Construction of deep learning-based convolutional neural network model for automatic detection of fluid hysteroscopic endometrial micropolyps in infertile women with chronic endometritis.

OBJECTIVE(S): Chronic endometritis (CE) is a localized mucosal inflammatory disorder associated with female infertility of unknown etiology, endometriosis, tubal factors, repeated implantation failure, and recurrent pregnancy loss, along with atypical uterine bleeding and iron deficiency anemia. Diagnosis of CE has traditionally relied on endometrial biopsy and detection of CD138(+) endometrial stromal plasmacytes. To develop a less invasive diagnostic system for CE, we aimed to construct a deep learning-based convolutional neural network (CNN) model for the automatic detection of endometrial micropolyps (EMiP), a fluid hysteroscopy (F-HSC) finding recognized as tiny protrusive lesions that are closely related to this disease. STUDY DESIGN: This is an in silico study using archival images of F-HSC performed at an infertility center in a private clinic. A total of 244 infertile women undergoing F-HSC on the days 6-12 of the menstrual cycle between April 2019 and December 2021 with histopathologically-confirmed CE with the aid of immunohistochemistry for CD138 were utilized. RESULTS: The archival F-HSC images of 208 women (78 with EMiP and 130 without EMiP) who met the inclusion criteria were finally subjected to analysis. Following preprocessing of the images, half a set was input into a CNN architecture for training, whereas the remaining images were utilized as the test set to evaluate the performance of the model, which was compared with that of the experienced gynecologists. The sensitivity, specificity, accuracy, precision, and F1-score of the CNN model-aided diagnosis were 93.6 %, 92.3 %, 92.8 %, 88.0 %, and 0.907, respectively. The area under the receiver operating characteristic curves of the CNN model-aided diagnosis (0.930) was at a similar level (p > .05) to the value of conventional diagnosis by three experienced gynecologists (0.927, 0.948, and 0.906). CONCLUSION: These findings indicate that our deep learning-based CNN is capable of recognizing EMiP in F-HSC images and holds promise for further development of the computer-aided diagnostic system for CE.

Rapid screening of infertility-associated gynecological conditions via ambient glow discharge mass spectrometry utilizing urine metabolic fingerprints.

Infertility presents a widespread challenge for many families worldwide, often arising from various gynecological diseases (GDs) that hinder successful pregnancies. Current diagnostic methods for GDs have disadvantages such as low efficiency, high cost, misdiagnose, invasive injury and etc. This paper introduces a rapid, non-invasive, efficient, and straightforward analytical method that utilizes desorption, separation, and ionization mass spectrometry (DSI-MS) platform in conjunction with machine learning (ML) to detect urine metabolite fingerprints in patients with different GDs. We analyzed 257 samples from patients diagnosed with polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), diminished ovarian reserve (DOR), endometriosis (EMS), recurrent pregnancy loss (RPL), recurrent implantation failure (RIF), and 87 samples from healthy control (HC) individuals. We identified metabolite differences and dysregulated pathways through dimensionality reduction methods, with the result of the discovery of 7 potential biomarkers for GDs diagnosis. The ML method effectively distinguished subtle differences in urine metabolite fingerprints. We anticipate that this innovative approach will offer a patient-friendly, rapid screening, and differentiation method for infertility-related GDs patients.

Biomarkers identification in follicular fluid in relation to live birth in in vitro fertilization of women with polycystic ovary syndrome in different subtypes by using UPLC-MS method.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common infertility disorder which affects reproductive-aged women. However, metabolic change profiles of follicular fluid (FF) in lean and obese women diagnosed with and without PCOS remains unclear. METHODS: 95 infertile women were divided into four subgroups: LC (lean control), OC (overweight control), LP (lean PCOS), and OP (overweight PCOS). The FF samples were collected during oocyte retrieval and assayed by ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) metabolomics. RESULTS: A total of 236 metabolites were identified by metabolic analysis. The pathway enrichment analysis revealed that the glycerophospholipid metabolism (impact = 0.11182), ether lipid metabolism (impact = 0.14458), and primary bile acid biosynthesis (impact = 0.03267) were related to metabolic pathway between PCOS and control. Correlation analyses showed that epitestosterone sulfate was found positively correlated with fertilization rate in PCOS, while falcarindione, lucidone C. and notoginsenoside I was found to be negatively correlated. The combined four biomarkers including lucidone C, epitestosterone sulfate, falcarindione, and notoginsenoside I was better in predicting live birth rate, with AUC of 0.779. CONCLUSION: The follicular fluid of women with PCOS showed unique metabolic characteristics. Our study provides better identification of PCOS follicular fluid metabolic dynamics, which may serve as potential biomarkers of live birth.

