ABSTRACT
The health of fetuses, neonates, and adults depends on normal development of the oocytes and embryos from which they arise. In addition, the ability of an embryo to implant, sustain a pregnancy, and give rise to a viable offspring is unquestionably rooted in oogenesis. Therefore, defining markers that can reliably predict the best quality oocytes will prove invaluable in the care and management of infertility patients. Furthermore, identification of the best quality oocyte will also permit the transfer of a single embryo, thereby increasing overall pregnancy rates and reducing multiple rates. Although a few potentially important predictors of oocyte quality have been identified, their application for routine use in the assisted reproductive technology (ART) laboratory remains to be established. With the critical need for markers to be noninvasive, reliable, and assayable with a rapid turnaround, key areas that will take advantage of recent technological advances are identified in this article. Oocyte quality also needs to be improved in the management of human infertility by ART programs. Given that mechanisms determining oocyte quality are multifactorial and complex, several possible areas that continue to necessitate optimization are discussed.
KEYWORDS
Oocyte quality - assessment - optimization - human assisted reproduction
REFERENCES
-
1
Kwong W Y, Wild A E, Roberts P, Willis A C, Fleming T P.
Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension.
Development.
2000;
127
4195-4202
-
2
Godfrey K M, Barker D J.
Fetal programming and adult health.
Public Health Nutr.
2001;
4
611-624
-
3
Edwards R G, Fishel S B, Cohen J et al..
Factors influencing the success of in vitro fertilization for alleviating human infertility.
J In Vitro Fert Embryo Transf.
1984;
1
3-23
-
4
Cummins J M, Breen T M, Harrison K L, Shaw J M, Wilson L M, Hennessey J F.
A formula for scoring human embryo growth rates in in vitro fertilization: its value in predicting pregnancy and in comparison with visual estimates of embryo quality.
J In Vitro Fert Embryo Transf.
1986;
3
284-295
-
5
Giorgetti C, Terriou P, Auquier P et al..
Embryo score to predict implantation after in-vitro fertilization: based on 957 single embryo transfers.
Hum Reprod.
1995;
10
2427-2431
-
6
Alikani M, Cohen J, Tomkin G, Garrisi G J, Mack C, Scott R T.
Human embryo fragmentation in vitro and its implications for pregnancy and implantation.
Fertil Steril.
1999;
71
836-842
-
7
Ebner T, Yaman C, Moser M, Sommergruber M, Polz W, Tews G.
Embryo fragmentation in vitro and its impact on treatment and pregnancy outcome.
Fertil Steril.
2001;
76
281-285
-
8
Hardarson T, Hanson C, Sjogren A, Lundin K.
Human embryos with unevenly sized blastomeres have lower pregnancy and implantation rates: indications for aneuploidy and multinucleation.
Hum Reprod.
2001;
16
313-318
-
9
Racowsky C, Combelles C M, Nureddin A et al..
Day 3 and day 5 morphological predictors of embryo viability.
Reprod Biomed Online.
2003;
6
323-331
-
10
Sakkas D, Percival G, D'Arcy Y, Sharif K, Afnan M.
Assessment of early cleaving in vitro fertilized human embryos at the 2-cell stage before transfer improves embryo selection.
Fertil Steril.
2001;
76
1150-1156
-
11
De Placido G, Wilding M, Strina I et al..
High outcome predictability after IVF using a combined score for zygote and embryo morphology and growth rate.
Hum Reprod.
2002;
17
2402-2409
-
12
Rienzi L, Ubaldi F, Iacobelli M et al..
Day 3 embryo transfer with combined evaluation at the pronuclear and cleavage stages compares favourably with day 5 blastocyst transfer.
Hum Reprod.
2002;
17
1852-1855
-
13
Fisch J D, Sher G, Adamowicz M, Keskintepe L.
The graduated embryo score predicts the outcome of assisted reproductive technologies better than a single day 3 evaluation and achieves results associated with blastocyst transfer from day 3 embryo transfer.
Fertil Steril.
2003;
80
1352-1358
-
14
Neuber E, Rinaudo P, Trimarchi J R, Sakkas D.
Sequential assessment of individually cultured human embryos as an indicator of subsequent good quality blastocyst development.
Hum Reprod.
2003;
18
1307-1312
-
15
Scott L.
The biological basis of non-invasive strategies for selection of human oocytes and embryos.
Hum Reprod Update.
2003;
9
237-249
-
16
Van Soom A, Mateusen B, Leroy J, De Kruif A.
Assessment of mammalian embryo quality: what can we learn from embryo morphology?.
Reprod Biomed Online.
2003;
7
664-670
-
17
Boiso I, Veiga A, Edwards R G.
Fundamentals of human embryonic growth in vitro and the selection of high-quality embryos for transfer.
Reprod Biomed Online.
2002;
5
328-350
-
18
Van Blerkom J.
Occurrence and developmental consequences of aberrant cellular organization in meiotically mature human oocytes after exogenous ovarian hyperstimulation.
J Electron Microsc Tech.
1990;
16
324-346
-
19
Van Blerkom J, Henry G.
Oocyte dysmorphism and aneuploidy in meiotically mature human oocytes after ovarian stimulation.
