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The market for technology that tracks ovulation to promote conception is rapidly expanding in the United States, targeting the growing audience of technologically proficient, reproductive-age female consumers. In this narrative review, 23 different, nonprescription wearables and devices designed to help women track their fertile window were identified as currently, commercially available in the United States. The majority of these utilize measurements of basal body temperature or combinations of various urinary hormones. This clinical opinion characterizes the scant available research validating the accuracy of these technologies. It further examines research oversight, discusses the utility of these wearables and devices to consumers, and considers these technologies through an equity lens. The discussion concludes with a call for innovation, describing promising new technologies that not only harness unique physiologic parameters to predict ovulation, but also focus on cost-effectiveness with the hope of increasing access to these currently costly devices and wearables., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Biochemical confirmation of ovulation typically involves measuring serum progesterone levels during the mid-luteal phase. Alternatively, this information could be obtained by monitoring urinary excretion of conjugated metabolites of ovarian steroids such as pregnanediol 3-glucuronide (PDG) using immunoassay techniques that have methodological limitations. The aim of the present study was to develop a mass spectrometry (MS)-based method for the rapid and accurate measurement of urinary PDG levels in spot urine samples. A "dilute and shoot" ultra-high-performance liquid cromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed for measuring PDG urinary concentration with a 6-min analysis time. The method underwent validation in accordance with ISO 17025 documentation for quantitative methods, proving an efficient separation of PDG from other structurally similar glucuro-conjugated steroid metabolites and ensuring a sufficient sensitivity for detecting the target analyte at concentrations as low as 0.01 μg/mL. The validation protocol yielded satisfactory results in terms of accuracy, repeatability, intermediate precision, and combined uncertainty. Additionally, the stability of both the samples and calibration curves was also conducted. The application to real urine samples confirmed the method's capability to measure PDG levels throughout an entire menstrual cycle and detecting ovulation. The rapidity of the analytical platform would therefore enable high throughput analysis, which is advantageous for large cohort clinical studies., (© 2024 The Author(s). Biomedical Chromatography published by John Wiley & Sons Ltd.)

Recent methodological recommendations suggest the use of the "3-step method," consisting of calendar-based counting, urinary ovulation testing, and serum blood sampling, for the identification of subtle menstrual disturbances (SMDs). However, the use of the 3-step method is not always feasible, so a less demanding combination of calendar-based counting and urinary ovulation testing, that is, the 2-step method, may be a viable alternative., Purpose: To investigate the agreement between the 2- and 3-step methods for the detection of SMDs., Methods: Menstrual cycles (MCs, 98) of 59 athletes were assessed using the 2- and 3-step methods. Regular-length MCs (ie, ≥21 and ≤35 d) were classified as either having no SMD (luteal phase length ≥10 d, midluteal progesterone concentration ≥16 nmol·L-1, and being ovulatory) or having an SMD (eg, short luteal phase [<10 d], inadequate luteal phase [midluteal progesterone concentration <16 nmol·L-1], or being anovulatory). Method agreement was assessed using the McNemar test and Cohen kappa (κ)., Results: Substantial agreement was observed between methods (κ = .72; 95% CI, .53-.91), but the 2-step method did not detect all MCs with an SMD, resulting in evidence of systematic bias (χ2 = 5.14; P = .023). The 2-step method detected 61.1% of MCs that had an SMD ([51.4, 70.8]), as verified using the 3-step method, and correctly identified 100% of MCs without an SMD., Conclusions: MCs classified as being disturbed using the 2-step method could be considered valid evidence of SMDs. However, MCs classified without SMDs do not definitively confirm their absence, due to the proven underdetection via the 2-step method.

Ovulation is a vital sign, as significant as body temperature, heart rate, respiratory rate, and blood pressure, in assessing overall health and identifying potential health issues. Ovulation is a key event of the menstrual cycle that provides insights into the hormonal and reproductive health aspects. Affected by the orchestra of hormones, namely thyroid, prolactin, and androgens, disruptions in ovulation can indicate endocrinological conditions and lead to gynecological problems, such as heavy menstrual bleeding, irregular periods, amenorrhea, dysmenorrhea, and difficulties in getting pregnant. Monitoring ovulation and detecting disruptions can aid in the early detection of health issues, extending beyond reproductive health concerns. It can help identify underlying causes of symptoms like excessive fatigue and abnormal hair growth. The integration of digital health technologies, such as mobile apps using machine learning algorithms, wearables tracking temperature, heart rate, breath rate, and sleep patterns, and devices measuring reproductive hormones in urine or saliva samples, offers a wealth of opportunities in family planning, early health issue diagnosis, treatment adjustment, and tracking menstrual cycles during assisted reproductive techniques. These advancements provide a comprehensive approach to health monitoring, addressing both reproductive and overall health concerns., Competing Interests: None declared., (Thieme. All rights reserved.)

Smartphone-based fertility awareness methods with home-based urinary hormonal testing are gaining popularity for fertility tracking. In our university-affiliated family practice, we integrated a previously developed ovulation tracking application into a protocol for monitoring urinary sex hormones and cervical secretions. Serum progesterone was used to confirm the luteal phase, with levels ≥ 15.9 nmol/L ensuring confirmation. Data from 110 women seen for infertility treatment ( n  = 95) or family planning advice ( n  = 15) and using our ovulation prediction protocol showed that most opted for a combination of cervical mucus and luteinizing hormone testing ( n  = 86). Among those using it for family planning, the median usage among women spanned 56 cycles, and 13 cycles per woman required progesterone testing for confirmation. Thirteen patients are still using the method without unintended pregnancies. No unintended pregnancies occurred. Confidence in tests based on serum progesterone was high (93%). For infertility, the method helped in the identification of anovulation, evaluating treatment response, and in diagnosing subfertility causes. This proof-of-concept retrospective descriptive case series suggests the potential for smartphone-based monitoring in fertility management, urging further studies for application enhancements and prospective validation., Competing Interests: We do not report any conflicts of interest and we are responsible for the writing of this article. This article is being submitted as a special issue invitation by the journal and the cost for open publication was provided by PreMom, but they had no role in any data gathering, analysis, and writing of this article., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Ovulation is critical for both conception and overall health, but many people who may ovulate are not tracking ovulation or any other part of their menstrual cycle. Failure to track ovulation, especially in those trying to conceive, can lead to fertility challenges due to absent ovulation, mistiming intercourse, or an undetected luteal phase defect. Ovulatory disorders and mistiming intercourse are both primary causes of infertility, and tracking ovulation is shown to decrease the average time to conception. While there are many tracking methods and apps available, the majority are predictive apps or ovulation predictor kits and do not test or track both successful ovulation and the health of the luteal phase, leading to missing information that could contribute to diagnosis or successful conception. Here, we review why ovulation tracking and a healthy luteal phase are important for those trying to conceive. We present currently available ovulation tracking methods that detect both ovulation and the luteal phase, including cervical mucus, urinary hormone testing, and basal body temperature, and discuss the use, advantages, and disadvantages of each. Finally, we consider the role of digital applications and tracking technologies in ovulation tracking., Competing Interests: A.B. is the CEO and founder of MFB Fertility, Inc., makers of Proov hormone testing products. A.K.W. is an independent contractor with MFB Fertility. A.E. is a medical advisor for MFB Fertility., (Thieme. All rights reserved.)

