Health needs, treatment decisions and experience of traditional complementary and integrative medicine use by women with diminished ovarian reserve: A cross-sectional survey.

BACKGROUND: Women with diminished ovarian reserve (DOR) have fewer eggs than would be expected at their age. It is estimated that 10% of women seeking fertility treatment are diagnosed with DOR. However, the success rate of medically assisted reproduction (MAR) is significantly lower in women with DOR, thus many seek additional approaches. AIM: To explore the health needs of women with DOR, treatment options and experience of treatment including traditional complementary integrative medicine (TCIM). METHODS: Anyone with a diagnosis of DOR, living in Australia or New Zealand, aged over 18 were invited to complete an online survey distributed via fertility support networks and social media platforms from April to December 2021. RESULTS: Data from 67 respondents were included. The main aspects of health that were impacted by DOR were fertility (91.0%) and mental health (52.2%). The main treatment recommended was MAR with most women either currently using MAR (38.8%) or having previously used MAR (37.3%). TCIM was widely used with 88.1% of women utilising supplements, 74.6% consulting with TCIM practitioners, and 65.7% adopting self-care practices. The main reasons for using TCIM were to improve fertility or support pregnancy, and to support general health and well-being. CONCLUSIONS: Women with DOR have additional health needs apart from infertility, most notably mental health support. The main form of treatment utilised is MAR, despite DOR being challenging for fertility clinicians. TCIM was widely used, and respondents perceived benefits related to improving fertility, supporting pregnancy, or improving well-being through use of acupuncture, meditation, naturopathy, massage, yoga.

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

Introduction Estimating ovarian reserve has been the cornerstone of designing treatment plans for female infertility over the last few years. The most reliable biomarker for assessing female fertility is the antral follicle count (AFC). Also, the anti-müllerian hormone (AMH) is a sensitive test for predicting ovarian reserve and is precisely associated with AFC value. Objective The study aimed to investigate the relationship between serum AFC and AMH levels. Methods This cross-sectional type of observational study included 101 healthy infertile women aged 20-35 years and with low serum AMH. The mean difference in basal AFC among different age groups was evaluated using an independent sample t-test, revealing no significant difference. A multiple regression model was used to assess the association between serum AMH, and other factors related to demographics and other aspects of infertile women with basal AFC. Results The mean age of infertile women in our study was 30.7±3.69, and 29.7% of females had secondary infertility. The highest ovarian reserve was notable among the group 20-25 years, and the lowest follicular volume was observed in the 31 to below 35 years. Multiple regression analyses revealed that serum AFC and AMH had a strong positive association with basal ovarian volume. Additionally, every one-unit surge in AFC and AMH was statistically significant (p<0.05) and concomitant increases with 0.45 cc and 3.98 cc in basal ovarian volume, respectively. Conclusion The AMH and AFC strongly associate with basal ovarian volume, which declines as age progresses.

Screening for diminished ovarian reserve in Portugal: a cost-saving answer to shorten the fertility journey.

Aim: Assess the budget impact of nationwide screening for diminished ovarian reserve (OR), via anti-Müllerian hormone (AMH) levels, to the Portugal National Health System (NHS). Patients & methods: The clinical journey was determined using literature and the family planning decision-making process/response using survey results. A panel of four local clinicians validated all assumptions/inputs. Results: Screening for OR led to an expected savings of € 9.4 million for the NHS, driven by a 24% reduction in medically assisted reproduction (MAR) use. When needed, referral for MAR was earlier and more women used first-line versus second-line techniques. The model estimated a 12% decrease in failure. Conclusion: This model shows AMH screening may allow more informed decisions, leading to a shorter fertility journey, more efficient use of treatments, and substantial cost-savings for the NHS.

