Serum Anti-Müllerian Hormone Levels and Risk of Premature Ovarian Insufficiency in Female Childhood Cancer Survivors: Systematic Review and Network Meta-Analysis

Abstract

Background: Female childhood cancer survivors (CCS) might have impaired ovarian reserves, especially after alkylating agents or radiotherapy. The purpose of this systematic review and network meta-analysis is to evaluate the role of serum anti-Müllerian hormone (AMH) for ovarian reserve screening and the risk of premature ovarian insufficiency (POI) according to the subtype of childhood cancer. (2) Methods: PRISMA-NMA guidelines were followed. We carried out a network meta-analysis based on a random effects model for mixed multiple treatment comparisons to rank childhood cancers effects on fertility by surface under the cumulative ranking curve (SUCRA). Studies were selected only if they had an age-matched control group. Quality assessment was performed using Newcastle–Ottawa Scale. The co-primary outcomes were mean AMH levels and the incidence of POI. (3) Results: A total of 8 studies (1303 participants) were included. Women treated for a neuroblastoma during infancy were more likely to be ranked first for impaired AMH levels (SUCRA = 65.4%), followed by mixed CCS (SUCRA = 29.6%). The greatest rates of POI were found in neuroblastoma survivors (SUCRA = 42.5%), followed by acute lymphoid leukemia (SUCRA = 26.3%) or any other neoplasia (SUCR A = 20.5%). (4) Conclusions: AMH represents a trustworthy approach for ovarian reserve screening. Direct and indirect comparisons found no differences in mean AMH levels and POI risk between subtypes of CCS and healthy controls. SUCRA analysis showed that female neuroblastoma survivors were more at risk for reduced serum AMH levels and increased risk of POI.

Anti‐Müllerian hormone for screening, diagnosis, evaluation, and prediction: A systematic review and expert opinions

“…Together, these findings suggest that measuring pre‐treatment AMH levels may be useful for predicting menstrual recovery. However, a meta‐analysis reported no significant association between AMH levels and the development of POI in pediatric patients with different cancer types 76 …”

“…However, a meta-analysis reported no significant association between AMH levels and the development of POI in pediatric patients with different cancer types. 76…”

Anti-Müllerian hormone beyond an ovarian reserve marker: the relationship with the physiology and pathology in the life-long follicle development

“…The persistence of undetectable serum AMH levels after treatment is useful as a predictor of continuous AMH deficiency reelevation and menstrual recovery (54). On the other hand, the evidence is not sufficient to conclude whether prediction of permanent POI at the end of treatment may be possible by pretreatment AMH levels (55), although this has been reported to be possible in early-stage breast cancer (56). Further studies are needed to determine which patients and treatments may or may not be feasible.…”

Premature Ovarian Insufficiency, an important cause of early menopause: Review of the literature with clinical case reports

“…Por otra parte, la patogenia de la IOP puede estar relacionada con mecanismos que incluyen reducción del número máximo de folículos, agotamiento folicular aumentado o por disfunción folicular [8]. El diferimiento de la maternidad por el que optan actualmente muchas mujeres por aspiraciones personales y profesionales, con menstruaciones aparentemente regulares, pero que presentan disminución en la respuesta adecuada a la estimulación ovárica, con valores de FSH y Hormona antimulleriana (HAM) alterados , así como el caso de pacientes que usan métodos anticonceptivos por largo tiempo, que luego de ser suspendidos, continúan con amenorrea, son situaciones que pueden causar un retraso en el diagnóstico oportuno y sólo se evidenciaría cuando los niveles de FSH permanecen elevados en el valor que caracteriza a la menopausia [14,15] Entre los factores biopsicosociales de riesgo para el desarrollo de una menopausia prematura se mencionan los factores genéticos, que incluyen la herencia compartida entre madres, hijas y hermanas; historia familiar, como demuestran estudios que indican riesgos de menopausia prematura entre mujeres con una hermana o varias con igual condición en unan probabilidad de 8 veces más; embarazo múltiple, que tienen 5 veces más probabilidades de IOP que en la población general; variantes genéticas; factores reproductivos que incluyen la edad de la menarquia, en la cual todavía hay debates en la relación entre la menarquia temprana y la edad de la menopausia [6]. Sin embargo, estudios como el InterLACE, que incluye datos de 50.000 mujeres post menopáusicas de 9 estudios realizados en Inglaterra, Escandinavia, Australia y Japón han mostrado que las mujeres con menarquia temprana (considerada en menores de 11 años) tenían un alto riego de menopausia prematura y menopausia temprana, en relación a las que tuvieron su menarquia a la edad de 13 años [16,17].…”