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Early cumulus cell removal increases cumulative live birth rate while having no negative effect on the malformation rate in in vitro fertilization: a propensity score-matched cohort study

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

The aim of this study was to investigate the efficacy and safety of early cumulus cell removal (ECCR) during human in vitro fertilization (IVF).

Methods

A retrospective analysis was performed between January 2011 and December 2019. The study enrolled 1131 couples who underwent IVF treatment with ECCR. After propensity score matching at a 1:1 ratio, 1131 couples who underwent overnight coincubation of gametes were selected. The main outcome measure was the cumulative live birth rate. Secondary outcome measures included the cumulative pregnancy rate, polyspermy rate, available embryo rate, miscarriage rate, malformation rate, time to live birth, and oocyte-to-baby rate.

Results

There were no significant differences found between the two groups in the polyspermy rate, available embryo rate, miscarriage rate, time to live birth, oocyte-to-baby rate, and neonatal congenital anomalies rate. The results of the study showed that ECCR was associated with a significantly higher cumulative live birth rate and cumulative pregnancy rate, along with a significantly lower fertilization rate.

Conclusions

ECCR tended to confer increased cumulative live birth rate and had no negative effect on the neonatal malformation rate.

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Data availability

The data sets used during the current study are available from the corresponding author on reasonable request.

References

  1. Barlow P, Englert Y, Puissant F et al (1990) Fertilization failure in IVF: why and what next? Hum Reprod 5(4):451–456

    Article  CAS  PubMed  Google Scholar 

  2. Molloy D, Harrison K, Breen T et al (1991) The predictive value of idiopathic failure to fertilize on the first in vitro fertilization attempt. Fertil Steril 56(2):285–289

    Article  CAS  PubMed  Google Scholar 

  3. Beck-Fruchter R, Lavee M, Weiss A et al (2014) Rescue intracytoplasmic sperm injection: a systematic review. Fertil Steril 101(3):690–698

    Article  PubMed  Google Scholar 

  4. Ebner T, Moser M, Shebl O, Mayer R, Tews G (2011) Assisting in vitro fertilization by manipulating cumulus-oocyte-complexes either mechanically or enzymatically does not prevent IVF failure. J Turk Ger Gynecol Assoc 12(3):135–139. https://doi.org/10.5152/jtgga.2011.32

    Article  PubMed  PubMed Central  Google Scholar 

  5. Tao T, Robichaud A, Nadeau S, Savoie R, Gallant B, Ouellette R (2004) Efect of cumulus cell removal on the fertilization and the day 3 embryo quality in human IVF. Int Congress Ser 1271:135–138

    Article  Google Scholar 

  6. Ebner T, Moser M, Sommergruber M, Shebl O, Tews G (2006) Incomplete denudation of oocytes prior to ICSI enhances embryo quality and blastocyst development. Hum Reprod 21(11):2972–2977. https://doi.org/10.1093/humrep/del272.]

    Article  CAS  PubMed  Google Scholar 

  7. Liu W, Liu J, Zhang X et al (2014) Short co-incubation of gametes combined with early rescue ICSI: an optimal strategy for complete fertilization failure after IVF. Hum Fertil 17(1):50–55

    Article  Google Scholar 

  8. Liu J, Zhang X, Yang Y et al (2016) Long-time vs. short-time insemination of sibling eggs. Exp Ther Med 12(6):3756–3760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ohgi S, Hagihara C, Anakubo H et al (2016) A comparison of the clinical outcomes of embryos derived from intracytoplasmic sperm injection after early fertilization check and conventional insemination using sibling oocytes. Arch Gynecol Obstet 293(4):887–892

    Article  PubMed  Google Scholar 

  10. He Y, Liu H, Zheng H et al (2018) Effect of early cumulus cells removal and early rescue ICSI on pregnancy outcomes in high-risk patients of fertilization failure. Gynecol Endocrinol 34(8):689–693

    Article  PubMed  Google Scholar 

  11. Kattera S, Chen C (2003) Short coincubation of gametes in in vitro fertilization improves implantation and pregnancy rates: a prospective, randomized, controlled study. Fertil Steril 80(4):1017–1021