Background: There is no consensus on tests required to either diagnose unexplained infertility or use for research inclusion criteria. This leads to heterogeneity and bias affecting meta-analysis and best practice advice., Objectives: This systematic review analyses the variability of inclusion criteria applied to couples with unexplained infertility. We propose standardised criteria for use both in future research studies and clinical diagnosis., Search Strategy: CINAHL and MEDLINE online databases were searched up to November 2022 for all published studies recruiting couples with unexplained infertility, available in full text in the English language., Data Collection and Analysis: Data were collected in an Excel spreadsheet. Results were analysed per category and methodology or reference range., Main Results: Of 375 relevant studies, only 258 defined their inclusion criteria. The most commonly applied inclusion criteria were semen analysis, tubal patency and assessment of ovulation in 220 (85%), 232 (90%), 205 (79.5%) respectively. Only 87/220 (39.5%) studies reporting semen analysis used the World Health Organization (WHO) limits. Tubal patency was accepted if bilateral in 145/232 (62.5%) and if unilateral in 24/232 (10.3%). Ovulation was assessed using mid-luteal serum progesterone in 115/205 (56.1%) and by a history of regular cycles in 87/205 (42.4%). Other criteria, including uterine cavity assessment and hormone profile, were applied in less than 50% of included studies., Conclusions: This review highlights the heterogeneity among studied populations with unexplained infertility. Development and application of internationally accepted criteria will improve the quality of research and future clinical care., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background and Objectives : Accuracy in detecting ovulation and estimating the fertile window in the menstrual cycle is essential for women to avoid or achieve pregnancy. There has been a rapid growth in fertility apps and home ovulation testing kits in recent years. Nevertheless, there lacks information on how well these apps perform in helping users understand their fertility in the menstrual cycle. This pilot study aimed to evaluate and compare the beginning, peak, and length of the fertile window as determined by a new luteinizing hormone (LH) fertility tracking app with the Clearblue Fertility Monitor (CBFM). Materials and Methods : A total of 30 women were randomized into either a quantitative Premom or a qualitative Easy@Home (EAH) LH testing system. The results of the two testing systems were compared with the results from the CBFM over three menstrual cycles of use. Potential LH levels for estimating the beginning of the fertile window were calculated along with user acceptability and satisfaction. Results : The estimates of peak fertility by the Premom and EAH LH testing were highly correlated with the CBFM peak results (R = 0.99, p < 0.001). The participants had higher satisfaction and ease-of-use ratings with the CBFM compared to the Premom and EAH LH testing systems. LH 95% confidence levels for estimating the beginning of the fertile window were provided for both the Premom and EAH LH testing results. Conclusions : Our pilot study findings suggest that the Premom and EAH LH fertility testing app can accurately detect impending ovulation for women and are easy to use at home. However, successful utilization of these low-cost LH testing tools and apps for fertility self-monitoring and family planning needs further evaluation with a large and more diverse population.

Fertility Awareness Based Methods Abstract. The so called natural family planning methods are based on the prospective detection of the few fertile days (fertile window) during the menstrual cycle. The existence of such a fertile window was originally based on observation of the menstrual cycle which showed that that the lowest fertlity was at the beginning and in the seccond half of the cycle. On this observation the calendar method was based. Later other signs of ovulation were detected (temperature, cervical mucus and even later the LH peak) which allowed to better predict the fertile phase. It became evident that the contraceptive efficacy was dependent on the number of ovulation related variables and the continuity and regularity of the measurements (user adherence). The new data collecting technologies facilitate correct and regular data collection and may such offer new opportunities.

Soft candy was discovered to be an excellent electronic material and was used to fabricate electrodes for salivary conductivity-based diagnostics. Using a simple molding process, a soft candy (Tootsie Roll) was made into 20 × 20 × 5 mm electrodes with a stable frequency response (0.1-100 kHz). The soft candy electrode-liquid interface circuit model was also developed for the first time. Using 0.01, 0.05, and 0.1 M phosphate-buffered saline and artificial saliva of varying conductivities, the performance of the soft candy (Tootsie Roll) electrode was evaluated. The electrode has a low temperature coefficient of ∼0.02 V/C, and the evaporation-induced mass change during measurement (<3 min) was negligible. Using a trenched surface, a limit of detection (LOD) of ∼1630 μS/cm was obtained and was lower than the saliva conductivity of a healthy adult at ∼3500 μS/cm. Thus, it is suitable for monitoring the ovulation cycle for natural family planning as well as chronic kidney disease diagnosis. Given the ubiquity of soft candy, the simplicity of the molding process, and the negligible medical waste stream, it is a more appropriate approach to diagnostics design for resource-scarce clinical settings, such as those in developing countries. The broader impact of this work will be the paradigm shift of soft candy from food to a new class of edible, moldable, high-resistivity, and stable electronic materials.

Background: Non-invasive self-testing using an objective chemical method to detect ovulation is valuable for women planning conception, practising contraception or undergoing infertility investigations or treatment., Methods: Based on luteal phase secretion of progesterone (P 4 ) and excretion of its major metabolite, pregnanediol glucuronide (PDG), we developed a novel direct liquid chromatography-mass spectrometry (LCMS) method to measure PDG and other steroid glucuronides in urine and in dried urine spots (DUS) without deconjugation or derivatization. Urine PDG by LCMS and immunoassay (P3G) and P 4 by immunoassay with and without adjustment for creatinine were evaluated in daily first void urine samples from 10 women through a single menstrual cycle in which ovulation was confirmed by serial transvaginal ultrasound., Results: Urine PDG with and without creatinine adjustment was stable during the follicular phase with the expected striking rise in the luteal phase peaking at 5 days after ovulation. Using a single spot urine sample (100 μL) or a DUS (<20 μL urine) and an optimal threshold to distinguish pre- from post-ovulatory samples, in ROC analysis urine PDG adjusted for creatinine accurately identified ovulation in 92 % of samples was comparable with P3G immunoassay and superior to urine P 4 with or without adjustment for creatinine. Extending the analysis to two or three consecutive daily samples reduced the false negative rate from 8% to 2.6 % for two and 1.9 % for three urine samples., Conclusions: This method holds promise as a non-invasive self-test method for women to determine by an objective chemical method their ovulatory status., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

A review of 23 research articles to examine fertility awareness-based methods revealed biologic indicators and tracking methods to identify the fertile window in reproductive-aged women. This literature review indicated that a woman's cycle regularity is a major determinant of which method is best. Additionally, the woman's desire to achieve a pregnancy and her preference regarding the intensity of training are factors in method choice. Some evidence suggests that use of at least two biologic indicators is most effective for determining the fertility window. Recommended web and mobile applications also are discussed.

We developed an electrolyte pre-deposition-based saliva pattern modulation method to detect ovulation with high accuracy and reliability. Ovulation tests using human saliva have advantages in terms of the earlier ovulation detection and more convenient sample collection procedure; however, accuracy is low, which is a critical limitation given that the concentrations of salivary constituents can vary depending on the health status of the tested individual and subjective user judgement of the test result. In this study, we quantitatively analyzed saliva patterns according to the concentrations of electrolytes and proteins in the ovulation test and found that changes in the saliva pattern during the ovulatory period can be controlled by sodium chloride (NaCl) pre-deposition, which directly affects the accuracy of ovulation detection. The 100 nmol NaCl pre-deposition condition proved optimal, being two-fold more sensitive to changes in saliva pattern versus the non-pre-deposition condition (accuracy of ovulation detection = 66.6% and 33.3%, respectively). Although accuracy remained insufficient for actual applications compared to the urine-based ovulation detection method, we expect that the electrolyte pre-deposition method will greatly contribute to enhancing the performance of saliva-based ovulation detection tests, toward a commercially satisfactory level of accuracy.

Objective: We present a non-invasive wearable device for fertility monitoring and propose an effective and flexible statistical learning algorithm to detect and predict ovulation using data captured by this device., Methods: The system consists of an earpiece, which measures the ear canal temperature every 5 min during night sleep hours, and a base station that transmits data to a smartphone application for analysis. We establish a data-cleaning protocol for data preprocessing and then fit a Hidden Markov Model (HMM) with two hidden states of high and low temperature to identify the more probable state of each time point via the predicted probabilities. Finally, a post-processing procedure is developed to incorporate biorhythm information to form a time-course biphasic profile for each subject., Results: The performance of the proposed algorithms applied to data collected by the device are compared with traditional methods in terms of match rate with self-reported ovulation days confirmed with an ovulation test kit. Empirical study results from a group of 34 users yielded significant improvements over the traditional methods in terms of detection accuracy (with sensitivity 92.31%) and prediction power (23.07-31.55% higher)., Conclusion: We demonstrated the feasibility for reliable ovulation detection and prediction with high-frequency temperature data collected by a non-invasive wearable device., Significance: Traditional fertility monitoring methods are often either inaccurate or inconvenient. The wearable device and learning algorithm presented in this paper provide a user friendly and reliable platform for tracking ovulation, which may have a broad impact on both fertility research and real-world family planning.

