To the best of our knowledge, a similar case has not been found in the relevant literature. There are illustrations of tetraploid embryos in assisted conception cycles, however, utilizing IVF or partial zona dissection (PZD) (5). Among those technologies, it is also probable that multispermic fertilization could occur. The most likely explanation for abnormally fertilized oocytes with 4PN after IVF and PZD is the penetration of three individual spermatozoa. In contrast to conventional IVF and PZD, the oocytes have to be freed from cumulus cells for ICSI and only mature female gametes in metaphase II (MII) are used further also oocyte maturity is judged by the presence of the first polar body (PB). Similarly, the suggested mechanism of molar pregnancies particularly incomplete moles is dispermic fertilization during natural conceptions. Furthermore, ICSI was recommended for individuals with repeated molar pregnancies (6). Despite to the protective effect of ICSI, triploidy in an incomplete molar pregnancy was reported in an ICSI cycle by ours (7)
Tetraploidy is a very rare finding in live-born infants. Tetraploid pregnancies in spontaneous conceptions have been reported. Phenotypes consist of prenatal and/or postnatal growth retardation, developmental delay, mental retardation, dysmorphic features, and skeletal and internal abnormalities (8). Those fetuses usually die during the first days or months of life. Moreover, tetraploidy can be observed in 1%–2% of early spontaneous abortions (9). Interestingly a case of a spontaneously conceived 26-month-old girl who had been diagnosed as tetraploidy with the karyotype of 92, XXXX resulted in dispermic fertilization of a diploid oocyte resulted by meiotic non-dysjunction was reported (10)
Polyovularity and dispermic fertilization is the supposed mechanism of the development of tetraploid embryos in natural conception cycles. However, the data regarding the incidence of polyovularity and the significance of gametes originating from polyovular follicles are limited in the literature and the low number of cases complicates the ability to decide about the fertilization and implantation potential of these oocytes. The accepted definition of polyovular follicle is the inclusion of two oocytes within a common zona pellucida or their fusion in the zonal region and the most reliable reason for the formation of binovular follicles is a failure of separation of two individual germ cells in early folliculogenesis (11). A recent case report showed that a genetically normal embryo can result from a con- joined oocyte, and subsequent pregnancy and live birth can be achieved (12). It has been suggested also that tetraploidy may be produced by “concomitant fertilization of both meiotic products, that is the ovum and its second polar body, with a consequent fusion of the two resulting cells” (13). In a case report fertilization and development of embryos with conjoined zona pellucida recovered from polyovular follicles were reported (14).
The fusion of two fertilized eggs is the second alternative mentioned by Guc-Scekic et al. (10). Tetraploidy can arise from the fused two oocytes in a common zona pelucida.
Moreover, tetraploidy caused by endoreduplication has been observed in a one-cell zygote and a two-cell embryo (15), suggesting that this process is a potential candidate for explaining some cases of polyploidy. It is of note that certain cancer cells have aneuploidies and tetraploidy can also be seen among them. In a study, centrosome duplication can result from extra chromosome gain and eventually lead to tetraploidy (16)
On the other hand, it is out of consideration that binovular oocytes can be ignored during micromanipulation of gametes under a high magnified microscope. Therefore, it can be concluded that tetraploidy would occur following assisted fertilization. It should be encountered that during the ICSI procedure, it is imperative to inject more than one spermatozoon erroneously.
Tripronuclear zygotes can be seen during assisted fertilization procedures even in ICSI cycles. Those embryos were discarded for embryo transfer for the possibility of abnormal implantation. Hence there are reports of healthy offspring following tripronuclear zygotes (17). Furthermore, in assisted conception cycles triploidy is encountered in severe male factor infertility. The sperm centrosome could be responsible for the complex polyploid chromosome patterns observed in cleavage-stage embryos from an OAT patient (18).
However, to our best knowledge, tetraploid pregnancy following the ICSI procedure has not been reported in the relevant literature. On the other hand, tetraploid embryos were demonstrated following assisted conception diagnosed by preimplantation genetic screening (PGS).
Preimplantation genetic analysis of embryos developed from unevenly cleaved zygotes revealed multinuclear tetraploid blastomeres, which points to a possible mitotic failure during embryogenesis (19). Of note, the constitution XYYY that has never been reported in spontaneous abortions can be found at the zygote level.
In our case double Y chromosome could be derived by 2 approaches. One is erroneously injecting 2 spermatozoa in the same micropipette and both spermatozoa have a Y chromosome. Even in this case, there should be 2 nuclei and 2 polar bodies inside the zona pellucida which depicts a binuclear oocyte. This scenario is very far to be incident. The possible second mechanism of mitotic failure following ICSI. There could be a defect during anaphase to telophase in the mitotic cycle of blastomeres. It is speculative that in which phase of embryonic development, the cleavage stage or blastocyst stage, this defect occurred. It should be realized that if tetraploidy occurred following the blastocyst stage, a mosaic fetus could be possible. In our case, this mitotic error could be seen just after the zygote stage. During the cleavage stage from day 1 to 3, the nucleus of blastomeres can be inspected easily and the records of the patient do not reveal any abnormality. Therefore, either failure in karyokinesis and cytokinesis at the 4- cell stage or at the 2-cell stage followed by faithful 4:4 chromosome segregation may be the most likely explanation
The incubation period of embryos was spent on a benchtop incubator. We could speculate that if our case, for the incubation period, if a time-lapse embryo monitoring system was used, karyokinesis and cytokinesis during the cleavage period could be detected, and therefore a possible abnormality should be detected.
In conclusion, the presented case of tetraploidy is unique because of 3 factors. 1) following ICSI, 2) frozen-thawed embryo transfer, and 3) implantation resulting from a clinical pregnancy