In Vitro Fertilization Outcomes Following Assisted Hatching of Embryos with Thick Zona Pellucida—A Prospective Randomized Study

Mara Koifman¹, Shirly Lahav-Baratz¹, Libby Shopen², Blais Idit¹, David Ishai¹, Zofnat Wiener-Megnazi¹, Ron Auslender^{1, 2}, Martha Dirnfeld^{1, 2}

¹Division of Fertility-In Vitro Fertilization, Department of Obstetrics and Gynecology, Carmel Medical Center, Haifa, Israel.
²Faculty of Medicine, Technion, Haifa, Israel.

DOI: 10.4236/arsci.2014.24009                

Abstract

Purpose: Impaired hatching is associated with implantation failure following in vitro fertilization (IVF). Thickening or hardening of the zona pellucida (ZP) has been proposed as a factor in this impairment. We examined whether selective assisted hatching (AH) is beneficial with embryos having a thick ZP. Methods: This prospective, randomized controlled study was performed in the IVF unit of an obstetrics and gynecology department in a university-affiliated hospital. Only patients undergoing IVF and having a ZP thickness of ≥17 μm measured in all their embryos were included. In the intervention group, AH was applied to all embryos, before their transfer. In the control group, embryos were transferred without AH. Implantation, clinical pregnancy and live birth rates were the study endpoints. Results: Both study arms were comparable in most baseline parameters. The two groups did not differ in implantation rates (14.1% control vs. 8.92% intervention, odds ratio (OR) = 0.5974, 95% confidence interval (CI) 0.325 - 1.1), clinical pregnancy rates (36.7% vs. 25.8%, OR = 0.6025, 95% CI 0.274 - 1.325), or live birth rates (25% vs. 18.9%, OR = 0.7021, 95% CI 0.291 - 1.691). Conclusions: Selecting embryos for AH by their ZP thickness as a sole parameter was not found to be beneficial and to improve IVF outcome.

Keywords

In Vitro Fertilization, Assisted Hatching, Zona Pellucida Thickness, Partial Zona Dissection, Implantation Rate