Background: Women trying to conceive are increasingly using fertility-tracking software applications to time intercourse. This study evaluated the difference in conception rates between women trying to conceive using an application-connected ovulation test system, which measures urinary luteinizing hormone and an estrogen metabolite, versus those trying without using ovulation testing. Materials and Methods: This home-based study involved 844 volunteers aged 18-40 years seeking to conceive. Volunteers randomized to the test arm were required to use the test system for the duration of the study while those randomized to the control arm were instructed not to use ovulation testing. Pregnancy rate differences across one and two cycles between the two groups were examined. Results: Volunteers in the test ( n  = 382) and control arms ( n  = 403) had similar baseline demographics. The proportion of women pregnant after one cycle was significantly greater in the test arm (25.4%) compared with the control arm (14.7%; p  < 0.001). After two cycles, there continued to be a greater proportion of women pregnant in the test arm compared with the control arm (36.2% vs. 28.6%; p  = 0.026). In the test arm, volunteers had intercourse less frequently per cycle compared with those not using ovulation testing (9 [range: 1-60] vs. 10 [range: 1-50]; p  = 0.027), but were more likely to target intercourse to a particular part of their cycle compared with those not using ovulation testing (88.5% vs. 57.8%; p  < 0.001). Conclusion: Using the test system to time intercourse within the fertile window increases the likelihood of conceiving within two menstrual cycles.

Purpose: This study aims to compare the accuracy of fertile window identification with the contraceptive app Natural Cycles against the Rhythm Method and Standard Days Method (SDM). Materials and methods: Menstruation dates, basal body temperature (BBT), and luteinising hormone (LH) test results were collected anonymously from Natural Cycles app users. The fraction of green days (GDs) and wrong green days (WGDs) allocated by the various algorithms was determined over 12 cycles. For comparison of Natural Cycles and the Rhythm Method, 26,626 cycles were analysed. Results: Natural Cycles' algorithms allocated 59% GDs (LH, BBT) in cycle 12, while the fraction of WGDs averaged 0.08%. The Rhythm Method requires monitoring of six cycles, resulting in no GDs or WGDs in cycle 1-6. In cycle 7, 49% GDs and 0.26% WGDs were allocated. GDs and WGDs decreased to 43% and 0.08% in cycle 12. The probabilities of WGDs on the day before ovulation with Natural Cycles were 0.31% (BBT) and 0% (LH, BBT), and 0.80% with the Rhythm Method. The probability of WGDs on the day before ovulation was 6.90% with the SDM. Conclusions: This study highlights that individualised algorithms are advantageous for accurate determination of the fertile window and that static algorithms are more likely to fail during the most fertile days.

The Coat-A-Count® radioimmunoassay has been long and widely used to determine the concentration of progesterone in serum or plasma of bitches (progRIA), but was discontinued in 2014. The Immulite® 1000 LKPG1 chemiluminescence immunoassay has gained prominence since 2003 to determine the concentration of progesterone in serum of bitches, but the assay changed in 2012 (Immulite® 1000 LKPW1). This study assessed the feasibility of using Immulite® 1000 LKPW1 (progImm) to estimate the time of clinically relevant events during oestrus and compared progRIA and progImm 2 and 3 days after the first or only day of the luteinizing hormone surge (LH1). ProgImm first exceeded 5.1 nmol/L on the same day that progRIA first exceeded 6 nmol/L, a proxy for the occurrence of the LH surge, or the day before in 28 of 31 (90%) of oestrous periods. ProgImm first exceeded 13.6 nmol/L on the same day that progRIA first exceeded 16 nmol/L (a proxy for the day of ovulation) or the day before in 34 of 35 (97%) oestrous periods. ProgImm first exceeded 5.4 nmol/L on LH1 or the day before in 24 of 25 (95%) of oestrous periods. The median of progImm 2 days after LH1 was 1.2 nmol/L lower than the 10.7 nmol/L of progRIA (p = 0.001). The mean of progImm 3 days after LH1 was 2.2 nmol/L lower than the 19.0 nmol/L of progRIA (p 0.001). In conclusion, the days on which progImm first exceeded 5.1 nmol/L, 13.6 nmol/L and 5.4 nmol/L effectively estimate the days on which progRIA reached 6 nmol/L or 16 nmol/L or LH1.

Our goal was to develop an objective computer-assisted volumetric method of assessing vascular flow from colour Doppler ultrasound data of ovarian structures recorded by free-hand movement. We hypothesized that a vascularity index (ratio of the region of blood flood to the region of ovarian structure) obtained from the three-dimensional volumetric analysis would be more precise (less variable) than conventional two-dimensional analysis of single images in estimating the functional status of the preovulatory follicles and corpus luteum. Doppler ultrasound cineloops of water buffaloes (Bubalus bubalis; n = 22) ovaries were recorded daily from 12 h before GnRH treatment to four days after ovulation. Cineloops were processed using Fiji and Imaris software packages for segmenting the area (two-dimensional analysis) and the volume (three-dimensional analysis) occupied by the blood-flow and associated tissue to calculate the vascularity index. For volumetric measurement, all images in a cineloop were used (i.e., no a-priori selection of images) while for two-dimensional analysis, three images from the region with apparent maximum vascularity were selected. The volumetric method was verified with theoretical ellipsoidal volume of the follicle (r = 0.96 P < 0.01) or corpus luteum (r = 0.58 P = 0.02). The variability in the follicular vascularity index among animals was lower using the volumetric method than two-dimensional analysis (0.018 ± 0.002 vs 0.030 ± 0.005, P < 0.01), while the variability for CL vascularity was similar between methods (P = 0.23). An increase in the follicular vascularity index was detected at 12 h after GnRH treatment using both methods (two-dimensional: 0.030 ± 0.008, P < 0.01; three-dimensional: 0.016 ± 0.006, P < 0.02). Buffaloes that ovulated tended to have a greater increase in 3D vascularity index than non-responding buffaloes (P = 0.06); the two-dimensional method was not able to detect these changes. Using the three-dimensional method, a moderate positive correlation (r = 0.59; P = 0.02) was evident between the follicular vascularity index at 14-16 h after GnRH treatment and follicular diameter. In conclusion, an objective volumetric method for assessing relative ovarian blood flow changes was developed using Doppler ultrasound cineloops recorded by free-hand movement. The 3-dimensional method eliminates the need for a-priori selection of images and is more precise as a result of decreased technical variability., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To investigate the validity of self-reported fertility data generated by a mobile application-based cohort in comparison with data collected by traditional clinical methodologies., Design: Data were collected from July 2013 to July 2018 through a mobile application designed to track fertility. Bayesian hierarchical models were used to assess day-specific pregnancy probabilities. Descriptive statistics were used to estimate differences in day of ovulation and lengths of menstrual phases and to assess changes in the cervix and ovulation-related symptoms drawing closer to the day of ovulation., Setting: Not applicable., Patient(s): Data consisted of 225,596 menstrual cycles from 98,903 women., Intervention(s): None., Main Outcome Measure(s): Day-specific probabilities of pregnancy, variability in lengths of the follicular and luteal phases, trends in prevalence of symptoms and cervix changes across the fertile window., Result(s): Analyses were consistent with established clinical knowledge. Probability of conception was highest during the 5 days before and day of ovulation, with the highest probability occurring the day before ovulation. The average cycle length was 29.6 days, and average lengths of the follicular and luteal phases were 15.8 and 13.7 days, respectively. Closer to day of ovulation, women were more likely to report changes in the cervix corresponding to fluid consistency, feel, position, and openness and symptoms associated with ovulation, including pelvic pain, tender breasts, increased sex drive, and cramps., Conclusion(s): Components of the menstrual cycle and fertile window, when re-evaluated with a mobile application-based cohort, were found to be consistent with established clinical knowledge, suggesting an agreement between traditional and modern data collection methodologies., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Liquid chromatography tandem mass spectrometry (LC-MS/MS) enables specific and sensitive quantification of steroids with a high throughput. Saliva sampling is advantageous for multisample profiling over longer periods of time, as it is non-invasive, cheap, can be carried out at home and does not require the attendance of clinical personnel. We developed a rapid LC-MS/MS for the measurement of salivary progesterone, frequently assessed as ovulation marker in patients desiring fertility., Methods: Samples (300 μL) were prepared by supported liquid extraction using dichloromethane and were reconstituted in 40% methanol. Chromatography was performed using a C8 column with a water/methanol gradient containing 0.1% formic acid and 2 mmol/L ammonium acetate. Quantification was performed with a Waters TQ-S mass spectrometer., Results: Total run time was 5.5 min. The lower limit of quantification was 20 pmol/L (1.2 fmol on column). Inter- and intra-assay comparison showed coefficients of variation and bias between measured and nominal concentrations of less than 11%. Mean recovery was 91%. Interference with a large set of natural and synthetic steroids was excluded. The assay was successfully applied to measure progesterone variation during the menstrual cycle ( n = 9) and diurnal variations during luteal phase ( n = 7) in regularly cycling women., Discussion: We present a novel LC-MS/MS assay for the determination of salivary progesterone with high-throughput potential. The applicability of the assay for progesterone profiling during the menstrual cycle is demonstrated.

