4). What type of test is this? Accessibility You should not use this test to help prevent pregnancy, because it is not reliable for that purpose. The sensitivity and specificity of the AI smartphone system in evaluating air-dried human saliva samples were 99.01% (CI: 94.61% to 99.97%) and 100% (CI: 96.34% to 100%), respectively (Fig. One of the important criteria for animal breeding is to determine the optimum time to breed an animal in-order-to achieve higher conception rate. A study has also shown that family planning services alone have helped in reducing unintended pregnancies and the costs related to it by nearly 70% 5, 6. The pH of normal saliva samples ranges from 6.2 to 7.6. This is likely due to the re-distribution of solute across the microfluidic device during the formation of the thin films combined with the uneven evaporation. The optical focus and uniform light intensity were fixed in the optical system to avoid errors from the manual adjustment. According to prior reports most women get pregnant within 6 cycles, therefore, we estimate that these non-reusable tests can cumulatively cost upwards of $200 for most women 42. Manual analysis was also performed for the presence of salivary ferning using a microscope during the training phase of the network. You should not use this test to help prevent pregnancy, because it is not reliable for that purpose. In this test, you get a small microscope with built-in or removable slides. The circuit diagram of the setup is provided in the supplementary information (Fig. Some animals are sensitive to these types of measurements and it becomes difficult for the animal breeders to test them through these methods. MobileNet structures have been built with depth-wise separable convolutions except for the first layer, which has been built with a standard 33 convolution. The image magnification achieved by the smartphone system was 4, which was comparable to the digital images taken using a standard lab-based microscope (Carl Zeiss AG Axio Observer D1) at 10 magnification. Traditional spot placement methods have no control on sample volume and thus often tend to induce false signal. Other devices such as electronic pedometers or activity tags are used to detect ovulation by monitoring changes in behavior such as restlessness, standing heat, mounting behavior, and elevated physical activity of animals 41. A pregnancy begins with conception. [], What is fertilisation? Ferning structures have been observed in ovulating women within a 4-day window around the day of ovulation 12. The accuracy of the neural network in predicting a saliva sample as ovulating and non-ovulating was 99.5% with CI ranging from 97.25% to 99.99% (Fig. 1, ,2).2). An android application was developed for image data acquisition using the smartphone optical attachment and analyzing the fern patterns present in air-dried saliva to predict the ovulation status. The maximum number of tablets is 96 of each type of the following medicine combinations; The maximum number of Co-codamol youre allowed to purchase is 32 tablets. Read more on the new rules here. Training accuracy is the percentage of correctly labeled images on training batch and validation accuracy is the percentage of correctly labeled images other than the images on training batch. The ovulation status for human saliva samples was established through the urine test (LH + estrogen) in addition to manual verification. There was a small marginal difference between the training and validation curves of accuracy indicating that the model was not overfitting (Fig. Your doctor may use other tests that are not yet available for home use (i.e., blood and urine laboratory tests) and information about your history to get a better view of your fertility status. 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The fertility tests your doctor uses are automated, and they may give more consistent results. When your estrogen increases near your time of ovulation, your dried saliva may form a fern-shaped pattern. 59566, Home Health (UK) Ltd, Unit A, Greatham Road Industrial Estate, Greatham Road, Bushey, Hertfordshire,WD23 2NZ, United KingdomVAT NO: 660 6203 60, REGISTERED IN ENGLAND NO. You should do this test if you want to know when you expect to ovulate and be in the most fertile part of your menstrual cycle. A small area (25 12 mm2) was left open on one end of the glass slide for handling the microfluidic device (Fig. S2A), however, the resolution of the cellphone optical system was 7 m, which was established by imaging a 1951 US Air Force (USAF) resolution target (Fig. Transparent PMMA and DSA sheets were cut using a laser cutter (VLS 2.3, Universal Laser Systems Inc.). This work is partially supported by the Brigham Research Institute Pilot Grant, the Innovation Evergreen Fund (Brigham Research Institute, Brigham and Womens Hospital, Harvard Medical School), 1R01AI118502 and P30ES000002, R21HD092828 (National Institute of Health) a Harvard National Institute of Environmental Health Sciences Grant (Harvard T.H. 4B, S5B). Animal breeding is mainly dependent on the breeding cycle of the species and it is time-constrained. The smearer block (12 8 9.6 mm) was printed using an Ultimaker 2 Extended (Ultimaker) 3D printer and PLA as