Rene Leiva

Use of urinary pregnanediol 3-glucuronide to confirm ovulation

OBJECTIVE Urinary hormonal markers may assist in increasing the efficacy of Fertility Awareness Based Methods (FABM). This study uses urinary pregnanediol-3a-glucuronide (PDG) testing to more accurately identify the infertile phase of the menstrual cycle in the setting of FABM. METHODS Secondary analysis of an observational and simulation study, multicentre, European study. The study includes 107 women and tracks daily first morning urine (FMU), observed the changes in cervical mucus discharge, and ultrasonography to identify the day of ovulation over 326 menstrual cycles. The following three scenarios were tested: (A) use of the daily pregnandiol-3a-glucuronide (PDG) test alone; (B) use of the PDG test after the first positive urine luteinizing hormone (LH) kit result; (C) use of the PDG test after the disappearance of fertile type mucus. Two models were used: (1) one day of PDG positivity; or (2) waiting for three days of PDG positivity before declaring infertility. RESULTS After the first positivity of a LH test or the end of fertile mucus, three consecutive days of PDG testing over a threshold of 5μg/mL resulted in a 100% specificity for ovulation confirmation. They were respectively associated an identification of an average of 6.1 and 7.6 recognized infertile days. CONCLUSIONS The results demonstrate a clinical scenario with 100% specificity for ovulation confirmation and provide the theoretical background for a future development of a competitive lateral flow assay for the detection of PDG in the urine.

Random serum progesterone threshold to confirm ovulation

BACKGROUND Serum progesterone (P) rises after ovulation in the luteinisation process. OBJECTIVE To identify an accurate progesterone threshold to confirm ovulation in the assessment of a womans fertility. METHODS In a secondary analysis of an observational European multicentre study, this study included 107 women over 326 menstrual cycles and tracked daily first morning urine (FMU), changes in observed cervical mucus discharge, serum progesterone, and ultrasonography to identify the day of ovulation. A serum progesterone level was available for 102 women over a total 260 cycles with one or two P levels per cycle. RESULTS It was found that a single serum P⩾5ng/ml is highly specific with a specificity of 98.4 (95% CI 96.0-99.5), with a sensitivity of 89.6 (95% CI 85.2-92.9). CONCLUSION A random serum progesterone level ⩾5ng/ml confirms ovulation. This may be of use for clinicians wanting to confirm that ovulation has occurred.

Maternal mortality and abortion

The launch of the Family Physician Project in Iran provided an opportunity for general practitioners to practise as regular primary care providers for designated rural popu lations. However, there is still a strong atmosphere of dissatisfaction among physicians. Most family doctors have to work under conditions that are unacceptable in terms of workload, payment, workplace, professional satisfaction and support, and living conditions. The most serious problem is the dysfunctional payment system. The unsatisfactory monthly salary is usually paid after several months of delay, and is calculated on the basis of performance evaluation procedures that mostly rely on uncontrollable factors. The services family physicians are allowed to provide and the resources they have access to are irrationally limited. For example, such a common investigation as urinary-tract ultrasonography can only be requested by a specialist if the expenses are to be covered by insurance, unless the patient can aff ord the entire cost, which is mostly not the case; not to mention the limited access to secondary and tertiary care in Iran. A similar problem exists with the limited number of medications a family physician can prescribe, many of which may not even be available! Para doxically, a strict limitation is set for referral to secondary care. Most contracts mandate that the physician stays within the limits of Maternal mortality and abortion

Urinary Luteinizing Hormone Tests: Which Concentration Threshold Best Predicts Ovulation?