The ability to accurately predict ovulation at-home using low-cost point-of-care diagnostics can be of significant help for couples who prefer natural family planning. Detecting ovulation-specific hormones in urine samples and monitoring basal body temperature are the current commonly home-based methods used for ovulation detection; however, these methods, relatively, are expensive for prolonged use and the results are difficult to comprehend. Here, we report a smartphone-based point-of-care device for automated ovulation testing using artificial intelligence (AI) by detecting fern patterns in a small volume (<100 μL) of saliva that is air-dried on a microfluidic device. We evaluated the performance of the device using artificial saliva and human saliva samples and observed that the device showed >99% accuracy in effectively predicting ovulation.

Objective: To develop clinical practice recommendations for the use of natural contraception and female and male barrier methods., Materials and Methods: A systematic review of English and French literatures related to the safety and effectiveness of natural contraceptive methods based on PubMed, Cochrane Library, practice recommendations issued by international scientific societies and guidelines provided by the World Health Organization (WHO) as well as updates from the Center for Disease Control and Prevention (CDC)., Results: Natural contraceptives methods include fertility awareness-based methods, lactational amenorrhea method (LAM) and withdrawal method. The prevalence is low (4.6% of users) and remains stable over the years. Identification of the fertile period can be symptom-based cervical mucus (Billings), two-day method, basal body temperature, symptom-thermal method or based on calendar calculation (Ogino-Knauss, standard day method). Pregnancy rate after one-year utilization varies from 0.4% to 5% in perfect use but 8% in common practice. Effectiveness increases with absence of vaginal sex and decreases when combined to barriers method inadequately implemented. Data is scarce on reliability and effectiveness of ovulation predictor kits readily available on internet. Lactational amenorrhea method (LAM) can be very effective (98%) provided three conditions are fulfilled: within 6 months after birth, amenorrhea is effective, and breastfeeding is exclusive or quasi exclusive (day/night). Withdrawal method is constraining and of limited effectiveness. Male and female condom, diaphragm, cervical cap and spermicides are mechanical and chemical barrier methods, preventing spermatozoids from passing through the cervix into the uterus and therefore preventing fecundation. Female and male condoms offer a double protection to avoid pregnancy and prevent STD's. They are effective provided strict conditions of use are fulfilled. Male condom is favored by teenagers (45.6% among 15 to 19 years old), sometimes in combination with contraceptive pill (16% of cases). Women on the pill decreases according to their age. Pregnancy rates within the first year of consistent and correct use of these methods vary between 5 to 26% and reach 20 to 32% in practical use. Diaphragm and cervical cap need to be used in combination with spermicides. Spermicides have limited effectiveness when used alone., Conclusion: In common practice, natural and barrier contraceptive methods are more constraining and less effective than modern contraceptive method. They can be an alternative at given time and/or in situations where the women or the couple accept the possibility of an unexpected pregnancy which might be terminated or not. Women/couples need to be properly informed on how to use such methods, on their disadvantages and possible failures in common practice. Reminders are to be given on emergency contraceptive methods (IUD, hormonal) after unprotected sex., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Study Objective: Understanding what constitutes a normal menstrual cycle during the first gynecological year (GY1) is a common concern of adolescents and clinicians. However, limited high-quality evidence exists. We aimed to summarize published literature regarding menstrual and ovulatory patterns in GY1. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Electronic databases (MEDLINE, Pre-MEDLINE, Embase, Web of Science, CINAHL, Cochrane Library) were systematically searched from database inception to 2018. Eligible studies described menstrual cycles, symptoms, or validated ovulatory data in healthy adolescents in GY1. Two authors independently screened studies, extracted data, and assessed methodological quality., Results: Twenty-two studies involving more than 2000 adolescents were included. Thirteen recorded menstrual cycle and/or symptom data and 14 measured ovulation. Mean cycle length ranged from 32 to 61 days and decreased throughout GY1. Mean menses length was 4.9 to 5.4 days. Frequent menstrual bleeding was reported in up to 23% of participants, infrequent menstrual bleeding in up to one-third, and "irregular menstrual bleeding" in up to 43%. Dysmenorrhea was reported by 30%-89% of participants. Prevalence of ovulatory cycles identified using luteal phase serum or salivary progesterone or urinary pregnanediol was 0 to 45% and increased throughout GY1. However, all used definitions that would be considered subovulatory in clinical practice., Conclusion: Menstrual and ovulatory patterns in GY1 are diverse and differ from those of adults. A transitional phase of menstrual and ovulatory immaturity is common. However, ovulation, irregular cycles, and dysmenorrhea are not uncommon. As such, safe sexual practice should be advocated and prompt medical management should be accessible., (Copyright © 2018 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Ovulation timing in bitches is a routine procedure in small animal practice around the world. It is most frequently used for supporting breeding management, high-risk pregnancy monitoring and determination of the time of parturition. To learn more about how and for what reasons veterinarians interested in small animal reproduction perform canine ovulation timing, an online survey was conducted in 2017. The link to the survey was distributed via the mailing list cafereprod-l@list.cornell.edu and the website, the Twitter account and the Facebook page of EVSSAR. All respondents recommended using quantitative progesterone measurement for ovulation timing alone or in combination with other diagnostic tests. Vaginal cytology was also a commonly used technique. The 63 respondents followed different protocols for sampling and staining vaginal epithelial cells. Interestingly, 50 respondents used vaginal cytology routinely, but only two consider it as a very reliable and another nine as a somewhat reliable test if used alone. In a second project, delegates attending the EVSSAR congress held in Vienna, Austria, in June 2017 had the opportunity to examine seven stained vaginal smear slides under optical microscopy in a blinded approach. The results showed a marked heterogeneity in the identification of vaginal cells and assessment of the time in relation to ovulation. This heterogeneity supports the opinion of survey participants that vaginal cytology alone is not a valid tool for determining the day of ovulation. Results of both projects suggest that there is no standard procedure for the examination of vaginal smears in dogs. It is not recommended to determine the optimal time for mating based on the examination of a single vaginal smear only. According to some comments of survey participants, it is more useful to assess vaginal samples repeatedly and to use the findings to determine when to start progesterone measurement., (© 2018 Blackwell Verlag GmbH.)

