Evidence map›Paper›PMID 25901188›Full record

ArticleClinical epigenetics2015

DNA methylation differences between in vitro- and in vivo-conceived children are associated with ART procedures rather than infertility.

Sisi Song, Jayashri Ghosh, Monica Mainigi, Nahid Turan, Rachel Weinerman, May Truongcao, Christos Coutifaris, Carmen Sapienza

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 1 pooled it
22.4field-weighted citation impact, top 1% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

56 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.

  1. Pooled it
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  8. Increased rate ofbioRxiv : the preprint server for biology · 2025
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  14. Pathomechanisms of Prenatally Programmed Adult Diseases.Antioxidants (Basel, Switzerland) · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Sisi SongFels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 N Broad Street, Philadelphia, PA 19140 USA.
Jayashri GhoshFels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 N Broad Street, Philadelphia, PA 19140 USA.
Monica MainigiDepartment of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, 3701 Market Street, 8th Floor, Philadelphia, PA 19119 USA.
Nahid TuranFels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 N Broad Street, Philadelphia, PA 19140 USA.
Rachel WeinermanDepartment of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, 3701 Market Street, 8th Floor, Philadelphia, PA 19119 USA.
May TruongcaoFels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 N Broad Street, Philadelphia, PA 19140 USA.
Christos CoutifarisDepartment of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, 3701 Market Street, 8th Floor, Philadelphia, PA 19119 USA.
Carmen SapienzaFels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 N Broad Street, Philadelphia, PA 19140 USA ; Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140 USA.
Temple University · USUniversity of Pennsylvania · US

Funding

Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Rebecca A Simmons · 2006 to 2026
$35.3M
Research Project 4: Epigenetic Regulation of Retrotransposon Silencing and Male Fertility in the MouseP50HD068157 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI Suneeta Senapati · 2014 to 2026
$16.3M
A National Training Program in Reproductive MedicineT32HD040135 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI COUTIFARIS, CHRISTOS · 2002 to 2016
$3.6M
NICHD NIH HHS P50 HD068157NICHD NIH HHS T32 HD040135
6 · The paper itself

Abstract

backgroundWe, and others, have demonstrated previously that there are differences in DNA methylation and transcript levels of a number of genes in cord blood and placenta between children conceived using assisted reproductive technologies (ART) and children conceived in vivo. The source of these differences (the effect of ART versus the underlying infertility) has never been determined in humans. In this study, we have attempted to resolve this issue by comparing placental DNA methylation levels at 37 CpG sites in 16 previously identified candidate genes in independent populations of children conceived in vivo ('fertile control' group) with ART children conceived from two groups: either autologous oocytes with infertility in one or both parents ('infertile ART' group) or donor oocytes (obtained from young fertile donors) without male infertility ('donor oocyte ART' group).

resultsOf the 37 CpG sites analyzed, significant differences between the three groups were found in 11 CpGs (29.73 %), using ANOVA. Tukey's post hoc test on the significant results indicated that seven (63.63 %) of these differences were significant between the donor oocyte ART and fertile control groups. In addition, 20 of the 37 CpGs analyzed had been identified as differentially methylated between ART and fertile control groups in an independent population in a prior study. Of these 20 CpG sites, 9 also showed significant differences in the present population. An additional 9 CpGs were found to be significantly different between the two groups. Of these 18 candidate CpGs, 12 CpGs (in seven candidate genes) also showed significant differences in placental DNA methylation levels between the donor oocyte ART and fertile control groups.

conclusionsThese data suggest strongly that the DNA methylation differences observed between ART and in vivo conceptions are associated with some aspect of ART protocols, not simply the underlying infertility.

Indexed as

Assisted reproductionDNA methylationDonor oocytesInfertilityPlacenta

Identifiers

PMID25901188
PMCPMC4404660
OpenAlexW2112484452

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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 OpenQuestion graph.