Urinary Luteinizing Hormone Research Articles

7269 Interim Analysis of Gonadotropin-Releasing Hormone Agonist (GnRHa) Treatment in Children with Central Precocious Puberty: Focus on FMV Urinary LH Levels and Clinical Outcomes

Abstract Disclosure: X. Luo: Advisory Board Member; Self; Takeda. L. Hou: Advisory Board Member; Self; Takeda. Y. Li: Advisory Board Member; Self; Takeda. Y. Sun: Advisory Board Member; Self; Takeda. X.K. Jin: Employee; Self; Takeda. Background: Central precocious puberty (CPP) refers to early activation of the hypothalamic–pituitary–gonadal (HPG) axis in children. There is an urgent need to understand the treatment pattern and clinical outcomes among children suffering from CPP. Studies have reported that first morning voided (FMV) urinary Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) have substantial association with CPP tested in GnRH stimulation test and can be useful in diagnosis and management of CPP in children. Gonadotropin-releasing hormone agonists (GnRHa) such as Leuprolide acetate (LA) are the recommended treatment for children suffering from CPP. The current study aimed to provide the information on level of LH and FSH in FMV urine when CPP diagnosis at baseline and the present results may also revealed trend of FMV-LH and FMV-FSH change during LA intervention in children with CPP. Here we present interim results from this study. Methods: This is an open-label, multicentre, single arm, prospective study that enrolled 31 subjects with CPP. Individuals were administered LA depot 11.25 mg, subcutaneously every 12 weeks. The study comprises a screening period; a 6-month treatment period: 24 weeks; and a post-treatment follow-up period: 12 weeks. The FMV urinary LH and FSH were diagnosed by Clopper-Pearson method with a 95% confidence interval. Results: Due to the data collection time point for the interim analysis, only 8 female subjects reached the 12-week visit time point and had a 12-week visit for FMV urinary Gn testing. Therefore, for this interim analysis, only FMV Gn decline at week 12 of the 8 subjects who had a 12-week visit will be presented. At baseline, the mean value of FMV urinary LH and FSH is 0.58 IU/L and 2.27 IU/L respectively. The FMV Gn urinary LH was demonstrated a decrease in 87.5% (95% CI: 47.35,99.68) of the children after LA intervention. Additionally, urinary FSH value of FMV urinary Gn was found to decrease in 75.00% of the children (95% CI: 34.91,96.81) compared to baseline FSH value. Conclusion: The present study reveals a decreasing trend in FMV Gn urinary LH and FSH levels in CPP children treated with LA during interim analysis. LA was shown to be safe and effective in ameliorating the level of LH and FSH in children suffering from CPP. From the study, it can be concluded that urinary LH and FSH may act as a potential biomarker for diagnosis and management of CPP. Presentation: 6/3/2024

Comparative Analysis of Commercial Immunoassays for the Determination of Total, Intact, and Nonintact Luteinizing Hormone in Urine.

In our recent publications, we reported the identification of three different molecular forms of total luteinizing hormone (LH) in urine, the intact LH, the free beta-subunit (LHβ), and its core fragment of LHβ (LHβcf), the latter two establishing the nonintact portion of LH. Following the discontinuation of the Delfia immunofluorometric assay (IFMA) (Wallac, PerkinElmer Finland, Finland), a leading method for detecting urinary LH for 30 years, this study seeks to assess the efficacy of three alternative commercial immunoassays in identifying various forms of U-LH. Diluted urine samples underwent gel filtration to separate them into fractions, each containing different forms of LH. These were then assayed using Delfia IFMA, Architect LH (Abbott, USA), Elecsys LH Cobas (Roche, Switzerland), and Immulite 2000 LH (Siemens, Germany) immunoassays. Both Delfia and Immulite assays detected total U-LH, that is, all three forms of U-LH, including intact LH, LHβ, and LHβcf. Cobas detected only intact LH and LHβ, whereas Architect detected solely the intact LH. Immulite assay can be an alternative tool to detect all forms of urinary LH, a feature likely to be instrumental in developing noninvasive, practical, and scalable solutions for evaluating total U-LH changes during minipuberty in neonates, during the onset of central puberty in peripubertal children, puberty-associated disorders in adolescents, and the fertility window in women, with a special focus on postpeak changes.

Hypothalamic-pituitary-ovarian axis suppression is common among women during US Army Basic Combat Training

ObjectiveLess than half of servicewomen report loss of menses during initial military training. However, self-reported menstrual status may not accurately reflect hypothalamic-pituitary-ovarian (HPO) axis suppression and may underestimate reproductive health...

At What Point in the Menstrual Cycle Are the Pelvic Floor Muscles at Their Weakest?