Study Objective: To evaluate rates of presumptive anovulation in eumenorrheic adolescents and young adults with moderate to severe primary dysmenorrhea and those without primary dysmenorrhea., Design: Participants completed luteinizing hormone surge ovulation predictor test kits. Anovulatory cycles were defined by never receiving a positive result before the next menstrual period; participants were grouped as anovulatory if they experienced at least 1 anovulatory cycle during study participation. Participants rated daily level of menstrual pain on a 0-10 numeric rating scale., Setting: A university-based clinical research laboratory., Participants: Thirty-nine adolescents and young adults (ages 16-24) with primary dysmenorrhea and 52 age-matched control girls., Interventions and Main Outcome Measures: Rates of presumptive anovulation., Results: One hundred sixty-eight cycles were monitored, 29.8% (N = 50) of which were anovulatory (37.1% [39/105] vs 17.5% [11/63] of cycles in control and dysmenorrhea groups, respectively). During study participation, control girls were significantly more likely to have had at least 1 anovulatory cycle than were girls with primary dysmenorrhea (44.2% [23/52] vs 17.9% [7/39] of participants, respectively; P < .01). Cycle length and number of bleeding days between ovulatory and anovulatory cycles were similar. The primary dysmenorrhea group's maximum menstrual pain ratings did not differ between ovulatory and anovulatory cycles (4.77 and 4.36, respectively; P > .05)., Conclusion: Our data support previous findings of increased rates of ovulation in primary dysmenorrhea. However, menstruation after anovulatory cycles can be as painful as menstruation after ovulatory cycles. These data support the idea that regular menses do not necessarily indicate that a normal ovulatory cycle has occurred. Previous implications that ovulation is necessary for the development of substantial menstrual pain are incomplete., (Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Background: Daysy is a fertility monitor that uses the fertility awareness method by tracking and analyzing the individual menstrual cycle. In addition, Daysy can be connected to the application DaysyView to transfer stored personal data from Daysy to a smartphone or tablet (IOS, Android). This combination is interesting because as it is shown in various studies, the use of apps is increasing patients´ focus on their disease or their health behavior. The aim of this study was to investigate if by the additional use of an App and thereby improved usability of the medical device, it is possible to enhance the typical-use related as well as the method-related pregnancy rates., Result: In the resultant group of 125 women (2076 cycles in total), 2 women indicated that they had been unintentionally pregnant during the use of the device, giving a typical-use related Pearl-Index of 1.3. Counting only the pregnancies which occurred as a result of unprotected intercourse during the infertile (green) phase, we found 1 pregnancy, giving a method-related Pearl-Index of 0.6. Calculating the pregnancy rate resulting from continuous use and unprotected intercourse exclusively on green days, gives a perfect-use Pearl-Index of 0.8., Conclusion: It seems that combining a specific biosensor-embedded device (Daysy), which gives the method a very high repeatable accuracy, and a mobile application (DaysyView) which leads to higher user engagement, results in higher overall usability of the method.

Background: Assessing menstrual cycle function in the general population using a non-invasive method is challenging, both in non-industrialized and industrialized countries., Subjects and Methods: The Observatory of Fecundity in France (Obseff) recruited on a nationwide basis a random sample of 943 women aged 18-44 years with unprotected intercourse. A sub-study was set up to assess the characteristics of a menstrual cycle by using a non-invasive method adapted to the general population. Voluntary women were sent a collection kit by the post and requested to collect urine samples on pH strips, together with daily recording of reproductive-related information during a full menstrual cycle. A total of 48 women collected urine every day, whereas 160 women collected urine every other day. Immunoassays were used to measure pregnanediol-3-α-glucuronide, estrone-3-glucuronide and creatinine. Ovulation occurrence and follicular phase duration were estimated using ovulation detection algorithms, compared to a gold standard consisting of three external experts in reproductive medicine., Results: Every other day urine collection gave consistent results in terms of ovulation detection with every day collection (intraclass coefficient of correlation, 0.84, 95% confidence interval, 0.76-0.98). The proportion of anovulatory menstrual cycles was 8%. The characteristics of the ovulatory cycles were length 28 (26-34), follicular phase 16 (12-23), luteal phase 13 (10-16) days median (10th-90th percentiles)., Discussion-Conclusion: Assessing menstrual cycle characteristics based on urine sample spot only collected every other day in population-based studies through a non-invasive, well accepted and cost-limited procedure not requiring any direct contact with the survey team appears feasible and accurate.

Determination of the optimal insemination time in dairy cows is vital for fertilization success and is a challenging task due to silent or weak signs of estrus shown by some cows. This can be overcome by combining several estrus detection methods, leading to higher detection rates. However, an efficient, noninvasive method for detecting estrus in cows is still needed. Chemical cues released by the cow during estrus have been proposed to have pheromonal properties and signal readiness to mate to the bull. Such cues could be used in an industrial setting to detect cows in estrus. However, no conclusive published data show temporal changes in putative sex pheromone levels during estrus. The goal of this study was to determine the temporal pattern of putative sex pheromone components during estrus and to assess the reproducibility of changes in pheromone concentration with respect to ovulation time. Two injections of the hormone PGF 2α were administered over a 2-wk interval to induce and synchronize the estrous cycles of 6 Holstein cows. The precise time of ovulation was determined by means of an ultrasound technique, and estrus was determined by visual observation. Using solid-phase microextraction gas chromatography-mass spectrometry techniques, we showed that acetic and propionic acids, which have been proposed to be putative sex pheromone components in cows, were present in the headspaces of all estrous and diestrous fecal samples, whereas 1-iodoundecane was not detected by solid-phase microextraction or by solvent extraction with diethyl ether. Low levels of acids were observed until 1 d before ovulation, at which point their concentrations increased, peaking around 0.5 d before ovulation. The application of labeled synthetic standards revealed that during the peak of release, 36 ± 8 ng (average ± SD) of acetic acid and 10 ± 3 ng of propionic acid were present in 0.5-g samples of estrous-phase fecal matter compared with 19 ± 5 and 2.3 ± 1 ng of acetic and propionic acids, respectively, in the control diestrous samples. After the peak, the amounts of the compounds decreased sharply to match those of the control samples and afterward returned to the baseline readings. This decrease in the amounts of putative pheromone components was registered about 12 h before ovulation, indicating that acetic and propionic acids could be used as biomarkers for the electronic detection of ovulation., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: Various aspects of fertility knowledge, including the timing of the fertile window, have consistently been found to be poor. Limited evidence also suggests ovulation monitoring to time intercourse could be common. However, there have been no studies that compare these two aspects of fertility and women's fertility/infertility experiences., Aim: To examine the frequency of ovulation monitoring and its relationship with fertility knowledge and experience., Method: A cross-sectional study of women aged 25-50 years resident in southern New Zealand was undertaken in 2011. Randomly selected women were asked to complete a fertility questionnaire. Outcome prevalence measures were calculated with 95% confidence intervals (CI) and associations investigated using χ 2 tests and Poisson regression., Results: Ovulation monitoring was common, having ever been undertaken by 31.4% (95% CI: 28.5-34.3%) of the 1034 participants. However, knowledge was poor, particularly regarding the fertile window. More women who had ever monitored ovulation correctly identified the fertile window, although the proportion was still very low (18.4 vs 13.1% in those who had not, P = 0.027). Regression modelling showed ovulation monitoring was independently associated with seeking medical help to conceive, education and fertility experience, but not with knowledge., Conclusion: This study confirms ovulation monitoring was commonly undertaken. However, many women, including those who had monitored their ovulation, had poor fertility knowledge and failed to identify the fertile window. Poor fertility knowledge needs to be addressed, especially among women intending to conceive., (© 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objective: To analyze the effectiveness of an online, nurse-managed natural family planning (NFP) program among breastfeeding women and subgroups of these women., Design: Longitudinal comparative cohort study., Setting: A university-based online NFP education program and menstrual cycle charting system., Participants: Women (N = 816) with a mean age of 30.3 years (standard deviation = 4.5) who registered to use the online NFP system and indicated they were breastfeeding., Methods: Participants tracked their fertile times with an electronic hormone fertility monitor (EHFM), cervical mucus monitoring, or both. All unintended pregnancies were evaluated by professional nurses., Results: The correct use pregnancy rates were 3 per 100 users over 12 cycles of use, and typical rates were 14 per 100 at 12 cycles of use. At 12 cycles of use, total pregnancy rates were 16 per 100 for electronic hormone fertility monitor users (n = 380), 81 per 100 among mucus-only users (n = 45), and 14 per 100 for electronic hormone fertility monitor plus mucus users (n = 391)., Conclusion: Use of a nurse-managed online NFP program for women can be effective to help women avoid pregnancy while breastfeeding, especially with correct and consistent use., (Copyright © 2017 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)

Purpose: The aims of this study were to determine and compare extended use-effectiveness of an online nurse-managed fertility education service program among women (and subgroups of women) seeking to avoid pregnancy., Study Design and Methods: This was a 24-month prospective study of a university-based online Web site with 663 nonbreastfeeding women using an online charting system to avoid pregnancy. Participants tracked their fertility online with either cervical mucus monitoring, electronic hormonal fertility monitoring, or both fertility indicators. Unintended pregnancies were validated by professional nurses., Results: Participants had a mean age of 30.4 years (SD = 6.3) and mean 1.7 children (SD = 2.0). Among the 663 nonbreastfeeding participants there were 2 unintended pregnancies per 100 at 24 cycles of correct use and 15 pregnancies at 24 cycles of typical use. However, the 212 women using the electronic fertility monitor had a typical use unintended pregnancy rate of 6 at 24 cycles of use in comparison with the 118 women using cervical mucus monitoring that had a typical use pregnancy rate of 19 at 24 cycles and with the 333 women using both fertility indicators that had a pregnancy rate of 18 at 24 cycles of use., Clinical Implications: Use of the fertility monitor to estimate fertility among nonbreastfeeding women provides the most secure method of avoiding pregnancy.