Assessment of the ovarian reserve in patients with beta-thalassemia major: a prospective longitudinal study

Objective: Repeated blood transfusions in women with beta-thalassemia major (BTM) may lead to iron overload and increase oxidative stress, consequently resulting in ovarian damage. The aim was to evaluate alterations in ovarian reserve in transfusion-dependent BTM patients over a time period of one year and to compare levels of anti-Mullerian hormone (AMH) in women with BTM and their healthy peers. Material and Methods: This longitudinal prospective study was conducted in women with transfusion-dependent BTM at a tertiary level hospital. The hospital database was interogated for women diagnosed with BTM between 1996 and 2021. AMH levels were assessed at baseline and one year later. Results: Forty-one women with BTM were identified, of whom 25 (60.9%) had amenorrhea and 16 (39.1%) had normal cycles. The mean AMH level of all women was 2.7±1.8 ng/mL at baseline, significantly lower than the age-matched nomogram value of 4.0±0.4 ng/mL for a healthy population (p=0.001). The baseline AMH level of patients with amenorrhea were significantly lower than patients with normal menstrual cycles (2.1±1.8 vs. 3.6±1.5 ng/mL, p=0.009). After one-year follow-up, there was a trend towards a decrease in the AMH levels of patients with normal menstrual cycles. Conclusion: Serum AMH values are decreased in patients with transfusion-dependent BTM. BTM patients should be educated about the possible effects of repeated blood transfusions on fertility.

Assessment of Nutritional Status and Its Influence on Ovarian Reserve: A Systematic Review.

BACKGROUND: Nowadays, there is a growing interest in the relationship among lifestyle, reproductive health, and fertility. Recent investigations highlight the influence of environmental and lifestyle factors such as stress, diet, and nutritional status on reproductive health. The aim of this review was to determine the influence of nutritional status on ovarian reserve in order to improve the reproductive health of women of childbearing age. METHODS: A systematic literature review was carried out following the PRISMA method. The quality of the studies was assessed using the Cochrane Collaboration Risk of Bias tool. Data were extracted, and the results were summarized into two blocks: according to the technique used to assess ovarian reserve and nutritional status; according to the results found in the relationship between ovarian reserve and nutritional status. RESULTS: A total of 22 articles involving 5929 women were included. In 12 of the included articles (54.5%), a relationship between nutritional status and ovarian reserve was demonstrated. In seven publications (31.8%), the increased body mass index (BMI) led to a decrease in ovarian reserve, two of them (0.9%) in patients with polycystic ovary syndrome, showing a decrease only if BMI > 25. In two articles (0.9%), there was a negative relationship between ovarian reserve and waist-to-hip ratio, and in one (0.45%), a positive relationship was shown between ovarian reserve and testosterone levels, the latter being related to body mass index. In five articles (22.7%), body mass index was used as a confounder and was negatively related to ovarian reserve, and in another four (18%), no correlation was found. CONCLUSIONS: Ovarian reserve appears to be influenced by nutritional status. A high body mass index has a negative impact on the ovary, decreasing antral follicle count and anti-Müllerian hormone. Oocyte quality is compromised, increasing the rate of reproductive problems and the demand for assisted reproductive techniques. Further studies are needed to understand which dietary factors have the greatest effect on ovarian reserve in order to promote reproductive health.

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

Background: 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. 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. Results: 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. Conclusion: 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.

Investigating the relationship between body composition, lifestyle factors, and anti-Müllerian hormone serum levels in women undergoing infertility assessment.

BACKGROUND: The impact of lifestyle factors such as adiposity, smoking, stress, exercise, and nutrition on anti-Müllerian hormone (AMH) levels remains an unresolved question. AIMS: This study aims to examine the anthropometric and lifestyle characteristics of women undergoing infertility investigations and to examine the relationship between serum AMH levels and body fat percentage, body mass index (BMI), and lifestyle factors including smoking, alcohol intake, nutrition, exercise, and stress. METHODS: Only women undergoing infertility investigations were included in the study. Those with a diagnosis of polycystic ovary syndrome (PCOS) were excluded. Body fat percentage was measured using the Tanita Body Composition Monitor and BMI calculated. Lifestyle factors were evaluated using the Simple Lifestyle Indicator Questionnaire (SLIQ). RESULTS: Ninety-six women took part in the study. Of these, 35.4% (n = 34) were obese, and 28.1% (n = 27) were overweight according to their BMI. According to body fat percentage, 47.9% (n = 46) were classified as obese. An "unhealthy " SLIQ score was measured in 25% (n = 24) of participating women. There was no relationship between AMH and anthropometric or lifestyle factors, namely, body fat percentage (B = - 0.11, p = 0.76), BMI (B = - 0.14, p = 0.76), smoking [currents smokers (B = - 1.86, p = 0.56), ex-smoker (B = 3.07, p = 0.41)], SLIQ score (B = 0.1.96, p = 0.29), stress (B = 0.12, p = 0.96), exercise (B = - 0.94, p = 0.77), alcohol (B = - 0.94, p = 0.77), or nutrition (B = - 3.14, p = 2.44). CONCLUSIONS: Body fat percentage, BMI, lifestyle choices, and high stress levels do not correlate with AMH levels in women seeking infertility investigations. We identified a high incidence of obesity and low levels of healthy lifestyle scores in our study population. Our study highlights the urgent need for patient education and optimization of pre-pregnancy health.

