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 Medicineb
a
Society for Assisted Reproductive Technology, Birmingham, Alabama and b American Society for Reproductive Medicine,
Birmingham, Alabama

This Committee Opinion reviews the published literature regarding appropriate usage of assisted hatching as a part
of in vitro fertilization. (Fertil Steril 2008;90:S196–8. 2008 by American Society for Reproductive Medicine.)

Hatching of the blastocyst is a critical step in the sequence of Success rates following the use of assisted hatching in dif-
physiologic events culminating in implantation. Failure to ferent ART programs have varied considerably. However,
hatch [due to intrinsic abnormalities in either the blastocyst differences in patient populations, operator experience,
or zona pellucida (ZP)] may be one of many factors limiting hatching technique, and study design make it difficult to com-
human reproductive efficiency. pare directly reports from different centers. A comprehensive
review and meta-analysis (12, 13) identified 23 randomized
Assisted hatching involves the artificial thinning or breach-
controlled trials involving 2,572 women undergoing assisted
ing of the ZP and has been proposed as one technique to im-
hatching during ART. Seven studies were identified in ab-
prove implantation and pregnancy rates following in vitro
stract form only and had not appeared in the peer-reviewed
fertilization (IVF). An increased implantation rate following
literature at the time of the review. Clinical pregnancy rates
mechanical opening of the ZP (partial zona dissection-PZD)
were evaluated in 19 trials (722 clinical pregnancies, 2,175
was first reported in 1990 (1). A randomized, prospective trial
women) and demonstrated an improvement following assis-
of selected assisted hatching 72 hours post-retrieval (zona
ted hatching (OR 1.63; 95% CI 1.27–2.09), but with signifi-
drilling with acidified Tyrode’s solution) suggested an im-
cant heterogeneity. Subgroups of patients who demonstrated
provement in implantation rates when the procedure was
the greatest improvement in clinical pregnancy rates were
selectively applied to embryos with a ‘‘poor prognosis’’
those with prior failed ART cycles (OR 2.33; 95% CI 1.63–
(based on zona thickness, blastomere number, fragmentation
3.34) and older women. Only six of the studies included in
rates, maternal age, etc.) (2). Since these early reports, many
the analysis (involving 523 women) reported live birth rates
assisted reproductive technology (ART) programs have in-
with and without assisted hatching (Table 1).
corporated the use of assisted hatching in efforts to improve
clinical outcomes. Overall, live birth rates in the two groups were not differ-
ent, although the various study populations were heteroge-
The assisted hatching procedure is generally performed on
neous (OR 1.26; 95% CI 0.82–1.78). Assuming a delivery
day 3 after fertilization using various methods. These include
rate of 30% in the control group overall, a total of 720 patients
the creation of an opening in the zona either by drilling with
would be required to detect a 10% difference in delivery rates
acidified Tyrode’s solution (3, 4), PZD with a glass micronee-
between the two groups (P<.05). The numbers of live births
dle (5), laser photoablation (6), or use of a piezomicromanipu-
reported in studies thus far therefore do not allow a confident
lator (7). The ZP can be artificially thinned without breaching
conclusion regarding the clinical efficacy of assisted hatching
its integrity with proteolytic enzymes, acidified Tyrode’s
procedures.
solution, or laser (8, 9).
Three studies (8, 9, 14) have evaluated the effects of differ-
The assisted hatching procedure may be associated with
ent methods of assisted hatching, including acidified
specific complications independent of the IVF procedure itself,
Tyrode’s solution, thinning with proteolytic enzymes, me-
including lethal damage to the embryo and damage to
chanical dissection, and laser energy. Results have varied
individual blastomeres with reduction of embryo viability. In
and likely reflect, at least in part, variations in the level of
addition, artificial manipulation of the ZP has been associated
experience and hatching methods.
with an increased risk of monozygotic twinning (10, 11). Pa-
tients whose embryos are hatched are often treated with antibi-
otics and steroids before and after embryo transfer, exposing RECOMMENDATIONS
them to the potential risks and side effects of such treatments.
The available published evidence does not support the rou-
tine or universal application of assisted hatching in all IVF
Committee Opinion
Reviewed June 2008.
cycles at this time. Assisted hatching may be clinically use-
Received October 21, 2005; revised and accepted December 2, 2005. ful in patients with a poor prognosis, including those with
Reprints will not be available. R2 failed IVF cycles and poor embryo quality and older

S196 Fertility and Sterility Vol. 90, Suppl 3, November 2008 0015-0282/08/$34.00
Copyright ª2008 American Society for Reproductive Medicine, Published by Elsevier Inc. doi:10.1016/j.fertnstert.2008.08.043
Fertility and Sterility

TABLE 1
Studies reporting ongoing pregnancies/live births.
Clinical
Implantation pregnancy
No. of patients No. of ET Mean age (y) rate (%) rate (%) Ongoing delivered (%)
Studies
included Ctrl AH Ctrl AH Ctrl AH Ctrl AH Ctrl AH Ctrl AH
Cohen et al. 68 69 229 239 36.7 36.5 21a 28a 47 54 25/68 (35) 34/69 (49) Delivered/ET
1992 (2)
Hellebaut et al. 60 60 162 168 30.8 30.9 17.1 17.9 38.1 42.1 21/60 (35) 23/60 (38.3) Delivered/ET
1996 (5)
Hurst et al. 7 13 4.0  0b 4.0  0b 30  0.9 30  0.8 10.7a 9.6c 42 23 3/7 (42) 2/13 (15) Delivered/Pt
1998 (3)
Lazendorf et al. 52 42 212 180 38.5 38.3 11.3c 11.1c 41.7 39.0 17/48 (35.4) 12/41 (29.3) Ongoing
1998 (4) pregnancy/Pt
Mansour et al. 25 27 75 86 33.2 32.1 N/A N/A 40 44 9/25 (36) 10/27 (37) Delivered/cycle
2000 (15)
Mansour et al. 41 30 155 117 36.3 37.3 N/A N/A 7.3y 23y 3/4 (7.3) 6/30 (20) Delivered/cycle
2000 (15)
Note: Ctrl ¼ control; AH ¼ assisted hatching; Pt ¼ patient.
a
Fetal heartbeat per embryo replaced.
b
Mean  SE.
c
Number of gestational sacs per number of embryos transferred.
y
Significantly different, P< .05, Fisher’s exact test.
ASRM Practice Committee. Assisted hatching. Fertil Steril 2008.
S197
women (R38 years of age) (15). Higher clinical pregnancy
and implantation rates have been observed after assisted
hatching. However, delivery rates have not significantly im-
proved, possibly because the small sample sizes in studies
reporting delivery rates have lacked sufficient power to de-
tect 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.
Acknowledgement: This report was developed under the direction of the
Practice Committee of the American Society for Reproductive Medicine
and the Society for Assisted Reproductive Technology as a service to their
members and other practicing clinicians. While this document reflects appro-
priate management of a problem encountered in the practice of reproductive
medicine, it is not intended to be the only approved standard of practice or to
dictate an exclusive course of treatment. Other plans of management may be
appropriate, taking into account the needs of the individual patient, available
resources, and institutional or clinical practice limitations. Non–FDA-
approved indications for various drugs may be discussed. The Board of
Directors of the American Society for Reproductive Medicine approved
this report in March 2005. The Practice Committee of the American Society
for Reproductive Medicine approved this report in August 2005.
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S198 ASRM Practice Committee Assisted hatching
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Vol. 90, Suppl 3, November 2008