    Article  PubMed  Google Scholar 

  12. Dirnfeld M, Shiloh H, Bider D et al (2003) A prospective randomized controlled study of the effect of short coincubation of gametes during insemination on zona pellucida thickness. Gynecol Endocrinol 17(5):397–403

    Article  CAS  PubMed  Google Scholar 

  13. Wei D, Zhang C, Yin B et al (2011) Early cumulus cell removal could reduce the available embryo rate in human IVF. J Assist Reprod Genet 28(12):1213–1216

    Article  PubMed  PubMed Central  Google Scholar 

  14. Turathum B, Gao EM, Chian RC (2021) The function of cumulus cells in oocyte growth and maturation and in subsequent ovulation and fertilization. Cells 10(9):2292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Canipari R (2006) oocyte–granulosa cell interactions. Hum Reprod Update 6:279–289

    Article  Google Scholar 

  16. Kong P, Yin M, Tang C et al (2021) Effects of early cumulus cell removal on treatment outcomes in patients undergoing in vitro fertilization: a retrospective cohort study. Front Endocrinol 12:669507

    Article  Google Scholar 

  17. Bungum L, Bungum M, Humaidan P et al (2004) A strategy for treatment of couples with unexplained infertility who failed to conceive after intrauterine insemination. Reprod Biomed Online 8(5):584–589

    Article  CAS  PubMed  Google Scholar 

  18. Johnson LN, Sasson IE, Sammel MD et al (2013) Does intracytoplasmic sperm injection improve the fertilization rate and decrease the total fertilization failure rate in couples with well-defined unexplained infertility? A systematic review and meta-analysis. Fertil Steril 100(3):704–711

    Article  PubMed  Google Scholar 

  19. Cecconi S, Ciccarelli C, Barberi M et al (2004) Granulosa cell-oocyte interanctions. Eur J Obstet Gynecol Reprod Biol 115(Suppl 1):S19-22

    Article  PubMed  Google Scholar 

  20. Bergh C, Waldenstrom U, Hamberger L (1996) Reducing the time of spermatozoa-oocyte interaction in human IVF improves the implantation rate. Hum Reprod 11(8):1809–1810. https://doi.org/10.1093/oxfordjournals.humrep.a019487

    Article  CAS  PubMed  Google Scholar 

  21. Coskun S, Roca GL, Elnour AM, Al MH, Hollanders JM, Jaroudi KA (1998) Effects of reducing insemination time in human in vitro fertilization and embryo development by using sibling oocytes. J Assist Reprod Genet 15(10):605–608. https://doi.org/10.1023/a:1020333427698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gianaroli L, Cristina MM, Ferraretti AP, Fiorentino A, Tosti E, Panzella S, Dale B (1996) Reducing the time of sperm-oocyte interaction in human in-vitro fertilization improves the implantation rate. Hum Reprod 11(1):166–171. https://doi.org/10.1093/oxfordjournals.humrep.a019011

    Article  CAS  PubMed  Google Scholar 

  23. Guo N, Yang F et al (2016) Effects of cumulus cell removal time during in vitro fertilization on embryo quality and pregnancy outcomes: a prospective randomized sibling-oocyte study. Reprod Biol Endocrinol 14:18–23

    Article  PubMed  PubMed Central  Google Scholar 

  24. Xiong S, Han W, Liu JX et al (2011) Effects of cumulus cells removal after 6 h co-incubation of gametes on the outcomes of human IVF. J Assist Reprod Genet 28(12):1205–1211

    Article  PubMed  PubMed Central  Google Scholar 

  25. Pongsuthirak P (2021) Comparison of embryonic competence and clinical outcomes between early andlate cumulus cell removal for in vitro fertilization. Clin Exp Reprod Med 48(4):362–367

    Article  PubMed  PubMed Central  Google Scholar 

  26. Liu Z, Liu Q, Jiang M et al (2021) Timing considerations for removal of early cumulus cells inshort-terminsemination strategies. Reprod Fertil Dev 33(18):881–885