Pelvic floor muscle (PFM) strength is a critical factor for optimal pelvic floor function. Fluctuations in strength values based on different phases of the menstrual cycle (MC) could signify a need for a paradigm shift in evaluating, approaching, and planning training. This research aims to examine and contrast the pelvic floor muscle strength during different phases of the menstrual cycle. A prospective observational study employing digital assessment with the modified Oxford scale and vaginal dynamometry measurements was performed, in order to assess the baseline strength and the contraction strength of the PFMs in eumenorrheic females at three different phases of the MC: the early follicular phase (EFP), the late follicular phase (LFP), and the mid-luteal phase (MLP). During two complete cycles, tympanic temperature and body weight were measured and the urinary luteinizing hormone concentration was tested to determine the time of ovulation. In total, 216 dynamometric measurements of PFM strength were obtained from eighteen nulliparous women (25.72 ± 5.03 years). There were no differences between the baseline strength (p = 0.886) and the contraction strength (p = 0.756) with the dynamometric speculum. In the post hoc analysis, the baseline strength, contraction strength, and strength showed no significant differences between MC phases. As no differences in PFM strength in women were found, the PFMs do not seem to be weaker at any time during the menstrual cycle. It appears that the assessment, establishment, and monitoring of a PFM training program could be initiated at any point in the cycle.

Comparison of Day-Specific Serum LH, Estradiol, and Progesterone with MiraTM Monitor Urinary LH, Estrone-3-glucuronide, and Pregnanediol-3-glucuronide Levels in Ovulatory Cycles.

Background and Objectives: Fertility tracking apps and devices are now currently available, but urinary hormone levels lack accuracy and sensitivity in timing the start of the 6-day fertile window and the precise 24 h interval of transition from ovulation to the luteal phase. We hypothesized the serum hormones estradiol (E2) and progesterone (P) might be better biomarkers for these major ovulatory cycle events, using appropriate mathematical tools. Materials and Methods: Four women provided daily blood samples for serum E2, P, and LH (luteinizing hormone) levels throughout their entire ovulatory cycles, which were indexed to the first day of dominant follicle (DF) collapse (defined as Day 0) determined by transvaginal sonography; therefore, ovulation occurred in the 24 h interval of Day -1 (last day of maximum diameter DF) to Day 0. For comparison, a MiraTM fertility monitor was used to measure daily morning urinary LH (ULH), estrone-3-glucuronide (E3G), and pregnanediol-3-glucuronide (PDG) levels in three of these cycles. Results: There were more fluctuations in the MiraTM hormone levels compared to the serum levels. Previously described methods, the Fertility Indicator Equation (FIE) and Area Under the Curve (AUC) algorithm, were tested for identifying the start of the fertile window and the ovulation/luteal transition point using the day-specific hormone levels. The FIE with E2 levels predicted the start of the 6-day fertile window on Day -7 (two cycles) and Day -5 (two cycles), whereas no identifying signal was found with E3G. However, both pairs of (E2, P) and (E3G, PDG) levels with the AUC algorithm signaled the Day -1 to Day 0 ovulation/luteal transition interval in all cycles. Conclusions: serum E2 and (E2, P) were better biomarkers for signaling the start of the 6-day fertile window, but both MiraTM and serum hormone levels were successful in timing the [Day -1, Day 0] ovulatory/luteal transition interval. These results can presently be applied to urinary hormone monitors for fertility tracking and have implications for the direction of future fertility tracking technology.

Novel Methodology for Identifying the Occurrence of Ovulation by Estimating Core Body Temperature During Sleeping: Validity and Effectiveness Study.

Body temperature is the most-used noninvasive biomarker to determine menstrual cycle and ovulation. However, issues related to its low accuracy are still under discussion. This study aimed to improve the accuracy of identifying the presence or absence of ovulation within a menstrual cycle. We investigated whether core body temperature (CBT) estimation can improve the accuracy of temperature biphasic shift discrimination in the menstrual cycle. The study consisted of 2 parts: experiment 1 assessed the validity of the CBT estimation method, while experiment 2 focused on the effectiveness of the method in discriminating biphasic temperature shifts. In experiment 1, healthy women aged between 18 and 40 years had their true CBT measured using an ingestible thermometer and their CBT estimated from skin temperature and ambient temperature measured during sleep in both the follicular and luteal phases of their menstrual cycles. This study analyzed the differences between these 2 measurements, the variations in temperature between the 2 phases, and the repeated measures correlation between the true and estimated CBT. Experiment 2 followed a similar methodology, but focused on evaluating the diagnostic accuracy of these 2 temperature measurement approaches (estimated CBT and traditional oral basal body temperature [BBT]) for identifying ovulatory cycles. This was performed using urine luteinizing hormone (LH) as the reference standard. Menstrual cycles were categorized based on the results of the LH tests, and a temperature shift was identified using a specific criterion called the "three-over-six rule." This rule and the nested design of the study facilitated the assessment of diagnostic measures, such as sensitivity and specificity. The main findings showed that CBT estimated from skin temperature and ambient temperature during sleep was consistently lower than directly measured CBT in both the follicular and luteal phases of the menstrual cycle. Despite this, the pattern of temperature variation between these phases was comparable for both the estimated and true CBT measurements, suggesting that the estimated CBT accurately reflected the cyclical variations in the true CBT. Significantly, the CBT estimation method showed higher sensitivity and specificity for detecting the occurrence of ovulation than traditional oral BBT measurements, highlighting its potential as an effective tool for reproductive health monitoring. The current method for estimating the CBT provides a practical and noninvasive method for monitoring CBT, which is essential for identifying biphasic shifts in the BBT throughout the menstrual cycle. This study demonstrated that the estimated CBT derived from skin temperature and ambient temperature during sleep accurately captures variations in true CBT and is more accurate in determining the presence or absence of ovulation than traditional oral BBT measurements. This method holds promise for improving reproductive health monitoring and understanding of menstrual cycle dynamics.