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Kilani, S.S., Cooke, S., Kan, A.K. and Chapman, M.G. (2006) Do Age and Extended Culture affect the Architecture of the Zona Pellucida of Human Oocytes and Embryos? Zygote, 14, 39-44. http://dx.doi.org/10.1017/S0967199406003625
[2]	Shiloh, H., Lahav-Baratz, S., Koifman, M., Ishai, D., Bidder, D., Weiner-Meganzi, Z. and Dirnfeld, M. (2004) The Impact of Cigarette Smoking on Zona Pellucida Thickness of Oocytes and Embryos Prior to Transfer into the Uterine Cavity. Human Reproduction, 19, 157-159. http://dx.doi.org/10.1093/humrep/deh029
[3]	Bertrand, E., Van Den Bergh, M. and Englart, Y. (1996) Clinical Parameters Influencing Human Zona Pellucida Thickness. Fertility and Sterility, 66, 408-411.
[4]	Cohen, J. and Laufer, N. (1991) Assisted Hatching of Human Embryos. Journal of in Vitro Fertilization and Embryo Transfer, 8, 179-190. http://dx.doi.org/10.1007/BF01130802
[5]	Cohen, J., Elsner, C., Kort, H., Malter, H., Massey, J. and Mayer, M.P. (1990) Impairment of the Hatching Process Following IVF in the Human and Improvement of Implantation by Assisting Hatching Using Micromanipulation. Human Reproduction, 5, 7-13.
[6]	The Practice Committee of the Society for Assisted Reproductive Technology and the Practice Committee for Reproductive Medicine (2008) The Role of Assisted Hatching in in Vitro Fertilization: A Review of Literature. A Committee Opinion. Fertility and Sterility, 90, 196-198.
[7]	Hammadeh, M.E., Fischer-Hammadeh, C. and Refaat Ali, K. (2011) Assisted Hatching in Assisted Reproduction: A State of the Art. Journal of Assisted Reproduction and Genetics, 28, 119-128. http://dx.doi.org/10.1007/s10815-010-9495-3
[8]	Cohen, J., Alikani, M., Trowbridge, J. and Rosenwaks, Z. (1992) Implantation Enhancement by Selective Assisted Hatching Using Zona Drilling of Human Embryos with Poor Prognosis. Human Reproduction, 7, 685-691.
[9]	Balaban, B., Urman, B., Alatas, C., Mercan, R., Mumcu, A. and Isiklar, A. (2002) A Comparison of Four Different Techniques of Assisted Hatching. Human Reproduction, 17, 1239-1243. http://dx.doi.org/10.1093/humrep/17.5.1239
[10]	Tucker, M.J., Luecke, N.M., Wiker, S.R. and Wright, G. (1993) Chemical Removal of the Outside of the Zona Pellucida of Day 3 Human Embryos Has No Impact on Implantation Rate. Journal of Assisted Reproduction and Genetics, 10, 187-191. http://dx.doi.org/10.1007/BF01239219
[11]	Edirisinghe, W.R., Ahnonkitpanit, V., Promviengchai, S., Suwajanakorn, S., Pruksananonda, K. and Chinpilas, V. (1999) A Study Failing to Determine Significant Benefits from Assisted Hatching: Patients Selected for Advanced Age, Zonal Thickness of Embryos, and Previous Failed Attempts. Journal of Assisted Reproduction and Genetics, 16, 294- 301. http://dx.doi.org/10.1023/A:1020497714495
[12]	Martins, W.P., Rocha, I.A., Ferriani, R.A. and Nastri, C.O. (2011) Assisted Hatching of Human Embryos: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Human Reproduction Update, 17, 438-453. http://dx.doi.org/10.1093/humupd/dmr012
[13]	Dirnfeld, M., Goldman, S. and Gonen, Y. (1993) Functional Differentiation in Progesterone Secretion by Granulosa versus Cumulus Cells in the Human Pre-Ovulatory Follicle and the Effect of Different Induction of Ovulation Protocols. Fertility and Sterility, 60, 1025-1030.
[14]	Van Steirteghem, A.C., Liu, J., Joris, H., Nagy, Z., Janssenswillen, C., Tournaye, H., et al. (1993) Higher Success Rate by Intracytoplasmic Sperm Injection than by Sub-Zonal Insemination. Report of a Second Series of 300 Consecutive Treatment Cycles. Human Reproduction, 8, 1055-1060.
[15]	Feng, H.L., Hershlag, A., Scholl, G.M. and Cohen, M.A. (2009) A Retroprospective Study Comparing Three Different Assisted Hatching Techniques. Fertility and Sterility, 91, 1323-1325. http://dx.doi.org/10.1016/j.fertnstert.2008.02.133
[16]	Lahav-Baratz, S., Koifman, M., Shiloh, H., Ishai, D., Wiener-Megnazi, Z. and Dirnfeld, M. (2003) Analyzing Factors Affecting the Success Rate of Frozen-Thawed Embryos. Journal of Assisted Reproduction and Genetics, 11, 444-448. http://dx.doi.org/10.1023/B:JARG.0000006705.46147.a2
[17]	Chang, H.J. and Suh, C.S. (2010) Ectopic Pregnancy after Assisted Reproductive Technology: What Are the Risk Factors? Current Opinion in Obstetrics & Gynecology, 22, 202-207. http://dx.doi.org/10.1097/GCO.0b013e32833848fd
[18]	Stein, A., Rufas, O., Avrech, O., Pinkas, H., Ovadia, J. and Fisch, B. (1995) Assisted Hatching by Partial Zona Dissection of Human Preembryos in Patients with Recurrent Implantation Failure after in Vitro Fertilization. Fertility and Sterility, 63, 838-841.
[19]	Frydman. N., Madoux, S., Hesters, L., Duvernoy, C., Feyereisen, E., Le Du, A., Tachdjian, G., Frydman, R. and 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. Human Reproduction, 21, 2131-2135. http://dx.doi.org/10.1093/humrep/del124
[20]	Vajta, G., Holm, P., Greve, T. and Callesen, H. (1997) Survival and Development of Bovine Blastocysts Produced in Vitro after Assisted Hatching, Vitrification and In-Straw Direct Rehydration. Journal of Reproduction and Fertility, 111, 65-70. http://dx.doi.org/10.1530/jrf.0.1110065
[21]	Paulson, R., Barbieri, R.L. and Barss, V.A. (2011) In Vitro Fertilization. http://uptodate.com/contents/in-vitro-fertilization