Assessment Of Ovarian Reserve Research Articles

Assessment of ovarian follicular reserve according to ultrasound data based on machine learning methods

Assessment of ovarian follicular reserve according to ultrasound data based on machine learning methods

P-624 Description of antral follicle count in a population of healthy French women based on age, ultrasound technique, and clinical factors

Abstract Study question How is the age-specific reference range for antral follicle count in healthy French women correlated with clinical markers ? Summary answer AFC declines linearly with age is correlated with weight, hormonal contraception, cycles duration, but not BMI, smoking or infertility history. What is known already AFC is related to the number of primordial follicles within the ovaries and is a widely used marker for baseline assessment of ovarian reserve, but there are no standardized norms for AFC, and major differences between the nomograms published in recent years notably due to the improvement of ultrasound techniques. Moreover, most published data are based on infertile women. Several factors are postulated to have influence on AFC of which ethnic origin, yet the largest cohorts published recently are Asian and therefore do not apply to a Caucasian population. Study design, size, duration In this retrospective study we used data from 640 women who had undergone a Fertility Check Up in our center, from 2018 to 2023. This concept, unique in France, offers all women of reproductive age who wish to undergo a complete ultrasound examination to check for infertility risk factors, whatever their parental plans. Participants/materials, setting, methods 640 healthy French women undergoing a Fertility Check Up were recruited. All participants completed a questionnaire about demographics, medical and surgical history, obstetrical records, familial medical history and any usage of hormonal contraception. AFC was conducted via transvaginal ultrasound using a three-dimensional acquisition, by one of three trained operators, utilizing a Voluson E10 ultrasound machine (GE Healthcare). Operators employed either the sonoAVC option (semi-automatic technique) or a manual two-dimensional counting of the acquired 3D-dimensional volume. Main results and the role of chance The distribution of AFC by age were modelized by a numerical and a graphic nomograms. AFC demonstrated a linear decline with a decrease of 1.11 follicle (IC95% 0.98 - 1.24) per year of age. Age accounted for 12.5% of the variation (R2) in AFC. Linear regression analysis showed a significant negative correlation between AFC and women’s weight (p = 0.02), but not with BMI (p = 0.23), and a significant impact of hormonal contraception (p = 0.001), with an overall reduction of 6.6 follicles in AFC compared with the women without any hormonal contraception (IC95% 4.6 - 8.6). Short menstrual cycles were associated with lower AFC (p < 0.001), when long cycles and amenorrhea were significantly associated with higher AFC (p < 0.01). There was no impact of age of menarche, smoking, family history of POI, or of a history of infertility of more than one year. Multivariate analysis showed that AFC was significantly higher with 3D-manual versus automated-3D follicular counting, the difference averaged 3.59 follicles, reducing as AFCs became smaller. Limitations, reasons for caution We present data from Caucasian women using our ultrasound machines, but in practice, each sonographer must familiarize himself with the capabilities of his own machine. Furthermore, our study does not answer the question of AFC evolution over time, for a given patient. Wider implications of the findings Some questions remain unanswered, including the longitudinal trajectory of AFC within an individual and the impact of ethnic origin. Future longitudinal studies reporting the evolution of AFC with age and involving women of diverse ethnic backgrounds are needed. Ultimately, this study highlights the impact of ultrasound equipment and technique. Trial registration number Not applicable

P-750 Is maximalization of the ovum pick-up (OPU) procedure beneficial for the outcome of assisted reproductive technology (ART) cycles?