P-674 Rescue oocyte collection: a strategy to reduce cycle cancellations in natural/natural modified IVF/ ICSI cycles with luteinising hormone (LH) surge among poor responder patients

Abstract Study question Can an early oocyte collection (OC) avoid cycle cancellation due to spontaneous ovulation in poor responders undergoing natural/ natural modified (N/NM) cycle-IVF? Summary answer Rescue OC may prevent premature ovulation following spontaneous LH surge in N/NM-IVF cycles allowing retrieval of mature oocytes, high-grade embryos that may result in livebirths. What is known already Natural IVF cycles carry an inherent higher risk of spontaneous LH surge and ovulation before OC. The introduction of gonadotropin releasing hormone antagonist with low-dose gonadotropin add-back has reduced these risks.Timing of ovulation trigger and trigger to OC interval are important to balance the risks of spontaneous ovulation with the chance of retrieving mature oocyte(s). In the absence of LH surge, the trigger to OC interval is normally 35 hours. However, it is challenging to schedule OC once LH surge has occurred.The effectiveness of rescue OC following LH surge has not been well explored. Study design, size, duration This is a retrospective analysis of all NC/NM-IVF/ICSI cycles in poor responders who had spontaneous urinary LH surge from over a period of 3 years, across five Fertility Centres under one company sharing the same treatment protocol. Participants/materials, setting, methods All women fulfilling the Bologna criteria for poor ovarian response underwent IVF/ICSI cycles with NC/ NM protocol. The study population included those who had a positive urinary LH surge without or despite the use of antagonist. A rescue OC scheduled 18 to 24 hours after a spontaneous urinary LH surge. Choriogonadotropin alfa (Ovitrelle) 250 micg was administered as soon as the surge was detected. Patients were also given indomethacin 8 hourly until OC. Main results and the role of chance Amongst 735 NC/NM-IVF/ ICSI cycles in poor responder women during the study period, 54 cycles (7.3%) had spontaneous urinary LH surge. Twenty-eight cycles were with NC-IVF and 26 NM-IVF protocol. Only 8 (14.8%) cycles did not progress to OC due to spontaneous ovulation. In 46 (85.2%) of cycles, at least one oocyte was successfully retrieved, with a total of59 retrieved oocytes. ICSI cycles identified at least one mature oocyte in 82% of the cycles. Fertilisation rate with IVF and ICSI cycles combined was 49.1% and at least one cleavage-stage embryo was created from 24 (44.4%) of all cycles (52.2% of retrieved cycles). High-grade embryo(s) was obtained in 42.5% of all cycles. Clinical pregnancy rate (CPR) and live birth rate (LBR) per embryo transfer were 18.7% and12.5%, respectively. Limitations, reasons for caution This study was retrospective in nature, without a comparator group. Combination of both NC-IVF and NM-IVF might not have implications in practical terms. Use ofindomethacin also could have delayed ovulation. Although population size was as expected for a rare event, it may not be adequate for a precise LBR. Wider implications of the findings An early scheduling of OC in the event of LH surge is an effective way to reduce cycle cancellation rate which is a risk in NC/NM-IVF cycles. It also can potentially result in livebirths. This approach may encourage clinicians practising NC/NM-IVF to test and validate our findings. Trial registration number not applicable

Diagnostic Value of Stimulated Urine Luteinizing Hormone After Triptorelin Stimulation Test in Girls with Central Precocious Puberty.

