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Objective: To determine the association between ovarian reserve biomarkers and future fertility among late reproductive-age women., Design: Cohort study of participants enrolled in Time to Conceive (TTC), a time-to-pregnancy cohort study of the ovarian reserve biomarkers., Setting: Community., Patient(s): Women aged 30-44 years without a history of infertility who provided a blood sample at enrollment in TTC and who agreed to future follow-up., Intervention(s): Not applicable., Main Outcome Measure(s): The primary outcomes were probability of achieving a live birth >3 years after enrollment in TTC, diagnosis of infertility at any time, and time-to-pregnancy in future pregnancy attempts., Result(s): Women with diminished ovarian reserve, defined as those with an antimüllerian hormone (AMH) level <0.7 ng/mL or follicle-stimulating hormone (FSH) level ≥10 mIU/mL, did not have low risk of future live birth (relative risk [RR], 1.32; 95% confidence interval [CI], 0.95-1.83 and RR, 1.28; 95% CI, 0.97-1.70, respectively) compared with women with normal ovarian reserve after adjusting for age at blood draw, race, obesity, use of hormonal contraception, and year of enrollment in original study. Among women in the cohort that attempted to conceive, there was not a significant association between diminished ovarian reserve, as measured by AMH or FSH, and risk of future infertility (RR, 0.65; 95% CI, 0.21-2.07 and RR,1.69; 95% CI, 0.86-3.31, respectively). Similarly, there was no association between AMH and FSH levels and future fecundability (fecundability ratio, 0.97; 95% CI, 0.59, 1.60; and fecundability ration, 0.86; 95% CI, 0.55-1.36, respectively)., Conclusion: Diminished ovarian reserve is not associated with reduced future reproductive capacity. Given the lack of association, women should be cautioned regarding use biomarkers of ovarian reserve as predictors of their future reproductive capacity., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Context: While age-related changes in menstrual cycle length are well known, it is unclear whether anti-Müllerian (AMH) or other ovarian reserve biomarkers have a direct association with cycle length., Objective: To determine the association between biomarkers of ovarian reserve and menstrual cycle length., Methods: Secondary analysis using data from time to conceive (TTC), a prospective time to pregnancy cohort study. The age-independent association between cycle length and biomarkers of ovarian reserve was analyzed using linear mixed and marginal models. Study participants were TTC-enrolled women aged 30-44 years with no history of infertility who were attempting to conceive for <3 months were enrolled. Serum AMH, follicle-stimulating hormone, and inhibin B levels were measured on cycle day 2, 3, or 4. Participants recorded daily menstrual cycle data for ≤4 months. The primary outcome was menstrual cycle length; follicular and luteal phase lengths were secondary outcomes., Results: Multivariable analysis included 1880 cycles from 632 women. Compared with AMH levels of 1.6 to 3.4 ng/mL, women with AMH <1.6 ng/mL had cycles and follicular phases that were 0.98 (95% CI -1.46, -0.50) and 1.58 days shorter (95% CI -2.53, -0.63), respectively, while women with AMH >8 ng/mL had cycles that were 2.15 days longer (95% CI 1.46, 2.83), follicular phases that were 2 days longer (95% CI 0.77, 3.24), and luteal phases that were 1.80 days longer (95% CI 0.71, 2.88)., Conclusion: Increasing AMH levels are associated with longer menstrual cycles due to both a lengthening of the follicular and the luteal phase independent of age., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The aim of the study was to examine the associations between 25-hydroxyvitamin D (25(OH)D) and biomarkers of ovarian reserve in a large community-based sample of women., Methods: In 2010 to 2016, women aged 30 to 44 years without any known fertility problems were recruited from the Chapel Hill, NC area for a prospective time-to-pregnancy cohort study. At enrollment 561 women provided a blood sample that was used to measure 25(OH)D, anti-Müllerian hormone (AMH), follicle-stimulating hormone, and inhibin-B. Unadjusted associations were estimated with Spearman correlation coefficients. Multivariable linear regression was used to estimate associations of 25(OH)D with ovarian reserve biomarkers, after adjusting for age, race, body mass index, smoking history, and recent use of hormonal birth control., Results: The mean 25(OH)D was 36 ng/mL (SD = 11 ng/mL). 25(OH)D was not correlated with AMH, follicle-stimulating hormone, or inhibin-B (all r < 0.03). Multivariable results with continuous hormonal outcomes were also null. For dichotomous outcomes, there was a tendency for insufficient 25(OH)D (<30 ng/mL) to be associated with low AMH (<0.7 ng/mL) (odds ratio [95% CI]: 1.8 [0.9-4])., Conclusions: For the most part, 25(OH)D was not associated with ovarian reserve biomarkers in a group of women trying to become pregnant. We found some evidence that low 25(OH)D (<30 ng/mL) was associated with low AMH, but this should be confirmed in studies with a higher prevalence of low 25(OH)D.

