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The most important results of Human Clinical Embryology:From the Zygote to-zygotic transition as a result of major changes in the molecular signals that control the arrest of meiotic

 

INTRODUCTION

 

A series of dynamic and complex events are triggered following sperm–oocyte interaction that sequentially leads to fertilization and the formation of a zygote. These events include sperm penetration, sperm–oocyte fusion and oocyte activation, male and female pronucleus (PN) development and gradual migration of the pronuclei (PNs) to a central position in the oocyte.

Induced by the sperm penetration and subsequent calcium oscillations, the fertilized oocyte undergoes maternal-to-zygotic transition as a result of major changes in the molecular signals that control the arrest of meiotic development at the metaphase II stage of the second meiotic division (Ajduk et al., 2011). In humans, the sperm centriole has the leading role in organizing the microtubules, which direct the migration of PNs and their rotation within the cytoplasm. In this way, PNs position their axis toward the second polar body and achieve a proper orientation at syngamy by controlling the plane of the first mitotic division. During PN formation, nuclear precursor bodies (NPBs) become evident and start to migrate and merge into nucleoli in a time-dependent manner. The NPBs do not form a functionally active nucleolus at the zygote stage; however, they can be used as an indirect measure of the location and the grade of condensation of DNA within the PNs. Nucleoli are the sites of synthesis of pre-rRNA and its availability is extremely important since newly synthesized rRNA is necessary for the translational processes when the embryonic genome becomes active (Gianaroli et al., 2003). Asynchrony in the timing of any of the events associated with fertilization could compromise embryo development.

Once PNs are aligned onto a polar axis, parental chromosomes then separate in preparation for mitosis. The human zygote’s mitotic potential is paternally inherited with the spermatozoon delivering the centrosome (Palermo et al., 1994Sathananthan et al., 1996).

A zygote’s morphological characteristics are accepted to be an inherent indicator of both gamete quality and subsequent embryo implantation potential (Alpha Scientists in Reproductive medicine and ESHRE Special Interest Group of Embryology, 2011). Many studies have underlined the predictive value of zygote morphological assessment through correlations with chromosome constitution and the incidence of zygotic arrest (Gianaroli et al., 2003Balaban et al., 2004Edirisinghe et al., 2005Zamora et al., 2011). Recent strategies in embryo selection include sequential morphology assessment where PN scoring has been shown to play an important role as an indicator of gamete constitution as well as a prognostic tool for embryo competence. Scoring of PNs has also proved to be useful in countries where restrictive legislation mandates selection at the zygote stage for embryo transfer and consecutive elimination or cryopreservation of sibling zygotes (Senn et al., 2006Zollner et al., 2005).

Although numerous studies have associated positive clinical results with the implementation of PN scoring, other reports have questioned the predictive value of PN scoring systems and see no benefits or improvement in the outcome (Nicoli et al., 2010Weitzman et al., 2010). The Istanbul consensus workshop comprised a worldwide panel of experts who just recently evaluated the current practice of oocyte to embryo scoring and established common criteria for assessment (Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology, 2011). Fertilization check is to be performed at 17 ± 1 h post-insemination which may establish uniformity in the future and eliminate the variability in PN scoring regimens that have confounded comparative analyses. It must be noted, however, that the processes associated with fertilization by conventional insemination lags 1h behind fertilization using ICSI (Nagy et al., 1998). A more complete elucidation of events during the zygote stage, however, can be expected with the application of continuous monitoring through the introduction of time-lapse imaging instead of the traditional isolated observations using light microscopy (Montag et al., 2011).

Normal fertilization is assessed by the presence of two centrally positioned, juxtaposed PNs with clearly defined membranes and two polar bodies. If an abnormal PN number is observed whether it be 1, or 3 or more, PNs, a low viable pregnancy is to be expected thus the transfer of these zygotes is to be avoided (Reichman et al., 2010). Aberrant PN size and position have been correlated with developmental arrest and aneuploidy and are represented by PNs of unequal size (>4 μm), localized far apart or peripherally or with the presence of fragmented or additional micronuclei (Munné and Cohen, 1998Sadowy et al., 1998Garello et al., 1999Nagy et al., 2003Scott et al., 2007). Panel experts also agreed and strongly advised that the assessment and elimination of dysmorphic zygotes with smooth endoplasmic reticulum (SER) discs (see Chapter One) due to the association with severely adverse clinical outcomes (Otsuki et al., 2004Ebner et al., 2008).