Abstract Study question Is aspiration of more oocytes than the antral follicle count (AFC) beneficial for the current (pregnancy/live birth rates) and future products of an ART cycle? Summary answer Aspirating more oocytes than the AFC does not influence the outcome of the fresh cycle but is beneficial for fertility preservation and cumulative pregnancy rates. What is known already AFC is a reliable and immediate indicator for ovarian reserve assessment and is in correlation with the ovarian response to gonadotropin stimulation. Additionally, correlation between AFC and embryo quality, clinical pregnancy and live birth rates was reported. There is no data concerning the impact of the ratio between the AFC and actual number of oocytes retrieved on cycle outcome. Study design, size, duration Data of the first oocyte aspiration for ICSI performed between 2018-2022 in attempt to conceive (ICSI, n = 399) or for planned oocyte vitrification (fertility preservation FP, n = 283) was retrieved. Each group was divided into two subgroups according to their ‘oocyte/AFC index’ (OAFCI): <1 and ≥1. The stimulation parameters, number of aspirated oocytes, their maturity rate, number of cryopreserved oocytes/embryos, clinical pregnancy (CPR) and live birth rates (LBR) were compared between the subgroups. Participants/materials, setting, methods The AFC was determined by professional sonographers using a 9 MHz transvaginal ultrasound probe. The most adjacent measurement to the stimulation initiation was used. Stimulation protocol and FSH dose were determined according to the AFC and individual clinical consideration. Patients not in their first cycle, natural cycle aspirations, and cases in which no oocytes were retrieved, were excluded. Main results and the role of chance OAFC≥1 was associated with higher pre-trigger estradiol (6159 pmol/L vs. 4304, p < 0.001 for ICSI, 4949 vs. 3488, p < 0.001 for FP), and longer duration of simulation (9.8 days vs. 9, p < 0.001 for both FP and ICSI). More oocytes were aspirated in OAFC≥1 groups in both FP (16.9±11.2 vs. 7.9±5.9, p < 0.001) and ICSI (17.4±9.8 vs. 10.7±6.7, p < 0.001). Oocyte maturity was unaffected by the OAFCI in the ICSI group, but was lower in FP group at OAFC≥1 (0.79 vs.0.84 p = 0.005). OAFCI≥1 was associated with a higher number of cryopreserved embryos (3.9 vs. 2.3, p < 0.001 for ICSI) and a higher number of vitrified oocytes (13.4 vs. 6.4 p < 0.001 for FP). The OAFCI had no impact on CPR (39% vs. 60%, p = 0.27) and LBR (19.9% vs. 24.8%, p = 0.33). On multivariate analysis controlling for age, gonadotropin dosage and duration of stimulation, OAFC≥1 was associated with a higher number of cryopreserved embryos (ICSI group aOR 1.2, 95% CI 1.1-1.3, p < 0.001), and vitrified oocytes (aOR 1.2, 95% CI 1.1-1.2, p < 0.001) and lower maturity index (aOR 0.1, 95% CI 0.03-0.51, p < 0.001) in the FP group. Limitations, reasons for caution Retrospective study analyzing results of treatment cycles without an intention to aspirate differently. Wider implications of the findings Aspiration of a more oocytes than the current AFC was not associated with higher CPR or LBR in the fresh cycle, but harbors the possibility to cryopreserve more oocytes and embryos. This might translate into higher cumulative pregnancy rates later on. Trial registration number Not applicable

Factors associated with fertility status assessment among female survivors of childhood cancer.

10072 Background: Female survivors of childhood cancer with prior gonadotoxic treatment are at risk for infertility. As such, fertility status assessment (FSA) with ovarian reserve assessment and antral follicle count in consultation with a fertility specialist may be indicated to evaluate options for biological parenthood. FSA is underutilized in this population. This study explored psychosocial, developmental, and clinical factors associated with FSA. Methods: Female survivors (aged 18-29 years, diagnosis < 21 years, > 1 year from treatment completion, prior gonadotoxic treatment) were recruited from four cancer centers in the U.S. Participants reported sociodemographics (race, sexual orientation, gender identity, relationship status), developmental milestones (living and financial independence, full-time employment), reproductive concerns (modified Reproductive Concerns Scale), knowledge of reproductive health, decisional factors, and history of FSA. Clinical characteristics (cancer diagnosis, treatment-related risk for infertility, hormonal testing, clinical encounter with pediatric reproductive health subspecialist [gynecology, endocrinology]) were abstracted from the medical record. Multivariate logistic regression was performed to calculate odds ratios (OR) and 95% confidence intervals (95%CI) for factors associated with FSA. Results: Of 325 participants, N = 260 completed all survey items of interest. Participants were an average of 23.7±3.1 years, 74% non-Hispanic white, 79% heterosexual and cisgender, and 48% in a committed relationship. Compared with those without FSA (N = 164), participants who completed an FSA (N = 96) reported greater attainment of developmental milestones (OR 2.20, 95%CI: 1.10-3.85, p = .027), greater desire for reproductive information (OR 1.86, 95%CI: 1.2-2.77, p = .001), greater knowledge regarding fertility-related procedures (OR 4.12, 95%CI: 2.36-7.57, p < .001) and fertility preservation (OR 1.76, 95%CI: 1.31-2.44, p < .001), having made an informed decision to pursue FSA (OR 1.82, 95%CI: 1.30-2.59, p = .001), clinical encounter with pediatric reproductive subspecialist (OR 3.37, 95%CI: 1.1-10.9, p = .032), and less knowledge regarding family building options (OR 0.47, 95%CI 0.27-0.79, p = .006). Diagnosis, infertility risk, and hormonal evaluation were not associated with FSA completion. Conclusions: Among emerging adult survivors, psychosocial factors associated with FSA completion include developmental milestones and knowledge of reproductive health. Clinical encounters with pediatric reproductive subspecialists may provide an opportunity for survivors to learn about and receive referrals to a fertility clinic. Psychoeducation is warranted to support survivors’ pursuit of FSA. Integration and consideration of survivor development and knowledge in these clinical encounters should potentiate optimal uptake of FSA.

