Jayne Ellis

Changes in Bone Resorption Across the Menopause Transition: Effects of Reproductive Hormones, Body Size, and Ethnicity

OBJECTIVE Our objective was to characterize changes in bone resorption in relation to the final menstrual period (FMP), reproductive hormones, body mass index (BMI), and ethnicity. METHODS Urinary type I collagen N-telopeptide (NTX), estradiol, and FSH levels were measured annually for up to 8 years spanning the menopause transition in 918 African American, Chinese, Japanese, or Caucasian women. RESULTS Urinary NTX began to increase sharply about 2 years before the FMP, reaching its peak level about 1 to 1.5 years after the FMP. NTX levels declined modestly from 2 to 6 years after the FMP but remained about 20% higher than before the menopause transition. The sharp rise in FSH occurred in conjunction with a sharp decline in estradiol and shortly after FSH levels began increasing rapidly. The mean increase in urinary NTX across the menopause transition was greatest in women with BMI <25 kg/m² and smallest in women with BMI >30 kg/m². Increases in NTX were greatest in Japanese women and smallest in African Americans. These differences were attenuated, but not eliminated, when analyses were adjusted for covariates, particularly BMI. SUMMARY During the menopause transition, a decline in ovarian function beginning about 2 years before the FMP is followed by an increase in bone resorption and subsequently by bone loss. The magnitude of the increase in bone resorption is inversely associated with BMI. Ethnic differences in changes in bone resorption are attenuated, but not eliminated, by adjustment for BMI. Ethnic differences in BMI, and corresponding ethnic differences in bone resorption, appear to account for much of the ethnic variation in perimenopausal bone loss.

Levels of urinary human chorionic gonadotrophin (hCG) following conception and variability of menstrual cycle length in a cohort of women attempting to conceive

ABSTRACT Objectives: To define the variability of menstrual cycle length and contribution of follicular and luteal phases to overall cycle variability, and to examine the rise in urinary hCG in early pregnancy. Methods: Menstrual cycle study. Urine samples from 101 women (recruited from two south-east counties in the UK) were assayed to determine day of luteinising hormone (LH) surge, lengths of follicular and luteal phases and correlations with total menstrual cycle length. HCG study. Daily urine samples collected from 86 women prior to conception until 43 days post-conception were assayed for hCG and examined versus time since LH surge, determined using fertility test kits. Results: Mean menstrual cycle length was 27.7 ± 3.4 days, mean follicular phase length was 14.5 ± 3.4 days and mean luteal phase length was 13.2 ± 1.9 days. Total cycle lengths varied between and within women. There was a significant correlation (r2 = 0.70) between follicular phase length and total cycle length; luteal phase length was less variable and showed no association with total cycle length. Concentrations of hCG were significantly similar between women when referenced against the day since LH surge. Three thresholds were determined to indicate time since conception as 1–2 weeks, 2–3 weeks and 3+ weeks. Conclusions: Total cycle length variation is mainly determined by follicular phase variation and predicting menses onset to estimate time of pregnancy testing is unreliable. Evaluating concentrations of hCG relative to LH surge results in consistent increases between women up to 21 days after conception. Therefore, urinary hCG concentration can be used to accurately estimate time since conception.

Comparison of accuracy and certainty of results of six home pregnancy tests available over-the-counter

ABSTRACT Background: The aim of the study was to determine the accuracy of home pregnancy tests (HPTs) in detecting human chorionic gonadotrophin (hCG) in human female urine and consumer certainty in reading the results. The Clearblue Digital Pregnancy Test (CBDPT) was compared with five alternative over-the-counter (OTC) brands of HPT. Methods: HPTs (CBDPT [SPD, Geneva, Switzerland], Answer [Church & Dwight, Princeton, NJ], Predictor [Omega Teknika, Dublin, Ireland], Clearblue (non-digital) [SPD], EPT [McNeill, Fort Washington, PA], First Response [Church & Dwight]) were tested by study co-ordinators on samples of pooled urine containing hCG at 0 IU/l (negative control) or 25 IU/l (positive standard, typical of level found in early pregnancy), in a coded, randomised scheme. Results and level of certainty about the results were interpreted by 120 female volunteers. Results: The CBDPT detected hCG in the 25 IU/l positive urine with 100 % accuracy when read by volunteers. Accuracy of four alternative HPTs ranged from 65.8 to 87.5 % , but was only 8.3 % with the fifth test, Predictor. CBDPT was statistically significantly better than any of the alternative brands. All volunteers (100 % ) rated the results with the CBDPT as ’very certain‚ or ’certain‚ (score 1 or 2), whereas a score of 1 or 2 was recorded by only 40.3–58.3 % for the other brands, except Predictor which was scored with certainty by 87.5 % , although volunteers interpreted the result for the positive standard as not pregnant. A certainty score of 1 or 2 was recorded by a significantly (p < 0.001) greater proportion of volunteers with CBDPT than any of the other HPTs. Conclusions: The CBDPT was significantly better in terms of accuracy and certainty than non-digital OTC HPTs tested at a low hCG concentration. These results demonstrate that a digital reading offers significant benefits to the consumer over traditional non-digital tests.

Mistiming of intercourse as a primary cause of failure to conceive: results of a survey on use of a home-use fertility monitor

ABSTRACT Objective: To assess demographics, fecundity characteristics and fertility history of couples who successfully conceived using a home-use Fertility Monitor. Study design: This was a retrospective US observational study of couples who successfully conceived using a Fertility Monitor. Data were self-reported by volunteers using a questionnaire supplied and collected by mail. Of 276 surveys distributed, 196 (71.0%) were returned and evaluated. Results: Length of time trying to conceive was < 12 months for 70% of women; proportions were similar across age groupings. After switching to the Fertility Monitor, 49.5% and 91.9% of women had conceived within first and third cycles, respectively. Prior to Fertility Monitor use, conception aids were used by 84.2% and 64.3% had consulted a physician to seek help in attempting to conceive. Average costs of prior treatment were (in US dollars)

Accuracy of perception of ovulation day in women trying to conceive

6637; median costs for infertility evaluation were

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

1075 per cycle. Fertility Monitor costs ranged from

Assay Reader, Device and Method of Measuring HCG

250 for one cycle to

Assessment of fertility

550 after 10 cycles. Conclusions: A probable cause for failure to conceive appeared to be mistiming of intercourse. The issue of early intervention with tests and medications were highlighted, resulting in escalating costs and strain on the couple. The use of a home Fertility Monitor that identifies all fertile days of the cycle and allows couples to target intercourse accordingly, should be considered as an alternative choice for couples seeking to conceive during the first year, before other attempts at infertility diagnosis are made, unless there are conflicting clinical reasons.

Erratum: Changes in bone resorption across the menopause transition: Effects of reproductive hormones, body size, and ethnicity (Journal of Clinical Endocrinology and Metabolism (2013) 98 (2854-2863) DOI: 10.1210/jc.2012-4113)

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.

Original article Accuracy of perception of ovulation day in women trying to conceive

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.