Correct alignment of PNs onto the polar axis is considered a fundamental feature for the completion of the first cleavage division and normal sequential development (Gardner, 1996, 1999, 2001Edwards and Beard, 19971999; Payne et al., 1997Garello et al., 1999Scott, 2001). Cell cycle-related dynamics of PN events have led many authors to investigate and correlate the presence, pattern and number of NPBs to embryo developmental potential. As shown for mitotic cells, the inequality in number, size or distribution of NPBs is correlated with abnormal development (Pedersen, 1998). Therefore, the panel experts from the consensus workshop established three categories for PN scoring that are based on the morphology of NPBs and PNs, namely: (i) symmetrical, (ii) non-symmetrical and (iii) abnormal (Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology, 2011). Category 1 includes zygotes presenting with equal numbers and size of NPBs, either aligned at the junction between PNs or scattered in both PNs. Category 2, non-symmetrical, comprises all other patterns including peripherally localized PNs. Category 3, abnormal, includes single NPB (‘bull’s eye’) or total absence of NPBs. The latter were found to be correlated with imprinting errors and delayed onset of functional NPBs and nucleoli formation in animal models (Svarcova et al., 2009).

Reports on early cleavage checks have been demonstrated to be a beneficial tool in selecting embryos with high implantation potential and decreased chromosomal anomalies (Sakkas et al., 1998Lundin et al., 2001). The consensus opinion on a second, Day 1 observation was to leave the choice to the operator’s discretion, but if applied, is to be performed 26 ± 1 and 28 ± 1 h post-insemination for ICSI and IVF embryos, respectively.

Sequential morphology assessment through time-lapse cinematography will certainly shed light on the discrepancies in the literature with respect to PN scoring and an in-depth analysis and correlation with the clinical background behind the gametes forming the zygote will possibly reveal even more reliable prognostic tools to improve clinical outcomes.

A. FERTILIZATION ASSESSMENT

A.1 2PN

When assessments are performed 17 ± 1 h post-insemination, taking into consideration that pronuclear formation in IVF zygotes lags ∼1 h behind ICSI zygotes, normally fertilized oocytes should be spherical and have two polar bodies and two PNs (Figs 85–87). PNs should be juxtaposed, approximately the same size, centrally positioned in the cytoplasm with two distinctly clear, visible membranes (Fig. 88). The presence of an equal number and size of NPBs aligned at the PN junction has been correlated with increased embryo competence (Tesarik and Greco, 1999Tesarik et al., 2000Scott, 2003).

A.2 1PN

The incidence of one pronucleates is around 1% after IVF or ICSI and may be parthenogenetic in origin as suggested by chromosomal analysis that shows a haploid set in approximately half of the studied oocytes (Plachot, 2000). In some cases, only one polar body is extruded into the perivitelline space (PVS) (Fig. 89).

The presence of 1PN can also be a result of errors in the fertilization process with asynchrony in PN formation or PN fusion. In these cases, the resulting oocyte could have a diploid set of chromosomes, and two polar bodies are normally observed (Figs 90–93). The transfer of these oocytes could be considered, but the incidence of aneuploidy in the resulting embryos has been reported to be significantly higher compared with embryos derived from 2PN oocytes (Yan et al., 2010).

A.3 ≥3PN

The formation of triploid zygotes differs in origin, depending on whether they are generated by ICSI or IVF. Only 1% of oocytes after ICSI result in tripronuclear zygotes and are digynic due to failure in extrusion of the second polar body (Fig. 94). An exception is represented by giant oocytes (Fig. 95) that follow different patterns of extrusion due to their generally diploid condition (see Chapter One).

Diandry is the most probable cause of tripronucleates following IVF and occurs in ∼5% of inseminated oocytes (Fig. 96). This condition arises from the entry of two spermatozoa into the cytoplasm owing to the incapacity of the oocyte to trigger protection against polyspermy. The second polar body is normally extruded and cleavage often occurs. In some cases, the presence of multiple PNs could be due to failed cytokinesis (Figs 94 and 97) or to penetration by a binucleate spermatozoon (Fig. 98).

