Chromosome abnormalities in human embryos

Purpose The aim of this study was to (1) investigate the incidence of embryos derived from Bunfertilized oocytes^i.e., oocytes not displaying pronuclei (0PN) at the time of the fertilization check and (2) determine the clinical pregnancy rates when transferring 0PN-derived embryos. Methods In this retrospective study, 4424 IVF-ET cycles were reviewed. Results In total, 11.3 % (4966/43,949) 0PN-derived embryos were observed. It was found that female age, number of oocytes, and the top-quality embryo rate were significantly correlated with 0PN-derived embryo occurrence. The source of embryos transferred did not impact significantly on clinical pregnancy and livebirth rates. Of the 183 cycles included in this study where 275 0PN-derived embryos were transferred in total, only 0PN-derived embryos were available in 70 of those cycles. It was noteworthy that 13 healthy infants resulted from 0PN-derived embryos with an implantation rate of 17.0 %. Conclusion These results indicate that the traditional method of excluding embryos because of those oocytes originally lacking any sign of a pronucleus at the fertilization check should be reconsidered as transferring 0PN-derived embryos with subsequent expected developmental performance may be considered as an option for those patients where no other embryos are available.Keywords Abnormal fertilization . Pronucleus . 0PN . Pregnancy . ImplantationIn in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment cycles, a fertilization check is performed at 17-20 h post insemination to exclude oocytes that have fertilized abnormally or not fertilized at all. Normal fertilization of an oocyte is defined by observing two distinct pronuclei (2PN) and two polar bodies after insemination. Oocytes showing no pronucleus (0PN), one pronucleus (1PN), or three pronuclei (3PN) (or more) are deemed as having fertilized abnormally and may be discarded. However, this assumption may not always be accurate. On the one hand, cytogenetic analysis has revealed that a proportion of diploid embryos can develop from 1PN zygotes [1]. Healthy babies developing from such embryos have been reported [2]. On the other hand, 2PN zygotes are not necessarily euploid. Furthermore, there are reports of 0PN-derived embryos present in 12 to 20 % of day 3 embryos [3][4][5] which result in healthy babies [4,6,7]. Although to transfer such embryos in the absence of the signs of normal fertilization may have become an option in clinical policy, it is still a dilemma for the clinical team when it comes to carrying this out in practice.In this study, fertilization results from conventional IVF were reviewed to (1) investigate the incidence of embryos derived from 0PN oocytes and (2) determine the clinical pregnancy rates (CPR) when transferring such 0PN embryos.

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“…Pronuclei can be difficult to visualize due to granularity [12]. The presence of 2 PB is also a critical sign for confirmation of fertilization.…”

Section: Discussionmentioning

confidence: 99%

Live births resulting from 0PN-derived embryos in conventional IVF cycles

Liu

Wang

Zhang³

et al. 2016

J Assist Reprod Genet

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“…Zygotes containing two pronuclei, in which the diameters differed by at least four microns, were found to arrest at a significantly higher rate and to have a significantly higher incidence of mosaicism than zygotes with pronuclear diameters that differed by less than four microns 4. Furthermore, two studies reported that zygotes with different pronuclear sizes lead to a significantly higher incidence of both embryo cleavage arrest and mosaicism in day 3 embryos than do zygotes with pronuclei of a similar size 4, 5. Following these findings, two studies reported that the blastocyst development rates were significantly higher in the zygotes with two pronuclear areas of similar size than in the zygotes that contained pronuclei of unequal size 6, 7.…”

Section: Introductionmentioning

confidence: 89%

Potential of zygotes to produce live births can be identified by the size of the male and female pronuclei just before their membranes break down

Otsuki

Iwasaki

Tsuji

et al. 2017

Reprod Medicine & Biology

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AimTo determine whether there are differences in size between the male and female pronuclei immediately before the pronuclear membrane breakdown (PNMBD) and to evaluate whether pronuclear size differences influence normal birth rates.MethodsTime‐lapse photography was used to measure the size of each pronucleus, while the outcome of 71 frozen‐thawed single blastocyst transfers in patients receiving hormone therapy was analyzed retrospectively. The pronuclear measurements were made 4 hours before the PNMBD, corresponding to 16‐20 hours after insemination or intracytoplasmic sperm injection, and immediately before the PNMBD. The differences in the areas between the pronuclei in the zygotes that were associated with the live births were compared with those that were associated with the failed pregnancies.ResultsThe average difference in the area between the pronuclei 4 hours before and immediately before the PNMBD in the patients with a live birth was significantly smaller than in the patients with a failed birth. In addition, the average area difference in the patients with a successful birth was significantly smaller when the measurements were made immediately before the PNMBD, compared with the measurements 4 hours before the PNMBD. Such differences were not detected among the patients who did not achieve a birth.ConclusionThe birth of healthy babies resulted from zygotes that contained pronuclei of similar size when the measurements were made immediately before the PNMBD. Evaluating the size of each pronucleus immediately before the PNMBD provides an effective indicator of the embryo's potential at an early stage of development.

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“…Abnormal zygotes with either 1PN or three or more PNs are often visualized at that stage. A review of chromosome abnormalities in human embryos after c-IVF and ICSI identified numerous reports that used fluorescence in situ hybridization to study chromosomal status [14][15][16][17][18]. More recently, we developed an in vitro culture system for TLC to analyze human embryonic development from fertilization to the hatched blastocyst stage [7,8,[19][20][21].…”

Section: Discussionmentioning

confidence: 99%

Diagnosis of abnormal human fertilization status based on pronuclear origin and/or centrosome number

Kai¹,

Iwata²,

Iba³

et al. 2015

J Assist Reprod Genet

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Purpose Normally fertilized zygotes generally show two pronuclei (2PN) and the extrusion of the second polar body. Conventional in vitro fertilization (c-IVF) and intracytoplasmic sperm injection (ICSI) often result in abnormal monopronuclear (1PN), tripronuclear (3PN), or other polypronuclear zygotes. In this study, we performed combined analyses of the methylation status of pronuclei (PN) and the number of centrosomes, to reveal the abnormal fertilization status in human zygotes. Method We used differences in DNA methylation status (5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC)) to discriminate between male and female PN in human zygotes. These results were also used to analyze the centrosome number to indicate how many sperm entered into the oocyte. Result Immunofluorescent analysis shows that all of the normal 2PN zygotes had one 5mC/5hmC double-positive PN and one 5mC-positive PN, whereas a parthenogenetically activated oocyte had only 5mC staining of the PN. All of the zygotes derived from ICSI (1PN, 3PN) had two centrosomes as did all of the 2PN zygotes derived from c-IVF. Of the 1PN zygotes derived from c-IVF, more than 50 % had staining for both 5mC and 5hmC in a single PN, and one or two centrosomes, indicating fertilization by a single sperm. Meanwhile, most of 3PN zygotes derived from c-IVF had a 5mC-positive PN and two 5mC/5hmC double-positive PNs, and had four or five centrosomes, suggesting polyspermy. Conclusions We have established a reliable method to identify the PN origin based on the epigenetic status of the genome and have complemented these results by counting the centrosomes of zygotes.

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Chromosome abnormalities in human embryos

Cited by 235 publications

References 66 publications

Live births resulting from 0PN-derived embryos in conventional IVF cycles

Live births resulting from 0PN-derived embryos in conventional IVF cycles

Potential of zygotes to produce live births can be identified by the size of the male and female pronuclei just before their membranes break down

Diagnosis of abnormal human fertilization status based on pronuclear origin and/or centrosome number

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