Early pronuclear breakdown is a good indicator of embryo quality and viability

doi:10.1016/j.fertnstert.2005.03.068

Fertility and Sterility

Volume 84, Issue 4, October 2005, Pages 881-887

https://doi.org/10.1016/j.fertnstert.2005.03.068 Get rights and content

Objective

To examine whether the timing of pronuclear breakdown can be a predictor of embryo quality and viability.

Design

Retrospective comparison of the development and quality of early and late developing zygotes.

Setting

Infertility and endocrinology unit in a university hospital.

Patient(s)

One thousand seven hundred eighty-two zygotes obtained in 383 consecutive IVF cycles.

Intervention(s)

Culture of all fertilized embryos.

Main Outcome Measure(s)

Number of fertilized zygotes showing early pronuclear breakdown at 22–25 hours postinsemination, embryo quality, pregnancy rates (PR), implantation rates.

Result(s)

Early pronuclear breakdown embryos had a significantly higher cell number (4.4 ± 1.2) compared with the late pronuclear breakdown embryos (3.6 ± 1.4). When comparing the frequency of the early pronuclear breakdown embryos according to the method of fertilization, we failed to find any significant difference between the IVF (37.1%) and the intracytoplasmic sperm injection (ICSI) (41.1%) groups. The transfer of early pronuclear breakdown embryos resulted in a significantly higher clinical pregnancy rate than those with late pronuclear breakdown (48.3% vs. 27.3%). The implantation rate was higher in the early pronuclear breakdown group than in the late pronuclear breakdown group (26.5% vs. 15.1%).

Conclusion(s)

Early pronuclear breakdown is a strong indicator of embryo viability, and may be used as an additional criterion in the selection of embryos for transfer.

Section snippets

Source of Embryos

This study was performed with the patients entering the IVF–embryo transfer program of the Division of Assisted Reproduction, First Department of Obstetrics and Gynaecology, Semmelweis University School of Medicine, Budapest, Hungary, between October 2001 and February 2004. The IVF treatments without normal (2 pronuclear) fertilization and those performed for preimplantation genetic diagnosis were excluded from this study. In total, 1,782 fertilized oocytes from 383 IVF/ICSI cycles with embryo

Results

During the study period, 1,782 normally fertilized oocytes from 383 IVF/ICSI cycles were assessed between 22 and 25 hours postinsemination. Forty-six oocytes (2.6%) were not cleaved and were excluded from the study. In total, 1,736 normally fertilized and cleaved embryos were included in the further analysis.

In 126 cycles (32.9%) the embryos were transferred on day 2. In all other cycles (257 cycles, 67.1%) embryo transfer was performed on day 3. In these cycles embryonic development was also

Discussion

The success of IVF treatment is influenced by many factors (e.g., woman’s age, endometrium receptivity, number and quality of oocytes, culture conditions). Traditionally, in most IVF centers, the transferred embryos are selected on the basis of the morphological assessment performed before embryo transfer. Recently, other morphological parameters of human oocytes and zygotes have been examined, for example, the morphology of the first polar body (23), the cytoplasmic granularity (24), or the

References (34)

H. Balakier et al.
Characterization of the first cell cycle in human zygotesimplication for cryopreservation
Fertil Steril
(1993)
D. Sakkas et al.
Assessment of early cleaving in vitro fertilized human embryos at 2-cell stage before transfer improves embryo selection
Fertil Steril
(2001)
Y.C. Tsai et al.
Clinical value of early cleavage embryo
Int J Gynec Obst
(2002)
E. Wharf et al.
Early embryo development is an indicator of implantation potential
Reprod Biomed Online
(2004)
T. Ebner et al.
Elective transfer of embryos selected on the basis of first polar body morphology is associated with increased rates of implantation and pregnancy
Fertil Steril
(1999)
G. Palermo et al.
Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte
Lancet
(1992)
M. Plachot
Fertilization
Hum Reprod
(2000)
B. Van Wissen et al.
Timing of pronuclear development and first cleavages in human embryos after subzonal inseminationinfluence of sperm phenotype
Hum Reprod
(1995)
G. Capmany et al.
The timing of pronuclear formation, DNA synthesis and cleavage in the human 1-cell embryo
Mol Hum Reprod
(1996)
Z.P. Nagy et al.
Time-course of oocyte activation, pronucleus formation and cleavage in human oocytes fertilized by intracytoplasmic sperm injection
Hum Reprod
(1994)

E. Neuber et al.

Sequential assessment of individually cultured human embryos as an indicator of subsequent good quality blastocyst development

Hum Reprod

(2003)

Y. Shoukir et al.

Early cleavage of in-vitro fertilized human embryos to the 2-cell stagea novel indicator of embryo quality and viability

Hum Reprod

(1997)

D. Sakkas et al.

Early cleavage of human embryos to the two-cell stage after intracytoplasmic sperm injection as an indicator of embryo viability

Hum Reprod

(1998)

A. Bos-Mikich et al.

Early cleavage of human embryosan effective method for predicting successful IVF/ICSI outcome

Hum Reprod

(2001)

C.G. Petersen et al.

