A Comparison of Two Hormonal Fertility Monitoring Systems for Ovulation Detection: A Pilot Study.

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]. / Natürliche Familienplanung.

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.

Modulation of saliva pattern and accurate detection of ovulation using an electrolyte pre-deposition-based method: a pilot study.

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.

Fertility Awareness-Based Methods for Family Planning: A Literature Review.

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.

Advantages of determining the fertile window with the individualised Natural Cycles algorithm over calendar-based methods.

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.

Published analysis of contraceptive effectiveness of Daysy and DaysyView app is fatally flawed.

BACKGROUND: In March 2018, Dr. Martin C. Koch and colleagues published an analysis purporting to measure the effectiveness of the Daysy device and DaysyView app for the prevention of unintended pregnancy. Unfortunately, the analysis was flawed in multiple ways which render the estimates unreliable. Unreliable estimates of contraceptive effectiveness can endanger public health. MAIN BODY: This commentary details multiple concerns pertaining to the collection and analysis of data in Koch et al. 2018. A key concern pertains to the inappropriate exclusion of all women with fewer than 13 cycles of use from the Pearl Index calculations, which has no basis in standard effectiveness calculations. Multiple additional methodological concerns, as well as prior attempts to directly convey concerns to the manufacturer regarding marketing materials based on prior inaccurate analyses, are also discussed. CONCLUSION: The Koch et al. 2018 publication produced unreliable estimates of contraceptive effectiveness for the Daysy device and DaysyView app, which are likely substantially higher than the actual contraceptive effectiveness of the device and app. Those estimates are being used in marketing materials which may inappropriately inflate consumer confidence and leave consumers more vulnerable than expected to the risk of unintended pregnancy. Prior attempts to directly convey concerns to the manufacturer of this device were unsuccessful in preventing publication of subsequent inaccurate analyses. To protect public health, concerns with this analysis should be documented in the published literature, the Koch et al. 2018 analysis should be retracted, and marketing materials on contraceptive effectiveness should be subjected to appropriate oversight.

Improving usability and pregnancy rates of a fertility monitor by an additional mobile application: results of a retrospective efficacy study of Daysy and DaysyView app.

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.

Canine ovulation timing: A survey on methodology and an assessment on reliability of vaginal cytology.

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.

Dynamics of putative sex pheromone components during heat periods in estrus-induced cows.

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 PGF2α 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.

Ovulation monitoring and fertility knowledge: Their relationship to fertility experience in a cross-sectional study.

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 χ2 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.

Ovulatory status and menstrual cycle duration assessed by self-collection of urine on pH strips in a population-based sample of French women not using hormonal contraception.

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.

Standardized protocols for characterizing women's fertility: A data-driven approach.

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.

Fertility awareness-based mobile application for contraception.

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.

Evaluation of the effectiveness of selected natural fertility symptoms used for contraception: estimation of the Pearl index of Lady-Comp, Pearly and Daysy cycle computers based on 10 years of observation in the Polish market.

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.

Timed intercourse for couples trying to conceive.

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.

Women's experiences of ovulation testing: a qualitative analysis.

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.

Evaluation and treatment of infertility.

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.

Identification and prediction of the fertile window using NaturalCycles.

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.

Monitoring the menstrual cycle: Comparison of urinary and serum reproductive hormones referenced to true ovulation.

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.

Synchronised approach for intrauterine insemination in subfertile couples.

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.