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.

Ovarian Reserve and Pelvic Ultrasound Assessment in Familial Mediterranean Fever.

Introduction Familial Mediterranean fever (FMF) is an inflammatory rheumatic disease that affects people in their reproductive period. The aim of this study was to investigate the number of gravida, ovarian reserve, and ovarian doppler characteristics in FMF patients. Methods The study design is cross-sectional. Between November 1, 2018, and October 31, 2019, 40 FMF patients, and 40 age-matched volunteers were included in the study. Early follicular phase follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), progesterone, and anti-Mullerian hormone (AMH) levels, as well as ovarian volume, antral follicle count (AFC), ovarian stromal artery doppler findings, and pelvic pathologies, were evaluated. Results The number of gravida, and the AFC was significantly higher in the control group (16.00 ± 5.22) compared to the patients with FMF (13.00 ± 4.09) (p = 0.026). LH values were significantly higher in the FMF group. Thirteen patients (32.5%) received anakinra and colchicine, and 27 patients (67.5%) received only colchicine. There was no significant difference between the patients receiving anakinra, and the patients receiving colchicine in terms of AMH, FSH, AFC, and E2 values. Conclusion FMF patients were found to have low gravida and AFC, and a significant portion was observed to have pelvic fluid and hydrosalpinx. In conclusion, the presence of pelvic fluid, hydrosalpinx, and low AFC persist in FMF patients despite colchicine and/or anti-interleukin-1 treatments. The low gravida may be related to these pathologies detected in patients with FMF.

Assessment of ovarian reserve in patients with type 1 diabetes: a systematic review and meta-analysis.

PURPOSE: Current knowledge about the ovarian reserve in patients with type 1 diabetes is inconsistent and based on studies with small sample size. This meta-analysis aimed to produce a comprehensive evaluation on the ovarian reserve of type 1 diabetes female patients and to analyze the associated factors with the ovarian reserve. METHODS: Systematic searches were conducted for studies published from the inception to December 2021. Original human observational studies either with case-control, cross-sectional, or longitudinal design evaluating ovarian reserve markers between type 1 diabetes patients and healthy controls were included. Levels of anti-müllerian hormone (AMH), follicle-stimulating hormone (FSH), and estradiol (E2) were extracted. RESULTS: It was indicated that women with type 1 diabetes were associated with decreased levels of AMH compared with healthy controls (weighted mean difference [WMD] -0.70 ng/ml, 95% confidence intervals [CI] -1.05 to -0.34 ng/ml, P = 0.0001). Subgroup analyses stratified by age showed that adult patients with type 1 diabetes were associated with decreased levels of AMH (WMD -0.70 ng/ml, 95% CI -1.06 to -0.34 ng/ml, P = 0.0001) and FSH (WMD -1.07 IU/L, 95% CI -1.75 to -0.39 IU/L, P = 0.002) compared with healthy controls. Meta-regression analysis showed no significant correlation between AMH, FSH, and clinical factors, while level of E2 was negatively correlated with daily insulin doses and glycosylated hemoglobin A1c (HbA1c) values. CONCLUSION: According to this meta-analysis, type 1 diabetes might be associated with decreased AMH levels. Further studies using different markers and fertility outcomes focus on the ovarian reserve of women with type 1 diabetes are urgently needed.

