The role of assisted hatching in in-vitro fertilization: a review of the literature. A Committee opinion
The Practice Committee of the Society for Assisted Reproductive Technologya and the Practice Committee of the American Society for
Reproductive Medicine b
a Society for Assisted Reproductive Technology and b American Society for Reproductive Medicine, Birmingham, Alabama
Hatching of the blastocyst is a critical step in the sequence of physiologic events culminating in implantation. Failure to hatch [due to intrinsic
abnormalities in either the blastocyst or zona pellucida (ZP)] may be one of many factors limiting human reproductive efficiency. Assisted
hatching involves the artificial thinning or breaching of the ZP and has been proposed as one technique to improve implantation and
pregnancy rates following in vitro fertilization (IVF). An increased implantation rate following mechanical opening of the ZP (partial zona
dissection-PZD) was first reported in 1990 (1). A randomized, prospective trial of selected assisted hatching 72 hours post-retrieval (zona
drilling with acidified Tyrode’s solution) suggested an improvement in implantation rates when the procedure was selectively applied to
embryos with a “poor prognosis” (based on zona thickness, blastomere number, fragmentation rates, maternal age, etc.) (2). Since these early
reports, many assisted reproductive technology (ART) programs have incorporated the use of assisted hatching in efforts to improve clinical
outcomes. The assisted hatching procedure is generally performed on day 3 after fertilization using various methods. These include the
creation of an opening in the zona either by drilling with acidified Tyrode’s solution (3, 4), PZD with a glass microneedle (5), laser
photoablation (6), or use of a piezo-micromanipulator (7). The ZP can be artificially thinned without breaching its integrity with proteolytic
enzymes, acidified Tyrode’s solution, or laser (8, 9). The assisted hatching procedure may be associated with specific complications
independent of the IVF procedure itself, including lethal damage to the embryo and damage to individual blastomeres with reduction of embryo
viability. In addition, artificial manipulation of the ZP has been associated with an increased risk of monozygotic twinning (10, 11). Patients
whose embryos are hatched are often treated with antibiotics and steroids before and after embryo transfer, exposing them to the potential
risks and side effects of such treatments. Success rates following the use of assisted hatching in different ART programs have varied
considerably. However, differences in patient populations, operator experience, hatching technique, and study design make it difficult to
compare directly reports from different centers. A comprehensive review and meta-analysis (12, 13) identified 23 randomized controlled trials
involving 2,572 women undergoing assisted hatching during ART. Seven studies were identified in abstract form only and had not appeared in
the peer-reviewed literature at the time of the review. Clinical pregnancy rates were evaluated in 19 trials (722 clinical pregnancies, 2,175
women) and demonstrated an improvement following assisted hatching (OR 1.63; 95% CI 1.27–2.09), but with significant heterogeneity.
Subgroups of patients who demonstrated the greatest improvement in clinical pregnancy rates were those with prior failed ART cycles (OR
2.33; 95% CI 1.63–3.34) and older women. Only six of the studies included in the analysis (involving 523 women) reported live birth rates with
and without assisted hatching (Table 1). Overall, live birth rates in the two groups were not different, although the various study populations
were heterogeneous (OR 1.26; 95% CI 0.82–1.78). Assuming a delivery rate of 30% in the control group overall, a total of 720 patients would
be required to detect a 10% difference in delivery rates between the two groups (P_.05). The numbers of live births reported in studies thus
far therefore do not allow a confident conclusion regarding the clinical efficacy of assisted hatching procedures. Three studies (8, 9, 14) have
evaluated the effects of different methods of assisted hatching, including acidified Tyrode’s solution, thinning with proteolytic enzymes,
mechanical dissection, and laser energy. Results have varied and likely reflect, at least in part, variations in the level of experience and
hatching methods.
RECOMMENDATIONS
The available published evidence does not support the routine or universal application of assisted hatching in all IVF cycles at this time.
Assisted hatching may be clinically useful in patients with a poor prognosis, including those with 2 failed IVF cycles and poor embryo quality
and older women (38 years of age) (15). Higher clinical pregnancy and implantation rates have been observed after assisted hatching.
However, delivery rates have not significantly improved, possibly because the small sample sizes in studies reporting delivery rates have
lacked sufficient power to detect a difference. Individual ART programs should evaluate their own unique patient populations to determine
which subgroup(s) of patients, if any, may benefit from assisted hatching.
Committee Opinion
Reviewed June 2006.
Received October 21, 2005; revised and accepted December 2, 2005.
Reprints will not be available.
S124 Fertility and Sterility_ Vol. 86, Suppl 4, November 2006 0015-0282/06/$32.00
Copyright ©2006 American Society for Reproductive Medicine, Published by Elsevier Inc. doi:10.1016/j.fertnstert.2006.09.001
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