the printing material. Maybe Baby is a mini-microscope that shows the link between oestrogen and the salt levels in your saliva. Bethesda, MD 20894, Web Policies Family planning reinforces peoples rights to determine the number and spacing of their children. We collected samples every day from each participant for one complete menstrual cycle and tested them using our microfluidic devices through both the ovulating and non-ovulating phases. Draz MS, Kochehbyoki KM, Vasan A, Battalapalli D, Sreeram A, Kanakasabapathy MK, Kallakuri S, Tsibris A, Kuritzkes DR and Shafiee H. Berg B, Cortazar B, Tseng D, Ozkan H, Feng S, Wei Q, Chan RY-L, Burbano J, Farooqui Q, Lewinski M, Di Carlo D, Garner OB and Ozcan A. Knowlton SM, Sencan I, Aytar Y, Khoory J, Heeney MM, Ghiran IC and Tasoglu S. Thirumalaraju P, Bormann CL, Kanakasabapathy M, Doshi F, Souter I, Dimitriadis I and Shafiee H. Dimitriadis I, Xu R, Kanaksabapathy MK, Thirumalaraju P, Yogesh V, Tanrikut C, Hsu J, Bormann CL and Shafiee H. Kanakasabapathy M, Thirumalaraju P, Yogesh V, Natarajan V, Bormann CL, Petrozza JC and Shafiee H. Kanakasabapathy MK, Sadasivam M, Singh A, Preston C, Thirumalaraju P, Venkataraman M, Bormann CL, Draz MS, Petrozza JC and Shafiee H. Kanakasabapathy M, Thirumalaraju P, Yogesh V, Natarajan V, Bormann CL, Bhowmick P, Veiga C, Petrozza JC and Shafiee H. Bormann CL, Kanakasabapathy M, Thirumalaraju P, Yogesh V, Natarajan V, Demick J, Blanchard A, Petrozza JC and Shafiee H. Draz MS, Lakshminaraasimulu NK, Krishnakumar S, Battalapalli D, Vasan A, Kanakasabapathy MK, Sreeram A, Kallakuri S, Thirumalaraju P, Li Y, Hua S, Yu XG, Kuritzkes DR and Shafiee H. Priye A, Bird SW, Light YK, Ball CS, Negrete OA and Meagher RJ. Using an additional 748 annotated images of human saliva samples comprising of 108 ovulating images and 640 non-ovulating images collected from subjects (n=6), we retrained and validated the developed neural network. Dash S, Chakravarty AK, Singh A, Upadhyay A, Singh M and Yousuf S. Gnoth C, Godehardt D, Godehardt E, FrankHerrmann P and Freundl G. It does not mean that you will definitely become pregnant. Maybe Baby Ovulation Saliva Tester is a mini-microscope that shows the link between oestrogen and the salt levels in your saliva. Simple, accurate health tests for the home and the workplace. Since calculating the outputs took a significant amount of time, we created bottleneck outputs to reduce the training time. Also, after smoking or alcohol consumption, an adequate amount of time gap should be provided before testing. Training performance was measured by cross-entropy, which was used as a loss function to know how well the network is learning. The lenses were aligned with the optical axis of the smartphones front camera. (D) An actual microfluidic device placed next to a US quarter coin. Transfer learning technique was used instead of training the model from scratch. The system is wirelessly controlled using a smartphone to image fern structures on the microfluidic device. Advances in microelectronics and machine learning have enabled current AI-based methods to work equally well on portable systems, especially smartphones. The Android application automatically captured video frames, analyzed the images locally, and reported the result in <31 s. It does not require access to the internet for analysis. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. Why should you do this test? A simple, low-cost tool, which can aid in family planning, will empower women in avoiding unintended pregnancies and will be of great value to those patients who are trying to conceive. Learn more Further, the inclusion of basal body temperature may help in overcoming the systems current limitations and thus warrants further research. These results suggest that the developed network generalizes well across different smartphones tested in this study. SmoothGrad applied to the output obtained from fully connected convolution layer was used to sharpen gradient-based sensitivity maps 33, 34. The system was motorized along a single axis and focal plane to automate the imaging of the microfluidic channel. The two different phases were identified using the Clear Blue urine test (LH + estrogen) as the reference. 2B2D). This is a home-use test kit to predict ovulation by looking at patterns formed by your saliva. The samples were loaded on the microfluidic device and analyzed using a smartphone-based optical system. Our system can detect the entire fertile window including the exact day of ovulation when the chances of conception are higher. The device was powered by a 9 V alkaline battery (B000099SKB, Energizer). If purchasing separately the maximum number of tablets is 96 of each type. The output from fully connected layer was used as an input in the classification layer. A rapid point-of-care ovulation testing also has an important application in animal breeding. A positive test indicates that you may be near ovulation. Does a positive test mean you are ovulating? Natural family planning uses physical signs, symptoms, and physiologic changes to predict a womans fertility 7, 8. ImageNet, an open source dataset that contains non-saliva images from various categories, helped in pre-training the network. The attachment was designed in SolidWorks (Dassault Systmes) for the Moto X smartphone (Motorola, XT1575). A good degree of separation was observed between the two patterns. The output from the fully connected layer remained the same for every image and the output was used multiple times. This is a qualitative test -- you find out whether or not you may be near your ovulation time, not if you will definitely become pregnant. 