Evidence mapPaperPMID 36916886Full record

ArticleThe Journal of clinical endocrinology and metabolism2023

Immunomodulatory Effects of Metformin Treatment in Pregnant Women With PCOS.

Mariell Ryssdal, Eszter Vanky, Live Marie T Stokkeland, Anders Hagen Jarmund, Bjørg Steinkjer, Tone Shetelig Løvvik, Torfinn Støve Madssen, Ann-Charlotte Iversen, Guro F Giskeødegård

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06064669 (Effect of Metformin on Healthy Live Birth After In-vitro Fertilization in Women With Prediabetes Mellitus), which is not on this map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06064669 narecruitingstarted 2024, after this paper: background citation

Effect of Metformin on Healthy Live Birth After In-vitro Fertilization in Women With Prediabetes Mellitus: a Multicenter Double-blind Placebo Controlled Randomized Trial

Ran2024Enrolled988Registered outcomes26Posted comparisons0ConditionsIn-Vitro Fertilization, Metformin, PrediabetesArmsMetformin pretreatment before endometrial preparation for frozen embryo transfer, Metformin pretreatment before ovarian stimulation, Placebo pretreatment before endometrial preparation for frozen embryo transfer, Placebo pretreatment before ovarian stimulation
Open the trial in the graph
3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Metformin use in pregnancy: What about long-term effects in offspring?Acta obstetricia et gynecologica Scandinavica · 2024
    Article
  9. Review
  10. Article
  11. Immunomodulatory Effects of Metformin Treatment in Pregnant Women With PCOS.The Journal of clinical endocrinology and metabolism · 2023 · on this map
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Mariell RyssdalDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.ORCID 0000-0003-4961-214X
Eszter VankyDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.
Live Marie T StokkelandDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.ORCID 0000-0002-2647-4947
Anders Hagen JarmundDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.
Bjørg SteinkjerDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.
Tone Shetelig LøvvikDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.
Torfinn Støve MadssenDepartment of Circulation and Medical Imaging, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
Ann-Charlotte IversenDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.
Guro F GiskeødegårdK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
Norwegian University of Science and Technology · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

contextPolycystic ovary syndrome (PCOS) is a common endocrine disorder associated with low-grade systemic inflammation and increased risk of pregnancy complications. Metformin treatment reduces the risk of late miscarriage and preterm birth in pregnant women with PCOS. Whether the protective effect of metformin involves immunological changes has not been determined.

objectiveTo investigate the effect of metformin on the maternal immunological status in women with PCOS.

methodsA post-hoc analysis was performed of two randomized controlled trials, PregMet and PregMet2, including longitudinal maternal serum samples from 615 women with PCOS. Women were randomized to metformin or placebo from first trimester to delivery. Twenty-two cytokines and C-reactive protein were measured in serum sampled at gestational weeks 5 to 12, 19, 32, and 36.

resultsMetformin treatment was associated with higher serum levels of several multifunctional cytokines throughout pregnancy, with the strongest effect on eotaxin (P < .001), interleukin-17 (P = .03), and basic fibroblast growth factor (P = .04). Assessment of the combined cytokine development confirmed the impact of metformin on half of the 22 cytokines. The immunomodulating effect of metformin was more potent in normal weight and overweight women than in obese women. Moreover, normoandrogenic women had the strongest effect of metformin in early pregnancy, whereas hyperandrogenic women presented increasing effect throughout pregnancy.

conclusionIt appears that metformin has immunomodulating rather than anti-inflammatory properties in pregnancy. Its effect on the serum levels of many multifunctional cytokines demonstrates robust, persisting, and body mass-dependent immune mobilization in pregnant women with PCOS.

Indexed as

Abortion, SpontaneousMetforminPolycystic Ovary SyndromePremature BirthCytokinesFemaleHumansHypoglycemic AgentsInfant, NewbornPregnancyPregnant PeopleRandomized Controlled Trials as TopicCytokinesHypoglycemic AgentsMetformincytokineimmunologymetforminmultivariate analysisPCOSpregnancy

Identifiers

PMID36916886
PMCPMC10438881
OpenAlexW4324130102

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.