To investigate the diagnostic value of urine luteinizing hormone (ULH) after the triptorelin stimulation test detected by immunochemiluminometric assay (ICMA) in girls with central precocious puberty (CPP). The girls with precocious puberty were included. The triptorelin stimulation test at 8:30 a.m. was performed. Two consecutive 12-hour urine samples were collected after the test, defined as the first 12-hour and second 12-hour urine, respectively. ICMA measured ULH. Urine creatinine (Cr) concentration was measured. CPP and peripheral precocious puberty (PPP) were diagnosed by the same pediatric endocrinologist based on clinical symptoms, signs, and progression of clinical development. A total of 97 cases (CPP n=69; PPP n=28) were included, with 12 cases not meeting the receiver operating characteristic analysis criteria. The first and second 12-hour ULH/Cr in the CPP group were higher than those in the PPP group. When the first 12-hour ULH/Cr was≥287.252 IU/mol, the sensitivity and specificity for diagnosing CPP were 87.3% and 90.9%, respectively. When the second 12-hour ULH/Cr was≥152.769 IU/mol, the sensitivity and specificity for diagnosing CPP were 92.1% and 90.9%, respectively. The area under the curve of the first and second 12-hour ULH/Cr were 0.933 and 0.954, respectively. The ULH detection method after the triptorelin stimulation test has clinical significance for diagnosing CPP in girls. When blood sampling compliance in girls with precocious puberty is poor, the first 12-hour ULH/Cr≥288 IU/mol (or second 12-hour≥153 IU/mol) after the triptorelin stimulation test can serve as a laboratory indicator for diagnosis of CPP.

The Variability of the Components of Fitness along the Menstrual Cycle.

This study aims to determine the variability of the components of fitness along the menstrual cycle (MC) of physically active eumenorrheic women. Fifteen subjects were monitored along two consecutive MCs through the calendar-based counting method in combination with a urine luteinizing hormone surge kit. Subjects were tested at the early follicular phase (EFP), pre-ovulatory or late follicular phase (LFP), and post-ovulatory or mid-luteal phase (MLP). In each session, the back squat one-repetition maximum (1-RM), maximum fat oxidation (MFO), maximum oxygen uptake (VO2max) and acute recovery capacity were determined. The results revealed a wide variability among components of fitness and a low to high variability among subjects (acute recovery: 3.6% [range 1.5 to 9.5%]; back squat 1-RM: 6.1% [range 2.2 to 11%]; VO2max: 6.6% [range 1.1 to 15%]; MFO: 23% [range 4.6 to 35%]). Despite the individual nature, considering the number and magnitude of the responses in each MC phase, VO2max and acute recovery capacity tended to be enhanced at the LFP, the MFO at the MLP, and the back squat 1-RM remained stable along the MC. Thus, practitioners are aware of which components are susceptible to change along the MC phase, but an individual monitoring is recommended.

Measurement of luteinizing hormone surge in vaginal discharge: a potential biomarker that enables simple, non-invasive prediction of the periovulatory period

BackgroundPredicting the periovulatory period is very important for conception. Current approaches to predicting the periovulatory period include monitoring of basal body temperature and urine luteinizing hormone (LH) concentration; however, these methods are time-consuming. Here, we examined the potential of using vaginal discharge (VD) as a non-invasive means of sample collection for determining the LH surge that indicates ovulation.MethodsUrine and VD samples were collected from 35 healthy women aged 20–39 years. VD samples were collected with panty liners to reduce the burden on participants. Daily first urine samples and used panty liners were collected from the 10th through 19th days of the menstrual cycle. Urine and VD LH (uLH and vLH) levels in the samples were measured by enzyme-linked immunosorbent assay. Measured vLH baseline and first surge values were analyzed using Student's t-test and ROC curves.ResultsSamples for a total of 55 menstrual cycles were collected. We used uLH surge to establish the date of ovulation. uLH surges were observed in 49 cycles, 34 of which had corresponding VD samples that qualified for measurement. Five cycles were excluded due to a lack of vLH data. In the remaining 29 cycles, the vLH surge appeared within the fertile window 90% of the time, and the sensitivity and specificity of the test were 86% and 83%, respectively.ConclusionsVD has potential for use as a sample for predicting the periovulatory period by measuring LH content.

Predicting Acute Changes in Suicidal Ideation and Planning: A Longitudinal Study of Symptom Mediators and the Role of the Menstrual Cycle in Female Psychiatric Outpatients With Suicidality.

Cross-sectional and preliminary longitudinal findings suggest that cyclical ovarian hormone fluctuations influence acute suicide risk. The authors provide the first analyses in females with suicidality to investigate which daily symptoms covary with suicidal ideation and planning thoughts, the role of the menstrual cycle in daily symptom variation, how daily fluctuations in symptoms mediate the menstrual cycle-suicidality relationship, and how these associations vary across individuals. Naturally cycling psychiatric outpatients (N=119) with past-month suicidal ideation provided daily ratings of psychiatric symptoms (depression, hopelessness, anxiety, feeling overwhelmed, agitation, anhedonia, worthlessness, rejection sensitivity, anger, perceived burdensomeness, and interpersonal conflict), suicidal ideation, and suicidal planning across at least one menstrual cycle. Symptom ratings were decomposed into trait (person-centered mean) and state (daily person-centered mean deviation) components. Five cycle phases were identified in relation to menses onset and ovulation (surge in urine luteinizing hormone level). Hypotheses were tested in multilevel structural equation models. Nearly all psychiatric symptoms covaried with fluctuations in daily suicidal ideation, and a limited set of symptoms (depression, hopelessness, rejection sensitivity, and perceived burdensomeness) predicted within-person increases in suicidal planning. Many patients demonstrated perimenstrual worsening of psychiatric symptoms, suicidal ideation, and suicidal planning. Depressive symptoms (depression, hopelessness, perceived burdensomeness, and anhedonia) were the most robust statistical mediators predicting perimenstrual exacerbation of suicidality. Research on the menstrual cycle and suicide has been limited historically by small, cross-sectional samples. This study provides the first evidence that measuring day-to-day correlates of suicidality in a large transdiagnostic sample of females with suicidal ideation can contribute to understanding the pathways by which the menstrual cycle influences acute suicide risk.