Embryo selection by the first cleavage parameter between 25 and 27 hours after ICSI

J Assist Reprod Genet

(2001)

K. Lundin et al.

Early embryo cleavage is a strong indicator of embryo quality in human IVF

Hum Reprod

(2001)

A. Salumets et al.

Early cleavage predicts the viability of human embryos in elective single embryo transfer procedures

Hum Reprod

(2003)

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Citation Excerpt :
It is likely that the rate of mitosis on day 3 reflects timing at earlier stages, such as the zygote. In particular, early pronuclear fading and cleavage behaviour (Fancsovits et al., 2005) are morphological criteria, which are known to be correlated with higher cell numbers on days 2 and 3. Evidence shows, however, that day-3 cell number allows only a rough estimation of embryo viability (Graham et al., 2000) owing to the fact that, in classical morphological evaluation, scoring takes place once daily and so most mitotic cleavages at later stages are missed.
Is live birth of patients with excessive slow (no blastocyst on day 5) and fast mitotic rate (full blastocyst development on day 4) comparable to a matched control standard (blastocyst formation on day 5)?
In this retrospective matched (age and anti-Müllerian hormone [AMH]) case-control study rates of fertilization, blastulation, implantation, clinical pregnancy and live birth were compared in couples with male factor indication, prolonged embryo culture and fresh single morula and blastocyst transfer.
The rates of implantation, clinical pregnancy and live birth in the slow-developing group were significantly (P < 0.001) lower (17.6%, 13.7%, and 11.8%, respectively) compared with the fast (58.5%, 52.5%, 47.5%) and normal growing counterparts (51.5%, 42.6%, 39.6%). No differences in neonatal outcome could be observed between the three groups. Sex ratio in the fast-growing group was not different from the other cohorts.
Extremely slow development, as assessed by the absence of blastulation on day 5, is a negative predictor of pregnancy and live birth. In contrast, the fear that extremely fast-growing embryos may represent an aneuploid cohort of embryos is unsubstantiated. Day-4 full blastocysts can preferentially be considered for transfer.
Combination of metabolism measurement and a time-lapse system provides an embryo selection method based on oxygen uptake and chronology of cytokinesis timing
2016, Fertility and Sterility
To evaluate correlations between oxygen consumption (OC) measurements before and after embryo cytokinesis, observing OC during embryo cleavages and combining that information with morphokinetics to relate to implantation potential.
Prospective cohort study.
University-affiliated private IVF unit.
A total of 1,150 injected oocytes in 86 first oocyte donation cycles with embryo transfer on day 3.
None.
We analyzed the embryo OC and combined this data with the cytokinesis event, exact timing (in hours) of blastomeric cleavages, with the use of an incubator equipped with time-lapse videography, gathering a total of 7,630 measurements during the cytokinesis (active phase) and consecutive measurements after this division (passive phase), correlating this data with embryo outcome.
OC was found to increase during embryo cleavage, showing high levels during first division with a strong correlation with implantation success. Moreover, those embryos with slow or fast development gave rise to lower OC levels, whereas higher levels were associated with optimal embryo division ranges linked to higher implantation potential.
A detailed analysis of OC by time-lapse observations enhances the value that these measurements represented as markers of embryo quality, especially during the cytokinesis events produced during preimplantation development.
The relationship between embryo quality assessed using routine embryology or time-lapse videography and serum progesterone concentration on the day of ovulatory trigger in in vitro fertilization cycles
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To investigate the relationship between elevated serum progesterone levels (EP) on the day of ovulatory trigger, live birth rates, and the growth of resulting embryos.
A total of 836 in vitro fertilization (IVF) cycles with 4 478 embryos in conventional culture were retrospectively analyzed, together with an additional 90 IVF cycles producing 618 embryos from culture and assessment using the Embryoscope™ time-lapse system.
In cycles using conventional culture, serum progesterone per follicle ≥14 mm (median 0.42 nmol/L/follicle, range 0.05-3.50 nmol/L/follicle) was a significant negative predictor of live-birth (ROC AUC = 0.395, 95% CI 0.345-0.445; P=0.000) as were progesterone/estradiol ratio (0.442, 0.391-0.494; P=0.027) and progesterone per oocyte (0.374, 0.326-0.421; P=0.000) but not progesterone alone (0.470, 0.419-0.521; P>0.05). Women with an EP/follicle (>0.42 nmol/L/follicle) had reduced live birth rates if they were ≥35 yrs (14.4% vs. 24.2%, P<0.05) but not <35 years (35.3% vs. 37.4%, ns). Despite reduced pregnancy rates, cycles with EP/follicle in women ≥35 years produced similar proportions of “good” and “top” quality embryos in conventional culture compared to women with low progesterone/follicle, and no difference in abnormalities of cleavage (direct cleavage or reverse cleavage), multinucleation or timings of division (pronuclear fading to 2-cell, 3-cell, 4-cell and 5-cell; cc2 and S2) observed with time-lapse videography.
EP/follicle ≥14 mm (>0.42 nmol/L/follicle) adversely affects embryo implantation in women aged ≥35 years, but not <35 yrs. However, no adverse features were seen in the embryos from these affected cycles in terms of morphological appearance, abnormal patterns of cleavage, or morphokinetic timings.
Noninvasive embryo viability assessment by quantitation of human haptoglobin alpha-1 fragment in the in vitro fertilization culture medium: An additional tool to increase success rate
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To find new candidate molecules to assess embryo viability in a noninvasive manner.
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Ninety embryos implanted in 53 randomly selected patients (mean ± SD age, 32.3 ± 5.1 years) were analyzed.
Superovulation treatment was initiated by the administration of the GnRh agonist triptorelin and individual dosages of recombinant FSH. Ovulation was induced by the injection of hCG. Oocytes were fertilized by intracytoplasmic sperm injection.
Liquid chromatography coupled mass spectrometric quantification of the α-1 fragment of human haptoglobin in the culture medium.
A novel polypeptide marker was found that might be helpful to differentiate between potentially viable and nonviable embryos. This molecule was identified with tandem mass spectrometry as the α-1 fragment of human haptoglobin. Significant correlation was found in the amount of the peptide fragment and the outcome of pregnancy. In the culture media of embryos that were assigned in the biochemical assay as nonviable (according to the amount of the haptoglobin fragment), there were no pregnancies detected; this assay revealed a 100% successful selection of the nonviable embryos. In the group assigned as viable, the rate of pregnancy was 54.7%.
Viability of the embryo during the IVF process is assessed by microscopic inspection, resulting in a pregnancy rate of 25%–30%. Detection and quantitation of the α-1 haptoglobin fragment of the culture medium proved to be a useful additional method for identifying nonviable embryos, increasing the success rate to 50%.
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View full text