Objective To study the best possible luteinizing hormone (LH) threshold to predict ovulation within the 24, 48, and 72 h. Design Observational study. Setting Multicenter collaborative study. Patients A total of 107 women. Interventions Women collected daily first morning urine for hormonal assessment and underwent serial ovarian ultrasound. This is a secondary analysis of 283 cycles. Main outcome measures The sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were estimated for varying ranges of LH thresholds. Receiver operating characteristic curves and cost–benefit ratios were used to estimate the best thresholds to predict ovulation. Results The best scenario to predict ovulation at random was within 24 h after the first single positive test. The false-positive rate was found to increase as (1) the cycle progressed or (2) two or three consecutive tests were used, or (3) ovulation was predicted within 48 or 72 h. Testing earlier in the cycle increases the predictive value of the test. The ideal thresholds to predict ovulation ranged between 25 and 30 mIU/ml with a PPV (50–60%), NPV (98%), LR+ (20–30), and LR− (0.5). At least, one day with LH ≥25 mIU/ml followed by three negatives (LH <25) occurred before ovulation in 31% of all cycles. When used throughout the cycle and evaluated together, peak-fertility type mucus with a positive LH test ≥25 mIU/ml provides a higher specificity than either mucus or LH testing alone (97–99 vs. 77–95 vs. 91%, respectively). Conclusion We identified that beginning LH testing earlier in the cycle (day 7) with a threshold of 25–30 mIU/ml may present the best predictive value for ovulation within 24 h. However, prediction by LH testing alone may be affected negatively by several confounding factors so LH testing alone should not be used to define the end of the fertile window. Complementary markers should be further investigated to predict ovulation and identify the fertile window. The use of the peak cervical mucus along with an LH test may provide a higher specificity and predictive value than either of them alone. We recommend that manufacturers disclose their tests’ threshold to the public.

A Quadriparametric Model to Describe the Diversity of Waves Applied to Hormonal Data

BACKGROUND Even in normally cycling women, hormone level shapes may widely vary between cycles and between women. Over decades, finding ways to characterize and compare cycle hormone waves was difficult and most solutions, in particular polynomials or splines, do not correspond to physiologically meaningful parameters. OBJECTIVE We present an original concept to characterize most hormone waves with only two parameters. METHODS The modelling attempt considered pregnanediol-3-alpha-glucuronide (PDG) and luteinising hormone (LH) levels in 266 cycles (with ultrasound-identified ovulation day) in 99 normally fertile women aged 18 to 45. The study searched for a convenient wave description process and carried out an extended search for the best fitting density distribution. RESULTS The highly flexible beta-binomial distribution offered the best fit of most hormone waves and required only two readily available and understandable wave parameters: location and scale. In bell-shaped waves (e.g., PDG curves), early peaks may be fitted with a low location parameter and a low scale parameter; plateau shapes are obtained with higher scale parameters. I-shaped, J-shaped, and U-shaped waves (sometimes the shapes of LH curves) may be fitted with high scale parameter and, respectively, low, high, and medium location parameter. These location and scale parameters will be later correlated with feminine physiological events. CONCLUSION Our results demonstrate that, with unimodal waves, complex methods (e.g., functional mixed effects models using smoothing splines, second-order growth mixture models, or functional principal-component- based methods) may be avoided. The use, application, and, especially, result interpretation of four-parameter analyses might be advantageous within the context of feminine physiological events.

Hormonal Predictors of Abnormal Luteal Phases in Normally Cycling Women

Objective: Explore potential relationships between preovulatory, periovulatory, and luteal-phase characteristics in normally cycling women. Design: Observational study. Setting: Eight European natural family planning clinics. Patient(s): Ninety-nine women contributing 266 menstrual cycles. Intervention(s): The participants collected first morning urine samples that were analyzed for estrone-3 glucuronide (E1G), pregnanediol-3- alpha-glucuronide (PDG), follicle stimulating hormone (FSH), and luteinizing hormone (LH). The participants underwent serial ovarian ultrasound examinations. Main Outcome Measure(s): Four outcome measures were analyzed: short luteal phase, low mid-luteal phase PDG level (mPDG), normal then low luteal PDG level, low then normal luteal PDG level. Results: A long preovulatory phase was a predictor of short luteal phase, with or without adjustment for other variables. A high periovulatory PDG level was a predictor for short luteal phase as well as normal then low luteal PDG level. A low periovulatory PDG level predicted low mPDG and low then normal luteal PDG level, with or without adjustment for other variables. A small maximum follicle predicted normal then low luteal PDG level, with or without adjustment for other variables. The relationship between small maximum follicle size and short luteal phase or small maximum follicle size and low mPDG was no longer present when the regression was adjusted for certain characteristics. A younger age at menarche and a high body mass index were both predictors of low mPDG. Conclusion: Luteal phase abnormalities exist over a spectrum where some ovulation disorders may exist as deviations from the normal ovulatory process.This study confirms the negative impact of a small follicle size on the quality of the luteal phase. The occurrence of normal then low luteal PDG level is confirmed as a potential sign of luteal phase abnormality.

We need a moral compass

Downie’s commentary on physician-assisted suicide states that “as a profession we must ensure that there are physicians willing and able” to further this end once it is legal and regulated.[1][1] Over two millennia ago, the Hippocratic Oath described how the push to end our patients’ lives