Urine Sampling Protocol Recommendations for Reliable Determination of Total Urinary Luteinizing Hormone Immunoreactivity in the Pediatric Population.

This study investigates day-to-day variations in urinary luteinizing hormone (U-LH) concentrations in children, focusing on potential minimization or correction methods. 95 children and adolescents (51 boys, 44 girls, ages 5-17) provided daytime and evening urine samples for U-LH determinations over three consecutive days. No consistent day-to-day differences in U-LH levels were observed, although random variations, particularly in adolescents aged 13 or older, were noted. The net inter-assay CV% for U-LH changes over three days showed high variability, averaging 24.6% to 28.0% for boys and 21.6% to 27.3% for girls, independent of sex, collection time, or U-LH level. To reliably determine total urinary luteinizing hormone immunoreactivity in the pediatric population, it is advisable to collect multiple first-morning voided samples for at least three consecutive days as an interim solution, pending the development of a standardized protocol or correction method for varying urine composition. Strict adherence, especially for adolescents aged 13 or older, is vital.

The negative impact of levothyroxine treatment on urinary luteinizing hormone measurements in pediatric patients with thyroid disease.

Previous studies suggest urinary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measurements by immunofluorometric assays (IFMA) as noninvasive alternatives to serum assays for puberty assessment. However, these studies excluded patients with other endocrine disorders and those taking medications. Besides, the recent discontinuation of IFMA manufacturing is a concern. We explored the utility of luminometric assays (LIA) for urinary gonadotropins and thyroid-stimulating hormone (TSH) determinations in euthyroid patients with thyroid pathologies. We used LIA and IFMA assays to measure serum and first-morning-voided (FMV) urine LH, FSH, and TSH concentrations in euthyroid patients with various thyroid disorders. Of the 47 euthyroid patients with normal serum TSH (S-TSH) levels, 14 were receiving levothyroxine therapy. FMV total urinary LH (U-LH) concentrations correlated significantly with those measured in serum using either LIA (r=0.67, P<.001) or IFMA (r=0.83, P=.003) in patients not receiving levothyroxine treatment; however, no significant correlation could be detected in patients receiving levothyroxine regardless of the assay method (for LIA: r=0.50, P=.08 and IFMA r=0.44, P=.15). Urinary TSH (U-TSH) concentrations correlated poorly with those in serum in both the untreated and the treated groups (r=-0.13, P=.49, and r=-0.45, P=.11, respectively). FMV total U-LH determinations by LIA can be used to assess pubertal development in patients with thyroid pathology, provided the euthyroid patient is not on levothyroxine treatment. U-TSH measurements by LIA cannot replace invasive S-TSH measurements at least in patients with normal S-TSH levels. Further research may reveal the utility of U-TSH determinations in patients with elevated S-TSH levels.

Late Luteal Subphase Food Craving Is Enhanced in Women with Obesity and Premenstrual Dysphoric Disorder (PMDD)

Dysregulated food craving is a complex weight-related behavior. To identify novel targets for enhancing the efficacy of weight loss interventions, we examined whether food craving varies across the menstrual cycle according to the abdominal obesity type and premenstrual dysphoric disorder (PMDD) diagnosis, and, if so, whether it is related to affective symptomatology. Reproductive-age women were classified into one of the four study groups according to whether they have abdominal obesity (AO) or are abdominally lean (AL), and the presence of PMDD: (1) AO:PMDD+ (n = 13), (2) AL:PMDD+ (n = 14), (3) AO:PMDD− (n = 15), and (4) AL:PMDD− (n = 16). Self-report measures as well as urinary luteinizing hormone (LH) tests were provided by the participants across 2–3 menstrual cycles. The ratings of food cravings were similar across the menstrual cycle, except the last, late luteal subphase as the AO:PMDD+ participants had the highest food craving rating. Irritability and depression were correlated with food cravings, but not in a distinctive manner across the menstrual cycle by group. Our study found that women with abdominal obesity and PMDD display a temporal vulnerability to a food-related behavior. The possibility of shared neurobiology between the two conditions is discussed and should be examined in future studies.