Investigating the Clinical Utility of the Anti-Mullerian Hormone Testing for the Prediction of Age at Menopause and Assessment of Functional Ovarian Reserve: A Practical Approach and Recent Updates.

Low ovarian reserve is a serious condition, leading to sterility in up to 10% of women in their mid-thirties. According to current knowledge, serum anti-Müllerian hormone (AMH) levels for age are the best available marker for the screening the quantity of a woman's functional ovarian reserve, better than age alone or other reproductive markers. This review summarizes recent findings, clinical utility and limitations in the application of serum AMH testing as an accurate marker for the screening of functional ovarian reserves and predicting age at menopause. AMH assessment hold promise in helping women make informed decisions about their future fertility and desired family size. However, screening of the functional ovarian reserve could be offered to all women at 26 years of age or older who seek to assess future fertility or in case of personal request, ovarian reserve screening may be considered beyond 30 years; however, it has never been advocated beyond 35 years, since it is not advisable to delay childbearing beyond this age. In this respect, an age-specific serum AMH levels lower than the 10th percentile may be used as a threshold for the identification of a low functional ovarian reserve in an individual woman. Its level should be interpreted with caution in the adolescent and young women aged below 25 years (since AMH levels peak at this age); recent users of hormonal contraceptives (since AMH levels transiently decrease until two months after discontinuation); and women with PCOS (which dramatically increases AMH levels). However, the ability of AMH levels to predict the time to menopause is promising but requires further investigation and routine AMH testing for the purposes of predicting the time to menopause is not recommended.

Uterine artery embolisation versus myomectomy for premenopausal women with uterine fibroids wishing to avoid hysterectomy: the FEMME RCT.

BACKGROUND: Uterine fibroids are the most common tumour in women of reproductive age and are associated with heavy menstrual bleeding, abdominal discomfort, subfertility and reduced quality of life. For women wishing to retain their uterus and who do not respond to medical treatment, myomectomy and uterine artery embolisation are therapeutic options. OBJECTIVES: We examined the clinical effectiveness and cost-effectiveness of uterine artery embolisation compared with myomectomy in the treatment of symptomatic fibroids. DESIGN: A multicentre, open, randomised trial with a parallel economic evaluation. SETTING: Twenty-nine UK hospitals. PARTICIPANTS: Premenopausal women who had symptomatic uterine fibroids amenable to myomectomy or uterine artery embolisation were recruited. Women were excluded if they had significant adenomyosis, any malignancy or pelvic inflammatory disease or if they had already had a previous open myomectomy or uterine artery embolisation. INTERVENTIONS: Participants were randomised to myomectomy or embolisation in a 1 : 1 ratio using a minimisation algorithm. Myomectomy could be open abdominal, laparoscopic or hysteroscopic. Embolisation of the uterine arteries was performed under fluoroscopic guidance. MAIN OUTCOME MEASURES: The primary outcome was the Uterine Fibroid Symptom Quality of Life questionnaire (with scores ranging from 0 to 100 and a higher score indicating better quality of life) at 2 years, adjusted for baseline score. The economic evaluation estimated quality-adjusted life-years (derived from EuroQol-5 Dimensions, three-level version, and costs from the NHS perspective). RESULTS: A total of 254 women were randomised - 127 to myomectomy (105 underwent myomectomy) and 127 to uterine artery embolisation (98 underwent embolisation). Information on the primary outcome at 2 years was available for 81% (n = 206) of women. Primary outcome scores at 2 years were 84.6 (standard deviation 21.5) in the myomectomy group and 80.0 (standard deviation 22.0) in the uterine artery embolisation group (intention-to-treat complete-case analysis mean adjusted difference 8.0, 95% confidence interval 1.8 to 14.1, p = 0.01; mean adjusted difference using multiple imputation for missing responses 6.5, 95% confidence interval 1.1 to 11.9). The mean difference in the primary outcome at the 4-year follow-up time point was 5.0 (95% CI -1.4 to 11.5; p = 0.13) in favour of myomectomy. Perioperative and postoperative complications from all initial procedures occurred in similar percentages of women in both groups (29% in the myomectomy group vs. 24% in the UAE group). Twelve women in the uterine embolisation group and six women in the myomectomy group reported pregnancies over 4 years, resulting in seven and five live births, respectively (hazard ratio 0.48, 95% confidence interval 0.18 to 1.28). Over a 2-year time horizon, uterine artery embolisation was associated with higher costs than myomectomy (mean cost £7958, 95% confidence interval £6304 to £9612, vs. mean cost £7314, 95% confidence interval £5854 to £8773), but with fewer quality-adjusted life-years gained (0.74, 95% confidence interval 0.70 to 0.78, vs. 0.83, 95% confidence interval 0.79 to 0.87). The differences in costs (difference £645, 95% confidence interval -£1381 to £2580) and quality-adjusted life-years (difference -0.09, 95% confidence interval -0.11 to -0.04) were small. Similar results were observed over the 4-year time horizon. At a threshold of willingness to pay for a gain of 1 QALY of £20,000, the probability of myomectomy being cost-effective is 98% at 2 years and 96% at 4 years. LIMITATIONS: There were a substantial number of women who were not recruited because of their preference for a particular treatment option. CONCLUSIONS: Among women with symptomatic uterine fibroids, myomectomy resulted in greater improvement in quality of life than did uterine artery embolisation. The differences in costs and quality-adjusted life-years are very small. Future research should involve women who are desiring pregnancy. TRIAL REGISTRATION: This trial is registered as ISRCTN70772394. FUNDING: This study was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme, and will be published in full in Health Technology Assessment; Vol. 26, No. 22. See the NIHR Journals Library website for further project information.