Objectives: The aim of the study was to retrospectively evaluate the effectiveness of a fertility awareness-based method supported by a mobile-based application to prevent unwanted pregnancies as a method of natural birth control., Methods: In a retrospective analysis, the application's efficiency as a contraceptive method was examined on data from 4054 women who used the application as contraception for a total of 2085 woman-years., Results: The number of identified unplanned pregnancies was 143 during 2053 woman-years, giving a Pearl Index of 7.0 for typical use. Ten of the pregnancies were due to the application falsely attributing a safe day within the fertile window, producing a perfect-use Pearl Index of 0.5. Calculating the cumulative pregnancy probability by life-table analysis resulted in a pregnancy rate of 7.5% per year (95% confidence interval 5.9%, 9.1% per year)., Conclusions: The application appears to improve the effectiveness of fertility awareness-based methods and can be used to prevent pregnancies if couples consistently protect themselves on fertile days.

A study was designed to determine the effect of stage of the estrous cycle on the proportion of animals that ovulated and the synchrony of ovulation of heifers treated with an aromatase inhibitor-based protocol. Forty-eight heifers were treated intramuscularly with 500 μg of cloprostenol (PGF) followed by 100 μg of GnRH 24 hours later to serve as control data for comparison of the ovulatory response to a subsequent aromatase inhibitor protocol. Daily ultrasound examinations were done to determine the incidence of and interval to ovulation. At the time of ovulation (Day 0), heifers were assigned randomly to five day-groups (n = 8-11/group) and given an intravaginal device containing 3 g of letrozole for 4 days starting on Day 0, 4, 8, 12, or 16. At the time of device removal, heifers were given PGF followed by GnRH 24 hours later. Ultrasound examinations were done daily from 2 days before device insertion to 9 days after the posttreatment ovulation. The preovulatory follicle diameter after letrozole treatment was larger in the Day 4 group compared to the Day 0 and 16 groups and intermediate in the Day 8 and 12 groups (P < 0.001). Compared to control data, the percentage of heifers that ovulated after letrozole treatment was greater (87.1% vs. 69.4%, respectively; P < 0.05) as was the synchrony of ovulation (residuals: 0.24 ± 0.07 vs. 0.68 ± 0.13; P < 0.01). The day on which letrozole treatment was initiated did not affect the proportion of heifers that ovulated or the interval to ovulation. Plasma estradiol concentrations at the time of removal of the letrozole device in the Day 0 and 4 groups was lower (P < 0.05) than in the corresponding controls. Estradiol concentrations in the Day 8 and 12 groups did not differ from already low concentrations in the respective controls. Corpus luteum diameter profiles and progesterone production were not affected by day-group although reduced luteal lifespan after letrozole treatment was observed and requires further investigation. In summary, a protocol involving a letrozole-impregnated intravaginal device for 4 days, PGF treatment at device removal, and GnRH 24 later resulted in a greater ovulation rate and greater synchrony of ovulation than in heifers not given letrozole. Results suggest that the protocol may be initiated effectively at random stages of the estrous cycle and may provide impetus for further studies to assess the efficacy of a letrozole-based synchronization protocol for fixed-time insemination., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Experts are divided on whether women's cognition and behavior differs between fertile and non-fertile phases of the menstrual cycle. One of the biggest criticisms of this literature concerns the use of indirect, imprecise, and flexible methodologies between studies to characterize women's fertility. To resolve this problem, we provide a data-driven method of best practices for characterizing women's fertile phase. We compared the accuracy of self-reported methods and counting procedures (i.e., the forward- and backward-counting methods) in estimating ovulation using data from 140 women whose fertility was verified with luteinizing hormone tests. Results revealed that no counting method was associated with ovulation with >30% accuracy. A minimum of 39.5% of the days in the six-day fertile window predicted by the counting methods were non-fertile, and correlations between counting method conception probabilities and actual conception probability were weak to moderate, rs=0.11-0.30. Poor results persisted when using a lenient window for predicting ovulation, across alternative estimators of the onset of the next cycle, and when removing outliers to increase the homogeneity of the sample. By contrast, combining counting methods with a relatively inexpensive test of luteinizing hormone predicted fertility with accuracy >95%, but only when specific guidelines were followed. To this end, herein we provide a cost-effective, pragmatic, and standardized protocol that will allow researchers to test whether fertility effects exist or not., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Cycle computers are medical devices which use sophisticated statistical methods in addition to a comprehensive on-board database. Their main function is to precisely indicate the fertile and infertile phases of the menstrual cycle, based on daily basal body temperature measurements. A recent medical research program aimed at evaluating the EFFECTIVENESS of cycle computers for contraceptive purposes was conducted., Material and Methods: This study was conducted between May and June 2016 on 3,450 Polish women. The Polish distributor sent an anonymous questionnaire to the participants. To date, 361 women, representing 17,322 cycles have returned accurately completed questionnaires., Results: In the resultant group only 4 unintended pregnancies were observed, resulting in a Pearl index of 0.4989. This suggests that fewer than 5 in 1000 women, who use a cycle computer correctly over a period of one year, may become pregnant unintentionally. This result is slightly better than the results from 2010, when the Pearl index was 0.64., Conclusions: The results obtained from the study indicate that the effectiveness of cycle computers for contraceptive purposes is comparable with other methods, such as hormonal contraception, and therefore cycle computers can be recommended for women who either cannot use or do not wish to use traditional contraception. These results confirm the effectiveness of using natural fertility symptoms, such as basal body temperature changes in the context of cycle computer technology for the purposes of contraception.

Background: The introduction of home digital ovulation tests (OTs) has provided a simple solution for women wishing to optimise the timing of intercourse when trying to conceive. However, despite this, very little is understood about women's experiences of using these tests., Methods: We carried out qualitative, semi-structured telephone interviews with women who were seeking to conceive (not actively undergoing clinical investigation/fertility treatment) from the general UK population. The interviews were conducted following participation in a randomised controlled trial (RCT) in which participants were either provided with digital home OTs to assist in timing intercourse (n = 18) or advised to have intercourse every 2-3 days (n = 18). The interviews were digitally recorded, transcribed and then analysed using Framework analysis to identify the themes., Results: Data saturation was reached after 36 interviews. The use of the OT appeared to elicit 10 key themes, which could be described within the context of three overarching issues: 1) a positive impact (understanding the menstrual cycle, confirming when ovulating, emotional support, improving the relationship), 2) a negative impact (changing sex life and relationship with their partner, the emotional consequences of prolonged use, questions and uncertainty about what their results mean for them) and 3) the experiences of trying to conceive in general (use of clinical guidance and emotional experience)., Conclusions: Overall, the use of home OTs were found to affect women's thoughts and feelings in multiple ways during attempts to conceive. Although some women reported a range of negative experiences when using OTs, they also reported similar negative experiences when trying to conceive without using the tests. However, there were many positive themes associated with OT use, including an increased understanding of the menstrual cycle, confirmation of ovulation timing and providing a source of help and support when trying to conceive. Overall, when women are trying to conceive, ensuring they have access to high-quality information, including use of OT, may be of benefit to help address some of the questions and uncertainties that were raised by the participants in this study., Trial Registration Number: NCT01084304.