Article References:

Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod 2011;26:1270-1283.
Abstract/FREE Full Text

Ajduk A, Ilozue T, Windsor S, Yu Y, Seres KB, Bomphrey RJ, Tom BD, Swann K, Thomas A, Graham C, et al. Rhythmic actomyosin-driven contractions induced by sperm entry predict mammalian embryo viability. Nat Commun 2011;2:417.
CrossRef | Medline | Google Scholar

Balaban B, Yakin K, Urman b, Isiklar A, Tesarik J. Pronuclear morphology predicts embryo development and chromosome constitution. Reprod Biomed Online 2004;8:695-700.
Medline Web of Science | Google Scholar

Ebner T, Moser M, Shebl O, Sommerguber M, Tews G. Prognosis of oocytes showing aggregation of smooth endoplasmic reticulum. Reprod Biomed Online 2008;16:113-118.
CrossRef | Medline Web of Science Google Scholar

Edirisinghe WR, Jemmott R, Smith C, Allan J. Association of pronuclear Z score with rates of aneuploidy in in-vitro fertilised embryos. Reprod Fertil Dev 2005;17:529-534.
CrossRef Medline Google Scholar

Edwards RG, Beard HK. Oocyte polarity and cell determination in early mammalian embryos. Mol Hum Reprod 1997;3:863-905.
Abstract/FREE Full Text

Edwards RG, Beard HK. Hypothesis: sex determination and germline formation are committed at the pronuclear stage in mammalian embryos. Mol Hum Reprod 1999;5:595-606.
FREE Full Text

Gardner RL. Can developmentally significant spatial patterning of the egg be discounted in mammals? Hum Reprod Update 1996;2:3-27.
Abstract/FREE Full Text

Gardner RL. Scrambled or bissected mouse eggs and the basis of patterning in mammals. BioEssays 1999;21:271-274.
CrossRef | Medline Web of Science Google Scholar

Gardner RL. Specification of embryonic axes begins before cleavage in normal mouse development. Development 2001;128:839-847.
Abstract

Garello C, Baker H, Rai J, Montgomery S, Wilson P, Kennedy CR, Hartshorne GM. Pronuclear orientation, polar body placement, and embryo quality after intracytoplasmic sperm injection and in vitro fertilization: further evidence for polarity in human oocytes? Hum Reprod 1999;14:2588-2595.
Abstract/FREE Full Text

Gianaroli L, Magli MC, Ferraretti AP, Fortini D, Grieco N. Pronuclear morphology and chromosomal abnormalities as scoring criteria for embryo selection. Fertil Steril 2003;80:341-349.
CrossRef Medline | Web of Science | Google Scholar

Lundin K, Bergh C, Hardarson T. Early embryo cleavage is a strong indicator of embryo quality in human IVF. Hum Reprod 2001;16:2652-2657.
Abstract/FREE Full Text

Montag M, Liebenthron J, Köster M. Which morphological scoring system is relevant in human embryo development? Placenta 2011;32:S252-S256.
CrossRef | Medline Web of Science | Google Scholar

Munné S, Cohen J. Chromosome abnormalities in human embryos. Hum Reprod Update 1998;4:842-855.
Abstract/FREE Full Text

Nagy ZP, Dozortsev D, Diamond M, Rienzi L, Ubaldi F, Abdelmassih R, Greco E. Pronuclear morphology evaluation with subsequent evaluation of embryo morphology significantly increases implantation rates. Fertil Steril 2003;80:67-74.
Medline | Web of Science Google Scholar

Nagy ZP, Janssenswillen C, Janssens R, De Vos A, Staessen C, Van deVelde H, Van Steirteghem AC. Timing of oocyte activation, pronucleus formation and cleavage in humans after intracytoplasmic sperm injection (ICSI) with testicular spermatozoa and after ICSI or in-vitro fertilization on sibling oocytes with ejaculated spermatozoa. Hum Reprod 1998;13:1606-1612.
Abstract/FREE Full Text

