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pmid:32430730
Combinational approach of retrospective clinical evidence and transcriptomics highlight AMH superiority to FSH, as successful ICSI outcome predictor.
Stavroula Lila Kastora · Olga Triantafyllidou · Georgios Kolovos · Athanasios Kastoras · Georgios Sigalos · Nikos Vlahos
Journal of assisted reproduction and genetics · 2020 doi:10.1007/s10815-020-01802-w
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Complete file
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We collected retrospectively patient data from 80 infertile patients selected according to pre-specified inclusion criteria.\nSETTING: Publicly available raw RNA-sequencing data were retrieved from the SRA database of NCBI resource GEO Accession (GSM21575/35-44; GEO Accession: GSM21575/45-55). Retrospective data were collected from referrals to the Institute of Reproductive Medicine, Lito Hospital of Athens and the Institute of Life, Iaso Hospital of Athens, between the periods of March 2015 and April 2018.\nINTERVENTION(S): A fixed human menopausal gonadotropin (hMG) antagonist protocol was used for all patients. All patients had serum AMH levels measured within a 3-month period prior to stimulation and serum levels of FSH and estradiol (day 2 of menstrual cycle; E2) (Clinical Trial code NV24042014).\nMAIN OUTCOME MEASURE(S): The primary outcomes were identification of transcriptomic variations among high (group A) vs. low (group B) AMH patients. Retrospective data primary outcomes were number of oocytes retrieved, fertilized successfully (grades A and B, day 2 embryos), and total number of day 3 embryos. Secondary outcome was live birth rate. Finally, we compared primary outcomes with AMH and FSH level as well as their genetic pathways (interacting genes) to demonstrate the predictive accuracy.\nRESULTS: Essential players of the AMH signaling cascade, namely, SMAD1, SMAD4, SMAD5, ALK1, and LEF1, were significantly upregulated in group A (n 10) transcriptome. This biological clue was further supported by retrospective clinical data (n 80 participants), where AMH was positively correlated with both oocytes retrieved and fertilized as well as number of day 3 (grades A and B) embryos from patients undergoing IVF, in a statistically significant manner. AMH was further positive trend of association with successful pregnancy outcomes.\nCONCLUSION: Overall, this study offers new insight on AMH effects upon cumulus cells and new aspects on how AMH might promote oocyte integrity and embryo viability at a biochemical level as well as add to the current body of evidence supporting AMH clinical potential as a more sensitive marker of IVF outcomes in comparison with FSH, regarding numbers of oocytes received and high-quality day 2 and day 3 embryos.", "claims": [{"id": "claim-method", "statement": "Pearson correlation analysis was performed considering all variables were continuous (age, FSH/AMH/E2) measurements.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32430730", "locator": "sections[10] \"Statistical analysis\" paragraph 2", "quote": "Pearson correlation analysis was performed considering all variables were continuous (age, FSH/AMH/E2) measurements."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available raw RNA-sequencing data were retrieved from the SRA database of NCBI resource GEO Accession (GSM21575/35-44; GEO Accession: GSM21575/45-55).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32430730", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Publicly available raw RNA-sequencing data were retrieved from the SRA database of NCBI resource GEO Accession (GSM21575/35-44; GEO Accession: GSM21575/45-55)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:32430730"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32430730", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1007/s10815-020-01802-w", "sha256": "sha256:ba5a0d8aaa71239ac6995733224d520a602cf9235ea2fd3eba16932f37f496f5", "bytes": 51515, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1007/s10815-020-01802-w", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7376803", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:32430730:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:981eb2b9d8577b56ec52f7c8152666c9141145f6fe228369b528aeef306d236e", "bytes": 971, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#Tab1", "version": null, "note": "Tabular results of correlation matrix of associated variables with number of day 3 embryos retrieved", "structure": {"pmcid": "PMC7376803", "section_index": 11, "section_title": "Results", "row_count": 7, "column_count": 7}, "table": {"label": "Table 1", "caption": "Tabular results of correlation matrix of associated variables with number of day 3 embryos retrieved", "rows": [["", "Day 3 embryos vs. AGE", "Day 3 embryos vs. FSH (mIU/ml)", "Day 3 embryos vs. E2 (pg/ml) (day 2)", "Day 3 embryos vs. AMH (ng/ml)", "Day 3 embryos vs. oocytes received", "Day 3 embryos vs. oocytes fertilized (day 2)"], ["Pearson r", "− 0.1764", "− 0.2266", "− 0.1548", "0.5939", "0.7965", "0.8554"], ["95% confidence interval", "− 0.3315 to − 0.01199", "− 0.3970 to − 0.04111", "− 0.3293 to 0.02999", "0.4546 to 0.7048", "0.7272 to 0.8497", "0.8040 to 0.8941"], ["R-squared", "0.03111", "0.05135", "0.02396", "0.3527", "0.6344", "0.7317"], ["p (two-tailed)", "0.04", "0.02", "0.10", "< 0.001", "< 0.001", "< 0.001"], ["p value summary", "*", "*", "ns", "***", "***", "***"], ["Significant? 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