Michael Zinaman

Home pregnancy test compared to standard-of-care ultrasound dating in the assessment of pregnancy duration

Abstract Objective: To determine the level of agreement between the Clearblue Digital Pregnancy Test with Conception Indicator home pregnancy test and standard-of-care ultrasound in assessing pregnancy duration in a real-life, observational setting encompassing routine, clinical care. Research design and methods: This was a prospective observational study of non-pregnant women seeking conception. Women collected daily urine samples from day 1 of their next menstrual cycle. If any volunteer became pregnant, daily urine samples continued to be collected for 43 days after the LH surge. Samples from day −7 to day +28 relative to the expected period (LH surge + 15 days) were tested using the home pregnancy test. This categorised any resulting pregnancies into one of three groups: 1–2 weeks, 2–3 weeks, and 3+ weeks since conception. Information from the standard UK ultrasound dating scan was also recorded by the midwife, including the expected delivery date according to ultrasound and the expected delivery date according to LMP. Main outcome measures: Full data were available from 52 pregnant women who had conceived naturally. During the study analysis, 4786 urine samples were cross-compared with 52 routine 12-week NHS ultrasound assessments and the level of agreement between home pregnancy testing and standard-of-care ultrasound in determining pregnancy duration was calculated. Results: The agreement between the gestational age as calculated by the home pregnancy test result and the exact midwife-recorded gestational age using ultrasound was 82.3%. However, when a ±5-day range was applied to the ultrasound reading (as per routine UK clinical practice), the level of agreement was 98%. Conclusions: The home pregnancy test provides a significantly high (98%) level of agreement with standard-of-care ultrasound when assessing pregnancy duration in a real-life, observational setting which closely mirrors daily clinical practice.

Accuracy of perception of ovulation day in women trying to conceive

Abstract Background: The likelihood of conception is increased if intercourse is timed to coincide with the fertile period (5 days up to ovulation). However, to be effective, this requires good awareness of the day of ovulation. The aim of this study was to examine the accuracy of women’s perceived ovulation day, compared with actual fertile days, in a cohort of women trying to conceive. Main outcome measures: Comparison of women’s estimated day of ovulation with their actual ovulation day (determined by detecting luteinising hormone). Methods: This was a sample collection study and volunteer women were recruited via online advertising. At recruitment volunteers reported the cycle day they believed they ovulated. They then used a home urine fertility monitor to test their daily fertility status to time intercourse to try and achieve conception, in addition to collecting early morning urine samples for laboratory analysis. The main outcome measure was a comparison of women’s estimated day of ovulation with their actual ovulation day, as determined by urine detection of luteinising hormone. Results: Three hundred and thirty women were recruited onto the study and data was available for 102 volunteers who became pregnant. Thirteen women (12.7%) correctly estimated their ovulation day; median difference +2 days, range −10 to +27 days. The most common days for estimation of ovulation were day 14 (35.5%) and day 15 (15.7%). Only 55% of estimated ovulation days fell within the volunteers’ fertile window; only 27% on days of peak fertility. Conclusions: Women trying to conceive may benefit from using a prospective method to identify their fertile phase, as a significant proportion could be incorrectly estimating their fertile days. These observations were made on women who were actively looking for knowledge on fertility and considered only cycles where conception occurred, inaccuracy could be greater if a broader population is considered.

Human chorionic gonadotropin as a measure of pregnancy duration

To compare gestational age (GA) estimates in early pregnancy, determined by last menstrual period (LMP), human chorionic gonadotropin (hCG) concentration, ultrasound crown–rump length (Hadlock formula), and ovulation day (luteinizing hormone surge plus 1 day).

Comparison of a digital ovulation test with three popular line ovulation tests to investigate user accuracy and certainty

OBJECTIVES To determine the accuracy and certainty with which volunteers interpreted results of a digital ovulation test, Clearblue digital ovulation test (CB-DOT), compared with three home use non-digital visual ovulation tests: Clearblue ovulation test (CB-OT), First Response (FR) and Answer (AN). METHODS A total of 72 female volunteers aged 18 - 45 years interpreted test results from each of the four ovulation tests to determine the day of the luteinising hormone surge in 40 individual menstrual cycles. We used urine previously collected from 25 volunteers. The accuracy with which volunteers interpreted the test results was calculated by comparing their results with results obtained by trained technicians using a blinded test regime. For each of the four tests, volunteers were also asked to rate seven attributes of certainty and eight attributes of preference. The primary objective was to compare the accuracy with which volunteers read results from CB-DOT when compared to three visual-based line ovulation tests. RESULTS A significantly higher percentage of volunteers/technicians agreed on the interpretation of the results from CB-DOT (97.3%) than for CB-OT (83.5%; p = 0.0153), AN (73%; p = 0.0011) or FR (64.3%; p = 0.0001). CB-DOT was also found to have significantly better Likert scores than CB-OT, FR and AN for all seven attributes of certainty and was the test that 97.2% of volunteers preferred. CONCLUSIONS Women can misread the results of line ovulation tests. Over 97% of volunteers correctly read the result of CB-DOT. CB-DOT was also the test that women read with most certainty and the test that most users preferred.