Nicoli A, Capodanno F, Moscato L, Rondini I, Villani MT, Tuzio A, La Sala GB. Analysis of pronuclear zygote configurations in 459 clinical pregnancies obtained with assisted reproductive technique procedures. Reprod Biol Endocrinol 2010;8:77.
CrossRef Medline | Google Scholar

Otsuki J, Okada A, Morimoto K, Nagai Y, Kubo H. The relationship between pregnancy outcome and smooth endoplasmic reticulum clusters in MII human oocytes. Hum Reprod 2004;19:1591-1597.
Abstract/FREE Full Text

Palermo G, Munné S, Cohen J. The human zygote inherits its mitotic potential from the male gamete. Fertil Steril 1994;9:1220-1225.
Google Scholar

Payne D, Flaherty SP, Barry MF, Matthews CD. Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography. Hum Reprod 1997;12:532-541.
Abstract/FREE Full Text

Pedersen T. Growth factors in the nucleolus? J Cell Biol 1998;143:279-281.
FREE Full Text

Reichman DE, Jackson KV, Racowscky C. Incidence and development of zygotes exhibiting abnormal pronuclear disposition after identification of two pronuclei at the fertilization check. Fertil Steril 2010;94:965-970.
CrossRef | Medline | Google Scholar

Sakkas D, Shoukir Y, Chardonnens D, Bianchi PG, Campana A. Early cleavage of human embryos to the two-cell stage after intracytoplasmic sperm injection as an indicator of embryo viability. Hum Reprod 1998;13:182-187.
Abstract/FREE Full Text

Sathananthan AH, Ratnam SS, Ng SC, Tarin JJ, Gianaroli L, Trounson A. The sperm centriole: its inheritance, replication and perpetuation in early embryos. Hum Reprod 1996;11:345-356.
Abstract/FREE Full Text

Scott L. Oocyte and embryo polarity. Semin Reprod Med 2001;18:171-183.
Google Scholar

Scott L, Finn A, O’Leary T, McLellan S, Hill J. Morphologic parameters of early cleavage-stage embryos that correlate with fetal development and delivery: prospective and applied data for increased pregnancy rates. Hum Reprod 2007;22:230-240.
Abstract/FREE Full Text

Senn A, Urner F, Chanson A, Primi MP, Wirthner DW, Germond M. Morphological scoring of human pronuclear zygotes for prediction of pregnancy outcome. Hum Reprod 2006;21:234-239.
Abstract/FREE Full Text

Svarcova O, Dinnyes A, Polgar Z, Bodo S, Adorjan M, Meng Q, Maddox-Hyttel P. Nucleolar re-activation is delayed in mouse embryos cloned from two different cell lines. Mol Reprod Dev 2009;76:132-141.
CrossRef | Medline | Web of Science Google Scholar

Weitzman VN, Schnee-Riesz J, Benadiva C, Nulsen J, Siano L, Maier D. Predictive value of embryo grading for embryos with known outcomes. Fertil Steril 2010;93:658-662.
CrossRef Medline Web of Science Google Scholar

Zamora RB, Sánchez RV, Pérez JG, Diaz RR, Quintana DB, Bethencourt JC. Human zygote morphological indicators of high rate of arrest at the first cleavage stage. Zygote 2011;19:339-344.
CrossRef Medline | Web of Science | Google Scholar

Zollner U, Zollner KP, Steck T, Dietl J. Pronuclear scoring: time for international standardization. J Reprod Med 2003;5:365-369.
Google Scholar

Plachot M. Fertilization. Hum Reprod 2000;15(Suppl. 4):19-30.
FREE Full Text

Scott L. Pronuclear scoring as a predictor of embryo development. Reprod Biomed Online 2003;6:201-214.
CrossRef | Medline Google Scholar

Tesarik J, Greco E. The probability of abnormal preimplantation development can be predicted by a single static observation on pronuclear stage morphology. Hum Reprod 1999;14:1318-1323.
Abstract/FREE Full Text

Tesarik J, Junca AM, Hazout A, Aubriot FX, Nathan C, Cohen-Bacrie P, Dumont-Hassan M. Embryos and high implantation potential after intracytoplasmic sperm injection can be recognized by a simple, non- invasive examination of pronuclear morphology. Hum Reprod 2000;15:1396-1399.
Abstract/FREE Full Text

