Developmental capacity and pregnancy rate of tetrahedral versus non-tetrahedral 4-cell stage human embryos

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According to the literature, the fertilized oocyte is converted into a multicellular embryo by cleavages that occur according to specific planes (Gulyas, 1975). A meridional first cleavage creates two cells with animal and vegetal cytoplasm. During the second cleavage, one cell divides meridionally, producing two identical cells, whereas the other daughter cell divides equatorially, creating one cell with animal cytoplasm and another with vegetal cytoplasm. This way of cleaving results in a tetrahedral arrangement of the four blastomeres (Payne et al., 2004; Edwards et al., 1970). However, also non-tetrahedral shaped 4-cell embryos have been described, assuming two meridionally or equatorially divisions during the second cleavage. Because oocytes might exhibit a polarized ooplasm, the distribution of maternally inherited factors may be different in tetrahedral and non-tetrahedral embryos (Antczak and Van Blerkom, 1997; Edwards and Beard, 1997). This study aimed to examine whether differences in the developmental capacities and pregnancy rates exist between tetrahedral and non-tetrahedral embryos.

Material and Methods:

The architecture of 1850 4-cell embryos of 540 patients was evaluated. The developmental capacity up to day 5 was studied in 698 4-cell embryos of 148 patients. The embryos were classified as top blastocysts, good blastocysts or bad quality embryos. Pregnancy rate was examined in 113 patients (<36 years, without severe male factor infertility) who received single embryo transfer (SET) on day 3 (n = 60) or on day 5 (n = 53) of an embryo that had 4-cells on day 2. The criterion for pregnancy was a positive hCG. Data were statistically analysed using the Fisher's Exact Test.


Of the 1850 4-cell embryos evaluated on day 2, 1215 (66%) had a tetrahedral shape and 635 (34%) did not. A similar distribution was seen in the 698 embryos that were followed until day 5: 471 (67%) tetrahedral and 227 (33%) non-tetrahedral shaped embryos. The number of 4-cell embryos developing into top, good and bad quality blastocysts was 114 (24%), 139 (30%) and 218 (46%) in the tetrahedral group, and 35 (15%), 50 (22%) and 142 (63%) in the non-tetrahedral group. The developmental capacity was significantly different between both groups (p <0.001). Out of 60 patients with a SET on day 3, 41 patients (68%) had a transfer of a previously tetrahedral embryo and 19 (32%) of a non-tetrahedral embryo. The pregnancy rates were 41% (n = 17) and 37% (n = 7), respectively (P = 0.784). Out of 53 patients with a SET on day 5, 44 patients (83%) had a transfer of a previously tetrahedral embryo and 9 (17%) of a non-tetrahedral embryo. The pregnancy rates were 52% (n = 23) and 56% (n = 5), respectively (P = 1.00).


Approximately one third of the 4-cell stage embryos did not exhibit a tetrahedral shape, suggesting that they did not follow the presumed cleaving planes and that they might have an altered distribution of maternally inherited factors within the embryo. Non-tetrahedral embryos showed a lower in-vitro developmental potential up to day 5 than tetrahedral embryos. This might explain why on day 5 a higher proportion (83%) of the embryos chosen for transfer originated from a tetrahedral embryo. No statistical difference in pregnancy rate was observed with the limited number of embryos transferred, especially in the non-tetrahedral group.
Original languageEnglish
Pages (from-to)59-60
Number of pages2
JournalHum Reprod
Publication statusPublished - Jul 2010
EventFinds and Results from the Swedish Cyprus Expedition: A Gender Perspective at the Medelhavsmuseet - Stockholm, Sweden
Duration: 21 Sep 200925 Sep 2009


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