Lasers in Medical Science

, Volume 34, Issue 9, pp 1889–1895 | Cite as

Effects of laser-assisted thinning versus opening on clinical outcomes according to maternal age in patients with repeated implantation failure

  • Jung-Woo Lee
  • Jeong-Ho ChaEmail author
  • Sun-Hee Shin
  • Yun-Jeong Kim
  • Seul-Ki Lee
  • Choon-keun Park
  • Kyung-Ah Pak
  • Ji-Sung Yoon
  • Seo-Young Park
Original Article


Laser-assisted thinning (LAT) and laser-assisted opening (LAO) are performed as part of human in vitro fertilization (IVF) to increase the implantation rate in patients with a poor prognosis and in cases of repeated implantation failure. However, an insufficient number of studies have directly compared LAT and LAO using the same methods. Therefore, we compared the effects of LAT and LAO on clinical outcomes according to maternal age in patients with repeated implantation failure. This retrospective study was performed in 509 IVF cycles (458 patients). The cycles were divided based on maternal age and the method used (< 38 years LAT, n = 119 vs. LAO, n = 179 and ≥ 38 years LAT, n = 72 vs. LAO, n = 139). Cleavage-stage embryos before transfer were either thinned or opened using a 1.46-μm noncontact diode laser. We compared the implantation rates and pregnancy outcomes of cycles between LAT and LAO according to maternal age. The characteristics of patients did not differ significantly among the groups (p > 0.05), with the exception of mixed factor infertility, which was more common in the LAT group than in the LAO group among patients < 38 years of age (10.1% vs. 2.8%, p = 0.008). The LAT and LAO groups showed similar rates of biochemical pregnancy, clinical pregnancy, ongoing pregnancy, abortion, implantation, singleton pregnancy, and twin pregnancy (p > 0.05). In conclusion, LAT and LAO had similar clinical outcomes. Therefore, we did not find any evidence that LAT is superior to LAO. In fact, the patients ≥ 38 years of age who underwent LAO tended to have a lower abortion rate. Further study is necessary to confirm these results in a larger population.


Laser-assisted hatching Laser-assisted thinning Laser-assisted opening Zona pellucid Pregnancy outcomes 



The authors express special thanks to the staff of the Agaon Fertility Clinic.


This study was self-funded.