Potential clinical application of anti-Müllerian hormone testing in radioiodine treatment of thyroid carcinoma

Differentiated thyroid cancer is the most common endocrinological malignancy. Radioiodine treatment has a clear benefit in locally aggressive and metastatic cancers. There are discussions about long-term and acute adverse events.Anti-Müllerian hormone is regarded as the best endocrine marker for evaluating the physiological loss of oocytes in healthy women with regard to age. The impact of radioiodine treatment on anti-Müllerian hormone levels has been more significantly reported in patients over 35 years of age. About reproductive dysfunction, calculations of individual absorbed doses of radioiodine in ovaries after thyroid cancer therapy have not been performed yet. The aim of our ongoing prospective study is to determine serum anti-Müllerian hormone to estimate ovarian reserve for premenopausal women treated with radioiodine and to compare anti-Müllerian hormone levels before and after radioiodine treatment. Predicting radioiodine side effects by evaluating a simple serum biomarker may help to select an appropriate treatment strategy for young women planning pregnancy, specifically in the assessment of ovarian reserve and premature ovarian failure with early onset of menopause.

Impact of bariatric surgery on ovarian reserve markers and its correlation with nutritional parameters and adipokines.

A reduction in anti-müllerian hormone (AMH) levels at short-term after bariatric surgery (BS) has been previously described. However, an assessment of ovarian reserve at longer-follow up, and a comprehensive evaluation of the potentially implicated factors has not been reported. Prospective cohort study. Twenty women aged 18-40 years with BMI 43.95 kg/m2 undergoing BS were studied at baseline (BS0), and at 1 month (BS1), 4 months (BS2), 12 months (BS3), and 24-36 months (BS4) after the surgery. Anthropometrics, reproductive hormones (AMH, FSH, LH, estradiol, testosterone, SHBG, androstenedione), metabolic parameters (adiponectin, leptin, ghrelin, insulin), and nutritional blood parameters (markers of nutritional status, vitamins, and minerals) were obtained at each study time point. Antral follicular count (AFC) was assessed by ultrasonography at BS0, BS3, and BS4. Mixed models were used for analysis of longitudinal data. The mean AMH level was 3.88 ng/mL at BS0, decreased at BS3 (mean= 2.59 ng/mL; p=0.009), and remained stable between BS3 and BS4 (mean= 2.96 ng/mL; p=0.409). We also observed a non-significant decrease in AFC at BS3 (mean=26.14 at BS0, mean 16.81 at BS3; p=0.088) that remained stable at BS4 (mean= 17.86; p=0.731). Mixed models analysis showed: (a) a decrease in 10kg of body weight was associated with an average decrease of 0.357 ng/mL in AMH (p=0.014); (b) a decrease in 1 BMI point was associated with an average decrease of 0.109 ng/mL in AMH (p=0.005); (c) an increase in 1 µg/mL of adiponectin was associated with an average decrease of 0.091 ng/ml in AMH (p=0.041) Significant positive correlations were found between the AMH levels after BS and plasma concentrations of testosterone, free androgen index, insulin and HOMA index. No significant correlations were detected between AMH levels and nutritional parameters. Our results were in line with previous observations, showing that AMH levels decreased significantly at 12 months after bariatric surgery, in parallel with a non-significant reduction in AFC. Both ovarian reserve markers showed a later stabilization up to the end of the study. Of note, postoperative AMH levels were positively correlated with key androgen and insulin resistance-related parameters.

