter, calculated from photographic images, be a significant predictor of implantation potential in single blastocyst transfer cycles? Summary answer A simple, non-invasive measurement of ICM:Blastocyst diameter ratio is a potentially effective predictor of high developmental potential, implantation, live-birth rates in single blastocyst transfer cycles. What is known already: Correlationship between quantitative measurements of blastocyst morphology such as size and shape of ICM and its implantation potential were first reported by Richter et al. Widely used Gardner and Schoolcraft’s qualitative scoring assessment is based on three major variables: expansion stage of blastocyst, cohesiveness of the inner cell mass (ICM), and consistency of trophectodermal (TE) cells. A top quality single blastocyst transfer yields implantation rate nearing 70% and live-birth rate about 50%. If an additional morphological but vital parameter evaluating ICM:Blastocyst diameter ratio is introduced to the Gardner’s blastocyst gradation system, it may help enhance IVF success rates still further. Study design, size, duration A prospective observational cohort study of women (n = 244) undergoing IVF treatment at our private fertility clinic from April 2018 until March 2020. Women with their autologous fertilized oocytes undergoing extended culture and transfer of a single fresh, at least fully expanded (Grade 3) blastocyst with a measurable ICM diameter and blastocyst inner diameter on day 5/6, irrespective of age, cycle number and indication for treatment, were included. Cryopreservation cycles were excluded. Participants/materials, setting, methods Each blastocyst was evaluated for expansion grade, ICM and TE according to Gardner et al. conventional method. Additionally, ratio of ICM diameter w.r.t. blastocyst inner diameter was also calculated from the photographic images on screen using the Hamilton-Thorne software package embedded with their laser system. Measurements were done on blastocysts where expansion had occurred between 114 and 120 hours after insemination. Implantation rates and live-birth rates were the major end-points. Main results and the role of chance A total of 244 blastocyst transfers were performed in same number of women, and 130 clinical pregnancies were achieved (53.3%). The average age of the women was 32.5 ± 4.2 years. The blastocysts that implanted successfully had an average ICM:blastocyst diameter ratio of 0. 469±0.082), whereas blastocysts that did not implant had a significantly lower ratio of 0.325±0.09 (P &amp;lt;.0001). No statistical significant difference was found in the TE grade between the blastocysts that implanted successfully and those that did not. Out of the 130 pregnancies achieved, 89 (68%) resulted in the delivery of a healthy baby. After ROC analysis, a cutoff value for the ICM/blastocyst ratio showed equal rank for sensitivity (0.81) and specificity (0.72). The resultant positive predictive value was 78%, and the negative predictive value was 74%. In our study, the conditional probability of achieving pregnancy upon transfer of a single blastocyst with an ICM:blastocyst ratio higher than the cutoff value of 0.4255 was 76%. This was significantly higher than the probability of pregnancy from blastocysts graded by conventional morphometry. Limitations, reasons for caution Our study is limited by the small sample size. Hence more multicentric studies are warranted to observe similar conclusion. Wider implications of the findings: The strengths of the study are the performance of single blastocyst transfers and using live births as the measurement endpoint. It is important to mention that embryo grading is inevitably subject to intra- and interobserver variations. However, with simple measurements of image data recording eliminates a degree of these variations. Trial registration number Not applicable

Human Papillomavirus Infection and Cervical Dysplasia in a Subset of Arab American Women.

Background: With limited health data on Arab Americans (AAs), we sought to describe the health-seeking behaviors, prevalence of abnormal cervical cytology and high-risk human papillomavirus (HPV) serotypes, and the relationship with socioeconomic factors among a subset of AA women.Methods: Retrospective observational cohort study of women undergoing routine cancer screening at the Arab-American Center for Economic and Social Services clinic. Data collected included demographics, tobacco use, gross monthly income, prior Papanicolaou (Pap) smear history, and results of cervical cytology and high-risk HPV testing.Results: Of 430 women, 74 (17%) reported that they had never had a Pap smear. Three hundred eighty-eight (90%) women had cervical cytology interpreted as “negative for intraepithelial lesion,” the remaining 42 (10%) women had abnormal results. Thirteen (3%) women reported prior abnormal Pap smear, which was significantly associated with additional abnormal Pap smear on multivariable analyses (odds ratio 65.46; 95% confidence interval [CI] 17.01–338.62; p < 0.001). One hundred twenty-five (29%) women were tested for high-risk HPV serotypes; 106 (91%) had negative results, 4 (3%) were positive for HPV-16, 7 (6%) were positive for other high-risk serotypes, and 8 results were not recorded. A negative HPV screen was significantly associated with a negative Pap smear (Fisher's exact test p = 0.006). There was no significant association between abnormal cervical cytology and evaluated socioeconomic factors.Conclusions: Additional population based-studies to determine cervical dysplasia/cancer and HPV prevalence in women of Middle Eastern descent are needed.