Compliance with ethical standards

This study was approved by the Institutional Review Board (IRB reference number, Agaon IRB-17-003) of Agaon Fertility Clinic.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. 1.
    Cohen J, Malter H, Fehilly C, Wright G, Elsner C, Kort H, Massey J (1988) Implantation of embryos after partial opening of oocyte zona pellucida to facilitate sperm penetration. Lancet 332(8603):162CrossRefGoogle Scholar
  2. 2.
    Hsieh Y, Huang C, Cheng T, Chang C, Tsai H, Lee M (2002) Laser-assisted hatching of embryos is better than the chemical method for enhancing the pregnancy rate in women with advanced age. Fertil Steril 78(1):179–182CrossRefGoogle Scholar
  3. 3.
    Frydman N, Madoux S, Hesters L, Duvernoy C, Feyereisen E, Le Du A, Tachdjian G, Frydman R, Fanchin R (2006) A randomized double-blind controlled study on the efficacy of laser zona pellucida thinning on live birth rates in cases of advanced female age. Hum Reprod 21(8):2131–2135CrossRefGoogle Scholar
  4. 4.
    Edirisinghe WR, Ahnonkitpanit V, Promviengchai S, Suwajanakorn S, Pruksananonda K, Chinpilas V, Virutamasen P (1999) A study failing to determine significant benefits from assisted hatching: patients selected for advanced age, zonal thickness of embryos, and previous failed attempts. J Assist Reprod Genet 16(6):294–301CrossRefGoogle Scholar
  5. 5.
    Petersen CG, Mauri A, Baruffi R, Oliveira J, Massaro F, Elder K, Franco J (2005) Implantation failures: success of assisted hatching with quarter-laser zona thinning. Reprod BioMed Online 10(2):224–229CrossRefGoogle Scholar
  6. 6.
    Valojerdi MR, Eftekhari-Yazdi P, Karimian L, Ashtiani SK (2008) Effect of laser zona pellucida opening on clinical outcome of assisted reproduction technology in patients with advanced female age, recurrent implantation failure, or frozen–thawed embryos. Fertil Steril 90(1):84–91CrossRefGoogle Scholar
  7. 7.
    Germond M, Nocera D, Senn A, Rink K, Delacrétaz G, Fakan S (1995) Microdissection of mouse and human zona pellucida using a 1.48μm diode laser beam: efficacy and safety of the procedure. Fertil Steril 64(3):604–611CrossRefGoogle Scholar
  8. 8.
    Mantoudis E, Podsiadly BT, Gorgy A, Venkat G, Craft IL (2001) A comparison between quarter, partial and total laser assisted hatching in selected infertility patients. Hum Reprod 16(10):2182–2186CrossRefGoogle Scholar
  9. 9.
    Hammadeh ME, Fischer-Hammadeh C, Ali KR (2011) Assisted hatching in assisted reproduction: a state of the art. J Assist Reprod Genet 28(2):119–128CrossRefGoogle Scholar
  10. 10.
    Kutlu P, Atvar O, Vanlioglu OF (2010) Laser assisted zona thinning technique has no beneficial effect on the ART outcomes of two different maternal age groups. J Assist Reprod Genet 27(8):457–461CrossRefGoogle Scholar
  11. 11.
    Padula F, Capriglione S, Iaconianni P, Gatti S, Lippa A, Minutolo SE, Giannarelli D, Giorlandino C (2017) Laser-assisted hatching of human embryos: may two alternative approaches (thinning versus drilling) impact on implant rate. Lasers Med Sci 32(7):1663–1666CrossRefGoogle Scholar
  12. 12.
    Stoop D, Ermini B, Polyzos NP, Haentjens P, De Vos M, Verheyen G, Devroey P (2012) Reproductive potential of a metaphase II oocyte retrieved after ovarian stimulation: an analysis of 23 354 ICSI cycles. Hum Reprod 27(7):2030–2035CrossRefGoogle Scholar
  13. 13.
    Cardona-Maya W, Berdugo J, Cadavid A (2008) Comparing the sperm concentration determined by the Makler and the Neubauer chambers. Actas Urol Esp 32(4):443–445CrossRefGoogle Scholar
  14. 14.
    World Health Organ (ed) (2010) WHO laboratory manual for the examination and processing of human semen, 5th edn. World Health Organization, GenevaGoogle Scholar
  15. 15.
    Younglai EV, Holt D, Brown P, Jurisicova A, Casper RF (2001) Sperm swim-up techniques and DNA fragmentation. Hum Reprod 16(9):1950–1953CrossRefGoogle Scholar
  16. 16.
    Lee JW, Cha JH, Shin SH, Kim YJ, Lee SK, Cha HJ, Kim JH, Ahn JH, Kim HY, Pak KA, Yoon JS, Park SY, Park CK (2016) Long cut straw provides stable the rates of survival, pregnancy and live birth for vitrification of human blasotcysts. Dev Reprod 20(3):219–225CrossRefGoogle Scholar
  17. 17.
    Lee JW, Cha JH, Shin SH, Kim YJ, Lee SK, Park CK, Pak KA, Yoon JS, Park SY (2017) Efficacy of embryo transfer on day 2 versus day 3 according to maternal age in patients with normal ovarian response. Clin Exp Reprod Med 44(3):141–145CrossRefGoogle Scholar
