Improved clinical outcomes after non-invasive oocyte selection and Day 3 eSET in ICSI patients

Abstract Background Non-invasive oocyte quality scoring, based on cumulus gene expression analysis, in combination with morphology scoring, can increase the clinical pregnancy (CPR) and live birth rates (LBR) in Day 3 eSET (elective single embryo transfer) ICSI patients. This was first investigated...

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Main Authors: Inge Van Vaerenbergh, Tom Adriaenssens, Wim Coucke, Lisbet Van Landuyt, Greta Verheyen, Michaël De Brucker, Michel Camus, Peter Platteau, Michel De Vos, Elien Van Hecke, André Rosenthal, Johan Smitz
Format: Article
Language:English
Published: BMC 2021-02-01
Series:Reproductive Biology and Endocrinology
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Online Access:https://doi.org/10.1186/s12958-021-00704-5
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author Inge Van Vaerenbergh
Tom Adriaenssens
Wim Coucke
Lisbet Van Landuyt
Greta Verheyen
Michaël De Brucker
Michel Camus
Peter Platteau
Michel De Vos
Elien Van Hecke
André Rosenthal
Johan Smitz
author_facet Inge Van Vaerenbergh
Tom Adriaenssens
Wim Coucke
Lisbet Van Landuyt
Greta Verheyen
Michaël De Brucker
Michel Camus
Peter Platteau
Michel De Vos
Elien Van Hecke
André Rosenthal
Johan Smitz
author_sort Inge Van Vaerenbergh
collection DOAJ
description Abstract Background Non-invasive oocyte quality scoring, based on cumulus gene expression analysis, in combination with morphology scoring, can increase the clinical pregnancy (CPR) and live birth rates (LBR) in Day 3 eSET (elective single embryo transfer) ICSI patients. This was first investigated in a pilot study and is now confirmed in a large patient cohort of 633 patients. It was investigated whether CPR, LBR and time-to-pregnancy could be improved by analyzing the gene expression profile of three predictive genes in the cumulus cells, compared to patients with morphology-based embryo selection only. Methods A large interventional, non-randomized, assessor-blinded cohort study with 633 ICSI patients was conducted in a tertiary fertility center. Non-PCOS patients, 22–39 years old, with good ovarian reserve, were stimulated with HP-hMG using a GnRH antagonist protocol and planned for fresh Day 3 eSET. The cumulus cells from individually denuded oocytes were ranked by a lab-developed cumulus cell test: qRT-PCR for three predictive genes (CAMK1D, EFNB2 and SASH1) and two control genes (UBC, B2M). The embryo selected for transfer was highest ranked from the pool of morphologically transferable Day 3 embryos. Patients in the control (n = 520) and experimental arm (n = 113) were compared for clinical pregnancy and live birth, using a weighted generalized linear model, and time-to-pregnancy using Kaplan-Meier curves. Results The CPR was 61% in the experimental arm (n = 113) vs 29% in the control arm (n = 520, p < 0.0001). The LBR in the experimental arm (50%) was significantly higher than in the control arm (27%,p < 0.0001). Time-to-pregnancy was significantly shortened by 3 transfer cycles independent of the number of embryos available on Day 3 (Kaplan-Meier, p < 0.0001). Cumulus cell tested patients < 35 years (n = 65) or ≥ 35 years (n = 48) had a CPR of 62 and 60% respectively (ns). For cumulus cell tested patients with 2, 3–4, or > 4 transferable embryos, the CPR was 66, 52, and 67% (ns) respectively, and thus independent of the number of transferable embryos on Day 3. Conclusions This study provides further evidence of the clinical usefulness of the non-invasive cumulus cell test over time in a larger patient cohort. Trial registration Clinicaltrials.gov, NCT03659786 / NCT02962466 (Registered 6Sep2018/11Nov2016, retrospectively registered.
