Lin, C., Jing, M., Zhu, W., Tu, X., Chen, Q., Wang, X., Zheng, Y., & Zhang, R. (2021). The Value of Anti-Müllerian Hormone in the Prediction of Spontaneous Pregnancy: A Systematic Review and Meta-Analysis. Frontiers in Endocrinology. https://doi.org/10.3389/fendo.2021.695157
Lin C, Jing M, Zhu W, Tu X, Chen Q, Wang X, Zheng Y, Zhang R. The Value of Anti-Müllerian Hormone in the Prediction of Spontaneous Pregnancy: A Systematic Review and Meta-Analysis. Frontiers in Endocrinology. 2021. doi:10.3389/fendo.2021.695157
Lin, C., et al. "The Value of Anti-Müllerian Hormone in the Prediction of Spontaneous Pregnancy: A Systematic Review and Meta-Analysis." Frontiers in Endocrinology, 2021.
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Women's Hospital, School of Medicine, Zhejiang University042t7yh44
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RRM Academy Synopsis
AMH blood level predicts natural pregnancy poorly in a meta-analysis
A 2021 meta-analysis of 11 studies found that AMH blood levels predicted natural pregnancy poorly. The studies included 4,388 women trying to conceive naturally. Prediction stayed weak in women under 35 and over 35.
Key Findings
Eleven studies (4,388 women) were pooled. The summary area under the curve (AUC) was 0.5932 and the Cochran's Q index was 0.5702.
Women younger than 35 years: AUC 0.6355 and Q index 0.6025 (six studies, n=2,908). Women older than 35 years: AUC 0.5536 and Q index 0.5403 (four studies, n=863).
Seven prospective studies (n=2,539) gave an AUC of 0.6186 and a Q index of 0.5895. Four studies of other designs (retrospective cohort, case-control, cross-sectional; n=1,849) gave 0.5707 and 0.5531.
Deeks' funnel plot did not suggest publication bias (p>0.05). A sensitivity analysis supported the result as robust.
The authors suggest low AMH levels are unrelated to reduced fertility in these studies.
Interpretation
The paper is a systematic review and meta-analysis of diagnostic accuracy studies. Its studies used different AMH cutoffs and assays, so the authors pooled them with a summary receiver operating characteristic curve. They call an AUC of 0.5 to 0.7 a limited predictive value. The outcome was clinical pregnancy. Live birth was not assessed. The studies came mainly from western countries, and most split AMH at a single cutoff. Too few studies separated low from extremely low AMH to test that group.
RRM Context
For young women, the authors suggest AMH may track follicle quantity more closely than egg quality. They add that regular ovulation may matter more for spontaneous pregnancy. Restorative reproductive medicine looks at the ovulatory cycle and at the cause of delayed conception in both partners. A single reserve number measures neither.
Our editorial summary of this paper, not the article's abstract.
Abstract
To determine whether serum anti-Müllerian hormone (AMH) level is a predictor of clinical pregnancy in women trying to achieve a natural conception. Eleven studies (4,388 women) were ultimately included in this meta-analysis. The AUC and Cochran Q indices were 0.5932 and 0.5702, respectively. Serum AMH levels have poor predictive value for natural pregnancy. Our findings suggest that low serum AMH levels are not associated with reduced fertility.
Li J et al., 2026·Communications Biology·Free full text on PubMed Central
Anti-Müllerian hormone (AMH), produced by ovarian granulosa cells, is a key regulator of female reproduction. Traditionally seen as a local follicular brake, emerging evidence calls for a paradigm shift. We propose that AMH acts as a context-dependent signaling hub. It primarily signals via the Smad1/5/8 pathway and interacts with Wnt/β-catenin and MAPK cascades to regulate follicle growth and steroidogenesis. Beyond the ovary, AMH and its receptors are expressed in the hypothalamus, pituitary, uterus, and placenta, modulating the hypothalamic-pituitary-gonadal axis and other reproductive processes. This review provides a comprehensive framework for understanding AMH as a context-dependent signaling hub in female mammals.