8600 Rockville Pike The https:// ensures that you are connecting to the Ovulation typically occurs around day 14 of your menstrual cycle. Is this test similar to the one my doctor uses? The total material cost for our approach is ~$14 USD and is completely reusable. The developed smartphone-based automated optical system can be potentially used for analyzing the saliva ferning patterns in animals such as buffalos 38, dogs 39, and other mammals to predict and confirm its ovulation and detect the optimum insemination time. What does this test do? A standard 2D convolution applies convolution kernel to all channels of the input image. government site. The annotations for ferning and non-ferning samples were achieved through manual inspection under a desktop microscope for simulated samples. How accurate is this test? Guida M, Tommaselli GA, Pellicano M, Palomba S and Nappi C, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 1, ,2).2). The microfluidic device containing the saliva sample was optimally focused by placing the device at the working distance of the lens setup, which helped eliminating manual focusing by the user. The true labels were fed to the network as ground truth and the accuracy, the cross-entropy, and the gradients were calculated (Fig. The Human Studies Institutional Review Boards of the Brigham and Womens Hospital approved the subject recruitment and use of human saliva specimens (IRB2017P002139). How do you do this test? When you and your partner are trying to have a baby you should be aware of the importance of the timing of sexual intercourse. The microfluidic device was composed of poly(methyl methacrylate) (PMMA) (8560K239, McMaster Carr), double-sided adhesive (DSA), polylactic acid (PLA) and glass slide (VWR, 48300025 corning 75 25 mm). The network makes use of depth-wise separable convolutions to build light-weight deep neural networks unlike traditional convolution neural networks that use standard 2D convolution. PMC legacy view The subjects were asked to spit on the reservoir of the microfluidic device and smear it on the microchannel for air drying. If you have any additional questions pleaseContact Us. Therefore, there is a need for advanced prediction of ovulation. 2C). By monitoring your saliva every day and comparing the image of your dried saliva in the viewfinder with the images provided in this guide, you can then determine your most fertile days. By the 4000th training step, the validation accuracy and cross entropy loss were saturated. (B) The actual image of the fabricated stand-alone optical system with a smartphone for imaging and analysis of the fern structures in air-dried saliva samples. A low-cost, rapid, automated smartphone-based microchip for ovulation testing through detecting fern structures in air-dried saliva samples using artificial intelligence. 3B). Unintended pregnancies can have adverse consequences to the health of both mother and child and are subject to significant economic and social burden. Rupture of membranes (ROM) is the breaking of amniotic sac that occurs before the onset of labor 36. The current home-based urinary test identifies sudden surge in LH that helps in finding out the ovulation phase. Do negative test results mean that you are not ovulating? We simulated 30 non-ovulating samples ranging from 0.1% to 1.4% and 34 ovulating samples ranging from 5.6% to 100% of the artificial saliva stock. The New Model from SD Biosensor (the manufacturers of the No.1 selling SD Codefree Blood Glucose Meter) has all the benefits of the Codefree plus it boasts a greater accuracy due to a wider haematocrit (HCT) range of 0-70% and GDH-FAD enzyme technology. On the other hand, dry eye disease is diagnosed by testing the ocular tear film for fern patterns. What is ovulation? The PPV and NPV of the system for the given test set was 100% and 99.0% (CI: 93.37% to 99.86%), respectively. Since this window is only open once a month and for a short period of time, being able to predict the L.H surge is [], As it is not possible to become pregnant outside of your fertile 2-3 days each cycle, which is around ovulation. Every month an egg matures and is released from the ovary. will also be available for a limited time. During the follicular phase of the menstrual cycle, with the increase of estradiol levels in the blood there is an increase in the salivary electrolytes which results in consistent ferning appearance, a crystallized structure resembling fern leaves, in air-dried saliva and can be used to determine the ovulation period 10, 11. The composition of artificial saliva is given in the following: 0.92 g/L xanthan gum (Q8185, MP Biomedicals), 1.2 g/L potassium chloride (L1117, Chemcruz), 0.85 g/L sodium chloride (031M0215V, Sigma), 0.05 g/L magnesium chloride (030M0060V, Sigma), 0.13 g/L calcium chloride (057K0005, Sigma), 0.13 g/L di-potassium hydrogen orthophosphate (SLBS6839, Sigma), and 0.35 g/L methyl p-hydroxybenzoate (Q7915, MP Biomedicals). Urine-based tests can range from $1-$2 per test, however, they are not reusable and thus per cycle the overall test can cost approximately $35-$40 for a user in the US. The pH of the artificially prepared saliva was 7.0. This period includes the 2 days before and the 2 days after your expected day of ovulation. Additionally, the ferning test may be more reliable in patients that have false positive responses to the urine LH kit, such as those women with polycystic ovarian syndrome and elevated LH levels. 