Алгоритм диференційованого лікування пацієнток з ендометріомою яєчників і безпліддям

Purpose - to improve fertility in women with ovarian endometrioma (ОЕ) and infertility using the proposed algorithm and treatment methods. Materials and methods. The prospective study was conducted in 2 stages. In the first stage, 93 women with infertility were included in the study, who were divided into the following groups depending on the surgery performed: the Group 1 - with ОЕ sclerotherapy followed by platelet-rich plasma (PRP) injection into the ovarian tissue; the Group 2 - laparoscopic cystectomy followed by PRP injection into the ovarian tissue; the Control (C) group - with classical laparoscopic cystectomy. After dynamic observation, assessment of ovarian reserve and control of pregnancy for 12 months, an algorithm for differentiated treatment of ОЕ in women with infertility was developed. At the 2nd stage, 20 women (the Group 3) were treated with the proposed methods of treatment, such as sclerotherapy with ОЕ + PRP (the Subgroup 3a) and laparoscopic excision of the ОЕ + PRP capsule (the Subgroup 3b), based on the algorithm, and analyzed. Statistical processing of the results was performed using Microsoft Excel. Results. The mean level of anti-mullerian hormone (AMH) in the Subgroup 3a increased from 1.76 (CI: 1.47-1.71) ng/ml to 1.87 (CI: 1.63-1.86) ng/ml (p=0.036). In the Subgroup 3b, AMH changed from 2.15 (CI: 1.89-2.48) ng/ml to 2.22 (CI: 1.91-2.53) ng/ml (p>0.05). The number of antral follicles (AF) in the Subgroup 3a increased from 8.88 (CI: 7.90-9.90) to 11.10 (CI: 10.40-11.80) (p<0.001). In the Subgroup 3b, from 10.60 (CI: 9.90-11.20) to 11.00 (CI: 10.50-11.50) (p>0.05). Spontaneous pregnancy within 6 months occurred in 6 (60%) patients from the Subgroup 3a, and in 4 (40%) women from the Subgroup 3b (p>0.05). After 6 months of follow-up, 2 underwent assisted reproductive technology. The remaining women from the Subgroup 3a (3 (30%)) and the Subgroup 3b (5 (50%)) also had spontaneous pregnancies by 1 year of follow-up (p>0.05). Conclusions. The proposed methods of treatment of ОЕ, sclerotherapy + PRP and laparoscopy + PRP, showed a significant positive effect on the preservation of ovarian reserve. A differential approach to the treatment of ОЕ based on the proposed algorithm increases the occurrence of spontaneous pregnancy. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Evaluation of ovarian reserve in women with thyroid autoimmunity.

To compare the ovarian reserve of women of reproductive age with and without thyroid autoimmunity (TAI). We performed a retrospective analysis of medical records from an assisted reproduction clinic from February 2017 to December 2021. Women aged between18 and 47 years with data on antithyroperoxidase and antithyroglobulin (anti-Tg) antibodies and assessment of ovarian reserve by anti-müllerian hormone (AMH) and antral follicle count (AFC) were included. Among the 188 participants included, 63 were diagnosed with TAI, and 125 had both antibodies negative. AMH and AFC were compared between groups. Subanalysis based on age, types of antibodies, and thyroid function markers were performed. In addition, bivariate analysis and regression models were used. Overall, there was no difference in the median levels of AMH or AFC between the two groups. However, in the subgroup analysis by age, we observed a trend towards lower median levels of AMH in women over 39 years with TAI (0.9 ng/mL vs. 1.5 ng/mL, p=0.08). In a subanalysis according to antibodies, we found a significantly lower median AFC in the group with anti-Tg than in the group without this antibody (8.0 follicles vs. 11.5 follicles, p=0.036). We also found a significantly higher prevalence of anti-Tg in patients with low ovarian reserve compared to those with normal reserve (60.7% vs. 39.3%, p=0.038). The ovarian reserve of women with TAI appears to be insidiously compromised over the years, with a decreased ovarian reserve in women with anti-Tg.