Sex-independent timing of the onset of central puberty revealed by nocturnal luteinizing hormone concentrations.

We designed a longitudinal study to investigate the association between the ages of central pubertal activation and the appearance of clinical signs of puberty and determined total luteinizing hormone (LH) immunoreactivity in daytime- and nocturnal sleeptime-excreted urine samples. Thirty healthy volunteers (17 boys and 13 girls, aged 3.4-15.2years and 4.3-14.3years, respectively, at the beginning of the study) were included. Male and female subjects were followed for an average of 15 visits during 5.5 and 5.8 years on average, respectively. At each visit, subjects provided 24-h urine samples divided into nocturnal sleeptime and waketime portions according to the participant's sleep-and-wake rhythm. Total urinary LH (U-LH) concentrations were measured in duplicate by Delfia® IFMA (Wallac), which has been designed specifically to detect intact LH as well as the beta subunit and its core fragment, but not the human chorionic gonadotropin. The initial increases in nocturnal sleeptime total U-LH concentrations over the cutoff value of 0.7 IU/L occurred at around the same time (around 9-10 years of age) in both sexes, which could not be detected in waketime urine samples. The mean first age for the nocturnal sleeptime total U-LH concentrations to reach or surpass the cutoff was 10.7 years (range: 10.2-11.6years) in boys and 11.8 years (range: 10.7-13.4years) in girls, showing no statistically significant difference between the sexes (p = .15). The mean time span from the age at which sleeptime total U-LH concentration first exceeded the 0.7 IU/L level to observing pubertal stage 2 was 1.5years in boys and 0.1years in girls. Findings in our population with a limited sample size suggest that the timing of central pubertal activation is a sex-independent phenomenon, which can be observed by monitoring the nocturnal sleeptime total LH concentrations in urine. The lag time from central pubertal activation of gonadotropin secretion to the clinical onset of puberty is significantly longer in boys.

Effect of ovulation on postural sway in association with sex hormone variation across the menstrual cycle in college students: an observational study

BackgroundPoor balance associated with increased postural sway is a risk factor for the high incidence of injuries found during specific menstrual cycle phases. This fact led to the hypothesis that female reproductive hormones affect soft tissue and neuromuscular function, reducing postural balance and resulting in a high injury prevalence among female college students. So, the current study aimed to identify the influence of ovulation in association with sex hormone variation across the menstrual cycle on postural sway in college students.Material and methodsForty female college students were enrolled in this study. They were recruited among physical therapy students at Deraya University, New Minya, Egypt. They were aged from 17 to 22 years. They were allocated to a single group. Progesterone and estradiol blood levels were measured to detect the timing of the follicular and luteal phases, and a urine luteinizing hormone (LH) strip test was used to determine when ovulation occurred. The dynamic postural sway index was assessed by using the Biodex Balance system. All measurements were taken on the early follicular (1st–3rd) day, the ovulatory (11th–13th) day, and the mid-luteal phase (21st–23rd) day from the onset of menstruation.ResultsStatistical analysis showed that the anteroposterior, mediolateral, and overall sway index increased significantly during the ovulatory phase compared to the earlier follicular and mid-luteal menstrual cycle phases in female college students (P < 0.05). There was no significant variance between the early follicular and mid-luteal phases (P > 0.05).ConclusionsIt can be concluded that increased female sex hormones during ovulation affect postural sway, which may disturb balance and increase the risk of injuries in college students.

P-675 Analysis of a digitally integrated ovulation date kit to determine ovulation precisely

