Implantation enhancement by selective assisted hatching using zona drilling of human embryos with poor prognosis

Abstract

Assisted hatching by zona drilling using acidic Tyrode's solution was performed during three randomized trials in 330 in-vitro fertilization patients. The trials were designed in order to study the overall effect of the procedure and whether characteristic patient [i.e. maternal age and basal levels of follicle stimulating hormone (FSH)] and embryonic features (i.e. zona pellucida thickness) are important for the decision to perform assisted hatching routinely. Couples (n = 137; Trial 1) in whom the female partner had normal basal FSH levels were randomized in a control group (without micromanipulation) and a zona drilling group (all embryos micromanipulated). The incidence of implantation (67/239; 28%) of zona-drilled embryos compared favourably with that of control embryos (49/229; 21%), but the difference was not significant. Retrospective analysis revealed that those embryos whose zonae were thicker than 15 microns were rescued. In order to test the validity of this finding, selective assisted hatching was performed on embryos with a poor prognosis in 163 other patients (Trial 2). The couples were randomized into a control group and a group in which embryos were selectively zona-drilled, based on zona thickness and other embryonic features. The rate of embryonic implantation in the selectively zona-drilled group was 25% (70/278), significantly (P less than 0.05) higher than that of control embryos (51/285; 18%). Although it was demonstrated retrospectively and prospectively that assisted hatching by zona drilling is effective in embryos with thick zonae (greater than or equal to 15 microns), patients whose embryos have thin (less than 13 microns) zonae may be jeopardized by the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Assisted hatching in assisted reproduction: a state of the art

“…Moreover, no correlation exists between zona pellucida thickness and zona pellucida hardness [39]. As a result, chemical removal of the outside of the zona pellucida of the Day 3 embryo has no impact on implantation rate, whereas the creation of a hole in the zona pellucida may improve embryo implantation [15]. As opposed to zona thickness and zona hardness, the rationale for performing assisted hatching procedure may be to overcome a deficiency in the production of an intrinsic embryonic lysin that promotes hatching following blastocyst expansion [39].…”

“…Further, although most molecules are able to cross the zona pellucida, the rate of transport may be related to zona thickness. A two-way transport of metabolites and growth factors across the zona pellucida may be altered due to the presence of the artificial gap [15,34]. Such contact may permit earlier exposure of the embryos to vital growth factors.…”

“…Assisted hatching using acid Tyrode's has been described in detail by Cohen et al [15,46]. The embryo is secured on a holding pipette and a microneedle is applied to an area of the zona pellucida overlying either empty perivitelline space or extracellular fragments (i.e.…”

“…Such environmental conditions either control the hatching important to recognize that there may be other factors reducing fertility in older women such as reduced quality and quantity of oocytes 'ovarian reserve' [71], an increase in the incidence of karyotypically abnormal embryos [15] may be spontaneous zona hardening due to age-related endocrine changes and/or the absence of lysins from surrounding tissues, which may act on embryos in vivo [17,72]. Such environmental conditions either control the hatching Nevertheless, it is and to some extent, a decline in uterine receptivity [16,73].…”

“…This pioneering work was followed by numerous publications. Some of these publications reported a significant increase in the pregnancy and/or implantation rate in all patients [11]; other publications reported significant improvement in patients with a poor prognosis, namely women over 38 years of age, patients with thick zonae, and patients with repeated implantation failures [12][13][14]; while a third group of publications reported a non significant improvement in the pregnancy rate in patients with poor prognosis [11,[15][16][17][18]. On the contrary, some publications reported no improvement in pregnancy or implantation [19][20][21].…”