The endometrial transcriptome of infertile women with and without implantation failure (2024)

Bui, B. N., Kukushkina, V., Meltsov, A., Olsen, C., van Hoogenhuijze, N., Altmäe, S., Mol, F., Teklenburg, G., de Bruin, J.-P., Besselink, D., Stevens Brentjens, L., Obukhova, D., Zamani Esteki, M., van Golde, R., Romano, A., Laisk, T., Steba, G., Mackens, S., Salumets, A. (2024). The endometrial transcriptome of infertile women with and without implantation failure. Acta Obstetricia et Gynecologica Scandinavica, 103(7), 1348-1365. https://doi.org/10.1111/aogs.14822

Bui, Bich Ngoc ; Kukushkina, Viktorija ; Meltsov, Alvin et al. / The endometrial transcriptome of infertile women with and without implantation failure. In: Acta Obstetricia et Gynecologica Scandinavica. 2024 ; Vol. 103, No. 7. pp. 1348-1365.

@article{934f6cb1496a45ed87ee32a6c3409fc0,

title = "The endometrial transcriptome of infertile women with and without implantation failure",

abstract = "INTRODUCTION: Implantation failure after transferring morphologically {"}good-quality{"} embryos in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) may be explained by impaired endometrial receptivity. Analyzing the endometrial transcriptome analysis may reveal the underlying processes and could help in guiding prognosis and using targeted interventions for infertility. This exploratory study investigated whether the endometrial transcriptome profile was associated with short-term or long-term implantation outcomes (ie success or failure).MATERIAL AND METHODS: Mid-luteal phase endometrial biopsies of 107 infertile women with one full failed IVF/ICSI cycle, obtained within an endometrial scratching trial, were subjected to RNA-sequencing and differentially expressed genes analysis with covariate adjustment (age, body mass index, luteinizing hormone [LH]-day). Endometrial transcriptomes were compared between implantation failure and success groups in the short term (after the second fresh IVF/ICSI cycle) and long term (including all fresh and frozen cycles within 12 months). The short-term analysis included 85/107 women (33 ongoing pregnancy vs 52 no pregnancy), excluding 22/107 women. The long-term analysis included 46/107 women (23 'fertile' group, ie infertile women with a live birth after ≤3 embryos transferred vs 23 recurrent implantation failure group, ie no live birth after ≥3 good quality embryos transferred), excluding 61/107 women not fitting these categories. As both analyses drew from the same pool of 107 samples, there was some sample overlap. Additionally, cell type enrichment scores and endometrial receptivity were analyzed, and an endometrial development pseudo-timeline was constructed to estimate transcriptomic deviations from the optimum receptivity day (LH + 7), denoted as ΔWOI (window of implantation).RESULTS: There were no significantly differentially expressed genes between implantation failure and success groups in either the short-term or long-term analyses. Principal component analysis initially showed two clusters in the long-term analysis, unrelated to clinical phenotype and no longer distinct following covariate adjustment. Cell type enrichment scores did not differ significantly between groups in both analyses. However, endometrial receptivity analysis demonstrated a potentially significant displacement of the WOI in the non-pregnant group compared with the ongoing pregnant group in the short-term analysis.CONCLUSIONS: No distinct endometrial transcriptome profile was associated with either implantation failure or success in infertile women. However, there may be differences in the extent to which the WOI is displaced.",

keywords = "implantation failure, IVF/ICSI outcome, assisted reproduction, endometrial receptivity, endometrium, gene expression",

author = "Bui, {Bich Ngoc} and Viktorija Kukushkina and Alvin Meltsov and Catharina Olsen and {van Hoogenhuijze}, Nienke and Signe Altm{\"a}e and Femke Mol and Gijs Teklenburg and {de Bruin}, Jan-Peter and Dagmar Besselink and {Stevens Brentjens}, Linda and Darina Obukhova and {Zamani Esteki}, Masoud and {van Golde}, Ron and Andrea Romano and Triin Laisk and Gaby Steba and Shari Mackens and Andres Salumets and Frank Broekmans",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).",

year = "2024",

month = jul,

doi = "10.1111/aogs.14822",

language = "English",

volume = "103",

pages = "1348--1365",

journal = "Acta Obstetricia et Gynecologica Scandinavica",

issn = "0001-6349",

publisher = "Wiley-Blackwell",

number = "7",

}

Bui, BN, Kukushkina, V, Meltsov, A, Olsen, C, van Hoogenhuijze, N, Altmäe, S, Mol, F, Teklenburg, G, de Bruin, J-P, Besselink, D, Stevens Brentjens, L, Obukhova, D, Zamani Esteki, M, van Golde, R, Romano, A, Laisk, T, Steba, G, Mackens, S, Salumets, A 2024, 'The endometrial transcriptome of infertile women with and without implantation failure', Acta Obstetricia et Gynecologica Scandinavica, vol. 103, no. 7, pp. 1348-1365. https://doi.org/10.1111/aogs.14822

The endometrial transcriptome of infertile women with and without implantation failure. / Bui, Bich Ngoc; Kukushkina, Viktorija; Meltsov, Alvin et al.
In: Acta Obstetricia et Gynecologica Scandinavica, Vol. 103, No. 7, 07.2024, p. 1348-1365.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - The endometrial transcriptome of infertile women with and without implantation failure

AU - Bui, Bich Ngoc

AU - Kukushkina, Viktorija

AU - Meltsov, Alvin

AU - Olsen, Catharina

AU - van Hoogenhuijze, Nienke

AU - Altmäe, Signe

AU - Mol, Femke

AU - Teklenburg, Gijs

AU - de Bruin, Jan-Peter

AU - Besselink, Dagmar

AU - Stevens Brentjens, Linda

AU - Obukhova, Darina

AU - Zamani Esteki, Masoud

AU - van Golde, Ron

AU - Romano, Andrea

AU - Laisk, Triin

AU - Steba, Gaby

AU - Mackens, Shari

AU - Salumets, Andres

AU - Broekmans, Frank

N1 - Publisher Copyright:© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).