Abstract Study question Do digitally integrated ovulation prediction kits (OPK) predict the fertile window and the ovulation date accurately? And can this prediction be proven by sonography? Summary answer Particularly for subfertile women with irregular cycles, OPKs can help predict their fertile window and ovulation day, in accordance with vaginal sonography. What is known already The fertile window is defined as the period of five days before ovulation including the day of ovulation itself. Prediction based only on cohort observations or historical datasets may be inaccurate for women with irregular cycles, particularly when unforeseen changes of ovarian function occur during reproductive life. Urinary luteinizing hormone (LH) assays and smartphone applications are already widely used to detect the optimal time for conception, but can only predict a likelihood of ovulation without proof. Study design, size, duration 100 healthy women between the ages of 21 and 45, cycle length up to 42 days, trying to conceive and without hormone intake were to be recruited in the gynecological outpatient clinics of the Technical University of Munich (TUM) and of the University of Ulm. Each participant entered the study for up to three consecutive cycles. Two vaginal ultrasound scans were performed per cycle – before and after the ovulation date prognosis by the app. Participants/materials, setting, methods After informed consent, participants downloaded the smartphone application “Pearl Fertility” and received OPKs consisting of four different sets of lateral flow immunoassay test strips (LFIA): for luteinizing hormone, follicle-stimulating hormone, progesterone and human chorionic gonadotropin. Home measurements with LFIAs were performed with morning urine. The phone camera feed analyzed the color information of the LFIAs. Three differently prioritized algorithms calculated the ovulation date. Two questionnaires evaluated patient baseline characteristics and their perception of the app. Main results and the role of chance 89 women were recruited. Mean age was 34.6 yrs. (SD ± 4.2). On average, the included women had tried to conceive for 7.5 (±5) months before joining the study. 8% (n = 7) became pregnant before the first cycle started.140 completed cycles in 71 remaining women were analyzed so far. 46% of the recruited women completed the study after 3 cycles, the drop-out-rate was 32.4%. The app predicted ovulation for cycle day 14.3 (mean, SD ± 3.5). In 25 cycles the date of ovulation was before day 12 and in 33 cycles on day 16 or later. The first ultrasound was done on cycle day 13.5 (mean, SD ± 3), the second ultrasound on cycle day 17.6 (mean, SD ± 3.6). In several cycles at least one (up to three) corrections of the prognosis occurred by the app, resulting in the day of predicted ovulation being moved either backward (retrospectively) or forward by 2.5 (mean, SD ± 1.9) days. Urinary progesterone measured with the OPK and post-ovulatory ultrasound were in accordance in the majority of cycles. 17% (n = 12) of the women became pregnant in the current analysis (mean duration to pregnancy: 1.3 cycles). In the ITT population (after informed consent) the rate was 23%. Limitations, reasons for caution This study was performed without a control group. Therefore, as an intraindividual control, a follow-up is planned to calculate the pregnancy rates and outcomes with and after the use of the app. Wider implications of the findings Our study shows that digitally integrated OPK are able to predict the fertile window and the ovulation date in a slightly subfertile cohort unselected for mild cycle irregularities. An early and accurate prediction may help couples to conceive, particularly if the date of ovulation is divergent from standard information. Trial registration number Not applicable

P-607 Interindividual variation of progesterone elevation post LH rise: Implications for natural cycle frozen embryo transfers in the individualized medicine era.

Abstract Study question To what extent does the period between LH-rise and P4-rise vary in ovulatory natural menstrual cycles? Summary answer Three distinct ovulatory patterns were noted defined as the period between LH-rise and P4-rise and varied by up to two days. What is known already The key to success of FET in a NC is the accurate diagnosis of ovulation to determine the optimal timing of embryo transfer. The most common method used to determine time of ovulation in NC is the detection of luteinizing hormone (LH) surge. It is well recognized that the endocrine profile of menstrual cycles varies not only amongst women but also from cycle to cycle for any given female. Most hormone trajectories in individual women differ considerably from the mean hormonal curves and LH surges culminating in ovulation appear to be highly variable in timing, amplitude and duration. Study design, size, duration Retrospective, observational study including 102 women who underwent endocrine monitoring during a frozen embryo transfer in a natural cycle between 1st January 2017 and 31st August 2021 in a tertiary IVF centre. Participants/materials, setting, methods Ultrasound scans were performed to monitor follicular growth. Serial measurements of serum LH, FSH, estradiol and P4 were commenced once a dominant follicle measuring ≥ 14mm was identified and on three consecutive days until (including) the day of ovulation. The LH surge was considered to have begun when the concentration rose by 180% above the most recent serum value. Progesterone concentrations of 1.0ng/ml and above were regarded as confirmation of ovulation to schedule FET. Main results and the role of chance Patients’ characteristics presented as median and (range): age 35 years (23-43), BMI 25.24kg/m2 (17.32-38.21), AMH 2.07 ng/ml (0.06-8.12). Twenty-one (20.6%) women had the LH-rise 2 days prior to P4 -rise, 71 (69.6%) had on the day immediately preceding and 10 (9.8%) on the same day of P4-rise. If FET was scheduled based on LH-rise, 30.4% of the patients would have their FET scheduled on a different day than FET scheduled according to P4-rise. The period between LH-rise and P4-rise would be approximately one day longer in 20.6% of the participants and one day shorter in 9.8% than the anticipated 24 hour period. There was a significant difference in body mass index between those women who had LH-rise 2 days prior to P4-rise (BMI 26.91 kg/m2 (range 23.74-30.75) and the women who had LH-rise on the same day (BMI 22.39 kg/m2 (range 20.91-24.96) (p = 0.03). The AMH levels were also found to be significantly lower in those women who had LH rise 2 days prior to P4-rise ( AMH 1.59 ng/ml (range: 0.82-2.09) as compared to those who had LH-rise on the same day (AMH 2.67ng/ml (range: 1.83—6.63) (p = 0.04). LH may not serve as the best benchmark to schedule FET. Limitations, reasons for caution Frozen embryo transfers were scheduled according to serum progesterone levels therefore our study does not provide a direct answer to the question whether FET scheduled according to serum progesterone levels provides higher live birth rates than FET scheduled based on urinary or serum LH levels in a natural cycle. Wider implications of the findings Variation in the period between LH rise and progesterone rise in ovulatory cycles has implications for the choice of marker for the start of secretory transformation in frozen embryo transfer cycles. The study participants are representative of the relevant population of women undergoing frozen embryo transfer in a natural cycle. Trial registration number Not Applicable

