Evaluating cut-off levels for progesterone, ß human chorionic gonadotropin and ß human chorionic gonadotropin ratio to exclude pregnancy viability in women with a pregnancy of unknown location: A prospective multicenter cohort study.

INTRODUCTION: There is no global agreement on how to best determine pregnancy of unknown location viability and location using biomarkers. Measurements of progesterone and ß human chorionic gonadotropin (ßhCG) are still used in clinical practice to exclude the possibility of a viable intrauterine pregnancy (VIUP). We evaluate the predictive value of progesterone, ßhCG, and ßhCG ratio cut-off levels to exclude a VIUP in women with a pregnancy of unknown location. MATERIAL AND METHODS: This was a secondary analysis of prospective multicenter study data of consecutive women with a pregnancy of unknown location between January 2015 and 2017 collected from dedicated early pregnancy assessment units of eight hospitals. Single progesterone and serial ßhCG measurements were taken. Women were followed up until final pregnancy outcome between 11 and 14 weeks of gestation was confirmed using transvaginal ultrasonography: (1) VIUP, (2) non-viable intrauterine pregnancy or failed pregnancy of unknown location, and (3) ectopic pregnancy or persisting pregnancy of unknown location. The predictive value of cut-off levels for ruling out VIUP were evaluated across a range of values likely to be encountered clinically for progesterone, ßhCG, and ßhCG ratio. RESULTS: Data from 2507 of 3272 (76.6%) women were suitable for analysis. All had data for ßhCG levels, 2248 (89.7%) had progesterone levels, and 1809 (72.2%) had ßhCG ratio. The likelihood of viability falls with the progesterone level. Although the median progesterone level associated with viability was 59 nmol/L, VIUP were identified with levels as low as 5 nmol/L. No single ßhCG cut-off reliably ruled out the presence of viability with certainty, even when the level was more than 3000 IU/L, there were 39/358 (11%) women who had a VIUP. The probability of viability decreases with the ßhCG ratio. Although the median ßhCG ratio associated with viability was 2.26, VIUP were identified with ratios as low as 1.02. A progesterone level below 2 nmol/L and ßhCG ratio below 0.87 were unlikely to be associated with viability but were not definitive when considering multiple imputation. CONCLUSIONS: Cut-off levels for ßhCG, ßhCG ratio, and progesterone are not safe to be used clinically to exclude viability in early pregnancy. Although ßhCG ratio and progesterone have slightly better performance in comparison, single ßhCG used in this manner is highly unreliable.

A Comparative Observational Study of the Use of Saline Uterine Hydrosonography for the Diagnosis and Assessment of Uterine Cavity Lesions in Women.

Aim of this study was to evaluate the performance of saline hydrosonography (HSGM) (also known as saline infusion sonography (SIS)) against transvaginal ultrasound scan (TVS) and hysteroscopy in the diagnosis of uterine cavity lesions. Diagnostic hysteroscopy with biopsy is considered as the "gold standard" to diagnose intrauterine abnormalities. The introduction of HSGM has improved the diagnostic capability of ultrasound. It is important to establish the efficacy and safety of HSGM before it is widely recommended for use. This retrospective observational data was collected from all 223 patients who underwent TVS, HSGM, and hysteroscopy as part of their gynaecological investigations from 1 January 2008 to 31 December 2010 at Central Middlesex Hospital, London. Endometrial Polyps. TVS: sensitivity 60.53%, specificity 97.06%, positive predictive value (PPV) 95.83%, and negative predictive value (NPV) 68.75% and HSGM: sensitivity 95%, specificity 97.14%, PPV 97.44%, and NPV 94.44%. Submucous Leiomyoma. TVS: sensitivity 57.14%, specificity 93.48%, PPV 84.21%, and NPV 78.18% and HSGM: sensitivity 96.55%, specificity 100.00%, PPV 100.00%, and NPV 97.92%. Diagnostic efficacy of HSGM is superior to TVS for the diagnosis of endometrial polyps and submucous fibroids. HSGM should be considered as an intermediate investigation after TVS to assess intracavity pathology and to confirm the diagnosis; hysteroscopy should become a therapeutic intervention.

Defining safe criteria to diagnose miscarriage: prospective observational multicentre study.