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spelling doaj.art-2c45fe1f83a14b4197a229d96fa0544b2022-12-21T20:30:19ZengBMCReproductive Biology and Endocrinology1477-78272021-02-0119111110.1186/s12958-021-00704-5Improved clinical outcomes after non-invasive oocyte selection and Day 3 eSET in ICSI patientsInge Van Vaerenbergh0Tom Adriaenssens1Wim Coucke2Lisbet Van Landuyt3Greta Verheyen4Michaël De Brucker5Michel Camus6Peter Platteau7Michel De Vos8Elien Van Hecke9André Rosenthal10Johan Smitz11Follicle Biology Laboratory, Vrije Universiteit BrusselFollicle Biology Laboratory, Vrije Universiteit BrusselQuality of LaboratoriesCentre for Reproductive Medicine, Universitair Ziekenhuis BrusselCentre for Reproductive Medicine, Universitair Ziekenhuis BrusselCentre for Reproductive Medicine, Universitair Ziekenhuis BrusselCentre for Reproductive Medicine, Universitair Ziekenhuis BrusselCentre for Reproductive Medicine, Universitair Ziekenhuis BrusselFollicle Biology Laboratory, Vrije Universiteit BrusselFertigaFertigaFollicle Biology Laboratory, Vrije Universiteit BrusselAbstract Background Non-invasive oocyte quality scoring, based on cumulus gene expression analysis, in combination with morphology scoring, can increase the clinical pregnancy (CPR) and live birth rates (LBR) in Day 3 eSET (elective single embryo transfer) ICSI patients. This was first investigated in a pilot study and is now confirmed in a large patient cohort of 633 patients. It was investigated whether CPR, LBR and time-to-pregnancy could be improved by analyzing the gene expression profile of three predictive genes in the cumulus cells, compared to patients with morphology-based embryo selection only. Methods A large interventional, non-randomized, assessor-blinded cohort study with 633 ICSI patients was conducted in a tertiary fertility center. Non-PCOS patients, 22–39 years old, with good ovarian reserve, were stimulated with HP-hMG using a GnRH antagonist protocol and planned for fresh Day 3 eSET. The cumulus cells from individually denuded oocytes were ranked by a lab-developed cumulus cell test: qRT-PCR for three predictive genes (CAMK1D, EFNB2 and SASH1) and two control genes (UBC, B2M). The embryo selected for transfer was highest ranked from the pool of morphologically transferable Day 3 embryos. Patients in the control (n = 520) and experimental arm (n = 113) were compared for clinical pregnancy and live birth, using a weighted generalized linear model, and time-to-pregnancy using Kaplan-Meier curves. Results The CPR was 61% in the experimental arm (n = 113) vs 29% in the control arm (n = 520, p < 0.0001). The LBR in the experimental arm (50%) was significantly higher than in the control arm (27%,p < 0.0001). Time-to-pregnancy was significantly shortened by 3 transfer cycles independent of the number of embryos available on Day 3 (Kaplan-Meier, p < 0.0001). Cumulus cell tested patients < 35 years (n = 65) or ≥ 35 years (n = 48) had a CPR of 62 and 60% respectively (ns). For cumulus cell tested patients with 2, 3–4, or > 4 transferable embryos, the CPR was 66, 52, and 67% (ns) respectively, and thus independent of the number of transferable embryos on Day 3. Conclusions This study provides further evidence of the clinical usefulness of the non-invasive cumulus cell test over time in a larger patient cohort. Trial registration Clinicaltrials.gov, NCT03659786 / NCT02962466 (Registered 6Sep2018/11Nov2016, retrospectively registered.https://doi.org/10.1186/s12958-021-00704-5Cumulus cellsNon-invasiveGene expressionSingle embryo transferClinical pregnancyLive birth
spellingShingle Inge Van Vaerenbergh
Tom Adriaenssens
Wim Coucke
Lisbet Van Landuyt
Greta Verheyen
Michaël De Brucker
Michel Camus
Peter Platteau
Michel De Vos
Elien Van Hecke
André Rosenthal
Johan Smitz
Improved clinical outcomes after non-invasive oocyte selection and Day 3 eSET in ICSI patients
Reproductive Biology and Endocrinology
Cumulus cells
Non-invasive
Gene expression
Single embryo transfer
Clinical pregnancy
Live birth
title Improved clinical outcomes after non-invasive oocyte selection and Day 3 eSET in ICSI patients
title_full Improved clinical outcomes after non-invasive oocyte selection and Day 3 eSET in ICSI patients
title_fullStr Improved clinical outcomes after non-invasive oocyte selection and Day 3 eSET in ICSI patients
title_full_unstemmed Improved clinical outcomes after non-invasive oocyte selection and Day 3 eSET in ICSI patients
title_short Improved clinical outcomes after non-invasive oocyte selection and Day 3 eSET in ICSI patients
title_sort improved clinical outcomes after non invasive oocyte selection and day 3 eset in icsi patients
topic Cumulus cells
Non-invasive
Gene expression
Single embryo transfer
Clinical pregnancy
Live birth
url https://doi.org/10.1186/s12958-021-00704-5
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