PY - 2024/7

Y1 - 2024/7

N2 - INTRODUCTION: Implantation failure after transferring morphologically "good-quality" embryos in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) may be explained by impaired endometrial receptivity. Analyzing the endometrial transcriptome analysis may reveal the underlying processes and could help in guiding prognosis and using targeted interventions for infertility. This exploratory study investigated whether the endometrial transcriptome profile was associated with short-term or long-term implantation outcomes (ie success or failure).MATERIAL AND METHODS: Mid-luteal phase endometrial biopsies of 107 infertile women with one full failed IVF/ICSI cycle, obtained within an endometrial scratching trial, were subjected to RNA-sequencing and differentially expressed genes analysis with covariate adjustment (age, body mass index, luteinizing hormone [LH]-day). Endometrial transcriptomes were compared between implantation failure and success groups in the short term (after the second fresh IVF/ICSI cycle) and long term (including all fresh and frozen cycles within 12 months). The short-term analysis included 85/107 women (33 ongoing pregnancy vs 52 no pregnancy), excluding 22/107 women. The long-term analysis included 46/107 women (23 'fertile' group, ie infertile women with a live birth after ≤3 embryos transferred vs 23 recurrent implantation failure group, ie no live birth after ≥3 good quality embryos transferred), excluding 61/107 women not fitting these categories. As both analyses drew from the same pool of 107 samples, there was some sample overlap. Additionally, cell type enrichment scores and endometrial receptivity were analyzed, and an endometrial development pseudo-timeline was constructed to estimate transcriptomic deviations from the optimum receptivity day (LH + 7), denoted as ΔWOI (window of implantation).RESULTS: There were no significantly differentially expressed genes between implantation failure and success groups in either the short-term or long-term analyses. Principal component analysis initially showed two clusters in the long-term analysis, unrelated to clinical phenotype and no longer distinct following covariate adjustment. Cell type enrichment scores did not differ significantly between groups in both analyses. However, endometrial receptivity analysis demonstrated a potentially significant displacement of the WOI in the non-pregnant group compared with the ongoing pregnant group in the short-term analysis.CONCLUSIONS: No distinct endometrial transcriptome profile was associated with either implantation failure or success in infertile women. However, there may be differences in the extent to which the WOI is displaced.

AB - INTRODUCTION: Implantation failure after transferring morphologically "good-quality" embryos in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) may be explained by impaired endometrial receptivity. Analyzing the endometrial transcriptome analysis may reveal the underlying processes and could help in guiding prognosis and using targeted interventions for infertility. This exploratory study investigated whether the endometrial transcriptome profile was associated with short-term or long-term implantation outcomes (ie success or failure).MATERIAL AND METHODS: Mid-luteal phase endometrial biopsies of 107 infertile women with one full failed IVF/ICSI cycle, obtained within an endometrial scratching trial, were subjected to RNA-sequencing and differentially expressed genes analysis with covariate adjustment (age, body mass index, luteinizing hormone [LH]-day). Endometrial transcriptomes were compared between implantation failure and success groups in the short term (after the second fresh IVF/ICSI cycle) and long term (including all fresh and frozen cycles within 12 months). The short-term analysis included 85/107 women (33 ongoing pregnancy vs 52 no pregnancy), excluding 22/107 women. The long-term analysis included 46/107 women (23 'fertile' group, ie infertile women with a live birth after ≤3 embryos transferred vs 23 recurrent implantation failure group, ie no live birth after ≥3 good quality embryos transferred), excluding 61/107 women not fitting these categories. As both analyses drew from the same pool of 107 samples, there was some sample overlap. Additionally, cell type enrichment scores and endometrial receptivity were analyzed, and an endometrial development pseudo-timeline was constructed to estimate transcriptomic deviations from the optimum receptivity day (LH + 7), denoted as ΔWOI (window of implantation).RESULTS: There were no significantly differentially expressed genes between implantation failure and success groups in either the short-term or long-term analyses. Principal component analysis initially showed two clusters in the long-term analysis, unrelated to clinical phenotype and no longer distinct following covariate adjustment. Cell type enrichment scores did not differ significantly between groups in both analyses. However, endometrial receptivity analysis demonstrated a potentially significant displacement of the WOI in the non-pregnant group compared with the ongoing pregnant group in the short-term analysis.CONCLUSIONS: No distinct endometrial transcriptome profile was associated with either implantation failure or success in infertile women. However, there may be differences in the extent to which the WOI is displaced.

KW - implantation failure

KW - IVF/ICSI outcome

KW - assisted reproduction

KW - endometrial receptivity

KW - endometrium

KW - gene expression

UR - http://www.scopus.com/inward/record.url?scp=85189176393&partnerID=8YFLogxK

U2 - 10.1111/aogs.14822

DO - 10.1111/aogs.14822

M3 - Article

C2 - 38520066

SN - 0001-6349

VL - 103

SP - 1348

EP - 1365

JO - Acta Obstetricia et Gynecologica Scandinavica

JF - Acta Obstetricia et Gynecologica Scandinavica

IS - 7

ER -

Bui BN, Kukushkina V, Meltsov A, Olsen C, van Hoogenhuijze N, Altmäe S et al. The endometrial transcriptome of infertile women with and without implantation failure. Acta Obstetricia et Gynecologica Scandinavica. 2024 Jul;103(7):1348-1365. Epub 2024 Mar 22. doi: 10.1111/aogs.14822