WHAT IS THE PROBLEM?: Uterine fibroids are the most common non-cancerous tumour in women of childbearing age. Uterine fibroids are associated with heavy bleeding, lower chances of having children and reduced quality of life. Traditional surgical options were either to remove the fibroids (via myomectomy) or to completely remove the womb. A newer approach, known as uterine artery embolisation, involves blocking the blood supply to the fibroids in the womb. WHAT DID WE PLAN TO DO?: We compared myomectomy with uterine artery embolisation in women with fibroids who wanted to keep their womb. We wanted to see which treatment improved quality of life, was associated with the fewest complications and was the best value for money for the NHS. We also wanted to see if either treatment had an impact on women's ability to get pregnant and give birth. We included 254 women in a clinical trial. Women were assigned to have myomectomy or uterine artery embolisation at random to ensure a fair comparison. Women completed questionnaires about their symptoms and quality of life at intervals up to 4 years after treatment. WHAT DID WE FIND?: We found that myomectomy improved women's quality of life more than uterine artery embolisation. Complications from the treatments occurred in a similar proportion of women. There appeared to be no difference on reproductive hormone levels between treatments. Too few women in the trial got pregnant for any difference in the numbers of women having children to be seen. The differences in costs and overall disease burden were small. WHAT DOES THIS MEAN?: Both treatments improve quality of life and cost about the same to the NHS but, on average, myomectomy will provide greater benefit to women. There is no evidence to suggest that either treatment is unsuitable for women wanting to get pregnant, but more research is needed in younger women.

Assessment of the Ovarian Reserve by Serum Anti-Müllerian Hormone in Rheumatoid Arthritis Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: The ovarian reserve has been reported to be diminished in patients with rheumatoid arthritis. However, these results are still controversial. Anti-Müllerian hormone (AMH) is considered a reliable biomarker for the ovarian reserve. We thus performed a meta-analysis to evaluate the AMH levels and the effect of DMARDs on the ovarian reserve in rheumatoid arthritis patients. METHODS: PubMed, EMBASE, the Cochrane Library, and 2 Chinese databases (CNKI and Wanfang database), up to September 2021, were searched for relevant studies. The Newcastle-Ottawa scale (NOS) was used to assess the quality of the included studies. Pooled standard mean difference (SMD) with 95% confidence intervals (CIs) were determined with the random-effects model. The heterogeneity was described by I2 statistic and p value from the Cochrane Q test. RESULTS: Eight eligible studies (679 patients and 1,460 controls) were included in the meta-analysis. Compared with healthy control, the AMH levels in RA patients were significantly lower with the pooled SMD of -0.40 (95% CI: -0.66 to -0.14). However, in comparison of AMH with and without DMARD treatment, there was no significant difference with the pooled SMD of -0.1 (95% CI: -0.39 to 0.19). CONCLUSION: The results indicated that there was an increased risk of ovarian failure in RA patients and which is not related to DMARD treatment.