137 Low risk of postpartum diabetes in women with gestational diabetes and normal early pregnancy HgbA1c

We sought to determine the association between early pregnancy glycosylated hemoglobin A1c (eHbA1c) and postpartum diabetes mellitus (DM). This is an observational cohort study of women delivering May 2016-July 2017 at a county hospital. Women presenting to prenatal care before 24 weeks had an eHbA1c drawn. Those with eHbA1c <6.5% were screened for gestational diabetes (GDM). Those with eHbA1c >6.5% received a new DM diagnoses (newDM). GDM patients tested for DM within one year postpartum were identified, and postpartum results for newDM patients were also abstracted. Proportions of patients with postpartum DM or prediabetes were compared according to eHbA1c. Amongst 2919 singleton deliveries remaining after exclusions, 221 women received a diagnosis of GDM or newDM: 196 GDM (97 normal eHbA1c <5.7%, 61 prediabetic eHbA1c 5.7-6.4%, 38 no eHbA1c) and 25 newDM (eHbA1c >6.5%, range 6.5-9.5%); median gestational age at eHbA1c was 9.4 weeks. 122 (62.2%) women with GDM and 18 (72.0%) women with newDM had postpartum results available; in total 25 (17.9%) had DM and 45 (32.1%) had prediabetes postpartum. When stratified by eHbA1c, the percent of patients with DM was statistically different overall between groups: normal eHbA1c <5.7%, 1.5%; eHbA1c 5.7-6.4%, 13.2%; no eHbA1c, 15.8%; eHbA1c >6.5%, 88.9%, p<0.001. Of 25 women with DM postpartum, 16 had DM at first visit; only 1 had a normal eHbA1c. Postpartum prediabetes was common in all GDM eHbA1c groups, 32.3-42.1%. The eHbA1c may provide a clinically useful risk assessment for postpartum DM. DM was rare among GDM patients with normal eHbA1c, although postpartum prediabetes was common. Universal postpartum testing of women with normal eHbA1c, which comprises the majority of women with GDM, may be less critical, although long term follow-up remains important. Nearly 90% of women with an eHbA1c of ≥6.5% were found to have postpartum DM and accounted for the majority of patients with postpartum DM.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

499 Midtrimester cervical length for the prediction of preterm birth: a new definition of short cervix?

To estimate the optimal midtrimester cervical for the prediction of spontaneous preterm birth in asymptomatic pregnant women with singleton pregnancy. Design: A prospective observational cohort study of women undergoing midtrimester ultrasound between April 2018 and December 2019. Setting: Open, population-based study. Participants: Asymptomatic pregnant women with singleton pregnancy between 19 0/7 and 21 6/7 weeks of gestation. Exposures: All participants underwent cervical length measurement by transabdominal and/or transvaginal ultrasound. All cervical length ≤30mm were confirmed by transvaginal ultrasound. Main outcomes and measures: Spontaneous preterm birth before 35 and before 37 weeks. Receiver operating characteristics curve analyses were performed to assess the predictive ability and to determine the optimal cervical length cut-offs. Our secondary outcome was preterm birth. Of 3449 participants, 28 (0.8%) and 99 (2.9%) had spontaneous preterm birth before 35 and 37 weeks, respectively, and 245 (7.1%) had preterm birth. Our ROC curve analyses suggest that a cut-off of 30mm was the optimal cervical to predict spontaneous preterm birth before 35 weeks (sensitivity: 43%; specificity: 97%) and 37 weeks (sensitivity: 21%; specificity: 97%). While a cervical length less than 25 mm was an important risk factor for spontaneous preterm birth (relative risk of 31.1; 95% confidence interval of 13.4 to 73.4), women with a cervical length between 25 and 29 mm remains also at very high risk for spontaneous preterm birth (relative risk of 11.5 with 95% confidence interval of 3.8 to 34.7). A midtrimester cervical length below 30mm (instead of 25 mm) should be used to identify women at high-risk of spontaneous preterm birth.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Food and Drug Administration Safety Communication on the Use of Transvaginal Mesh in Pelvic Organ Prolapse Repair Surgery: The Impact of Social Determinants of Health.