Objective: To compare the predictive value of manual two-dimensional follicular monitoring with that of sonography-based automated volume calculation (SonoAVC) in routine follicular tracking in in vitro fertilization (IVF)., Methods: A prospective study was undertaken of women undergoing IVF with controlled ovarian hyperstimulation at a center in New Delhi, India, between October and November 2013. Follicular monitoring was performed both manually and in three dimensions with SonoAVC. On the day of oocyte retrieval, the follicular count and dimensions were calculated with both techniques and correlated with the number of oocytes retrieved., Results: Overall, 46 patients and 91 ovaries were studied. The mean times taken to perform manual and SonoAVC measurements were 209.2 ± 47.4 s and 156.6 ± 38.6 s, respectively (P < 0.001). The mean follicular count was significantly lower when measured manually than with SonoAVC (8.46 ± 3.35 vs 9.91 ± 4.60; P = 0.016). However, the mean leading follicle diameter measured manually (19.45 ± 2.46 mm) was similar to both the mean diameter (21.12 ± 2.65 mm) and the volume-based diameter (19.56 ± 2.16 mm) measured with SonoAVC., Conclusion: Three-dimensional SonoAVC could be a useful adjunct for follicular monitoring, with a significant reduction in time and a good correlation with manual counts. However, further studies with larger sample sizes are required., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Objective: To assess the sensitivity and specificity of the self-identified fertile window., Design: Observational study., Setting: Not applicable., Patient(s): A total of 107 women., Intervention(s): Women recorded cervical mucus observation and basal body temperature daily while undergoing daily ovarian ultrasound., Main Outcome Measure(s): The biological fertile window, defined as the 6 days up to and including the day of ovulation; and the 2-day ovulation window, defined as the day before and the day of ovulation., Result(s): The self-identification of the biological fertile window by the observation of any type of cervical mucus provides 100% sensitivity but poor specificity, yielding a clinical fertile window of 11 days. However, the identification of the biological fertile window by peak mucus (defined as clear, slippery, or stretchy mucus related to estrogen) yielded 96% sensitivity and improved specificity. The appearance of the peak mucus preceded the biological fertile window in less than 10% of the cycles. Likewise, this type of mucus identified the ovulation window with 88% sensitivity., Conclusion(s): These results suggest that, when perceived accurately, more accurate clinical self-detection of the fertile window can be obtained by identification of peak mucus. This may improve efforts to focus intercourse in the fertile phase for couples with fertility concerns., (Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.)

Background: Fertility problems are very common, as subfertility affects about 10% to 15% of couples trying to conceive. There are many factors that may impact a couple's ability to conceive and one of these may be incorrect timing of intercourse. Conception is only possible from approximately five days before up to several hours after ovulation. Therefore, to be effective, intercourse must take place during this fertile period. 'Timed intercourse' is the practice of prospectively identifying ovulation and, thus, the fertile period to increase the likelihood of conception. Whilst timed intercourse may increase conception rates and reduce unnecessary intervention and costs, there may be associated adverse aspects including time consumption and stress. Ovulation prediction methods used for timing intercourse include urinary hormone measurement (luteinizing hormone (LH), estrogen), tracking basal body temperatures, cervical mucus investigation, calendar charting and ultrasonography. This review considered the evidence from randomised controlled trials for the use of timed intercourse on positive pregnancy outcomes., Objectives: To assess the benefits and risks of ovulation prediction methods for timing intercourse on conception in couples trying to conceive., Search Methods: We searched the following sources to identify relevant randomised controlled trials, the Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, PubMed, LILACS, Web of Knowledge, the World Health Organization (WHO) Clinical Trials Register Platform and ClinicalTrials.gov. Furthermore, we manually searched the references of relevant articles. The search was not restricted by language or publication status. The last search was on 5 August 2014., Selection Criteria: We included randomised controlled trials (RCTs) comparing timed intercourse versus intercourse without ovulation prediction or comparing different methods of ovulation prediction for timing intercourse against each other in couples trying to conceive., Data Collection and Analysis: Two review authors independently assessed trial eligibility and risk of bias and extracted the data. The primary review outcomes were cumulative live birth and adverse events (such as quality of life, depression and stress). Secondary outcomes were clinical pregnancy, pregnancy (clinical or self-reported pregnancy, not yet confirmed by ultrasound) and time to conception. We combined data to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I(2) statistic. We assessed the overall quality of the evidence for the main comparisons using GRADE methods., Main Results: We included five RCTs (2840 women or couples) comparing timed intercourse versus intercourse without ovulation prediction. Unfortunately one large study (n = 1453) reporting live birth and pregnancy had not published outcome data by randomised group and therefore could not be analysed. Consequently, four RCTs (n = 1387) were included in the meta-analysis. The evidence was of low to very low quality. Main limitations for downgrading the evidence included imprecision, lack of reporting clinically relevant outcomes and the high risk of publication bias.One study reported live birth, but the sample size was too small to draw any relevant conclusions on the effect of timed intercourse (RR 0.75, 95% CI 0.16 to 3.41, 1 RCT, n = 17, very low quality).One study reported stress as an adverse event. There was no evidence of a difference in levels of stress (mean difference 1.98, 95 CI% -0.87 to 4.83, 1 RCT, n = 77, low level evidence). No other studies reported adverse events.Two studies reported clinical pregnancy. There was no evidence of a difference in clinical pregnancy rates (RR 1.10, 95% CI 0.57 to 2.12, 2 RCTs, n = 177, I(2) = 0%, low level evidence). This suggested that if the chance of a clinical pregnancy following intercourse without ovulation prediction is assumed to be 16%, the chance of success following timed intercourse would be between 9% and 33%.Four studies reported pregnancy rate (clinical or self-reported pregnancy). Timed intercourse was associated with higher pregnancy rates compared to intercourse without ovulation prediction in couples trying to conceive (RR 1.35, 95% CI 1.06 to 1.71, 4 RCTs, n = 1387, I(2) = 0%, very low level evidence). This suggests that if the chance of a pregnancy following intercourse without ovulation prediction is assumed to be 13%, the chance following timed intercourse would be between 14% and 23%. Subgroup analysis by duration of subfertility showed no difference in effect between couples trying to conceive for < 12 months versus couples trying for ≥ 12 months. One trial reported time to conception data and showed no evidence of a difference in time to conception., Authors' Conclusions: There are insufficient data available to draw conclusions on the effectiveness of timed intercourse for the outcomes of live birth, adverse events and clinical pregnancy. Timed intercourse may improve pregnancy rates (clinical or self-reported pregnancy, not yet confirmed by ultrasound) compared to intercourse without ovulation prediction. The quality of this evidence is low to very low and therefore findings should be regarded with caution. There is a high risk of publication bias, as one large study remains unpublished 8 years after recruitment finished. Further research is required, reporting clinically relevant outcomes (live birth, clinical pregnancy rates and adverse effects), to determine if timed intercourse is safe and effective in couples trying to conceive.

Infertility is defined as the inability to achieve pregnancy after one year of regular, unprotected intercourse. Evaluation may be initiated sooner in patients who have risk factors for infertility or if the female partner is older than 35 years. Causes of infertility include male factors, ovulatory dysfunction, uterine abnormalities, tubal obstruction, peritoneal factors, or cervical factors. A history and physical examination can help direct the evaluation. Men should undergo evaluation with a semen analysis. Abnormalities of sperm may be treated with gonadotropin therapy, intrauterine insemination, or in vitro fertilization. Ovulation should be documented by serum progesterone level measurement at cycle day 21. Evaluation of the uterus and fallopian tubes can be performed by hysterosalpingography in women with no risk of obstruction. For patients with a history of endometriosis, pelvic infections, or ectopic pregnancy, evaluation with hysteroscopy or laparoscopy is recommended. Women with anovulation may be treated in the primary care setting with clomiphene to induce ovulation. Treatment of tubal obstruction generally requires referral for subspecialty care. Unexplained infertility in women or men may be managed with another year of unprotected intercourse, or may proceed to assisted reproductive technologies, such as intrauterine insemination or in vitro fertilization.

Ovulation is an important physiological process in human, and its effect may reflect in body fluids via secretion of biomolecules such as proteins, amino acids, antioxidants, antimicrobial peptides and so on. Recently, the non-invasive sampling approaches are used to diagnose disease status and access health condition of human. Saliva comprises various proteins which are secreted through salivary glands. The proteins present in the saliva may vary in their expression according to the hormonal level and physiological nature of the body which are said to be hormone receptors, stress proteins and antimicrobial peptides. Therefore, it is postulated that saliva can be used in the detection of ovulation time in human using specific protein(s) expression and which can be considered as a best non-invasive method. The identification of these proteins by adopting LC-MS/MS followed by Western blot analysis are possible to identify a promising biomarker for ovulation detection in human., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: The aim of the study was to evaluate the ability of a novel web and mobile application to identify a woman's ovulation day and fertile window, in order to use it as a method of natural birth control., Methods: A retrospective study was performed on 1501 cycles of 317 women aged 18 to 39 years. Women entered their basal body temperatures, ovulation test results and date of menstruation into the application., Results: The mean delay from the first positive ovulation test to the temperature-based estimation of the ovulation day was 1.9 days; the length of the luteal phase varied on average by 1.25 days per user. Only 0.05% of non-fertile days were falsely attributed and found within the fertile window., Conclusions: The method is effective at identifying a user's ovulation day and fertile window and can therefore be used as a natural method of birth control.