Assessment of different markers of ovarian reserve in women with papillary thyroid cancer treated with radioactive iodine.

Treatment with radioactive iodine (RAI) in women with differentiated thyroid cancer is associated with decreased serum concentrations of anti-Müllerian hormone (AMH); however, other markers have not been investigated. Therefore, this study aimed to evaluate the effect of RAI treatment on antral follicle count (AFC) and the serum concentration of inhibin B, follicle-stimulating hormone (FSH), and AMH in women with papillary thyroid cancer (PTC) treated with RAI. We examined 25 women at a median age of 33 years treated with a single dose of RAI. We divided the participants into women over (n = 11) and under 35 years of age (n = 14). Serum concentrations of inhibin B, FSH, AMH, and AFC were assessed at baseline and 1 year after RAI treatment. We found decreased AFC (P = 0.03), serum levels of AMH (P < 0.01), inhibin B (P = 0.03), but not FSH (P = 0.23), 1 year after RAI treatment in comparison to baseline in the whole group. When we compared serum levels of AMH in younger vs older women separately, we observed a significant reduction of this hormone's serum level after RAI treatment in both groups (P < 0.01; P = 0.04, respectively). We concluded that RAI treatment significantly impacts the functional ovarian reserve in premenopausal women with PTC.

Ovarian reserve assessment in crohn patients of reproductive age.

OBJECTIVES: Crohn's disease (CD) is a repeating bowel disease characterized by remission and exacerbation periods. The disease mostly affects adults of reproductive age. Women with desires to conceive are concerned about the effects of CD on their fertility. To demonstrate the relationship between ovarian reserve and CD anti-Müllerian hormone (AMH) levels, antral follicle count (AFC) and ovarian volüme were evaluated. MATERIAL AND METHODS: The prospective case-controlled study was conducted at a tertiary referral center in Istanbul between March-August 2019. Ovarian functions were evaluated in 50 patients with CD and in 95 healthy women. Serum gonadotropin and AMH levels were determined. AFCs and ovarian volumes were calculated for all subjects. RESULTS: AMH levels were significantly lower in CD patients (2.1 ± 0.8) compared to the control group (3.3 ± 0.9) (p = 0.001). Serum AMH levels were significantly lower in patients with active CD (2.1 ± 0.6) than the CD patients in remission (2.6 ± 0.8) (p = 0.002). Ovarian volumes and AFC values were significantly lower in both ovaries in CD patients compared to the controls (p < 0.05). CONCLUSIONS: AMH levels, ovarian volume and AFC counts, and thus ovarian reserve was shown to be decreased in CD patients of reproductive age compared to healthy control subjects. Because possible effects of inflammatory damage may be seen in newly diagnosed female CD patients who desire to have a child, we believe that CD patients should be comprehensively assessed for ovarian reserve.

Thyroid autoimmunity is associated with higher risk of premature ovarian insufficiency-a nationwide Health Insurance Research Database study.