In vitro fertilizationEarly pronuclear breakdown is a good indicator of embryo quality and viability

Objective

Design

Setting

Patient(s)

Intervention(s)

Main Outcome Measure(s)

Result(s)

Conclusion(s)

Section snippets

Source of Embryos

Results

Discussion

Fertil Steril

Fertil Steril

Int J Gynec Obst

Reprod Biomed Online

Fertil Steril

Lancet

Fertilization

Hum Reprod

Timing of pronuclear development and first cleavages in human embryos after subzonal inseminationinfluence of sperm phenotype

Hum Reprod

The timing of pronuclear formation, DNA synthesis and cleavage in the human 1-cell embryo

Mol Hum Reprod

Time-course of oocyte activation, pronucleus formation and cleavage in human oocytes fertilized by intracytoplasmic sperm injection

Hum Reprod

Sequential assessment of individually cultured human embryos as an indicator of subsequent good quality blastocyst development

Hum Reprod

Early cleavage of in-vitro fertilized human embryos to the 2-cell stagea novel indicator of embryo quality and viability

Hum Reprod

Early cleavage of human embryos to the two-cell stage after intracytoplasmic sperm injection as an indicator of embryo viability

Hum Reprod

Early cleavage of human embryosan effective method for predicting successful IVF/ICSI outcome

Hum Reprod

Embryo selection by the first cleavage parameter between 25 and 27 hours after ICSI

J Assist Reprod Genet

Early embryo cleavage is a strong indicator of embryo quality in human IVF

Hum Reprod

Early cleavage predicts the viability of human embryos in elective single embryo transfer procedures

Hum Reprod

In vitro fertilization
Early pronuclear breakdown is a good indicator of embryo quality and viability