Assisted hatching in assisted reproduction: a state of the art

Abstract

The World Health Organization estimates that one in six couples experience some delay in conception and an increasing number require treatment by the assisted conception (AC) procedures of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).The implantation rate of embryos resulting from in vitro fertilization cycles is generally less than 20%. The exposure of oocytes and embryos to the artificial conditions of in vitro culture may have negative effects on the embryo's ability to undergo normal hatching, resulting in low rates of implantation following IVF and embryo transfer. Human embryos resulting from superovulation develop more slowly in vitro compared to embryos in vivo, manifest a relatively high degree of cytogenetic abnormalities and undergo cellular fragmentation. Artificially disrupting the zona pellucida is known as assisted hatching (AH) and there is some evidence that embryos that have undergone zona manipulation for assisted hatching tend to implant one day earlier than unhatched embryos. A variety of techniques have since been employed to assist embryo hatching, including partial mechanical zona dissection, zona drilling and zona thinning, making use of acid tyrodes, proteinases, piezon vibrator manipulators and lasers. This review will consider the impact of IVF conditions on zona pellucida physiology, zona hardening, different techniques of assisted hatching, who may benefit from assisted hatching and potential hazards.

Laser Pulse Application in IVF

“…It is unclear what the diameter of the complete hatch site was in this study. Another concerning trend in this study was 22% of pregnancies were multiple pregnancies, more than typically seen (Mantoudis et al, 2001), which is not unique to this trial (Hammadeh et al, 2011). In contrast to the findings of Mantoudis et al, Wong et al found improved hatching rates with complete hatching compared to partial hatching, 38% vs. 25%, respectively (Wong et al, 2003).…”

“…Ultraviolet wavelengths are close to the absorption wavelength of DNA (260 nm). As a result, these lasers are minimally used in reproductive technologies due to concern for mutagenic effects (Green et al, 1987;Hammadeh et al, 2011;Kochevar et al, 1989). The next generation of lasers were designed to circumvent dangers of UV wavelength and cytotoxicity by emitting wavelengths in the infrared region (>800 nm) (Ebner et al, 2005).…”

“…It also helps when a non-contact mode is employed to avoid any unnecessary manipulation of the fragile embryo. Contact mode lasers requiring glass pipettes (UV wavelength) or quartz fibers (infrared wavelengths) add a layer of complexity with respect to additional manipulation of the embryo (Hammadeh et al, 2011). Similarly, no additional changes or alternations of media should be made to avoid undue stress on the embryo's environment, which should be kept at a physiologic pH of 7.2 and at 37 degrees Celsius at all times to optimize growth (Douglas-Hamilton & Conia, 2001 as cited in Al-Katanani et al, 2002).…”

“…This is compared with hatching independently of cell mass in vivo, likely related to lytic enzymes found in vivo (Montag et al, 2000a). It has become relatively common practice to facilitate the hatching of blastocysts by creating an artificial opening in the zona pellucida either by mechanical, chemical or optical methods, although the exact population benefiting most from this procedure is yet to be determined (Hammadeh et al, 2011). Assisted hatching has been proposed to be potentially more beneficial in patients over 40, with thicker zonae or poor prognosis patients (Balaban et al, 2002;De Vos & Van Steirteghem, 2000;Hammadeh et al, 2011;Sagoskin et al, 2007;Lanzendorf et al, 1998).…”

Assessment and treatment of repeated implantation failure (RIF)

“…This is supported by the early reports that observed a significant improvement in human embryo implantation rates when assisted hatching (artificial thinning or breaching of the ZP) was attempted [25,26,70,100]. Many assisted reproductive technology (ART) programs have since incorporated the use of assisted hatching in efforts to improve clinical outcomes [47]. However, differences in patient populations, operator experience, hatching technique and study design make it difficult to compare findings from different centers.…”