The Relationship Between Serum Anti-Müllerian Hormone and Basal Antral Follicle Count in Infertile Women Under 35 Years: An Assessment of Ovarian Reserve

The Relationship Between Serum Anti-Müllerian Hormone and Basal Antral Follicle Count in Infertile Women Under 35 Years: An Assessment of Ovarian Reserve

#143 : Assessment of Ovarian Reserve in Infertile Women with Hypothyroidism

Background: Impaired thyroid function may affect the follicular growth and development and reduces the number of follicles in ovaries. Thus, hypothyroidism may cause the reduction of ovarian reserve in women with reproductive age group. This study aimed to assess the ovarian reserve in infertile hypothyroid women. Methods: This cross-sectional study was conducted in Reproductive Endocrinology and Infertility Unit, Dhaka Medical College Hospital, Bangladesh from July 2021 to June 2022. Total 167 hypothyroid infertile women of 20–35 years of age who had S. TSH level >2.5 mIU/L with normal/low free T4 were included. Ovarian reserve was evaluated by serum anti-Mullerian hormone (AMH) and antral follicle count (AFC). Thyroid autoimmunity was also assessed by measuring anti thyroid per oxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb). Then the relationship of ovarian reserve, thyroid hormones and anti-thyroid antibodies were assessed. Results: Among the 167 women with hypothyroidism, 124 (74.3%) patients had sub-clinical hypothyroidism (SCH) and rest 43 (25.7%) had overt hypothyroidism. Infertile women with overt hypothyroidism had significantly higher TPOAb(+) (67.4%) and TgAb (+) (46.5%) than those of subclinical hypothyroid women (TPOAb+ve : 29%, TgAb+ve : 29.8%, p-value: 0.014). Correlation analysis showed that there was significant negative correlation between AMH and TSH (r: −0.029, p-value: 0.024), TPOAb (r: −0.053, p value: 0.011), TgAb (r: −0.083, p-value: 0.018). Diminished ovarian reserve was significantly associated with overt hypothyroidism in this study population (p-value: 0.001). 33(26.6%) and 23(53.5%) of SCH and overt hypothyroid women had diminished ovarian reserve respectively. Conclusion: Anti-Mullerian hormone was negatively associated with increased TSH level and with anti-thyroid antibodies (TPOAb and TgAb). Diminished ovarian reserve was significantly associated overt hypothyroidism. So, the study findings suggest that hypothyroidism has a negative effect on ovarian reserve.

A Comparative Study of Anti-Mullerian Hormone (AMH) and Follicle Stimulating Hormone (FSH) In Assessment of Ovarian Reserve

A Comparative Study of Anti-Mullerian Hormone (AMH) and Follicle Stimulating Hormone (FSH) In Assessment of Ovarian Reserve

A-055 Clinical Performance Evaluation of the ADVIA Centaur AMH Assay

Abstract Background Anti-Müllerian hormone (AMH) is a transforming growth factor beta protein synthesized by granulosa cells of small growing follicles in ovaries in females and by Sertoli cells of the testes in males. AMH measurements are increasingly being used in the assessment of ovarian reserve, prediction of response to controlled ovarian stimulation in women undergoing assisted reproductive technologies, as an aid in the diagnostic evaluation of polycystic ovary syndrome, and prediction of menopause. The objective of this study was to evaluate the clinical performance of the ADVIA Centaur® AMH assay in the assessment of ovarian reserve and compare performance to the Beckman ACCESS 2 AMH assay. In addition, an exploratory analysis evaluated ADVIA Centaur AMH assay performance in distinguishing women with expected poor ovarian response per published criteria. Methods Clinical specimens were collected from 577 women at 11 U.S. fertility centers. Women enrolled were 22–45 years old and possessed both ovaries. They underwent blood draw and transvaginal ultrasound to measure the antral follicle count on days 2–4 of menstrual cycle. Women with BMI ≥40; pregnancy within 3 months; on contraceptives, hormonal medications; undergoing treatment for malignancy, ovarian abnormalities, surgery in the past 6 months; or with endocrine or metabolic disorders (including PCOS) were excluded. Results Results were considered positive (high ovarian reserve) if the AMH concentration was >1.77 ng/mL and AFC was >15 and negative (normal-to-diminished ovarian reserve) if the AMH concentration was ≤1.77 ng/mL and AFC was ≤15. The estimated sensitivity, specificity, and two-sided 95% Wilson score confidence intervals (CI) of each parameter were determined to be 90.76% (86.97–93.53) and 52.19% (46.29–58.03) using the ADVIA Centaur AMH assay, and 90.10% (86.22–92.98) and 52.19% (46.29–58.03) with the ACCESS 2 AMH assay, respectively.A secondary analysis was completed to investigate poor ovarian response (POR) according to the Bologna criteria, published by the ESHRE. These criteria define poor ovarian response as an AMH measurement of less than 1.1 ng/mL and AFC of less than 7. Of the 577 women included in the study, 32 women had an antral follicle count less than 7, of whom 26 also had a AMH concentration of less than 1.1 ng/mL. Of the 545 women with an antral follicle count greater than or equal to 7, 480 also had AMH measurements of greater than or equal to 1.1 ng/mL. Using the Bologna criteria, the ADVIA Centaur AMH assay performs with a sensitivity of 81.25% and specificity of 88.07%. Conclusions In this clinical population, the sensitivity and specificity of AMH assays on the ADVIA Centaur XP and Beckman ACCESS 2 systems were almost identical when using an AMH cutoff ≤1.77 ng/mL and AFC ≤15 to identify normal-to-diminished ovarian reserve. Using published criteria for POR resulted in a sensitivity and specificity of 81.25% and 88.07% for the ADVIA Centaur AMH assay. Not available for sale in the U.S. Future availability cannot be guaranteed. Product availability varies by county. HOOD#05162003331923

