Targeted Metabolomics and Spent Embryo Culture Medium

Targeted Metabolomics of Spent Embryo Culture Medium

More than 8 million babies have been born through in vitro fertilization (IVF). Non-invasive observation of embryos in vitro to better understand their development is becoming increasingly important. Morphology has been used as standard from the beginning, but has the disadvantage of subjectivity. Now the emphasis in basic and clinical research is on developing rapid, quantitative, non-invasive tests. Hence comes the idea of metabolic profiling of spent embryo culture medium (SECM) as a biomarker. This could be useful for understanding and improving the nutritional environment of oocytes and embryos. The goal of our study is to determine metabolic profiles of the SECM in combination with morphological assessments to better understand the nutritional requirements of the embryo. The goal would be to optimize media specifically, depending on patient and embryo characteristics ("personalized medicine") ("the embryo in vitro as patient").

Study Overview

• Status: Recruiting
• Conditions: Metabolomics; Embryo Culture Media

Detailed Description

Following successful fertilization (day 1), each embryo will be cultured for 5-6 days (day 5-6) to form the blastocyst. Then, morphological evaluation will be performed by an expert embryologist to confirm poor and good embryo quality. At the end of the culture, 50 µl of SECM will be collected from each embryo and stored for metabolomics analysis. Samples including medium only and no embryos will be used as controls. The metabolome will be characterized in SECM samples using the respective assay targeted kit.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Andreas Schmutzler, PD Dr. med.; Phone Number: +49-551-41337; Email: a.schmutzler@gyn-medicum.de
• Study Contact Backup: Name: Alireza Alizadeh Moghadam Masouleh, PhD; Phone Number: +49-551-41337; Email: a.alizadeh@gyn-medicum.de

Study Locations

• Germany
  • Niedersachsen
    • Göttingen, Niedersachsen, Germany, 37073
      • Recruiting
      • Gyn-Medicum
      • Contact: Andreas Schmutzler, PD Dr. med.; Phone Number: 0049 551 41337; Email: a.schmutzler@gyn-medicum.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The available spent embryo culture medium (SECM) samples (n> 50 samples) will be collected from embryos produced by IVF and ICSI during nine months. The experimental groups will include: I) SECM obtained from good quality embryos and II) SECM obtained from poor quality embryos. In this study, the samples are classified according to their morphological characteristics of embryos, BMI and age of the women.

Description

Inclusion Criteria:

- Available spent embryo culture medium (SECM) samples with Informed consent

Exclusion Criteria:

• Diabetes

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
good or poor embryo quality; morphological evaluation will be performed by an expert embryologist to confirm poor and good embryo quality
metabolomics profiles; metabolomics profiles will be performed by a Metabolomics core facility

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolomics profiles of good vs. Metabolomics profiles of poor quality embryos	The metabolome will be characterized in SECM samples of good and poor quality embryos using the respective assay kit. This method needs to be developed and analyses are planned in cooperation with the metabolomics core facility; the targeted metabolomics approach using the MxP® Quant 500 kit assay (BIOCRATES Life Sciences AG, Innsbruck, Austria) will be used. The kit plates are used for the quantification of amino acids, acylcarnitines, sphingomyelins, phosphatidylcholines, hexoses, and biogenic amines in SECM of good and poor quality embryos. Results of metabolic set enrichment analysis (MSEA) and metabolic pathway analysis (MetPA) will be used as the final results to compare the metabolite profiles of good and poor quality embryos .	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
amino acids profiles of good vs. amino acids profiles of poor quality embryos	amino acids profiles	24 months

Collaborators and Investigators

• Sponsor: gyn-medicum Göttingen
• Investigators: Study Chair: Andreas Schmutzler, PD Dr. med., gyn-medicum Göttingen

Publications and helpful links

General Publications

• Inoue N, Nishida Y, Harada E, Sakai K, Narahara H. GC-MS/MS analysis of metabolites derived from a single human blastocyst. Metabolomics. 2021 Jan 25;17(2):17. doi: 10.1007/s11306-021-01770-x.
• Siristatidis C, Dafopoulos K, Papapanou M, Stavros S, Pouliakis A, Eleftheriades A, Sidiropoulou T, Vlahos N. Why Has Metabolomics So Far Not Managed to Efficiently Contribute to the Improvement of Assisted Reproduction Outcomes? The Answer through a Review of the Best Available Current Evidence. Diagnostics (Basel). 2021 Sep 2;11(9):1602. doi: 10.3390/diagnostics11091602.
• Cimadomo D, Rienzi L, Conforti A, Forman E, Canosa S, Innocenti F, Poli M, Hynes J, Gemmell L, Vaiarelli A, Alviggi C, Ubaldi FM, Capalbo A. Opening the black box: why do euploid blastocysts fail to implant? A systematic review and meta-analysis. Hum Reprod Update. 2023 Sep 5;29(5):570-633. doi: 10.1093/humupd/dmad010.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: October 16, 2023
• First Submitted That Met QC Criteria: October 16, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 26, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: gyn-medicumGöttingen

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Current study dose not contain any individual person's data in any form (including any individual details, images or videos).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No