Thyroid and Metabolic Function · Insulin and Metabolism
Abstract What gut microbiota and metabolic alterations are associated with Polycystic ovary syndrome (PCOS) and linked to adverse pregnancy outcomes (APOs)? In PCOS, P. merdae decreases, BCAAs increase, raising the risk of APOs. Meanwhile, endometrial senescence and decidualization impairment are found, worsening with higher Ile concentration. PCOS, a prevalent and complex endocrine disorder, stands as the primary cause of anovulatory infertility. The rising prevalence of PCOS in China over the past decade has led to a substantial increase in disease burden. Our previous ten-year retrospective analysis revealed that PCOS patients undergoing their first fresh embryo transfer faced a heightened risk of APOs, such as miscarriage. However, the factors influencing disease progression and future obstetric outcomes in PCOS remain elusive. Study design, size, duration
This prospective cohort study encompassed a diverse cohort of 220 women (110 with PCOS and 110 controls) from 44 cities across China, with a median follow-up duration of 16.6 months. Participants/materials, setting, Women aged < 35 years with PCOS (Rotterdam criteria) and age-/BMI-matched controls were recruited. Fecal microbiomes were analyzed using 16S rRNA sequencing and metagenomics, while serum metabolites were assessed through both untargeted and targeted metabolomics. Endometrial stromal cell senescence was evaluated based on a constellation of markers, including cell proliferation, senescence-associated secretory phenotype factors, cell cycle, ROS levels, and SA-β-Gal activity. Endometrial decidualization was gauged by measuring prolactin and IGFBP-1 levels using ELISA. Main Our study revealed significant gut microbiota alterations, including reduced α-diversity and a notable decline in Parabacteroides merdae (P. merdae), a key species differentiating PCOS from controls. Serum metabolomics identified 45 differential metabolites, with branched-chain amino acids (BCAAs), especially isoleucine (Ile), exhibiting strong diagnostic potential. Targeted metabolomics further validated BCAAs’ (Valine, Leucine, and Ile) upregulation and short-chain fatty acids’ downregulation in PCOS.
During follow - up, PCOS patients had a higher cumulative incidence of APOs despite similar pregnancy rates. And the adjustment for potential confounders did not substantially change the estimates. Intriguingly, individuals who experienced APOs showed a reduction in gut P. merdae levels and an elevation in serum BCAAs, suggesting their potential association with APOs occurrence.
Further analysis revealed increased Ile levels in the endometrial tissue of PCOS (P < 0.05) and higher proportions of cells positive for senescence markers (P21, P16, IL6, and IL1β), indicating aggravated cellular senescence, particularly in endometrial stromal cells (ESCs). ESCs from PCOS patients displayed classical senescence features, including proliferation loss, increased SA-β-Gal activity, cell cycle arrest, and elevated ROS levels. The accumulation of senescent ESCs in PCOS endometrium ultimately resulted in a disrupted decidualization process, which was exacerbated by increasing concentrations of Ile supplementation. Limitations, However, we must acknowledge certain limitations of this study. While our study makes a significant contribution to existing scientific knowledge, it is crucial to validate these findings in diverse populations. In addition, clinical translatability of biomarkers needs further exploration. This study highlights gut microbiota-metabolite crosstalk as a novel axis influencing reproductive health in PCOS. Moreover, the identification of P. merdae and BCAAs as potential biomarkers for PCOS patients and the associated APOs risk opens up new avenues for risk stratification and personalized interventions. No
To evaluate the effect of birth ball abdominal core training on fatigue, waist pain, and delivery outcomes in middle and late pregnancy. A prospective study of 209 primipara in total with 24–27 weeks of gestation were recruited and divided into the training group (109 cases) and the control group (100 cases). The control group received routine prenatal exercise. On the basis of routine prenatal exercise, pregnant women in the training group were given birth ball exercises based on abdominal core training. The difference in pregnancy fatigue, waist discomfort, and delivery outcomes between the two groups were compared. The waist pain and fatigue ratings of women were significantly lower and the vaginal delivery rate (74.3%) was significantly higher (62%) (P < 0.001) in the training group. There were no significant differences in the total stage of labor, postpartum hemorrhage, neonatal weight and 1‐min neonatal Apgar score between the two groups. The rate of episiotomy in the training group (14.7%) was significantly lower than that in the control group (25.0%) (P < 0.05). Birth ball exercises can relieve fatigue and waist pain in middle and late 2021 pregnancy, reduce the rate of episiotomy, and promote spontaneous vaginal delivery.