Yan J, Li Y, Shi Y, Feng HL, Gao S, Chenz Z. Assessment of sex chromosomes of human embryos arising from monopronucleus zygotes in in vitro fertilization and intracytoplasmic sperm injection cycles of Chinese women. Gynecol Obstet Invest 2010;69:20-23.
CrossRef Medline Google Scholar

Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod 2011;26:1270-1283.
Abstract/FREE Full Text

Munné S, Cohen J. Chromosome abnormalities in human embryos. Hum Reprod Update 1998;4:842-855.
Abstract/FREE Full Text

Nagy ZP, Dozortsev D, Diamond M, Rienzi L, Ubaldi F, Abdelmassih R, Greco E. Pronuclear morphology evaluation with subsequent evaluation of embryo morphology significantly increases implantation rates. Fertil Steril 2003;80:67-74.
Medline | Web of Science Google Scholar

Payne D, Flaherty SP, Barry MF, Matthews CD. Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography. Hum Reprod 1997;12:532-541.
Abstract/FREE Full Text

Sadowy S, Tomkin G, Munné S, Ferrara-Congedo T, Cohen J. Impaired development of zygotes with uneven pronuclear size. Zygote 1998;6:137-141.
CrossRef | Medline | Web of Science | Google Scholar

Scott L, Alvero R, Leondires M, Miller B. The morphology of human pronuclear embryos is positively related to blastocyst development and implantation. Hum Reprod 2000;15:2394-2403.
Abstract/FREE Full Text

Scott L, Finn A, O’Leary T, McLellan S, Hill J. Morphologic parameters of early cleavage-stage embryos that correlate with fetal development and delivery: prospective and applied data for increased pregnancy rates. Hum Reprod 2007;22:230-240.
Abstract/FREE Full Text

Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod 2011;26:1270-1283.
Abstract/FREE Full Text

Edwards RG, Beard HK. Oocyte polarity and cell determination in early mammalian embryos. Mol Hum Reprod 1997;3:863-905.
Abstract/FREE Full Text

Gardner RL. Specification of embryonic axes begins before cleavage in normal mouse development. Development 2001;128:839-847.
Abstract

Garello C, Baker H, Rai J, Montgomery S, Wilson P, Kennedy CR, Hartshorne GM. Pronuclear orientation, polar body placement, and embryo quality after intracytoplasmic sperm injection and in vitro fertilization: further evidence for polarity in human oocytes? Hum Reprod 1999;14:2588-2595.
Abstract/FREE Full Text

Gianaroli L, Magli MC, Ferraretti AP, Fortini D, Grieco N. Pronuclear morphology and chromosomal abnormalities as scoring criteria for embryo selection. Fertil Steril 2003;80:341-349.
CrossRef | Medline Web of Science | Google Scholar

Montag M, Liebenthron J, Köster M. Which morphological scoring system is relevant in human embryo development? Placenta 2011;32:S252-S256.
CrossRef | Medline | Web of Science | Google Scholar

Payne D, Flaherty SP, Barry MF, Matthews CD. Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography. Hum Reprod 1997;12:532-541.
Abstract/FREE Full Text

Payne JF, Raburn DJ, Couchman GM, Price TM, Jamison MG, Walmer DK. Relationship between pre-embryo pronuclear morphology (zygote score) and standard day 2 or 3 embryo morphology with regard to assisted reproductive technique outcomes. Fertil Steril 2005;84:900-909.
CrossRef | Medline Web of Science Google Scholar

Scott L. Oocyte and embryo polarity. Semin Reprod Med 2001;18:171-183.
Google Scholar

Scott L. Pronuclear scoring as a predictor of embryo development. Reprod Biomed Online 2003;6:201-214.
CrossRef | Medline | Google Scholar

Senn A, Urner F, Chanson A, Primi MP, Wirthner DW, Germond M. Morphological scoring of human pronuclear zygotes for prediction of pregnancy outcome. Hum Reprod 2006;21:234-239.
Abstract/FREE Full Text

Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod 2011;26:1270-1283.
Abstract/FREE Full Text

Balaban B, Urman B, Isiklar A, Alatas C, Aksoy S, Mercan R, Mumcu A, Nuhoglu A. The effect of pronuclear morphology on embryo quality parameters and blastocyst transfer outcome. Hum Reprod 2001;16:2357-2361.
Abstract/FREE Full Text