OBJECTIVES: To validate recent guidance changes by establishing the performance of cut-off values for embryo crown-rump length and mean gestational sac diameter to diagnose miscarriage with high levels of certainty. Secondary aims were to examine the influence of gestational age on interpretation of mean gestational sac diameter and crown-rump length values, determine the optimal intervals between scans and findings on repeat scans that definitively diagnose pregnancy failure.) DESIGN: Prospective multicentre observational trial. SETTING: Seven hospital based early pregnancy assessment units in the United Kingdom. PARTICIPANTS: 2845 women with intrauterine pregnancies of unknown viability included if transvaginal ultrasonography showed an intrauterine pregnancy of uncertain viability. In three hospitals this was initially defined as an empty gestational sac <20 mm mean diameter with or without a visible yolk sac but no embryo, or an embryo with crown-rump length <6 mm with no heartbeat. Following amended guidance in December 2011 this definition changed to a gestational sac size <25 mm or embryo crown-rump length <7 mm. At one unit the definition was extended throughout to include a mean gestational sac diameter <30 mm or embryo crown-rump length <8 mm. MAIN OUTCOME MEASURES: Mean gestational sac diameter, crown-rump length, and presence or absence of embryo heart activity at initial and repeat transvaginal ultrasonography around 7-14 days later. The final outcome was pregnancy viability at 11-14 weeks' gestation. RESULTS: The following indicated a miscarriage at initial scan: mean gestational sac diameter ≥ 25 mm with an empty sac (364/364 specificity: 100%, 95% confidence interval 99.0% to 100%), embryo with crown-rump length ≥ 7 mm without visible embryo heart activity (110/110 specificity: 100%, 96.7% to 100%), mean gestational sac diameter ≥ 18 mm for gestational sacs without an embryo presenting after 70 days' gestation (907/907 specificity: 100%, 99.6% to 100%), embryo with crown-rump length ≥ 3 mm without visible heart activity presenting after 70 days' gestation (87/87 specificity: 100%, 95.8% to 100%). The following were indicative of miscarriage at a repeat scan: initial scan and repeat scan after seven days or more showing an embryo without visible heart activity (103/103 specificity: 100%, 96.5% to 100%), pregnancies without an embryo and mean gestational sac diameter <12 mm where the mean diameter has not doubled after 14 days or more (478/478 specificity: 100%, 99.2% to 100%), pregnancies without an embryo and mean gestational sac diameter ≥ 12 mm showing no embryo heartbeat after seven days or more (150/150 specificity: 100%, 97.6% to 100%). CONCLUSIONS: Recently changed cut-off values of gestational sac and embryo size defining miscarriage are appropriate and not too conservative but do not take into account gestational age. Guidance on timing between scans and expected findings on repeat scans are still too liberal. Protocols for miscarriage diagnosis should be reviewed to account for this evidence to avoid misdiagnosis and the risk of terminating viable pregnancies.

Obstetric anal sphincter injury risk reduction: a retrospective observational analysis.

OBJECTIVE: To identify the risks of sustaining obstetric anal sphincter injury (OASI) during childbirth. METHODS: Data were analysed from 12,612 vaginal deliveries recorded at Northwick Park District General Hospital, London, from 1 January 2006 to 30 November 2009. RESULTS: A total of 85.6% were spontaneous deliveries and 14.2% were instrument deliveries. The majority (64.5%) sustained some form of perineal damage, 3.7% being OASI. Logistic regression analyses revealed the risk factors for OASI to be Asian ethnicity [odds ratio (OR) 4.798, 95% confidence interval (CI) 2.998-7.679], a maternal age of >40 years (OR 2.722, 95% CI 1.315-5.636), higher foetal birth weight (>4500 g; OR 6.228, 95% CI 2.695-14.392), lower parity (para 0; OR 16.803, 95% CI 7.697-36.685), and instrumental delivery. Forceps delivery posed the greatest risk (OR 8.4, 95% CI 5.822-12.151). Not having an episiotomy increased the risk of OASI by five times compared with having one. CONCLUSIONS: Risk factors for OASI include maternal age >40 years, higher foetal birth weight, lower parity, instrumental delivery, and Asian ethnicity. Mediolateral episiotomy appears to reduce the risk of OASI. Specific variables have been identified for incorporation into a risk-reduction strategy that could be introduced antenatally to evaluate and assess OASI risk.

The urine protein heat coagulation test--a useful screening test for proteinuria in pregnancy in developing countries: a method validation study.

In many parts of the developing world, the urine protein heat coagulation test is routinely used to screen for proteinuria in pregnancy. The aim of this study was to determine whether > or =1+ on a standardised heat coagulation test reliably detects significant proteinuria and to compare it with the dipstick test for urinary protein. Heat coagulation test, dipstick test and 24-hour urine protein excretion results of 102 women were compared. > or =1+ on heat coagulation test is as sensitive and specific as > or =2+ on the dipstick test in detecting proteinuria of > or =500 mg/day. The heat coagulation test, however, is less sensitive than > or =1+ on dipstick in detecting lesser degrees of proteinuria.