Objective: Vitamin D has been linked to antimüllerian hormone levels, suggesting a possible association with greater ovarian reserve, but large population-based studies are lacking. Our objective was to explore the association between vitamin D and follicle-stimulating hormone (FSH) in premenopausal women., Methods: The Uterine Fibroid Study (1996-1999) enrolled randomly selected 30- to 49-year-old members of a Washington, DC, health plan (N = 1,430). Women provided blood and urine samples in addition to questionnaire data. The vitamin D metabolite 25-hydroxyvitamin D (25(OH)D) was measured in stored plasma samples. Urinary FSH (mIU/mg creatinine) was measured by immunofluorometric assay. To obtain baseline measures, we limited this investigation to urine samples collected in the first 5 days of the menstrual cycle or 5 days before menses onset. In addition, postmenopausal women and women using oral contraceptives were excluded, leaving 527 women for analysis. FSH was creatinine-adjusted, normalized by log transformation, and modeled with multivariable linear regression., Results: The median 25(OH)D level was 12 ng/mL, with approximately 75% of participants below the recommended level of 20 ng/mL. FSH and 25(OH)D were inversely related. For every 10-ng/mL increase in 25(OH)D, urinary FSH decreased by 14% (95% CI, -23 to -5; P = 0.003)., Conclusions: Vitamin D is inversely related to FSH. This is consistent with literature relating low vitamin D levels to lower antimüllerian hormone levels. Prospective studies should investigate whether low vitamin D levels contribute to decreased ovarian reserve.

Study Question: Are serum omega-3 and omega-6 essential fatty acid concentrations associated with the probability of conceiving?Summary Answer: There is no strong association between serum concentrations of omega-3 and omega-6 fatty acids and the probability of conceiving naturally.What Is Known Already: Omega-3 and omega-6 fatty acid serum concentrations have been shown to play an important role in reproduction in animal models, while conflicting results have been reported in human studies of infertile women. It is unknown to what extent omega fatty acid serum concentrations impact natural fertility.Study Design, Size, Duration: A nested, case-control study was conducted consisting of 200 participants [fertile: conceived within 3 cycles of attempt (n = 50), subfertile: conceived within 4 and 12 cycles of attempt (n = 100) and infertile: did not conceive within 12 cycles of attempt (n = 50)] randomly selected from the Time to Conceive cohort, a prospective time-to-pregnancy study (2008 to 2015).Participants/materials, Setting, Methods: In the Time to Conceive study, women aged 30-44 years who were trying to conceive for <3 months and had no history of infertility were recruited and followed until the end of their pregnancy or ~1 year of pregnancy attempt. For this study, serum collected early in the woman's pregnancy attempt was analysed for anti-Müllerian hormone (AMH) and omega-3 and omega-6 fatty acid concentrations by liquid chromatography-mass spectrometry. The primary outcome was a positive home pregnancy test. The secondary outcomes were miscarriage and serum AMH level. A discrete-time Cox proportional hazards model was used to estimate the fecundability ratio. The odds ratios for miscarriage were calculated using logistic regression. The association between serum omega fatty acid concentrations and AMH level (natural log transformed) was analysed using Pearson's Correlation.Main Results and the Role Of Chance: A total of 200 women provided 1321 cycles for analysis.Mean omega-3, omega-6 and omega-6:omega-3 ratios did not significantly differ between the fertile, subfertile and infertile groups. There were no associations (all fecundability ratios ~1.0) between pregnancy and individual omega-3 fatty acid concentrations, including alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid, or omega-6 fatty acids, including linoleic acid (LA), dihommo-gamma linolenic acid and arachidonic acid. There was no significant association between any individual omega fatty acid serum concentration and the age-adjusted odds of miscarriage. No association was found between any serum omega fatty acid concentration and AMH.Limitations, Reasons For Caution: This study is limited by the sample size. Omega-3 and omega-6 fatty acid concentrations were derived from serum provided at a single timepoint in the first cycle of enrollment. Serum concentrations