03176158 Copyright Home Health (UK) Ltd, info@homehealth-uk.com 0044 (0)1923 711 511 0044 (0)1923 711 550. The saliency map was extracted from the network to highlight the highest weighted features of the image. Blue squares and circles represent non-ovulating saliva samples while red squares and circles represent ovulating saliva samples. The grooves were etched on the PMMA such that the inner side of the fully built microfluidic chip would act as guide-ways for the smear block. If these conditions are not looked upon properly, they may cause fern structures in the absence of ovulation. The timing of sexual intercourse in relation to ovulation strongly influences the chance of successful conception and can be an effective method for natural family planning 1. The networks performance in evaluating air-dried saliva samples was 90% with 95% confidence intervals (CI) that ranged from 84.98% to 93.78% (Fig 4A, S5A). 3A). The whole network was trained for 4000 training steps with a learning rate of 0.01, using which the lowest validation weights were achieved. GPhC Reg No: 2077944 NPA Membership No. The work demonstrated here is an example of how AI integrated with smartphones along with inexpensive hardware can be developed into an effective point-of-care diagnostic assay that can address a need in home-based fertility management and family planning. The neural network utilizes the MobileNet architecture pre-trained with 1.4 million ImageNet images and retrained with salivary ferning images. If purchasing as a combination then the maximum allowed is 96 tablets in total. At 1000th training step, validation cross entropy was 0.1177 and validation accuracy was 97.45%. A single-board microcontroller (NodeMCU) was used to control the movement of the microfluidic device. In addition, expenditure on births, abortion, and miscarriages resulting from unintended pregnancies have cost over $21 billion of public funds in the US in 2010 alone 4, 5. You will see dots and circles, a fern (full or partial), or a combination depending on where you are in your monthly cycle. You will get your best results when you use the test within the 5-day period around your expected ovulation. 3B). Federal government websites often end in .gov or .mil. However, current ovulation tests based on salivary ferning are manual and highly subjective, which causes misinterpretation when performed by a lay consumer 13. The authors have no conflicts to declare. The saliva samples were collected during their ovulating and non-ovulating phases. The t-Distribution Stochastic Neighbor Embedding (t-SNE) was performed to observe the distribution of the test dataset in a 2D space and to verify if our model was able to differentiate ovulating and non-ovulating samples accurately. (A) The exploded image of the stand-alone optical system and its various components. The last layer of MobileNet contains an average pooling layer to reduce the spatial resolution to 1 followed by a fully connected layer that was fed to our classification layer for detection. It is therefore very important that you know when you are ovulating. surge. For an egg fertilized later in its maturity, the chances for abortion are greater. Our microfluidic device enables rapid (<7min) saliva sample drying by creating thin films and provides a controlled sample volume for the analysis. 6 healthy women, aged from 20 to 22 participated in the study. HHS Vulnerability Disclosure, Help The following was the breakdown of concentrations of artificial saliva showing the three phases of ferning: non-ferning 0.1% to 1.4%, transitional 1.5% to 5.6% and ferning 5.6% to 100% of the artificial saliva stock prepared. A 5 V diffused white light emitting diode (LED) (IL153, Microtivity) was used to illuminate the microfluidic chip. Count the first day of your last period as day 1. Through the saliency maps 34, we could identify the pixels that are being used by the network and confirmed that it focused on features pertaining to the ferning pattern in its decision-making process (Fig. The Maybe Baby mini-microscope has a 52x power magnification lens. The network performed with excellent consistency across all tested devices achieving an excellent score of 1.0 (lower 95% CI: 1.0) in a Cronbach alphas test for consistency (n=15 with 5 phones) (Table S2). As a part of the training process, the dimensions of all images used during training were resized to 224224 pixels using computer vision libraries (OpenCV) and was trained within the TensorFlow environment. Successful fertilisation is most likely during a 24-hour period following the L.H.
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