    Article  CAS  PubMed  Google Scholar 

  27. Fan Y, Wu Z, Peng F, Peng H, Liang X, Zhu S (2023) Brief and long co-incubation of sperm and oocytes for in vitro fertilization: a meta-analysis of randomized controlled trials. BMC Pregnancy Childbirth 23(1):200. https://doi.org/10.1186/s12884-023-05490-z

    Article  PubMed  PubMed Central  Google Scholar 

  28. Le Bras A, Hesters L, Gallot V, Tallet C, Tachdjian G, Frydman N (2017) Shortening gametes co-incubation time improves live birth rate for couples with a history of fragmented embryos. Syst Biol Reprod Med 63(5):331–337. https://doi.org/10.1080/19396368.2017.1336581

    Article  PubMed  Google Scholar 

  29. Aitken RJ, Clarkson JS (1987) Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. J Reprod Fertil 81(2):459–469. https://doi.org/10.1530/jrf.0.0810459

    Article  CAS  PubMed  Google Scholar 

  30. Zhou L, Wang J, Xiao L et al (2016) Differential effects of short co-incubation of gametes and early removal of cumulus cells in patients with different fertilizing capabilities. Reprod Biomed Online 32(6):591–596

    Article  PubMed  Google Scholar 

  31. Drevet JR, Aitken RJ (2020) Oxidation of sperm nucleus in mammals: a physiological necessity to some extent with adverse impacts on oocyte and offspring. Antioxidants. https://doi.org/10.3390/antiox9020095

    Article  PubMed  PubMed Central  Google Scholar 

  32. Huang Z, Li J, Wang L et al (2013) Brief co-incubation of sperm and oocytes for in vitro fertilization techniques. Cochrane Database Syst Rev 30(4):CD009391

    Google Scholar 

  33. Chen ZQ, Wang Y, Ng EHY et al (2019) A randomized triple blind controlled trial comparing the live birth rate of IVF following brief incubation versus standard incubation of gametes. Hum Reprod 34(1):100–108

    Article  CAS  PubMed  Google Scholar 

  34. Bedaiwy MA, Falcone T, Mohamed MS et al (2004) Differential growth of human embryos in vitro: role of reactive oxygen species. Fertil Steril 82(3):593–600

    Article  CAS  PubMed  Google Scholar 

  35. Enkhmaa D, Kasai T, Hoshi K (2009) Long-time exposure of mouse embryos to the sperm produces high levels of reactive oxygen species in culture medium and relates to poor embryo development. Reprod Domest Anim 44(4):634–637

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank staffs at the Department of Reproductive Medicine (Shanghai First Maternity and Infant Hospital) for their scientific advice and encouragement. And thanks Shanghai Public Health Bureau for the financial support.

Funding

This work was supported by the Shanghai Public Health Bureau under Grant number 201440005.

Author information

Author notes

  1. Li Juan Sun and Shan Shan Liang contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Department of Reproductive Medicine, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China

    Li Juan Sun, Shan Shan Liang, Min Hao Liu, Jia Ping Pan, Mei Yuan Huang, Xiao Ming Teng & Hai Xia Wu

  2. Department of Reproductive Medicine, Longhua Women and Children’s Health Hospital, 68 Huawang Road, Shenzhen, China

    Hai Xia Wu

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  1. Li Juan Sun
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Contributions

Data collection and analysis: MHL, LJS and MYH. Data analysis and interpretation: JPP and SSL. Study design and writing: XMT and HXW.

Corresponding author

Correspondence to Hai Xia Wu.

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Conflict of interest

The authors report no conflict of interest.

Ethical approval

This study was approved by the Institutional Reviews Boards and Ethics Committee of Shanghai First Maternity and Infant Hospital, China on August 15, 2019 (reference number: 2019-57).

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Written informed consent was obtained from the parents.

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Sun, L.J., Liang, S.S., Liu, M.H. et al. Early cumulus cell removal increases cumulative live birth rate while having no negative effect on the malformation rate in in vitro fertilization: a propensity score-matched cohort study. Arch Gynecol Obstet 309, 287–293 (2024). https://doi.org/10.1007/s00404-023-07212-4

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  • DOI: https://doi.org/10.1007/s00404-023-07212-4

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