Elevated HbA1c Level has a Linear Association with Infertility in Women.

BACKGROUND: Hemoglobin A1c (HbA1c) is commonly known as a plasma glucose monitoring indicator. However, the relationship between HbA1c and fertility has not been clarified in previous literature. This study aims to investigate the association between HbA1c and the incidence of infertility. METHODS: Data from the U.S. National Health and Nutrition Examination Survey (NHANES) 2013 - 2018 was utilized. The final study contained 3,319 women aged 18 to 45 years. Multivariable logistic regression models were performed to analyze the correlation of HbA1c on female infertility with adjustment for relevant covariates including demographic characteristics, lifestyle, clinical laboratory biomarkers, and comorbidities. RESULTS: We found a significant linear correlation between HbA1c and infertility even in the fully-adjusted model (OR: 1.27, 95% CI: 1.07 - 1.5). Subgroup analysis stratified by age showed a significant linear association with HbA1c and infertility in the younger group (age < 35 years). Whereas, results showed a lack of significant association in the older group (age > 35 years). CONCLUSIONS: Data from a population-based sample in US women aged 18 to 45 years suggest that elevated HbA1c level correlated with increasing risk of infertility, even HbA1c is within the normal range. Further well-designed randomized controlled trials are needed to determine whether strategies to reduce HbA1c levels are effective in decreasing the incidence of female infertility.

Laparoscopic transfundal approach to cervical dilation: a novel treatment for cervical stenosis and cervical factor infertility.

OBJECTIVE: To demonstrate a novel technique used to restore cervical patency in a patient with severe iatrogenic cervical stenosis. DESIGN: Surgical video case report. SETTING: A single academic institution. PATIENT(S): We highlight the case of a 35-year-old nulliparous woman with a history of primary infertility. Her past medical history was significant for focal, invasive, well-differentiated squamous cell carcinoma of the cervix, for which she underwent a loop electrosurgical excision procedure. During her infertility assessment, she was found to have an extremely stenotic cervix that was refractory to conventional treatment options. INTERVENTIONS: This video highlights our innovative laparoscopic transfundal technique used to restore her cervical patency. MAIN OUTCOME MEASURES: None, as this is a descriptive case report. RESULTS: Postoperatively, the patient had continued cervical patency for >1 year with successful fertility treatment resulting in pregnancy. CONCLUSIONS: To our knowledge, this is the first case report describing a laparoscopic transfundal approach used to reestablish cervical patency. This approach may be considered for patients with cervical stenosis who have not responded to standard conservative therapies.

A comprehensive review of the new FIGO classification of ovulatory disorders.

BACKGROUND: The World Health Organization (WHO) system for the classification of disorders of ovulation was produced 50 years ago and, by international consensus, has been updated by the International Federation of Gynecology and Obstetrics (FIGO). OBJECTIVE AND RATIONALE: This review outlines in detail each component of the FIGO HyPO-P (hypothalamic, pituitary, ovarian, PCOS) classification with a concise description of each cause, and thereby provides a systematic method for diagnosis and management. SEARCH METHODS: We searched the published articles in the PubMed database in the English-language literature until October 2022, containing the keywords ovulatory disorders; ovulatory dysfunction; anovulation, and each subheading in the FIGO HyPO-P classification. We did not include abstracts or conference proceedings because the data are usually difficult to assess. OUTCOMES: We present the most comprehensive review of all disorders of ovulation, published systematically according to the logical FIGO classification. WIDER IMPLICATIONS: Improving the diagnosis of an individual's ovulatory dysfunction will significantly impact clinical practice by enabling healthcare practitioners to make a precise diagnosis and plan appropriate management.

