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Prediction of postchemotherapy ovarian function using markers of ovarian reserve.

ABSTRACT: Reproductive-aged women frequently receive both chemotherapy and endocrine therapy as part of their treatment regimen for early stage hormone receptor-positive breast cancer. Chemotherapy results in transient or permanent ovarian failure in the majority of women. The difficulty in determining which patients will recover ovarian function has implications for adjuvant endocrine therapy decision making. We hypothesized that pretreatment serum anti-Müllerian hormone (AMH) and inhibin B concentrations would predict for ovarian function following chemotherapy.Pre- and perimenopausal women aged 25-50 years with newly diagnosed breast cancer were enrolled. Subjects underwent phlebotomy for assessment of serum AMH, inhibin B, follicle-stimulating hormone, and estradiol prior to chemotherapy and 1 month and 1 year following completion of treatment. Associations among hormone concentrations, clinical factors, and biochemically assessed ovarian function were assessed.Twenty-seven subjects were evaluable for the primary endpoint. Median age was 41. Twenty subjects (74.1%) experienced recovery of ovarian function within 18 months. Of the 26 evaluable subjects assessed prior to chemotherapy, 19 (73.1%) had detectable serum concentrations of AMH. The positive predictive value of a detectable baseline serum AMH concentration for recovery of ovarian function was 94.7%, and the negative predictive value was 85.7%. On univariate analysis, younger age and detectable serum AMH concentration at chemotherapy initiation were predictive of increased likelihood of recovery of ovarian function.Prechemotherapy assessment of serum AMH may be useful for predicting postchemotherapy ovarian function. This finding has implications for decision making about adjuvant endocrine therapy in premenopausal women treated with chemotherapy.

SUBMITTER: Henry NL

PROVIDER: S-EPMC3903057 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Prediction of postchemotherapy ovarian function using markers of ovarian reserve.

Henry N Lynn NL Xia Rong R Schott Anne F AF McConnell Daniel D Banerjee Mousumi M Hayes Daniel F DF

The oncologist 20131206 1

<h4>Background</h4>Reproductive-aged women frequently receive both chemotherapy and endocrine therapy as part of their treatment regimen for early stage hormone receptor-positive breast cancer. Chemotherapy results in transient or permanent ovarian failure in the majority of women. The difficulty in determining which patients will recover ovarian function has implications for adjuvant endocrine therapy decision making. We hypothesized that pretreatment serum anti-Müllerian hormone (AMH) and inhi ...[more]

PMID: 24319018

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Project description:BackgroundPredicting the number of oocytes retrieved (NOR) following controlled ovarian stimulation (COS) is the only way to ensure effective and safe treatment in assisted reproductive technology (ART). To date, there have been limited studies about predicting specific NOR, which hinders the development of individualized treatment in ART.ObjectiveTo establish an online tool for predicting NOR.Materials and methodsIn total, 621 prospective routine gonadotropin releasing hormone (GnRH) antagonist COS cycles were studied. Independent variables included age, body mass index, antral follicle counts, basal FSH, basal and increment of anti-mullerian hormone, Luteinizing hormon, estradiol, testosterone, androstenedione, and inhibin B. The outcome variable was NOR. The independent variables underwent appropriate transformation to achieve a better fit for a linear relationship with NOR. Pruned forward selection with holdback validation was then used to establish predictive models. Corrected Akaike's information criterion, Schwarz-Bayesian information criterion, scaled -log[likelihood], and the generalized coefficient of determination (R 2) were used for model evaluation.ResultsA multiple negative binomial regression model was used for predicting NOR because it fitted a negative binomial distribution. We established Model 1, using basal ovarian reserve markers, and Model 2, using both basal and early dynamic markers for predicting NOR following COS. The generalized R 2 values were 0.54 and 0.51 for Model 1 and 0.64 and 0.62 for Model 2 in the training and validation sets, respectively.ConclusionModels 1 and 2 could be applied to different scenarios. For directing the starting dose of recombinant follicle stimulation hormone (rFSH), Model 1 using basic predictors could be used prior to COS. Model 2 could be used for directing the adjustment of rFSH dosages during COS. An online tool (http://121.43.113.123:8002/) based on these two models is also developed. We anticipate that the clinical application of this tool could help the ART clinics to reduce iatrogenic ovarian under- or over-responses, and could reduce costs during COS for ART.

Project description:IntroductionA 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.DesignProspective cohort study.Materials and methodsTwenty 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.ResultsThe 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 10 kg 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.ConclusionsOur 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.

Project description:Background The role of excess androgen in ovarian reserve remains unclear in patients with polycystic ovary syndrome (PCOS). Our study highlights the associations of serum androgen levels and ovarian reserve markers in PCOS and non-PCOS women. Methods Totally 584 menstrual abnormalities women of 20-45 years were retrospectively evaluated at the Beijing Obstetrics and Gynecology Hospital between January 2021 to October 2021. The enrolled patients were classified into two groups: the PCOS group (n=288) and the non-PCOS group (n=296) based on the Rotterdam consensus for PCOS diagnosis. The serum androgens, including testosterone (T), free testosterone (FT, calculated), bioavailable testosterone (Bio-T, calculated), androstenedione (A2), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS) were assessed with an in-house developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The associations between the serum androgens and the hormone markers commonly used for evaluating ovarian reserve function, such as anti-mullerian hormone (AMH) and the ratio of luteinizing hormone (LH)/follicle stimulating hormone (FSH) were explored. Results The serum T, FT, Bio-T, A2, DHT, DHEA, DHEAS, AMH and LH/FSH of the PCOS group were 51.7 ± 23.2 ng/dL/mL, 8.5 ± 5.0 pg/mL, 210.1 ± 127.7 pg/mL, 1.9 ± 0.8 ng/mL, 0.2 ± 0.1 ng/mL, 6.4 ± 4.2 ng/mL, 2431.0 ± 1030.7 ng/mL, 6.7 ± 3.8 ng/mL, and 1.8 ± 1.4 respectively, which were significantly higher than those in the non-PCOS group (p<0.05). In the group of PCOS patients, T and A2 levels were positively associated with AMH in both multivariate linear regression analysis and Pearson’s correlation analysis. Similar but weaker associations were observed in the non-PCOS patients. In the PCOS patients with hyperandrogenemia (HA), the AMH level was significantly higher in the subjects with T increased than in the subjects with non-T androgen(s) increased (A2, DHT, DHEA or DHEAS). Conclusions The serum androgen levels are positively associated with ovarian reserve markers in both of the PCOS and the non-PCOS patients in our study. In the PCOS group, the highest AMH level was observed in the subjects with the T elevation subgroup, suggesting that T is more closely related with the increase of AMH when compared with other androgens investigated.

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Prediction of postchemotherapy ovarian function using markers of ovarian reserve.

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Prediction of postchemotherapy ovarian function using markers of ovarian reserve.

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