This study was to examine the impact of the July 2011 Food and Drug Administration (FDA) safety communication on the use of transvaginal mesh in pelvic organ prolapse (POP) repair by patients' race and ethnicity. We conducted an observational cohort study of women undergoing POP repairs in 2008 to 2015 in New York State. We examined the changes in transvaginal mesh use in POP repairs before and after the FDA communication by patients' race and ethnicity. Piecewise logistic regression models were used to assess the trends of mesh use, adjusting for patient characteristics. We performed a subgroup analysis of the trends of transvaginal mesh use by racial groups, stratifying by patients' neighborhood socioeconomic status. We included 49,848 women (78% white, 7% black, and 15% Hispanic) with an average ± SD age of 60.2 ± 13.0 years. After the safety communication, the use of transvaginal mesh in POP repairs decreased among white women (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.41-0.50) and African Americans (OR, 0.48; 95% CI, 0.35-0.67) but remained stable among Hispanic women (OR, 0.88; 95% CI, 0.70-1.11). Only in the subgroup of patients from high-income areas, there was a trend toward decreasing mesh use among Hispanic patients after 2011 (OR, 0.71; 95% CI, 0.49-1.04). The communications related to the safety of transvaginal mesh did not have an equal impact across racial groups. Mesh use decreased among white and African American women but not among Hispanic women after the 2011 FDA safety communication. Particular attention is warranted for patients from disadvantaged groups, especially low-income minorities, when disseminating medical device safety messages.

Racial/ethnic differences in supplemental imaging for breast cancer screening in women with dense breasts.

Mammography is limited when analyzing dense breasts for 2 reasons: (1) breast density masks underlying cancers and (2) breast density is an independent risk factor for cancer. We undertook this study to assess whether there is a racial/ethnic difference in supplemental image ordering for women with dense breasts. We conducted a retrospective, observational cohort study of women aged 50-75 from an academic medical center who had completed a screening mammogram between 2014 and 2016 that was read as BI-RADS 1 with heterogeneously or extremely dense breasts or BI-RADS 2 with extremely dense breasts. Data were abstracted on type, timing and frequency of supplemental imaging tests ordered within two years of an initial screening mammogram. Patient characteristics (age, race/ethnicity, insurance, and comorbidities) were also abstracted. We used bivariate and multivariate logistic regression to assess for differences in supplemental imaging ordered by race/ethnicity. Three hundred twenty-six women met inclusion criteria. Mean age was 58years: 25% were non-Hispanic white, 30% were non-Hispanic black, 27% were Hispanic, 6% were Asian and 14% unknown. Seventy-nine (24%) women were ordered a supplemental breast ultrasound after the initial screening mammogram. Non-Hispanic black and Hispanic women were less likely to have supplemental imaging ordered compared to non-Hispanic white women (15% and 10%, respectively, vs. 45%, p < 0.0001). After controlling for patient age, ordering physician specialty, insurance, BI-RADS score, breast density, and family history of breast cancer, non-Hispanic black and Hispanic women remained less likely to be ordered supplemental imaging (OR 0.38 [95% CI 0.17-0.85] and OR 0.24 [95% CI 0.10-0.61], respectively, p < 0.0001). Minority women with dense breasts are less likely to be ordered supplemental breast imaging. Further research should investigate physician and patient behaviors to determine barriers in supplemental imaging. Understanding these differences may help reduce disparities in breast cancer care and mortality.

First-trimester intrauterine hematoma and pregnancy complications.