Prophecy, prediction, and prognosis - can we improve the advice we give on the chance of pregnancy and treatment options for infertility?

Giving patients an accurate prognosis of their chances of achieving pregnancy is difficult with our current knowledge and technology. We need new approaches and thinking to provide truthful information.

Exposure to air pollution and ovarian reserve parameters.

Exposure to air pollution is associated with many different health effects, especially cardiovascular and respiratory diseases. Additionally, highly significant links between exposure to air pollution and fertility, particularly male fertility was observed, however the studies regarding exposure to selected air pollutants and female fertility assessed by ovarian reserve are rare. Hence, the main aim of the study was to analyze relationship between exposure to ambient air pollution and ovarian reserve parameters among Polish women. The study population consisted of 511 women, who attended to infertility clinic because of diagnostic purposes. Participants filled in the questionnaire about social-demographic, lifestyle and health factors. Infertility specialists assessed ovarian parameters such as: antral follicle count (AFC) and concentration of hormones: Anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH) and estradiol (E2). The air pollutants level (sulfur dioxide, nitrogen dioxide, carbon monoxide, ozone, particulate matters) were obtained via National Environmental Protection Inspectorate database. Significant negative association between PM2,5 and AHM (p = 0.032) as well as AFC (p = 0.044) was observed. Moreover, SO2 concentrations decrease AFC (p = 0.038). The results also suggest that PM10, PM2.5, SO2 exposure on antral follicle count may be more pronounced among women with a female factor infertility diagnosis. Additionally, exposure to PM2.5 and NOx on AFC and AMH was stronger among older women (> 35 years of age). To conclude, the present study found that air pollution could lead to decrease in follicle antral count and Anti-Müllerian hormone level, especially exposure to PM2,5 and SO2 thus the evidence suggest negative impact to ovarian reserve.

Subclinical hypothyroidism in the infertile female population: a guideline.

There is controversy regarding whether to treat subtle abnormalities of thyroid function in infertile female patients. This guideline document reviews the risks and benefits of treating subclinical hypothyroidism in female patients with a history of infertility and miscarriage, as well as obstetric and neonatal outcomes in this population.

Chlamydial Antibody Test in Screening of Tubal Infertility: Specificity and Sensitivity Analysis.

Sexually transmitted infection is a frequent cause of tubal factor abnormality. Chlamydia trachomatis is a common causative organism for sexually transmitted infection. There are studies indicating association of chlamydial antibodies in serum with tubal abnormalities. In many centers chlamydial antibody test is done as part of routine work up for infertility. The objective of the study was to evaluate the sensitivity and specificity of chlamydial antibody test in screening infertile women for tubal factor infertility. This cross-sectional observational study was performed for one year from January 2019 to December 2019 in the Department of Reproductive Endocrinology and Infertility of Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh. The infertile women having laparoscopy as part of infertility work up were enrolled in the study. The women had their serum tested for chlamydial antibody IgG by enzyme linked immune-sorbent assay. The sero-positivity for chlamydial antibody was tested against the findings of laparoscopy and dye test as gold standard for diagnosing tubal factor infertility. Statistical analysis was done to find out the sensitivity and specificity of the chlamydial antibody test in screening infertile women for tubal factor infertility. The study population included 163 infertile women with mean age 29.8±5.8 years. The tubal factor infertility was present in 56.4% of the women. The sero-positivity of Chlamydia trachomatis IgG was 36.6%. Sensitivity and specificity of Chlamydial antibody test (IgG positive) in detecting tubal factor infertility is 47.8% and 70.4% respectively. Positive predictive value of chlamydial antibody test in detecting tubal factor infertility is 41.5% and negative predictive value is 72.4%. Positive likelihood ratio is 1.59. Negative likelihood ratio is 0.74. Accuracy is 57.67%. In conclusion, the chlamydial antibody test may not be an appropriate screening test for tubal factor infertility in women of Bangladesh because of low sensitivity and moderately high specificity.