STUDY QUESTION: Is thyroid autoimmunity associated with a higher risk of low ovarian reserve and POI? SUMMARY ANSWER: Thyroid autoimmunity significantly increases the risk of POI in women. WHAT IS KNOWN ALREADY: POI is closely related with autoimmune disease, and according to some studies, thyroid autoimmunity (TAI) may account for diminished ovarian reserve. However, no large-scale cohort study has demonstrated the association between TAI and POI. STUDY DESIGN, SIZE, DURATION: A longitudinal population-based retrospective cohort study on the National Health Insurance Research Database (NHIRD) was designed. Since 1 March 1995, the National Health Insurance (NHI) programme in Taiwan has included 99.9% of the 23 million population of Taiwan. Patients between 1 January 2000 and 31 December 2012 were eligible for recruitment, and 21 325 subjects were analysed in our study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two cohorts, Hashimoto's and Grave's disease, were composed of patients with autoimmune thyroid disease between 20 and 40 years of age. The comparison cohorts consisted of patients in the NHIRD without autoimmune thyroid disease matched by age at a ratio of 1:4 in subject numbers. MAIN RESULTS AND THE ROLE OF CHANCE: The Hashimoto's disease (HD) cohort, Grave's disease (GD) cohort and two comparison cohorts were followed up until a diagnosis of amenorrhoea, menopausal syndrome, other ovarian failure or infertility due to ovarian failure had been made. Compared statistically with the non-HD cohort, patients with HD exhibited an 89% higher risk of amenorrhoea (95% CI =1.36-2.61). The HD patients exhibited a 2.40-fold higher risk of infertility due to ovarian failure than the non-HD subjects (hazard ratio (HR)=2.40, 95% confidence interval (CI)=1.02-5.68). In comparison with the non-GD cohort, patients with GD exhibited a 68% higher risk of amenorrhoea (95% CI = 1.43-1.98) after adjustment. According to the Kaplan-Meier analysis, the cumulative incidence of amenorrhoea and menopausal syndrome was significantly higher in the TAI groups than in the control groups. LIMITATIONS, REASONS FOR CAUTION: This is a retrospective study using ICD-9 disease code analysis to determine the statistical association between two diseases. WIDER IMPLICATIONS OF THE FINDINGS: Given that autoimmune thyroid disease is highly associated with early diminished ovarian reserve or even premature ovarian failure or POI, the options for infertility treatment may be re-directed to more efficient methods in infertile patients diagnosed with the disease. If the ovarian reserve is normal at the time of diagnosis of thyroid autoimmune disease, close follow-up of ovarian reserve may be highly recommended. STUDY FUNDING/COMPETING INTEREST(S): This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial Center, Grant Number: MOHW109-TDU-B-212-114004. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Possible modification of BRSK1 on the risk of alkylating chemotherapy-related reduced ovarian function.

STUDY QUESTION: Do genetic variations in the DNA damage response pathway modify the adverse effect of alkylating agents on ovarian function in female childhood cancer survivors (CCS)? SUMMARY ANSWER: Female CCS carrying a common BR serine/threonine kinase 1 (BRSK1) gene variant appear to be at 2.5-fold increased odds of reduced ovarian function after treatment with high doses of alkylating chemotherapy. WHAT IS KNOWN ALREADY: Female CCS show large inter-individual variability in the impact of DNA-damaging alkylating chemotherapy, given as treatment of childhood cancer, on adult ovarian function. Genetic variants in DNA repair genes affecting ovarian function might explain this variability. STUDY DESIGN, SIZE, DURATION: CCS for the discovery cohort were identified from the Dutch Childhood Oncology Group (DCOG) LATER VEVO-study, a multi-centre retrospective cohort study evaluating fertility, ovarian reserve and risk of premature menopause among adult female 5-year survivors of childhood cancer. Female 5-year CCS, diagnosed with cancer and treated with chemotherapy before the age of 25 years, and aged 18 years or older at time of study were enrolled in the current study. Results from the discovery Dutch DCOG-LATER VEVO cohort (n = 285) were validated in the pan-European PanCareLIFE (n = 465) and the USA-based St. Jude Lifetime Cohort (n = 391). PARTICIPANTS/MATERIALS, SETTING, METHODS: To evaluate ovarian function, anti-Müllerian hormone (AMH) levels were assessed in both the discovery cohort and the replication cohorts. Using additive genetic models in linear and logistic regression, five genetic variants involved in DNA damage response were analysed in relation to cyclophosphamide equivalent dose (CED) score and their impact on ovarian function. Results were then examined using fixed-effect meta-analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Meta-analysis across the three independent cohorts showed a significant interaction effect (P = 3.0 × 10-4) between rs11668344 of BRSK1 (allele frequency = 0.34) among CCS treated with high-dose alkylating agents (CED score ≥8000 mg/m2), resulting in a 2.5-fold increased odds of a reduced ovarian function (lowest AMH tertile) for CCS carrying one G allele compared to CCS without this allele (odds ratio genotype AA: 2.01 vs AG: 5.00). LIMITATIONS, REASONS FOR CAUTION: While low AMH levels can also identify poor responders in assisted reproductive technology, it needs to be emphasized that AMH remains a surrogate marker of ovarian function. WIDER IMPLICATIONS OF THE FINDINGS: Further research, validating our findings and identifying additional risk-contributing genetic variants, may enable individualized counselling regarding treatment-related risks and necessity of fertility preservation procedures in girls with cancer. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the PanCareLIFE project that has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no 602030. In addition, the DCOG-LATER VEVO study was funded by the Dutch Cancer Society (Grant no. VU 2006-3622) and by the Children Cancer Free Foundation (Project no. 20) and the St Jude Lifetime cohort study by NCI U01 CA195547. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

