Insufficient Cumulus Expansion and Poor Oocyte Retrieval in Endometriosis-Related Infertile Women

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Endometriosis is associated with decreased cumulus expansion-related gene expression in cumulus cells and poorer oocyte retrieval rates during IVF.

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The paper studied whether endometriosis-related infertility is associated with insufficient cumulus expansion and whether this could relate to difficulty obtaining oocytes during IVF. It analyzed cumulus cell mRNA levels of cumulus expansion–related genes (HAS2, PTGS2, PTX3, TNFAIP6) by real-time PCR in cumulus cells from 19 women with surgically diagnosed endometriosis and 24 controls, and then compared IVF clinical outcomes in a retrospective cohort of 635 endometriosis-associated infertility patients versus 4634 patients with male factor infertility. Cumulus expansion–related gene expression was significantly decreased in the endometriosis group, especially PTGS2, and the endometriosis group had lower mean oocyte retrieval rates along with higher flushing times per follicle. The authors’ limitation is that gene expression testing in cumulus cells was performed in a small subset, which may constrain how broadly the mechanistic findings explain the broader clinical outcome patterns; this paper is centrally about endometriosis — it focuses on how reduced cumulus expansion–related gene expression may contribute to poor oocyte retrieval in endometriosis-related infertile women.

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Abstract

Endometriosis (EMs) is a common cause for female infertility, leading to the need for in vitro fertilization (IVF). In clinics, we found the operative oocyte retrieval to be more or less difficult in women with EMs. We hypothesized that EMs may be involved in the insufficient cumulus expansion that partially explained the lower oocyte retrieval in EMs-related infertile women undergoing assisted reproductive technology (ART). To explore whether the insufficient cumulus expansion exists in EMs-related infertile women and whether there is a possible relationship between the insufficient cumulus expansion and the clinical phenomenon of difficulty in oocyte retrieval. Those infertile women undergoing IVF recorded in our database between January 2013 and October 2017 were included. The expression levels of cumulus expansion–related genes (HAS2/PTGS2/PTX3/TNFAIP6) in the cumulus cells (CCs) from 19 infertile women with EMs and 24 controls were analyzed by real-time PCR. After that, 635 women with EMs-associated infertility (the EMs group) and 4634 women with male factor–associated infertility (the control group) were included in the retrospective analysis. The clinical outcomes were compared between the two groups. The relative mRNA levels of cumulus expansion–related genes were significantly decreased in the CCs from those infertile women with EMs when compared to the control group (all p < 0.05), especially the expression of PTGS2. The mean oocyte retrieval rates (proportion of obtained oocytes in punctured follicles) were (76.33 ± 2.58)% and (71.80 ± 0.58)% (p < 0.01). The mean numbers of flushing times per follicle were 1.11 ± 0.65 and 3.86 ± 1.53 (p < 0.001). The lower expression of cumulus expansion–related genes in CCs suggests the insufficient cumulus expansion in EMs-related infertile women, which partially explains a possible mechanism related to poor oocyte retrieval. Similar content being viewed by others Data Availability All data utilized and analyzed in this study are included in the published manuscript.

References

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Cancer Res. 2001;61:4628–35. Acknowledgments The authors gratefully acknowledge the efforts of the doctors, nurses, embryologists, and the entire staff at the Clinical Reproductive Medicine Center, Nanjing, China. Funding This study was supported by the National Key Research and Development Program of China (2017YFC1001604, 2017YFC1001300) and the National Nature and Science Foundation of China (81730041, 81671438), and the program SKLRM-K201805. The funding bodies had no role in the design of the study, the collection, analysis, and interpretation of the data, and the writing of the manuscript. Author information Authors and Affiliations Contributions In this study, Yaoxue Yin collected data by interviewing the infertile women, performed the molecular biological analysis, and wrote the final draft of the manuscript. Yundong Mao and Li Shu participated in the initial conception of the study and the protocol. Anthony Liu modified and polished the entire manuscript. Chun Yuan helped in the statistical methods and revision of the manuscript. Yugui Cui provided the design and protocol of the research and reviewed and modified the final version of the manuscript. Jiayin Liu and Zhen Hou, as the main investigators, conceived of this project and reviewed and ensured the final version of this manuscript. All authors read and approved the final manuscript. Corresponding authors Ethics declarations Ethics Approval and Consent to Participate A retrospective cohort study was conducted at the Center of Clinical Reproductive Medicine, First Affiliated Hospital of NMU. This study was approved by the Research Ethics Committee of the hospital on 12 October 2012. All infertile women who met the eligibility criteria and agreed to participate in the study provided written informed consent. Study Size This retrospective study was referred to as clinical data analysis. In total, 5629 women were included for analysis, 635 women with a diagnosis of EMs via laparoscopic surgery, and 4634 women with male factor infertility as control. The above eligible patients who consented to participate were analyzed from January 2013 to October 2017. In addition, we also collected the CCs from 19 women in the EMs group and 24 women in the control group who underwent IVF to test the cumulus expansion–related genes in June 2019. Consent for Publication No applicable. Competing Interests The authors declare that they have no competing interests. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Yin, Y., Mao, Y., Liu, A. et al. Insufficient Cumulus Expansion and Poor Oocyte Retrieval in Endometriosis-Related Infertile Women. Reprod. Sci. 28, 1412–1420 (2021). https://doi.org/10.1007/s43032-020-00410-4 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-020-00410-4

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endometriosis

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Cumulus Cells Endometriosis Fertilization in Vitro Infertility, Female Oocyte Retrieval Cumulus Cells Endometriosis Female Gene Expression Humans Infertility, Female Retrospective Studies

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