The "freeze-all" strategy seems to improve the chances of birth in adenomyosis-affected women.

OBJECTIVE: To compare assisted reproductive technologies (ARTs) outcomes between fresh vs. freeze-all strategies in infertile women affected by adenomyosis. DESIGN: A single-center observational study. SETTINGS: University hospital-based research center. PATIENTS: Adenomyosis-affected women undergoing blastocyst embryo transfer after in vitro fertilization and intracytoplasmic sperm injection between January 1, 2018, and November 31, 2021. The diagnosis of adenomyosis was based on imaging criteria (i.e., transvaginal ultrasound and/or magnetic resonance imaging). INTERVENTION(S): Women who underwent a freeze-all strategy were compared with those who underwent a fresh embryo transfer (ET) strategy. MAIN OUTCOME MEASURE(S): Cumulative live birth rate (LBR). RESULTS: A total of 306 women were included in the analysis: 111 in the fresh ET group and 195 in the freeze-all group. The adenomyosis phenotype (internal diffuse adenomyosis, external focal adenomyosis, and adenomyoma) was not significantly different between the two groups. The cumulative LBR (86 [44.1%] vs. 34 [30.6%], respectively), and the cumulative ongoing pregnancy rate (88 [45.1%] vs. 36 [32.4%], respectively) were significantly higher in the freeze-all group compared with the fresh ET group. After multivariate logistic regression analysis, the freeze-all strategy in women with adenomyosis was associated with significantly higher odds of live birth compared with fresh ET (odds ratio = 1.80; 95% confidence interval = 1.02-3.16). CONCLUSION: The freeze-all strategy in women afflicted with adenomyosis undergoing ART was associated with significantly higher cumulative LBRs. Our preliminary results suggest that the freeze-all strategy is an attractive option that increases ART success rates. Additional studies, with a randomized design, should be conducted to further test whether the freeze-all strategy enhances the pregnancy rate in adenomyosis-affected women.

Leukocyte telomere length and DNA methylome as biomarkers of ovarian reserve and embryo aneuploidy: the intricate relationship between somatic and reproductive aging.

The average childbearing age among women continues to rise, leading to an increased prevalence of infertility and a subsequent increased use of assisted reproductive technologies (ARTs). Ovarian aging, especially diminished ovarian reserve and poor ovarian response, have been implicated as common causes of infertility. Telomere length and DNA methylation-based epigenetic clocks are established hallmarks of cellular aging; however, the interplay between somatic and ovarian aging remains unclear. There appears to be a lack of correlation between leukocyte telomere length and the DNA methylation age of somatic and ovarian cells. Both the telomere length and methylome of follicular somatic cells (granulosa and cumulus) appear to be unaffected by chronologic age, infertility, or processes that result in diminished ovarian reserve and poor ovarian response. As such, they are unlikely candidates as surrogate biomarkers of reproductive potential, response to stimulation, or ART outcome. Meanwhile, telomere or methylome changes in leukocytes associated with aging seem to correlate with reproductive function and may have the potential to aid the characterization of women with reproductive decline; however, current data are limited and larger studies evaluating this within an ART setting are warranted.

Antimüllerian hormone level predicts ovulation in women with polycystic ovary syndrome treated with clomiphene and metformin.

