Role of diagnostic intracytoplasmic sperm injection (ICSI) in the management of genetically determined zona pellucida-free oocytes during in vitro fertilization: a case report

Abstract

Purpose: To report the utilization of diagnostic intracytoplasmic sperm injection (D-ICSI), an ICSI cycle performed in the natural cycle, to obtain information about embryo development potential after sperm injection into zona pellucida (ZP)-free oocytes. Materials and Methods: We report the case of a couple with primary unexplained infertility with a history of previous failed, in vitro fertilization intracytoplasmic sperm injection (IVF-ICSI) cycles characterized by the presence of ZP-free oocytes. Whole exome sequencing (WES) was carried out to analyse the possible genetic basis of oocyte abnormality. Results: Diagnostic ICSI provided information about the embryo development potential from ZP-free oocytes and allowed better planning of the subsequent ICSI cycle. WES revealed that the absence of ZP was likely to be due to a new (ZP1) mutation. The subsequent ICSI cycle resulted in the delivery of a healthy baby. Discussion: To the best of our knowledge, our report is the first to describe the use of D-ICSI to determine the feasibility of embryo development and implantation in a patient with ZP1 mutation, resulting in the subsequent delivery of a healthy baby. We used ‘diagnostic’ ICSI in the normal menstrual cycle to explore the feasibility of embryo development after sperm injection into ZP-free oocytes. Our results may expand the spectrum of diagnostic procedures associated with unexplained infertility.

ZP1-Y262C mutation causes abnormal zona pellucida formation and female infertility in humans

“…Mutations in the ZP1 gene can lead to two abnormal oocyte phenotypes: zona pellucida deficiency and empty follicle syndrome (EFS). The novel mutation we present in this study has been identified in the trefoil domain of ZP1, similar to what were previously reported ( Metwalley et al, 2020 ; Xu et al, 2020 ). Interestingly, the trefoil domain is unique to the hZP1 protein and is not found in hZP2 and hZP3.…”

Can successful pregnancy be achieved and predicted from patients with identified ZP mutations? A literature review

“…The third patient carried homozygous missense mutation c.706 T > C; after the first failed ART, diagnostic intracytoplasmic sperm injection (D-ICSI) was used in the normal menstrual cycle to explore the feasibility of embryo development, then a new ART cycle was started to obtain 8 ZFO, 6 of them were fertilized successfully via ICSI, and finally delivered a healthy baby at 38 weeks of gestation by cesarean section. Additionally, we get the information from the author’s email that she is currently pregnant with twins through ICSI with the modified protocol [ 30 , 34 ].…”

“…If oocytes with ZP defects could be obtained from the affected patients, ICSI could be preferentially chosen instead of the traditional IVF, which may improve the probability of successful pregnancy via ART. Metwalley et al proposed a new method called D-ICSI, an ICSI cycle performed in the natural cycle, to obtain information about embryo development potential before therapeutic ICSI [ 34 ]. For patients with the most severe phenotypes of EFS caused by ZP gene mutations, the current optimal treatment choice would be egg donation.…”