Validation of urinary reproductive hormone measurements using a novel smartphone connected reader

Home use tests to monitor hormone trends during the menstrual cycle have been available over-the-counter for a long time. However, these tests often depend upon manual readouts and hence may lead to false analysis. Furthermore, a lot of these tests are also not quantitative. The aim of this study was to evaluate the accuracy of the quantitative home-based fertility monitor, Inito Fertility Monitor (IFM) and to use it to identify novel hormone trends in natural menstrual cycles. There were two aspects to our analysis: (i) Evaluating the efficacy of Inito Fertility Monitor in the measurement of urinary Estrone-3-glucuronide (E3G), Pregnanediol glucuronide (PdG) and Luteinizing hormone (LH), and (ii) A retrospective study of patients' hormone profiles using IFM. To evaluate the efficacy, the recovery percentage of the three hormones from IFM was evaluated using standard spiked solutions, the accuracy of measurement was calculated and the correlation between reproducible values from IFM and ELISA was established. During the validation of IFM, novel hormone trends were also observed. In order to reinforce the observations, a second group of 52 women was recruited. Assessment of the accuracy of IFM and evaluation of the volunteer urine samples was performed in a laboratory. Home assessment of hormone analysis was carried out using IFM. For the validation study, 100 women aged 21–45 years with cycle lengths ranging from 21 to 42 days were recruited. The participants had no previously diagnosed infertility conditions and their cycle lengths did not vary for more than 3 days from the expected cycle length. Daily first morning urine samples were collected from these 100 women. For the second group, 52 women were selected meeting the same criteria set for the validation study and IFM was provided to these women for testing at home. Coefficient of variation and recovery percentage of IFM with respect to laboratory based ELISA. Percentage occurrence of novel hormone trends and AUC analysis of a novel criteria identified for confirming ovulation. We observed that with all three hormones, IFM had an accurate recovery percentage. We found that the assay has an average CV of 5.05% in PdG measurement, 4.95% in E3G measurement and 5.57% in LH measurement. Furthermore, in predicting the concentration of E3G, PdG and LH in urine samples, we show that IFM has a high correlation with ELISA. In this study, we could also reproduce hormones trends across the menstrual cycle that have been observed by previous studies. We also identified a novel criterion for earlier confirmation of ovulation which could accurately distinguish ovulatory from anovulatory cycles with 100% specificity and had an area under the ROC curve of 0.98. In addition, we identified a new hormone trend which could be observed in 94.5% of the ovulatory cycles. The Inito Fertility Monitor is an effective tool for calculating the urinary concentrations of E3G, PdG and LH and can also be used to provide accurate fertility scores and confirm ovulation. We show that certain hormone trends associated with urinary E3G, PdG and LH could be accurately captured using IFM. In addition, we report a novel criterion for earlier confirmation of ovulation compared to existing criteria. Finally, we present a novel hormone pattern associated with most of the menstrual cycles by examining hormone profiles from the volunteers recruited for the clinical trial.Trial registration: The trial is registered at the current controlled trials ISRCTN registry #ISRCTN15534557.

Natural cycle versus modified natural cycle for endometrial preparation in women undergoing frozen-thawed embryo transfer: An RCT.

Studies have evaluated different endometrial preparation methods, but the optimal frozen-thawed embryo transfer (FET) cycle strategy in terms of the in-vitro fertilization outcome is still debated. To compare the natural versus modified natural cycles for endometrial preparation in women undergoing FET. This study was designed as a randomized clinical trial, and it was performed at the Arash women's hospital between August 2016-2018. Hundred and forty eligible participants were enrolled in this study and were randomly divided into 2 groups by using the block randomization method, including true natural FET (n = 70) and modified natural FET (mNFET) (n = 70) cycles. Both groups were monitored for endometrial thickness and follicular size; simultaneously spontaneous luteinizing hormone surge using urinary luteinizing hormone testing kits. The mNFET group received 5000 IU of human chorionic gonadotropin injection to trigger final follicular maturation. Luteal support by vaginal progesterone (cyclogest 400 mg twice daily) was used in true natural FET from the day of transfer until the 10 wk of pregnancy. Chemical and clinical pregnancy and abortion rates were considered as the primary outcomes. There were no differences in the participants' baseline characteristics between groups. There was no difference in clinical pregnancy and abortion rate between groups, while the implantation rate was significantly higher in the mNFET group (29.2% vs. 17.6%; p = 0.036). The results demonstrated that both types of natural cycles were similar in pregnancy outcomes, while modified cycles might be associated with a higher implantation rate.