  18. 18.
    Cohen J, Malter H, Wright G, Kort H, Massey J, Mitchell D (1989) Partial zona dissection of human oocytes when failure of zona pellucida penetration is anticipated. Hum Reprod 4(4):435–442CrossRefGoogle Scholar
  19. 19.
    Antinori S, Selman H, Caffa B, Panci C, Dani G, Versaci C (1996) Zona opening of human embryos using a non-contact UV laser for assisted hatching in patients with poor prognosis of pregnancy. Hum Reprod 11(11):2488–2492CrossRefGoogle Scholar
  20. 20.
    Magli MC, Gianaroli L, Ferraretti AP, Fortini D, Aicardi G, Montanaro N (1998) Rescue of implantation potential in embryos with poor prognosis by assisted zona hatching. Hum Reprod 13(5):1331–1335CrossRefGoogle Scholar
  21. 21.
    Nakayama T, Fujiwara H, Yamada S, Tastumi K, Honda T, Fujii S (1999) Clinical application of a new assisted hatching method using a piezo-micromanipulator for morphologically low-quality embryos in poor-prognosis infertile patients. Fertil Steril 71(6):1014–1018CrossRefGoogle Scholar
  22. 22.
    Bider D, Livshits A, Yonish M, Yemini Z, Mashiach S, Dor J (1997) Assisted hatching by zona drilling of human embryos in women of advanced age. Hum Reprod 12(2):317–320CrossRefGoogle Scholar
  23. 23.
    Wang E, Wang A, Wang B, Li B (2016) Outcomes of vitrified-warmed cleavage-stage embryo hatching after in vitro laser-assisted zona pellucida thinning in patients. Biomed Rep 5(3):376–382CrossRefGoogle Scholar
  24. 24.
    Cohen J, Elsner C, Kort H, Malter H, Massey J, Mayer MP, Wiemer K (1990) Impairment of the hatching process following IVF in the human and improvement of implantation by assisting hatching using micromanipulation. Hum Reprod 5(1):7–13CrossRefGoogle Scholar
  25. 25.
    Cohen J (1991) Assisted hatching of human embryos. J In Vitro Fert Embryo Transf 8(4):179–190CrossRefGoogle Scholar
  26. 26.
    Martins WP, Rocha IA, Ferriani RA, Nastri CO (2011) Assisted hatching of human embryos: a systematic review and meta-analysis of randomized controlled trials. Hum Reprod Update 17(4):438–453CrossRefGoogle Scholar
  27. 27.
    Alikani M, Noyes N, Cohen J, Rosenwaks Z (1994) Monozygotic twinning in the human is associated with the zona pellucida architecture. Hum Reprod 9(7):1318–1321CrossRefGoogle Scholar
  28. 28.
    Luke B, Brown MB, Wantman E, Stern JE (2014) Factors associated with monozygosity in assisted reproductive technology pregnancies and the risk of recurrence using linked cycles. Fertil Steril 101(3):683–689CrossRefGoogle Scholar
  29. 29.
    Blake D, Forsberg A, Johansson B, Wikland M (2001) Laser zona pellucida thinning—an alternative approach to assisted hatching. Hum Reprod 16(9):1959–1964CrossRefGoogle Scholar
  30. 30.
    Tucker MJ, Luecke NM, Wiker SR, Wright G (1993) Chemical removal of the outside of the zona pellucida of day 3 human embryos has no impact on implantation rate. J Assist Reprod Genet 10(3):187–191CrossRefGoogle Scholar
  31. 31.
    Schimmel T, Cohen J, Saunders H, Alikani M (2014) Laser-assisted zona pellucida thinning does not facilitate hatching and may disrupt the in vitro hatching process: a morphokinetic study in the mouse. Hum Reprod 29(12):2670–2679CrossRefGoogle Scholar
  32. 32.
    Watanabe H, Suzuki R, Kobayashi M, Hasegawa H, Tsukamoto K, Saitou S, Kobayashi J (2015) To what degree should the zona pellucida be cut open in assisted hatching for best clinical results? Fertil Steril 104(3):e185CrossRefGoogle Scholar
  33. 33.
    Hartshorn C, Anshelevich A, Wangh LJ (2005) Rapid, single-tube method for quantitative preparation and analysis of RNA and DNA in samples as small as one cell. BMC Biotechnol 5:2CrossRefGoogle Scholar
  34. 34.
    Al-Katanani YM, Hansen PJ (2002) Induced thermotolerance in bovine two-cell embryos and the role of heat shock protein 70 in embryonic development. Mol Reprod Dev 62(2):174–180CrossRefGoogle Scholar
  35. 35.
    Hartshorn C, Anshelevich A, Wangh LJ (2005) Laser zona drilling does not induce hsp70i transcription in blastomeres of eight-cell mouse embryos. Fertil Steril 84(5):1547–1550CrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2019

Authors and Affiliations

  1. 1.Agaon Fertility ClinicSeoulSouth Korea
  2. 2.College of Animal Life ScienceKangwon National UniversityChuncheonSouth Korea

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