may therefore not be representative of all critical timepoints in the menstrual cycle or throughout their attempts to conceive. Additionally, women enrolled in this study were 30 years of age and older, and therefore the findings may not apply to younger women.Wider Implications Of the Findings: These data would suggest that omega-3 and omega-6 serum levels are not associated with natural fertility or risk of miscarriage. However, due to the above-mentioned limitations, future investigation is still needed to determine whether omega-3 fatty acid supplementation may benefit women planning to conceive naturally.Study Funding/competing Interest(s): This study was supported by the Division of Reproductive Endocrinology and Infertility at the University of North Carolina at Chapel Hill, by the NIH/NICHD (R21 HD060229-01 and R01 HD067683-01) and, in part, by the Intramural Research Program of the National Institute of Environmental Health Sciences (Z01ES103333). Dr. Jukic received vitamin D supplements for a research study from Theralogix, Inc. The authors have no other conflicts of interest to disclose.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

To examine the association between serum 25-hydroxyvitamin D [25(OH)D] levels and ovarian reserve as measured using antimüllerian hormone (AMH) levels. Cross-sectional study. Detroit, Michigan area. Data were obtained from a prospective cohort of self-identified Black or African American women aged 23–35 years at the time of enrollment (N = 1,593), who had no prior diagnosis of polycystic ovary syndrome, were not currently pregnant, and were not missing AMH or 25(OH)D level measures. Serum 25(OH)D. The serum AMH level was the main outcome. Linear regression was used to examine the associations between categorical 25(OH)D levels (<12, 12–<20, 20–<30, and ≥30 ng/mL) and continuous natural log-transformed AMH levels. Associations between 25(OH)D and high (upper 10th percentile: >7.8 ng/mL) or low AMH (<0.7 ng/mL) levels were estimated with logistic regression. Models were adjusted for age, age-squared, body mass index (kg/m2), hormonal contraceptive use, smoking, and exercise. The 25(OH)D levels were low; 70% of participants were below 20 ng/mL. In fully adjusted models, compared with 25(OH)D levels <12 ng/mL, those with 25(OH)D levels of 12–<20, 20–<30, and ≥30 ng/mL had an AMH level that was 7% (95% confidence interval [CI]: −4, 20), 7% {95% CI: −6, 22}, or 11% {95% CI: −7, 34} higher, respectively. Moreover, these groups had lower odds of having low AMH levels (odds ratio [95% CI]: 0.63 {0.40, 0.99}, 0.60 {0.34, 1.07}, and 0.76 {0.35, 1.65}, respectively), and the highest category of 25(OH)D levels had higher odds of having high AMH levels (odds ratio [95% CI]: 1.42 {0.74, 2.72}). Exclusion of participants with either irregular cycles or very high AMH (>25 ng/mL) levels did not alter the associations. Taken together, these results indicate that higher levels of 25(OH)D are associated with slightly higher AMH levels, lower odds of low AMH levels, and higher odds of high AMH levels. This evidence is weak, however, because only a small percentage of participants had high 25(OH)D levels. Future studies should examine populations with a wide distribution of 25(OH)D levels (both high and low), with a clinical trial design, or with longitudinal measures of both 25(OH)D and AMH levels. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between antimüllerian hormone (AMH), a measure of ovarian reserve, and miscarriage among naturally conceived pregnancies.Design: Prospective cohort study.Setting: Not applicable.Patient(s): Women (n = 533), between 30 and 44 years of age with no known history of infertility, polycystic ovarian syndrome, or endometriosis who conceived naturally.Intervention(s): None.Main Outcome Measure(s): Miscarriage, defined as an intrauterine pregnancy loss before 20 weeks' gestation.Result(s): After adjusting for maternal age, race, history of recurrent miscarriage, and obesity, risk of miscarriage decreased as AMH increased (risk ratio per unit increase in natural log of AMH = 0.83; 95% confidence interval [CI], 0.73, 0.94). Women with severely diminished ovarian reserve (AMH ≤ 0.4 ng/mL) miscarried at over twice the rate of women with an AMH ≥ 1 ng/mL (hazard ratio, 2.3; 95% CI, 1.3, 4.3).Conclusion(s): AMH levels are inversely associated with the risk of miscarriage. Women with severely diminished ovarian reserve are at an increased risk of miscarriage. [ABSTRACT FROM AUTHOR]