P-622 Age-specific reference intervals for anti-müllerian hormone in Mexico: A population-based study. implications for Latin America

Abstract Study question To determine the age-specific normal range of antimullerian hormone (AMH) levels in a female Latin American population. Summary answer Age-related nomograms for general population for the 3rd-97th percentiles were produced. These nomograms could provide a reference guide for clinicians to consult women with infertility. What is known already The variation of AMH levels among different races and ethnicities has been well documented (Seifer et al., 2009). Despite the wide use of AMH measurements in clinical assessment of ovarian reserve, a population-based estimate for its reference range in Latin America is not available. Study design, size, duration A longitudinal, observational, retrospective, real-world study was carried out, including all AMH measurements performed from January 2017 to December 2018 at a large clinical laboratory network in the Mexico City area, encompassing 35 locations. A total of 6444 AMH measurements were included. Participants/materials, setting, methods AMH was assayed using either the cobas or ELISA methodologies. All AMH measurements from women 25-45 years were included. The Kolmogorov-Smirnov test was used to confirm that AMH levels between patients assayed with cobas were comparable to those assayed with ELISA at every age. Main results and the role of chance In total, 6444 measurements were identified and available for analysis. Age-related normograms for the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles of AMH were produced. The overall rate of AMH decline accelerated after 40 years of age. In women 25-30 years, 11.4% (63/554) had an AMH <1.0ng/mL. In women 30-35 years, 18.6% (276/1484) had an AMH <1.0ng/mL. In women 35-40 yeras, 35.8% (830/2319) had an AMH <1.0ng/mL. In women 40-45 years, 58.0% (1120/1932) had an AMH <1.0ng/mL. Limitations, reasons for caution The lack of medical history for patients precluded identification and exclusión of patients with iatrogenically abnormal AMH levels (e.g. due to oophorectomy). Patients undergoing measurement of AMH were primarily referred through fertility clinics, limiting the potential for extrapolation to the general population. Wider implications of the findings The study reports age-specific AMH levels drawn from a large sample of women around Mexico City. The study includes the largest dataset to date. Latin American patients considering fertility preservation should be aware of the high prevalence of diminished ovarian reserve in this large cohort, including among women 35-39. Trial registration number Not Applicable

Assessment of Ovarian Reserve and Response using Anti-Mullerian Hormone

Kenneth Egwuda, MBBS, ESGE, FMAS, FWACS, PGA-ART, FICS, MCP, DMA1, Comfort A. Egwuda, FWACS2, Felix A. Elachi, FWACS, FMCOG, MBBS3, Adeola O. Blessing, B.sc. Ana., MPH.4,

Anti-Müllerian hormone - clinical use and future possibilities.