OBJECTIVE: To describe the serum anti-Müllerian hormone (AMH) concentrations in a large, well-phenotyped cohort of women with polycystic ovary syndrome (PCOS) and evaluate whether AMH predicts successful ovulation induction in women treated with clomiphene and metformin. DESIGN: Secondary analysis of randomized controlled trial. SETTING: Not applicable. PATIENT(S): A total of 333 women with anovulatory infertility attributed to PCOS who participated in the double-blind randomized trial entitled the Pregnancy in Polycystic Ovary Syndrome I (PPCOS I) study (registration number, NCT00068861) who had serum samples from baseline laboratory testing available for further serum analysis were studied. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): The association between the baseline AMH levels in each of the 3 treatment groups and ovulation, pregnancy, and live birth rates were assessed. RESULT(S): A total of 322 individuals had a baseline AMH concentration available, of which the mean AMH was 11.7 ± 8.3 ng/mL (range 0.1-43.0 ng/mL). With each unit (1 ng/mL) increase in baseline AMH, the odds of ovulation decreased by 10% (odds ratio, 0.90; 95% confidence interval, 0.86-0.93); this effect did not differ by treatment group. Women with a high baseline AMH concentration (>8 ng/mL) were significantly less likely to ovulate compared with those with a normal baseline AMH concentration (<4 ng/mL) (odds ratio, 0.23; 95% confidence interval, 0.05-0.68). This remained statistically significant when controlling for confounders, including age, body mass index, time in study, and Homeostatic Model Assessment for Insulin Resistance score. Ovulation occurred even at very high AMH concentrations; there was no maximum level noted at which no ovulation events occurred. Baseline AMH concentration was not associated with pregnancy or live birth rates when controlling for confounders. CONCLUSION(S): These AMH values in well-phenotyped individuals with PCOS add to the literature and will aid in identifying AMH criteria for the diagnosis of PCOS. In women with infertility and PCOS, a higher AMH concentration was associated with reduced odds of ovulation with ovulation induction with clomiphene, clomiphene + metformin, and metformin. CLINICAL TRIAL REGISTRATION NUMBER: The original trial from which this analysis is derived was entitled "Pregnancy in Polycystic Ovary Syndrome: A 30 Week Double-Blind Randomized Trial of Clomiphene Citrate, Metformin XR, and Combined Clomiphene Citrate/Metformin XR For the Treatment of Infertility in Women With Polycystic Ovary Syndrome" and was registered on ClinicalTrials.gov as number NCT00068861. The URL for the trial is https://clinicaltrials.gov/study/NCT00068861. The first subject was enrolled in November 2002.

Developing a Predictive Model for Minimal or Mild Endometriosis as a Clinical Screening Tool in Infertile Women: Uterosacral Tenderness as a Key Predictor.

STUDY OBJECTIVE: To develop a noninvasive predictive model based on patients with infertility for identifying minimal or mild endometriosis. DESIGN: A retrospective cohort study. SETTING: This study was conducted at a tertiary referral center. PATIENTS: A total of consecutive 1365 patients with infertility who underwent laparoscopy between January 2013 and August 2020 were divided into a training set (n = 910) for developing the predictive model and a validation set (n = 455) to confirm the model's prediction efficiency. The patients were randomly assigned in a 2:1 ratio. INTERVENTIONS: Sensitivities, specificities, area under the curve, the Hosmer-Lemeshow goodness of fit test, Net Reclassification Improvement index, and Integrated Discrimination Improvement index were evaluated in the training set to select the optimum model. In the validation set, the model's discriminations, calibrations, and clinical use were tested for validation. MEASUREMENTS AND MAIN RESULTS: In the training set, there were 587 patients with minimal or mild endometriosis and 323 patients without endometriosis. The combination of clinical parameters in the model was evaluated for both statistical and clinical significance. The best-performing model ultimately included body mass index, dysmenorrhea, dyspareunia, uterosacral tenderness, and serum cancer antigen 125 (CA-125). The nomogram based on this model demonstrated sensitivities of 87.7% and 93.3%, specificities of 68.6% and 66.4%, and area under the curve of 0.84 (95% confidence interval 0.81-0.87) and 0.85 (95% confidence interval 0.80-0.89) for the training and validation sets, respectively. Calibration curves and decision curve analyses also indicated that the model had good calibration and clinical value. Uterosacral tenderness emerged as the most valuable predictor. CONCLUSION: This study successfully developed a predictive model with high accuracy in identifying infertile women with minimal or mild endometriosis based on clinical characteristics, signs, and cost-effective blood tests. This model would assist clinicians in screening infertile women for minimal or mild endometriosis, thereby facilitating early diagnosis and treatment.