An assessment of the protective effect of gonadotropin-releasing hormone agonist and antagonist on bleomycin-induced ovarian toxicity in rats.

The aim of this study is to evaluate the effect of GnRH agonist or GnRH antagonist therapy on bleomycin-administered rats by examining ovarian follicle counts and AMH levels. A total of 30 female Wistar albino rats aged 4-6 months were randomly divided into 4 groups. First, an intramuscular injection of bleomycin (30 mg/m2) was administered to all except the control group on the 1st, 8th and 15th days. The control group (Group I) was administered 0.1 mL intramuscular saline on those days. The bleomycin group (Group II) was followed up without any further treatment. The bleomycin + GnRH agonist group (Group III) was administered subcutaneous GnRH agonist triptorelin (1 mg/kg) at the same time as the bleomycin injections. The bleomycin + GnRH antagonist group (Group IV) was administered 1 mg/kg cetrorelix acetate subcutaneously, concurrently with the bleomycin. Although AMH levels were lower in the bleomycin group than in all the other groups, there was no statistically significant difference between the groups in terms of AMH levels (p > .05). In the bleomycin + cetrorelix acetate and bleomycin + triptorelin groups, significantly higher primordial, secondary and tertiary follicle counts were determined compared to the bleomycin group (p < .001). In conclusion the harmful effects of bleomycin on ovarian reserve can be reduced by the simultaneous administration of GnRH agonist or GnRH antagonist.

Female adolescents and young women previously treated for pediatric malignancies: assessment of ovarian reserve and gonadotoxicity risk stratification for early identification of patients at increased infertility risk.

OBJECTIVES: Childhood and adolescent cancer survivors (CACSs) are at risk of adverse reproductive outcomes. Assessment of follicle-stimulating hormone (FSH) levels is the most common test used to diagnose premature ovarian insufficiency (POI) whereas anti-m|llerian hormone (AMH) and antral follicle count (AFC) have been proposed as ovarian reserve markers. We assessed the correlation between these markers and treatment gonadotoxicity risk (GR) in CACSs. METHODS: A total of 55 female CACSs were enrolled. GR was graded as low, medium, or high according to classifications based on disease and treatments and on cyclophosphamide equivalent dose score. FSH, AMH, and AFC were determined. POI was defined by amenorrhea and FSH>30 IU/L. For remaining patients, diminished ovarian reserve (DOR) was defined by AMH<5th centile. FSH and AFC cut-offs proposed in the literature as DOR markers were also considered (FSH>10 IU/L or >95th centile; AFC<8 or <5th centile). RESULTS: Ovarian reserve results to be compromised in 23 (41.8%) patients: 14 with DOR and 9 with an established POI. Results showed GR classifications to be a good predictor of ovarian reserve, with significantly lower AMH and AFC in the high-risk groups. AFC resulted to be directly correlated with AMH (r=0.75, p<0.001). CONCLUSIONS: In CACSs, GR classifications correlate with post-treatment AMH and AFC. These are useful tools in the early identification of young patients with DOR, who may benefit from reproductive and fertility preservation counseling. Further studies are needed to determine the rate and time of progression from DOR to POI in this population.