Anti-Müllerian hormone (AMH) is a protein produced already in human fetus. It has an essential role in the differentiation of the reproductive tract, regulation of the ovaries and testes. The determination of serum AMH levels is used in clinical practice. Today, especially in reproductive medicine in the assessment of ovarian reserve and in the prediction of the response to ovarian stimulation. However, in young cancer patients, it can also predict the risk of ovarian failure after anticancer treatment. It finds further use in pediatric endocrinology in the diagnosis of sexual differentiation disorders. In oncology, it is used as a tumor marker for monitoring patients with granulosa tumors. In the future, however, it is also promising to use the knowledge of AMH function for the treatment of gynecological as well as other solid malignancies expressing a tissue-specific receptor for AMH.

Assessment and quantification of ovarian reserve on the basis of machine learning models.

Early detection of ovarian aging is of huge importance, although no ideal marker or acknowledged evaluation system exists. The purpose of this study was to develop a better prediction model to assess and quantify ovarian reserve using machine learning methods. This is a multicenter, nationwide population-based study including a total of 1,020 healthy women. For these healthy women, their ovarian reserve was quantified in the form of ovarian age, which was assumed equal to their chronological age, and least absolute shrinkage and selection operator (LASSO) regression was used to select features to construct models. Seven machine learning methods, namely artificial neural network (ANN), support vector machine (SVM), generalized linear model (GLM), K-nearest neighbors regression (KNN), gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and light gradient boosting machine (LightGBM) were applied to construct prediction models separately. Pearson's correlation coefficient (PCC), mean absolute error (MAE), and mean squared error (MSE) were used to compare the efficiency and stability of these models. Anti-Müllerian hormone (AMH) and antral follicle count (AFC) were detected to have the highest absolute PCC values of 0.45 and 0.43 with age and held similar age distribution curves. The LightGBM model was thought to be the most suitable model for ovarian age after ranking analysis, combining PCC, MAE, and MSE values. The LightGBM model obtained PCC values of 0.82, 0.56, and 0.70 for the training set, the test set, and the entire dataset, respectively. The LightGBM method still held the lowest MAE and cross-validated MSE values. Further, in two different age groups (20-35 and >35 years), the LightGBM model also obtained the lowest MAE value of 2.88 for women between the ages of 20 and 35 years and the second lowest MAE value of 5.12 for women over the age of 35 years. Machine learning methods combining multi-features were reliable in assessing and quantifying ovarian reserve, and the LightGBM method turned out to be the approach with the best result, especially in the child-bearing age group of 20 to 35 years.

Measurement of ovarian reserve in infertile versus fertile women: A case control study in Edo State, Nigeria.

The reproductive potential in a woman is age related. Nevertheless, the female reproductive system undergoes ovarian follicular development, resulting in ovulation of matured ovum for fertilization. Consequently, female reproductive aging parallels the depletion of the store of follicles until menopause is attained. This is the essential reason for evaluating ovarian reserve in women of reproductive age for infertility screening. The objective of the present study is to compare the serum FSH, LH, estradiol and progesterone levels in infertile women with fertile controls. The study was designed as a case control descriptive study conducted in Benin City Edo State, Nigeria. Data were obtained through Questionnaire interview, while ELISA technique was used in the hormone analysis. Seventy-one women participated, of which 42 of them were infertile; and 29 age-matched fertile women (as controls). Secondary infertility was higher (64.3%) with 35% of them married between 3 and 5 years. The infertile patients had a significantly higher BMI than the controls (p <0.001). There was a significant difference in the serum levels of FSH and LH of the infertile women compared to the controls (p-value =0.001 and <0.001) respectively. Similarly, day 3 and day 21 serum progesterone levels of controls were significantly higher than those of the infertile women (p-value = 0.001 and 0.001) respectively. Though mean serum estradiol levels were higher in controls than the infertile women it was however not statistically significant (P=0.191). Sexually transmitted infections / pelvic inflammatory disease was identified to be treated in 52% of the infertile women. In conclusion, measurement of serum FSH, LH, Estradiol, Days 3 and 21 Progesterone collectively or FSH / LH ratio could be useful as markers for the assessment of ovarian reserve in women with infertility.