Brezinova J, Oborna I, Svobodova M, Fingerova H. Evaluation of day one embryo quality and IVF outcome—a comparison of two scoring systems. Reprod Biol Endocrinol 2009;7:9.
CrossRef Medline | Google Scholar

Ebner T, Moser M, Sommergruber M, Gaiswinkler U, Wiesinger R, Puchner M, Tews G. Presence, but not type or degree of extension, of a cytoplasmic halo has a significant influence on preimplantation development and implantation behaviour. Hum Reprod 2003;18:2406-2412.
Abstract/FREE Full Text

Edwards RG, Beard HK. Oocyte polarity and cell determination in early mammalian embryos. Mol Hum Reprod 1997;3:863-905.
Abstract/FREE Full Text

James AN, Hennessy S, Reggio B, Wiemer K, Larsen F, Cohen J. The limited importance of pronuclear scoring of human zygotes. Hum Reprod 2006;21:1599-1604.
Abstract/FREE Full Text

Montag M, van der Ven H. Evaluation of pronuclear morphology as the only selection criterion for further embryo culture and transfer: results of a prospective multicentre study. Hum Reprod 2001;16:2384-2389.
Abstract/FREE Full Text

Montag M, Liebenthron J, Köster M. Which morphological scoring system is relevant in human embryo development? Placenta 2011;32:S252-S256.
CrossRef | Medline | Web of Science | Google Scholar

Nicoli A, Valli B, Di Girolamo R, Di Tommaso B, Gallinelli A, La Sala GB. Limited importance of pre-embryo pronuclear morphology (zygote score) in assisted reproduction outcome in the absence of embryo cryopreservation. Fertil Steril 2007;88:1167-1173.
CrossRef Medline | Web of Science Google Scholar

Payne D, Flaherty SP, Barry MF, Matthews CD. Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography. Hum Reprod 1997;12:532-541.
Abstract/FREE Full Text

Payne JF, Raburn DJ, Couchman GM, Price TM, Jamison MG, Walmer DK. Relationship between pre-embryo pronuclear morphology (zygote score) and standard day 2 or 3 embryo morphology with regard to assisted reproductive technique outcomes. Fertil Steril 2005;84:900-909.
CrossRef | Medline Web of Science Google Scholar

Pedersen T. Growth factors in the nucleolus? J Cell Biol 1998;143:279-281.
FREE Full Text

Scott LA, Smith S. The successful use of pronuclear embryo transfers the day following oocyte retrieval. Hum Reprod 1998;13:1003-1013.
Abstract/FREE Full Text

Scott L, Alvero R, Leondires M, Miller B. The morphology of human pronuclear embryos is positively related to blastocyst development and implantation. Hum Reprod 2000;15:2394-2403.
Abstract/FREE Full Text

Scott L. Oocyte and embryo polarity. Semin Reprod Med 2001;18:171-183.
Google Scholar

Scott L. Pronuclear scoring as a predictor of embryo development. Reprod Biomed Online 2003;6:201-214.
CrossRef | Medline | Google Scholar

Senn A, Urner F, Chanson A, Primi MP, Wirthner DW, Germond M. Morphological scoring of human pronuclear zygotes for prediction of pregnancy outcome. Hum Reprod 2006;21:234-239.
Abstract/FREE Full Text

Svarcova O, Dinnyes A, Polgar Z, Bodo S, Adorjan M, Meng Q, Maddox-Hyttel P. Nucleolar re-activation is delayed in mouse embryos cloned from two different cell lines. Mol Reprod Dev 2009;76:132-141.
CrossRef Medline | Web of Science | Google Scholar

Tesarik J, Greco E. The probability of abnormal preimplantation development can be predicted by a single static observation on pronuclear stage morphology. Hum Reprod 1999;14:1318-1323.
Abstract/FREE Full Text

Van Blerkom J, Antczak M, Schrader R. The developmental potential of the human oocyte is related to the dissolved oxygen content of follicular fluid: association with vascular endothelial growth factor levels and perifollicular blood flow characteristics. Hum Reprod 1997;12:1047-1055.
Abstract/FREE Full Text

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