Objective: The aim of the study was to examine relationships and interindividual variations in urinary and serum reproductive hormone levels relative to ultrasound-observed ovulation in menstrual cycles of apparently normally menstruating women., Methods: This was a prospective study of normally menstruating women (no known subfertility), aged 18-40 years (n = 40), who collected daily urine samples and attended the study centre for blood samples and transvaginal ultrasound during one complete menstrual cycle. Serum luteinising hormone (LH), progesterone, estradiol, urinary LH, pregnanediol-3- glucuronide (P3G) and estrone-3-glucuronide were measured. Ultrasound was conducted by two physicians and interpreted by central expert review., Results: Menstrual cycle length varied from 22 to 37 days (median 27 days). Ovulation by ultrasound ranged from day 8 to day 26 (median day 15). Serum and urinary hormone profiles showed excellent agreement. Estrogen and LH hormone peaks in urine and serum showed a range of signal characteristics across the study group before and after ovulation. The rise in estrogen and LH always occurred before ovulation; the progesterone rise from baseline always occurred after ovulation., Conclusions: Urinary and serum reproductive hormones showed excellent agreement and may be used interchangeably. The beginning of the surge in serum and urinary LH was an excellent predictor of ovulation. The rise in progesterone and P3G above baseline was a consistent marker of luteinisation confirming ovulation. Both LH and progesterone surges delivered clear, sharp signals in all volunteers, allowing reliable detection and confirmation of ovulation.

Background: In many countries intrauterine insemination (IUI) is the treatment of first choice for a subfertile couple when the infertility work up reveals an ovulatory cycle, at least one open Fallopian tube and sufficient spermatozoa. The final goal of this treatment is to achieve a pregnancy and deliver a healthy (singleton) live birth. The probability of conceiving with IUI depends on various factors including age of the couple, type of subfertility, ovarian stimulation and the timing of insemination. IUI should logically be performed around the moment of ovulation. Since spermatozoa and oocytes have only limited survival time correct timing of the insemination is essential. As it is not known which technique of timing for IUI results in the best treatment outcome, we compared different techniques for timing IUI and different time intervals., Objectives: To evaluate the effectiveness of different synchronisation methods in natural and stimulated cycles for IUI in subfertile couples., Search Methods: We searched for all publications which described randomised controlled trials of the timing of IUI. We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (1966 to October 2014), EMBASE (1974 to October 2014), MEDLINE (1966 to October 2014) and PsycINFO (inception to October 2014) electronic databases and prospective trial registers. Furthermore, we checked the reference lists of all obtained studies and performed a handsearch of conference abstracts., Selection Criteria: Randomised controlled trials (RCTs) comparing different timing methods for IUI were included. The following interventions were evaluated: detection of luteinising hormone (LH) in urine or blood, single test; human chorionic gonadotropin (hCG) administration; combination of LH detection and hCG administration; basal body temperature chart; ultrasound detection of ovulation; gonadotropin-releasing hormone (GnRH) agonist administration; or other timing methods., Data Collection and Analysis: Two review authors independently selected the trials, extracted the data and assessed study risk of bias. We performed statistical analyses in accordance with the guidelines for statistical analysis developed by The Cochrane Collaboration. The overall quality of the evidence was assessed using GRADE methods., Main Results: Eighteen RCTs were included in the review, of which 14 were included in the meta-analyses (in total 2279 couples). The evidence was current to October 2013. The quality of the evidence was low or very low for most comparisons . The main limitations in the evidence were failure to describe study methods, serious imprecision and attrition bias.Ten RCTs compared different methods of timing for IUI. We found no evidence of a difference in live birth rates between hCG injection versus LH surge (odds ratio (OR) 1.0, 95% confidence interval (CI) 0.06 to 18, 1 RCT, 24 women, very low quality evidence), urinary hCG versus recombinant hCG (OR 1.17, 95% CI 0.68 to 2.03, 1 RCT, 284 women, low quality evidence) or hCG versus GnRH agonist (OR 1.04, 95% CI 0.42 to 2.6, 3 RCTS, 104 women, I(2) = 0%, low quality evidence).Two RCTs compared the optimum time interval from hCG injection to IUI, comparing different time frames that ranged from 24 hours to 48 hours. Only one of these studies reported live birth rates, and found no difference between the groups (OR 0.52, 95% CI 0.27 to 1.00, 1 RCT, 204 couples). One study compared early versus late hCG administration and one study compared different dosages of hCG, but neither reported the primary outcome of live birth.We found no evidence of a difference between any of the groups in rates of pregnancy or adverse events (multiple pregnancy, miscarriage, ovarian hyperstimulation syndrome (OHSS)). However, most of these data were very low quality., Authors' Conclusions: There is insufficient evidence to determine whether there is any difference in safety and effectiveness between different methods of synchronization of ovulation and insemination. More research is needed.

Objective: To test if nucleolar channel system (NCS) prevalence matches the accuracy of the endometrial receptivity array (ERA) for identification of the window of endometrial receptivity., Design: Comparative retrospective study, May 2008-May 2012., Setting: University-affiliated infertility clinic., Patient(s): Forty-nine healthy oocyte donors, regularly cycling, aged 20-34 years with a body mass index of 19-25 kg/m2., Intervention(s): Endometrial biopsies were collected throughout the menstrual cycle. All samples underwent transcriptomic signature identification by ERA testing (performed in a prior study) and quantification of NCS prevalence by using indirect immunofluorescence (performed in the present study)., Main Outcome Measure(s): Concordance of ERA results determining the window of implantation with NCS prevalence was statistically analyzed using the kappa index. Based on dating according to the luteinizing hormone surge, specimens were dichotomized into receptive (n=24) and nonreceptive (n=25). The NCS prevalence was expressed as percentage of NCSs per endometrial epithelial cells in each endometrial biopsy., Result(s): Concordance of ERA and NCS dating vs. luteinizing hormone yielded comparable kappa indices of 0.878 and 0.836, respectively. Direct comparison of ERA and NCS dating resulted in a kappa index of 0.796., Conclusion(s): Prevalence of NCS identifies the window of endometrial receptivity previously identified by their transcriptomic signature using the ERA., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The prediction of ovulation time is one of the most important and yet difficult processes in pig production, and it has a considerable impact on the fertility of the herd and litter size. The objective of this study was to assess the vulvar skin temperature of sows during proestrus and estrus using infrared thermography and to establish a possible relationship between the variations in vulvar temperature and ovulation. The experimental group comprised 36 crossbred Large White × Landrace females, of which 6 were gilts and 30 were multiparous sows. Estrus was detected twice daily and the temperature was obtained every 6 hours from the vulvar area and from two control points in the gluteal area (Gluteal skin temperature [GST]). A third variable, vulvar-gluteal temperature (VGT) was obtained from the difference between the vulvar skin temperature and the GST values. The animals were divided into two subgroups: group A consisting of 11 animals with estrus detected at 6:00 AM, Day 4 postweaning, and group B comprising seven animals with estrus detected at 6:00 AM, Day 5 post-weaning. Both groups showed a similar trend in the VGT. The VGT increased during the proestrus, reaching a peak 24 hours before estrus in group A and 48 hours before estrus in group B. The VGT then decreased markedly reaching the lowest value in groups A and B, respectively, 12 and 6 hours after estrus. Although the time of ovulation was only estimated on the basis of a literature review, the matching between the temporal variations of the VGT values and the predicted time of the peak of estradiol secretion that ultimately leads to the ovulation processes suggests that the VGT values represent a potential predictive marker of the ovulatory events., (Copyright © 2014 Elsevier Inc. All rights reserved.)