Accuracy of a home-based device for giving an early estimate of pregnancy duration compared with reference methods

OBJECTIVE To assess a home pregnancy tests accuracy to concurrently detect pregnancy and determine pregnancy duration. DESIGN Multicenter, prospective study. SETTING Study sites in the United States. PATIENT(S) Women actively attempting to conceive who have menstrual bleeds (18-45 years). INTERVENTION(S) Volunteers collected early morning urine samples (three or fewer menstrual cycles). Pregnant volunteers underwent ultrasound dating scans. Ovulation day (LH surge +1 day) during pregnancy-resulting cycles was determined by quantitative measurement of LH. Random urine samples were tested with the hCG-measuring pregnancy test from 4 days before the expected period until 4 weeks later. MAIN OUTCOME MEASURE(S) A home pregnancy tests accuracy in determining pregnancy duration compared with ultrasound and ovulation day. RESULT(S) Agreement between pregnancy test results and time since ovulation was 93% (confidence interval [CI], 91.5-94.4). Agreement with ultrasound was dependent on the formula: there was 99% agreement when calculated with adjustment for Hadlock formula bias (Pexsters; CI, 98.2-99.4) or using a nonbias formula (Wu; CI, 98.6-99.6), when ultrasound error was accommodated. Agreement was lower when bias/measurement errors were not accounted for (Wu, 86%, CI, 83.9-88; Hadlock, 80.8, CI, 78.2-83.3). CONCLUSION(S) This home pregnancy test provides an accurate estimation of pregnancy duration in weeks categories, 1-2, 2-3, 3+ weeks since ovulation, thereby showing utility in dating pregnancy.

Analysis of Human Chorionic Gonadotropin Levels in Normal and Failing Pregnancies [40].

INTRODUCTION: Serum human chorionic gonadotropin (hCG) measurement often is used for assessment of pregnancy viability. Urine hCG levels closely mirror those in serum, providing a noninvasive monitoring method. This study examined daily urinary hCG to assess pregnancy viability. METHODS: Daily urine samples from 129 women who became pregnant were collected from last menstrual period. Levels of hCG and luteinizing hormone were measured by AutoDELFIA. Miscarriages (n=44) were classified into early losses (less than 6 weeks) and clinical losses (after 6 weeks). Day of ovulation assigned gestational age. Longitudinal models were created to profile hCG levels. Cox proportional hazards model was used to identify miscarriage risk factors (demographic and hCG level). RESULTS: Models showed a significant difference between the early loss group and the other two groups. Early loss profiles rose rapidly (10–14 days from ovulation) before dropping. Clinical losses and healthy pregnancies had a steady increase in hCG level before plateau 30 days postovulation. Factors relating to high risk of miscarriage were maternal age, longest reported cycle length, and time from ovulation to hCGs reaching 25 milli-international units/mL. The latter was of particular importance because each additional day increased risk by 44% (hazard ratio 1.44, 95% confidence interval 1.25–1.66). CONCLUSION: Urinary hCG profiles in viable pregnancies are consistent but significantly different from those in early losses, making early loss identifiable by hCG trajectory before any clinical symptoms. The most significant predictor was delay of appearance of hCG after ovulation. Level of hCG could not consistently differentiate between viable pregnancy and loss after 6 weeks before onset of loss.

Urinary Levels of Intact, Free Beta, and Beta Core Fragment of hCG in Early Pregnancy [35].

INTRODUCTION: Reference ranges have been published for intact urinary human chorionic gonadotropin (hCG) but not for other forms. Free &bgr; and &bgr; core fragment have different profiles of daily rise of hCG compared with intact hCG. Very high levels of &bgr; core can cause false-negative point-of-care pregnancy test results, and ratio of intact to free &bgr; hCG has been related to pregnancy viability. Therefore, we sought to improve the understanding of the levels of free &bgr; and &bgr; core hCG in viable pregnancies. METHODS: Early morning urine samples were collected from 37 women with viable pregnancies throughout early pregnancy. Intact, free &bgr;, and &bgr; core hCG were measured using DELFIA immunoassays. Median levels and centile ranges by day of pregnancy were derived. RESULTS: As expected, intact hCG was present 8 days after ovulation; however, free &bgr; hCG was not measurable until day 21. Free &bgr; hCG occurred at a constant 1/100th ratio of intact hCG. Beta core hCG had a different profile, appearing in urine later than intact hCG (day 19) yet becoming the predominant form by day 35. CONCLUSION: The ranges of free &bgr; and &bgr; core hCG in viable pregnancies provide a valuable reference tool. Although levels of &bgr; core hCG in early pregnancy are negligible, they can reach 500,000 pmol/L by day 28 postovulation, a level shown to cause false-negative results in some tests. Therefore, only assays that demonstrate they are unaffected by &bgr; core hCG interference should be used in later pregnancy.