Laser assisted zona hatching: What is the evidence to justify its use?

1. IntroductionHatching of the human embryo is necessary for endometrialimplantation. Therefore, this step necessarily has to occur inall successful pregnancies (1). Problems with the hatching pro-cess are thought to be a core reason for pregnancy failure inassisted reproductive technologies (ART) cycles (2). ART, par-ticularly in vitro fertilization (IVF), has been thought to beassociated with a thickened or dense zona that decreases thelikelihood of embryo hatching (3). Speciﬁcally, advancedmaternal age, repeated implantation failure, poor embryoquality, IVF culture environment, and cryopreservation haveall been cited as factors that may be associated with a de-creased rate of unassisted hatching (3,4).Assisted hatching (AH) was devised in an attempt to artiﬁ-cially thin the zona pellucida (ZP) of cleavage embryos or blas-tocysts before embryo transfer, thus aiding the hatchingprocess (1,3). In 1990, Cohen and colleagues described theuse of micromanipulation to promote hatching followingIVF by introducing an artiﬁcial incision in the ZP of embryosjust prior to replacement in the uterus (5). This process wasnamed ‘assisted hatching’ (5). This 1990 report was the ﬁrstto show that AH confers a favorable impact on pregnancy(5). Since that time, multiple methods for AH have been ex-plored. Protocols have been described that create a full thick-ness hole through the entire zona, accomplished by mechanicalmanipulation (often with either a glass microneedle or piezo-micromanipulator), chemical application (often with acidiﬁedTyrode’s solution), or laser (1,2). Other methods describe thin-ning the zona, accomplished through proteolytic enzymes,acidiﬁed Tyrode’s solution, or laser (2,4).2. ControversiesThe role of AH has been the source of much debate. Irrespec-tive of the technical approach, AH remains a procedure of lar-gely unproven worth, regardless of how theoretically appealingit might seem to apply to poorer prognosis IVF cases (6).While some centers have adopted the practice of routinely per-forming assisted hatching, others do not believe that this tech-nology confers a signiﬁcant clinical beneﬁt (7). Two meta-analyses of studies evaluating potential beneﬁts of AH re-ported signiﬁcant heterogeneity among study results, suggest-ing that effects of AH may differ depending on patientcharacteristics (8). Both concluded that there is strong evidencethat AH increases pregnancy rates among patients with a his-tory of previous IVF failures (8). An in vitro observation ofover 300 research embryos left in culture till day-9 of develop-ment showed a distinct reduction in both blastocyst formationand hatching relative to increased age of the patients (6). Thisobservation suggested that a compromised ZP may play a rolein restricting blastocyst hatching both in older women and incouples whose embryos develop more slowly (6). However, itremains uncertain whether AH is beneﬁcial to other patientpopulations. The belief by many that AH has a role to playin improving pregnancy rates in certain patient populationshas led to a number of trials evaluating the efﬁcacy of AH ina variety of different clinical situations (2).A recent Cochrane review evaluated 28 AH trials encom-passing 1229 clinical pregnancies and 3646 women (2). The re-sults from this review concluded that assisted hatching maynot only improve clinical pregnancy rates but may also carrya risk of an increased incidence of multiple pregnancies. Thisreview did not ﬁnd a statistical advantage to one method ofAH versus another. There are numerous recent studies thatdo indicate an advantage to assisted hatching in the properlyselected clinical indications, such as patients whose embryoshave a thickened zona, patients with elevated FSH, older pa-tients, and patients using cryopreserved embryos (6,8). Onthe other hand, the beneﬁt of AH in good prognosis patientsis less clear (4,8). Furthermore, one could argue that the evi-dence used to justify the application of AH to poorer qualityembryos appears circumstantial (6).