Zeng Q et al., 2020·Front Aging Neurosci·Free full text on PubMed Central
The National Institute on Aging-Alzheimer's Association (NIA-AA) has proposed a biological definition of Alzheimer's disease (AD): individuals with both abnormal amyloid and tau biomarkers (A+T+) would be defined as AD. It remains unclear why different cognitive status is present in subjects with biological AD. Resting-state functional magnetic resonance imaging (rsfMRI) has provided an opportunity to reveal the brain activity patterns in a biologically-defined AD cohort. Accordingly, we aimed to investigate distinct brain activity patterns in subjects with existed AD pathology but in the different cognitive stages. We selected individuals with AD pathology (A+T+) and healthy controls (HC, A-T-) based on the cerebrospinal fluid (CSF) biomarkers. According to the cognitive stage, we divided the A+T+ cohort into three groups: (1) preclinical AD; (2) prodromal AD; and (3) AD with dementia (d-AD). We compared spontaneous brain activity measured by a fractional amplitude of low-frequency fluctuation (fALFF) approach among four groups. The analysis of covariance (ANCOVA) results showed significant differences in fALFF in the posterior cingulate cortex/precuneus (PCC/PCu). Further, compared to HC, we found increased fALFF values in the right inferior frontal gyrus (IFG) in the preclinical AD stage, whereas prodromal AD patients showed reduced fALFF in the bilateral precuneus, right middle frontal gyrus (MFG), right precentral gyrus, and postcentral gyrus. Within the d-AD group, both hyperactivity (right fusiform gyrus, right parahippocampal gyrus (PHG)/hippocampus, and inferior temporal gyrus) and hypoactivity (bilateral precuneus, left posterior cingulate cortex, left cuneus and superior occipital gyrus) were detected. We found the distinct brain activity patterns in different cognitive stages among the subjects defined as AD biologically. Our findings may be helpful in understanding mechanisms leading to cognitive changes in the AD pathophysiological process.
Galati G et al., 2024·Archives of gynecology and obstetrics·Free full text on PubMed Central
There is several albeit not univocal evidence suggesting that ovarian reserve is not related to the chance of natural pregnancy, provided that the remnant follicular pool is sufficient to ensure regular menstrual cycles. Nevertheless, available studies have some methodological limitations, and the issue cannot be considered definitively ascertained. To further address this issue, we retrospectively selected infertile women whose infertility diagnostic work-up was unremarkable (unexplained infertility-cases) and matched them by age and study period to a group of infertile women who were diagnosed with severe male infertility (controls). If ovarian reserve impacts on natural fertility, one had to expect lower ovarian reserve among women with unexplained infertility. Tested biomarkers included AMH, AFC and day 2-3 serum FSH. The primary aim was the frequency of women with serum AMH < 0.7 ng/ml. Two-hundred fifty-two women with unexplained infertility and 252 women with male infertility were included. All biomarkers of ovarian reserve did not differ between the study groups. AMH levels < 0.7 ng/mL were observed in 26 (10%) women with unexplained infertility and 35 (14%) women with male infertility (p = 0.28). The adjusted OR was 0.76 (95% CI: 0.44-1.33). Significant differences did not also emerge when repeating this dichotomous analysis using other biomarkers and other thresholds for the definition of low-ovarian reserve. This study confirms that ovarian reserve is unremarkable to natural conception. Physicians and patients should be aware of this concept to avoid inappropriate counseling and undue clinical decisions.
AMH levels are commonly measured in fertility clinics to assess ovarian reserve and give an indication of female fertility potential. AMH levels are useful in deciding on stimulation protocols for IVF cycles. High AMH levels are useful to confirm a diagnosis of polycystic ovaries. Currently AMH levels cannot be used to predict a couple's ability to conceive naturally.
