The Association of Vitamin D with Uterine Fibroids in Premenopausal Patients: a Systematic Review and Meta-Analysis.

OBJECTIVE: This study aims to consolidate existing literature regarding the association between vitamin D and uterine fibroid presence and growth. DATA SOURCES: A comprehensive search across databases including MEDLINE, Embase, CINAHL, Web of Science, ClinicalTrials.gov, and grey literature was conducted from inception to February 2023, using relevant keywords. Authors were contacted for unpublished data. STUDY SELECTION: From 9931 studies screened based on title and abstract, those evaluating serum vitamin D levels or vitamin D treatment effects, using ultrasonography for diagnosis, and involving at least 25 pre-menopausal participants were included. Case reports, case series, and reviews were excluded. DATA EXTRACTION AND SYNTHESIS: Data were extracted using a predefined form. Methodological quality was assessed through the Newcastle-Ottawa Scale and the Risk of Bias-2 tools. Evidence quality was evaluated using Grading of Recommendations Assessment, Development, and Evaluation. Data from three randomized controlled trials (n = 328) and 23 observational studies (n = 5650) were meta-analyzed via random effects modeling. Patients receiving oral vitamin D supplementation had a significantly different change in fibroid size (SMD -5.7%, CI -10.63 to -0.76, P = 0.02, I2 = 99%), as measured by percentage change in diameter or volume, compared to controls, over the span of 2-6 months. Those receiving supplementation had vitamin D insufficiency; regimens varied between 50 000 IU weekly for 12 weeks, 50 000 IU weekly for 8 weeks, and 50 000 IU biweekly for 10 weeks. Patients with fibroids exhibited lower serum vitamin D concentrations (MD -5.50 ng/mL, CI 6.99 to -4.01, P < 0.001, I2 = 87%) and higher odds of vitamin D deficiency (OR 3.71, CI 1.90-7.24, P < 0.001, I2 = 80%). CONCLUSION: This review underscores the potential of vitamin D in mitigating fibroid development and growth. While promising, further research is warranted to optimize dosage and treatment duration, potentially offering a non-invasive solution for at-risk patients. Continued exploration of vitamin D's role in fibroid treatment is encouraged. OBJECTIF: Cette étude vise à consolider la littérature existante concernant l'association entre la vitamine D et la présence et la croissance des fibromes utérins. SOURCE DES DONNéES: Une recherche exhaustive a été réalisée dans les bases de données MEDLINE, Embase, CINAHL, Web of Science et ClinicalTrials.gov et dans la littérature à l'aide de mots-clés pertinents pour la période allant de leur création à février 2023. Les auteurs ont été contactés pour obtenir des données non publiées. SéLECTION DES éTUDES: Dans les 9 931 études sélectionnées d'après leurs titre et résumé, seules celles ayant évalué les taux sériques de vitamine D ou les effets d'un traitement à la vitamine D, utilisé l'échographie pour le diagnostic et comptant au moins 25 participantes non ménopausées ont été retenues. Les études de cas, les études de série de cas et les revues n'ont pas été retenues. EXTRACTION DES DONNéES ET SYNTHèSE: Les données ont été extraites au moyen d'un formulaire prédéfini. La qualité méthodologique a été évaluée au moyen de l'échelle de Newcastle-Ottawa et de l'outil d'évaluation du risque de biais RoB-2. La qualité des données a été évaluée à l'aide de la méthodologie GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Les données de trois essais cliniques randomisés (n = 328) et de 23 études observationnelles (n = 5650) ont été méta-analysées à l'aide d'une modélisation à effets aléatoires. Les patientes recevant une supplémentation orale en vitamine D ont présenté un changement significativement différent de la taille des fibromes (différence des moyennes standardisées : -5,7 %; IC : -10,63 à -0,76; P = 0,02; I2 = 99 %), tel que mesuré par le changement en pourcentage du diamètre ou du volume, par rapport aux témoins, sur une période de 2 à 6 mois. Les personnes recevant une supplémentation présentaient une insuffisance en vitamine D; les schémas posologiques étaient de 50 000 UI par semaine pendant 12 semaines, 50 000 UI par semaine pendant 8 semaines ou 50 000 UI toutes les deux semaines pendant 10 semaines. Les patientes atteintes de fibromes avaient des concentrations sériques de vitamine D plus faibles (différence moyenne : -5,50 ng/mL; IC : 6,99 à -4,01; P < 0,001; I2 = 87 %) et un risque plus élevé de carence en vitamine D (RC : 3,71; IC : 1,90-7,24; P < 0,001; I2 = 80 %). CONCLUSION: Cette étude souligne le potentiel de la vitamine D dans l'atténuation du développement et de la croissance des fibromes. Bien que ces conclusions soient prometteuses, la recherche doit se poursuivre afin d'optimiser le dosage et la durée du traitement, ce qui pourrait constituer une solution non invasive pour les patientes à risque. La poursuite de l'étude du rôle de la vitamine D dans le traitement des fibromes est encouragée.