To assess whether sonographic diagnosis of intrauterine hematoma (IUH) in the first trimester of pregnancy is associated with first-trimester miscarriage and antenatal, delivery and neonatal complications. This was a prospective observational cohort study of women with an intrauterine singleton pregnancy between 5 and 14 weeks' gestation recruited at Queen Charlotte's and Chelsea Hospital, London, UK, between March 2014 and March 2016. Participants underwent serial ultrasound examinations in the first trimester, and the presence, location, size and persistence of any IUH was evaluated. First-trimester miscarriage was defined as pregnancy loss before 14 weeks' gestation. Clinical symptoms, including pelvic pain and vaginal bleeding, were recorded at each visit using validated symptom scores. Antenatal, delivery and neonatal outcomes were obtained from hospital records. Logistic regression analysis and the chi-square test were used to assess the association between the presence and features of IUH and the incidence of adverse pregnancy outcome. Odds ratios (OR) were first adjusted for maternal age (aOR) and then further adjusted for the presence of vaginal bleeding or pelvic pain in the first trimester. Of 1003 women recruited to the study, 946 were included in the final analysis and of these, 268 (28.3%) were diagnosed with an IUH in the first trimester. The presence of IUH was associated with the incidence of preterm birth (aOR, 1.94 (95% CI, 1.07-3.52)), but no other individual or overall antenatal, delivery or neonatal complications. No association was found between the presence of IUH in the first trimester and first-trimester miscarriage (aOR, 0.81 (95% CI, 0.44-1.50)). These findings were independent of the absolute size of the hematoma and the presence of vaginal bleeding or pelvic pain in the first trimester. When IUH was present in the first trimester, there was no association between its size, content or position in relation to the gestational sac and overall antenatal, delivery and neonatal complications. Diagnosis of a retroplacental IUH was associated with an increased risk of overall antenatal complications (P = 0.04). Our findings demonstrate that there is no association between the presence of IUH in the first trimester and first-trimester miscarriage. However, an association with preterm birth, independently of the presence of symptoms of pelvic pain and/or vaginal bleeding, is evident. Women diagnosed with IUH in the first trimester should be counseled about their increased risk of preterm birth and possibly be offered increased surveillance during the course of their pregnancy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Preterm birth prediction in asymptomatic women at mid-gestation using a panel of novel protein biomarkers: the Prediction of PreTerm Labor (PPeTaL) study

Accurate prediction of spontaneous preterm labor/preterm birth in asymptomatic women remains an elusive clinicalchallenge because of the multi-etiological nature of preterm birth. The aim of this study was to develop and validate an immunoassay-based, multi-biomarker test to predict spontaneous preterm birth. This was an observational cohort study of women delivering from December 2017 to February 2019 at 2 maternity hospitals in Melbourne, Australia. Cervicovaginal fluid samples were collected from asymptomatic women at gestational week 16+0-24+0, and biomarker concentrations were quantified by enzyme-linked immunosorbent assay. Women were assigned to a training cohort (n= 136) and a validation cohort (n= 150) based on chronological delivery dates. Seven candidate biomarkers representing key pathways in utero-cervical remodeling were discovered by high-throughput bioinformatic search, and their significance in both invivo and invitro studies was assessed. Using a combination of the biomarkers for the first 136 women allocated to the training cohort, we developed an algorithm to stratify term birth (n= 124) and spontaneous preterm birth (n= 12) samples with a sensitivity of 100% (95% confidence interval, 76-100%) and a specificity of 74% (95% confidence interval, 66-81%). The algorithm was further validated in a subsequent cohort of 150 women (n= 139 term birth and n= 11 preterm birth), achieving a sensitivity of 91% (95% confidence interval, 62-100%) and a specificity of 78% (95% confidence interval, 70-84%). We have identified a panel of biomarkers that yield clinically useful diagnostic values when combined in a multiplex algorithm. The early identification of asymptomatic women at risk for preterm birth would allow women to be triaged to specialist clinics for further assessment and appropriate preventive treatment.

Neonatal Outcome After Hexoprenaline Compared with Atosiban After Preterm Premature Rupture of Membranes

Preterm premature rupture of membranes (PPROM) occurs in up to 3% of all pregnancies. Only few comparative studies have investigated potential risks and benefits between different tocolytic substances in women with PPROM. The aim of this study was to compare the neonatal short term outcome after tocolysis with Atosiban or Hexoprenaline in women with PPROM. This is a retrospective observational cohort study of women with PPROM between 24 and 32 weeks of gestation comparing neonatal and maternal outcome after tocolysis with atosiban or hexoprenaline. Outcome parameters were short term neonatal outcome, maternal tocolytic efficacy, effectiveness and tolerability and neonatal neurodevelopmental long-term outcome. Continuous variables were compared using t-Test or Mann–Whitney U test, as appropriate. For categorical variables Chi-square after Pearson and Fisher exact-test were used to compare the two groups. 93 women were included into this study with 42 women receiving hexoprenaline and 51 women receiving atosiban as primary tocolytic treatment. Mean gestational age was 29 weeks in both groups at the time PPROM. No differences were found for any short term neonatal outcome parameters, tocolytic efficacy, effectiveness and tolerability and neonatal neurodevelopmental long-term outcome. Both hexoprenaline and atosiban do not affect the short and long term neonatal outcome in women with PPROM for the time of lung maturation.