Grynnerup AG et al., 2012·Acta obstetricia et gynecologica Scandinavica
Anti-Müllerian hormone (AMH) plasma levels reflect the continuous non-cyclic growth of small follicles, thereby mirroring the size of the resting primordial follicle pool and thus acting as a useful marker of ovarian reserve. Anti-Müllerian hormone seems to be the best endocrine marker for assessing the age-related decline of the ovarian pool in healthy women; thus, it has a potential ability to predict future reproductive lifespan. The most established role for AMH measurements is before in vitro fertilization is initiated, because AMH can be predictive of the ovarian response, namely poor and hyper-responses. However, recent research has also highlighted the use of AMH in a variety of ovarian pathological conditions, including polycystic ovary syndrome, granulosa cell tumors and premature ovarian failure. A new commercial enzyme-linked immunosorbent assay for measuring AMH levels has been developed, making results from different studies more comparable. Nevertheless, widespread clinical application awaits an international standard for AMH, so that results using future assays can be reliably compared.
Kissell KA et al., 2014·Hum Reprod·Free full text on PubMed Central
Does serum anti-Müllerian hormone (AMH) vary significantly throughout both ovulatory and sporadic anovulatory menstrual cycles in healthy premenopausal women? Serum AMH levels vary statistically significantly across the menstrual cycle in both ovulatory and sporadic anovulatory cycles of healthy eumenorrheic women. Studies to date evaluating serum AMH levels throughout the menstrual cycle have conflicting results regarding intra-woman cyclicity. No previous studies have evaluated an association between AMH and sporadic anovulation. STUDY DESIGN, SIZE, Duration: We conducted a prospective cohort study of 259 regularly menstruating women recruited between 2005 and 2007. PARTICIPANTS/MATERIALS, SETTING, Women aged 18-44 years were followed for one (n = 9) or two (n = 250) menstrual cycles. Anovulatory cycles were defined as any cycle with peak progesterone concentration ≤5 ng/ml and no serum LH peak on the mid or late luteal visits. Serum AMH was measured at up to eight-time points throughout each cycle. Main Geometric mean AMH levels were observed to vary across the menstrual cycle (P < 0.01) with the highest levels observed during the mid-follicular phase at 2.06 ng/ml, decreasing around the time of ovulation to 1.79 ng/ml and increasing thereafter to 1.93 (mid-follicular versus ovulation, P < 0.01; ovulation versus late luteal, P = 0.01; mid-follicular versus late luteal, P = 0.05). Patterns were similar across all age groups and during ovulatory and anovulatory cycles, with higher levels of AMH observed among women with one or more anovulatory cycles (P = 0.03). LIMITATIONS, Ovulatory status was not verified by direct visualization. AMH was analyzed using the original Generation II enzymatically amplified two-site immunoassay, which has been shown to be susceptible to assay interference. Thus, absolute levels should be interpreted with caution, however, patterns and associations remain consistent and any potential bias would be non-differential. This study demonstrates a significant variation in serum AMH levels across the menstrual cycle regardless of ovulatory status. This variability, although statistically significant, is not large enough to warrant a change in current clinical practice to time AMH measurements to cycle day/phase. This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD (Contracts # HHSN275200403394C, HHSN275201100002I Task 1 HHSN27500001). The authors have no conflicts of interest to declare.
PMID 34721287 34721287 DOI 10.3389/fendo.2021.695157 10.3389/fendo.2021.695157 Lin et al. 2021, Lin 2021
Cite this article
Lin, C., Jing, M., Zhu, W., Tu, X., Chen, Q., Wang, X., Zheng, Y., & Zhang, R. (2021). The Value of Anti-Müllerian Hormone in the Prediction of Spontaneous Pregnancy: A Systematic Review and Meta-Analysis. Frontiers in Endocrinology. https://doi.org/10.3389/fendo.2021.695157
Lin C, Jing M, Zhu W, Tu X, Chen Q, Wang X, Zheng Y, Zhang R. The Value of Anti-Müllerian Hormone in the Prediction of Spontaneous Pregnancy: A Systematic Review and Meta-Analysis. Frontiers in Endocrinology. 2021. doi:10.3389/fendo.2021.695157
Lin, C., et al. "The Value of Anti-Müllerian Hormone in the Prediction of Spontaneous Pregnancy: A Systematic Review and Meta-Analysis." Frontiers in Endocrinology, 2021.