Multifetal Pregnancy After Implementation of a Publicly Funded Fertility Program.

Importance: A publicly funded fertility program was introduced in Ontario, Canada, in 2015 to increase access to fertility treatment. For in vitro fertilization (IVF), the program mandated an elective single-embryo transfer (eSET) policy. However, ovulation induction and intrauterine insemination (OI/IUI)-2 other common forms of fertility treatment-were more difficult to regulate in this manner. Furthermore, prior epidemiologic studies only assessed fetuses at birth and did not account for potential fetal reductions that may have been performed earlier in pregnancy. Objective: To examine the association between fertility treatment and the risk of multifetal pregnancy in a publicly funded fertility program, accounting for both fetal reductions and all live births and stillbirths. Design, Setting, and Participants: This population-based, retrospective cohort study used linked administrative health databases at ICES to examine all births and fetal reductions in Ontario, Canada, from April 1, 2006, to March 31, 2021. Exposure: Mode of conception: (1) unassisted conception, (2) OI/IUI, or (3) IVF. Main Outcomes and Measures: The main outcome was multifetal pregnancy (ie, a twin or higher-order pregnancy). Modified Poisson regression generated adjusted relative risks (ARRs) and derived population attributable fractions (PAFs) for multifetal pregnancies attributable to fertility treatment. Absolute rate differences (ARDs) were used to compare the era before eSET was promoted (2006-2011) with the era after the introduction of the eSET mandate (2016-2021). Results: Of all 1 724 899 pregnancies, 1 670 825 (96.9%) were by unassisted conception (mean [SD] maternal age, 30.6 [5.2] years), 24 395 (1.4%) by OI/IUI (mean [SD] maternal age, 33.1 [4.4] years), and 29 679 (1.7%) by IVF (mean [SD] maternal age, 35.8 [4.7] years). In contrast to unassisted conception, individuals who received OI/IUI or IVF tended to be older, reside in a high-income quintile neighborhood, or have preexisting health conditions. Multifetal pregnancy rates were 1.4% (95% CI, 1.4%-1.4%) for unassisted conception, 10.5% (95% CI, 10.2%-10.9%) after OI/IUI, and 15.5% (95% CI, 15.1%-15.9%) after IVF. Compared with unassisted conception, the ARR of any multifetal pregnancy was 7.0 (95% CI, 6.7-7.3) after OI/IUI and 9.9 (95% CI, 9.6-10.3) after IVF, with corresponding PAFs of 7.1% (95% CI, 7.1%-7.2%) and 13.4% (95% CI, 13.3%-13.4%). Between the eras of 2006 to 2011 and 2016 to 2021, multifetal pregnancy rates decreased from 12.9% to 9.1% with OI/IUI (ARD, -3.8%; 95% CI, -4.2% to -3.4%) and from 29.4% to 7.1% with IVF (ARD, -22.3%; 95% CI, -23.2% to -21.6%). Conclusions and Relevance: In this cohort study of more than 1.7 million pregnancies in Ontario, Canada, a publicly funded IVF program mandating an eSET policy was associated with a reduction in multifetal pregnancy rates. Nevertheless, ongoing strategies are needed to decrease multifetal pregnancy, especially in those undergoing OI/IUI.