Factors associated with metabolic complications in patients with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) affects 4–20% of reproductive aged women. In the literature, it has been shown that PCOS can be associated with insulin resistance (IR) and metabolic syndrome (MS). The aim of the study was to identify which factors (hormonal, metabolic, clinical or sonographic) were associated with MS and IR in women with PCOS. We conducted a retrospective cohort study of 1,040 women with PCOS, aged from18 to 43 years, who consulted at the Lille University Hospital between 2008 and 2020. The examinations performed included: clinical characteristics, hormonal assessment of ovarian reserve and antral follicular count by vaginal ultrasound, androgen assay, glucose tolerance parameters and lipids. The evaluation of IR was performed according to HOMA (IR if HOMA ≥ 2). When BMI increased within one category, the risk of developing MS raised (OR: 2.80; 95% CI: 2.013–3.918). The presence of IR also increased the risk of developing MS (OR: 3.99; 95% CI: 2.757–5.802). Conversely, SHBG was negatively associated with MS. When the BMI category increased, the risk of developing IR increased (OR: 2.90; 95% CI: 2.12–3.96). The risk of developing IR increased with increasing testosterone (OR: 4.399; 95% CI: 2.68–7.22). Conversely as SHBG and androstenedione decreased, the risk of having an IR was higher. There was no significant association between the occurrence of MS and intrinsic PCOS factors indicating ovarian dysfunction. This study has shown that only clinical characteristics (age, BMI) and metabolic parameters as IR were associated with PCOS. Among biological parameters only SHBG were associated. The link between MS and PCOS is therefore probably not related to ovarian factors, but rather to metabolic parameters. The association between IR and ovarian parameters as testosterone and androstenedione, confirms the close link between insulin and ovarian function.

Age Group-specific Reference Intervals for the Elecsys Anti-Müllerian Hormone Assay in Healthy Korean Women: a Nationwide Population-based Study.

Anti-Müllerian hormone (AMH) is one of the most reliable markers of ovarian reserve. Automated AMH assays are widely used in clinical laboratories, but reference intervals for the Elecsys AMH assay for Asian populations have not yet been determined. We aimed to determine reference intervals in healthy Korean women. The study included 1,450 women aged 19 to 54 years who participated in the Korea National Health and Nutrition Examination Survey between 2013 and 2016. The study participants were divided into seven 5-year age groups. AMH and progesterone concentrations were measured using Roche Elecsys assays, and bone morphogenetic protein-15 (BMP15) was genotyped for the detection of major variants. Age group-specific reference intervals for AMH were established as recommended by the CLSI EP28-A3c guidelines. The mean age was 37.4 years. AMH concentrations decreased with increasing age, especially after 40 years, with the median AMH decreasing from 30.9 pmol/L in participants of 19-24 years to 0.071 pmol/L in participants of 50-54 years. The mid-95 percentile AMH reference intervals decreased from 7.93-81.21 pmol/L in participants of 19-24 years to 0.07-3.86 pmol/L in participants of 50-54 years. Disease-associated BMP15 variants were not detected. We determined Elecsys AMH assay reference intervals in healthy Korean women. The results may provide basic information for the interpretation of AMH concentrations and assessment of ovarian reserve in Korean women.

Development of a digital anti-Müllerian hormone immunoassay: ultrasensitive, accurate and practical strategy for reduced ovarian reserve monitoring and assessment

Anti-Müllerian hormone (AMH) is an ideal biomarker for the assessment of ovarian reserve. However, its application in determining ovarian reserve reduction is restricted due to the low sensitivity of existing AMH assays. Herein, a homebrew ultrasensitive digital AMH assay (UD-AMH) was established based on a single-molecule array (SiMoA, HD-X platform), and the analytical performance of UD-AMH was evaluated systematically. The limit of detection (LoD) and limit of quantitation (LoQ) of UD-AMH were 0.13 and 0.14 pg/mL, respectively, which is approximately 100-fold higher than that of the current reported general clinical AMH assay. A comparison study showed a high correlation, with r = 0.988 for the Beckman Access AMH assay and r = 0.945 for the Kangrun AMH assay. In addition, we found that the AMH concentrations of premature ovarian insufficiency (POI) patients were very low (2.59 (0.86, 31.79) pg/mL) and similar to those of perimenopausal women (2.37 (0.65, 35.88) pg/mL) but significantly higher than those of menopausal women (0.43 (0.28, 1.17) pg/mL). Furthermore, we observed that the AMH concentration of most hormone therapy (HT) treated POI patients decreased sharply, suggesting that the ovarian reserve of POI patients declines over time even under HT-treatment.