Hum Reprod.
1992;
7
379-390
-
20
Sousa M, Tesarik J.
Ultrastructural analysis of fertilization failure after intracytoplasmic sperm injection.
Hum Reprod.
1994;
9
2374-2380
-
21
Alikani M, Palermo G, Adler A, Bertoli M, Blake M, Cohen J.
Intracytoplasmic sperm injection in dysmorphic human oocytes.
Zygote.
1995;
3
283-288
-
22
De Sutter P, Dozortsev D, Qian C, Dhont M.
Oocyte morphology does not correlate with fertilization rate and embryo quality after intracytoplasmic sperm injection.
Hum Reprod.
1996;
11
595-597
-
23
Balaban B, Urman B, Sertac A, Alatas C, Aksoy S, Mercan R.
Oocyte morphology does not affect fertilization rate, embryo quality and implantation rate after intracytoplasmic sperm injection.
Hum Reprod.
1998;
13
3431-3433
-
24
Xia P.
Intracytoplasmic sperm injection: correlation of oocyte grade based on polar body, perivitelline space and cytoplasmic inclusions with fertilization rate and embryo quality.
Hum Reprod.
1997;
12
1750-1755
-
25
Ebner T, Yaman C, Moser M, Sommergruber M, Feichtinger O, Tews G.
Prognostic value of first polar body morphology on fertilization rate and embryo quality in intracytoplasmic sperm injection.
Hum Reprod.
2000;
15
427-430
-
26
Hassan-Ali H, Hisham-Saleh A, El-Gezeiry D, Baghdady I, Ismaeil I, Mandelbaum J.
Perivitelline space granularity: a sign of human menopausal gonadotrophin overdose in intracytoplasmic sperm injection.
Hum Reprod.
1998;
13
3425-3430
-
27
Talbot P, Dandekar P.
Perivitelline space: does it play a role in blocking polyspermy in mammals?.
Microsc Res Tech.
2003;
61
349-357
-
28
Talevi R, Gualtieri R, Tartaglione G, Fortunato A.
Heterogeneity of the zona pellucida carbohydrate distribution in human oocytes failing to fertilize in vitro.
Hum Reprod.
1997;
12
2773-2780
-
29
Gabrielsen A, Lindenberg S, Petersen K.
The impact of the zona pellucida thickness variation of human embryos on pregnancy outcome in relation to suboptimal embryo development. A prospective randomized controlled study.
Hum Reprod.
2001;
16
2166-2170
-
30
Pelletier C, Keefe D L, Trimarchi J R.
Noninvasive polarized light microscopy quantitatively distinguishes the multilaminar structure of the zona pellucida of living human eggs and embryos.
Fertil Steril.
2004;
81(suppl 1)
850-856
-
31
Keefe D, Liu L, Wang W, Silva C.
Imaging meiotic spindles by polarization light microscopy: principles and applications to IVF.
Reprod Biomed Online.
2003;
7
24-29
-
32
Sandalinas M, Sadowy S, Alikani M, Calderon G, Cohen J, Munne S.
Developmental ability of chromosomally abnormal human embryos to develop to the blastocyst stage.
Hum Reprod.
2001;
16
1954-1958
-
33
Van Blerkom J, Davis P, Alexander S.
Differential mitochondrial distribution in human pronuclear embryos leads to disproportionate inheritance between blastomeres: relationship to microtubular organization, ATP content and competence.
Hum Reprod.
2000;
15
2621-2633
-
34
Van Blerkom J, Davis P, Mathwig V, Alexander S.
Domains of high-polarized and low-polarized mitochondria may occur in mouse and human oocytes and early embryos.
Hum Reprod.
2002;
17
393-406
-
35
Squirrell J M, Schramm R D, Paprocki A M, Wokosin D L, Bavister B D.
Imaging mitochondrial organization in living primate oocytes and embryos using multiphoton microscopy.
Microsc Microanal.
2003;
9
190-201
-
36
Veeck L L, Wortham Jr J W, Witmyer J et al..
Maturation and fertilization of morphologically immature human oocytes in a program of in vitro fertilization.
Fertil Steril.
1983;
39
594-602
-
37
Lin Y C, Chang S Y, Lan K C et al..
Human oocyte maturity in vivo determines the outcome of blastocyst development in vitro.
J Assist Reprod Genet.
2003;
20
506-512
-
38
Gregory L, Booth A D, Wells C, Walker S M.
A study of the cumulus-corona cell complex in in-vitro fertilization and embryo transfer: a prognostic indicator of the failure of implantation.
Hum Reprod.
1994;
9
1308-1317
-
39
Enien W M, Chantler E, Seif M W, Elstein M.
Human ovarian granulosa cells and follicular fluid indices: the relationship to oocyte maturity and fertilization in vitro.
Hum Reprod.
1998;
13
1303-1306
-
40 Salmina A B, Svetlakov A V, Pozhilenkova E A, Yamanova M V, Serebrennikova O A. Lack of correlation between granulosa cells apoptosis and oocyte quality. Presented at: annual meeting of the European Society of Human Reproduction and Embryology June 30-July 2, 2003 Madrid, Spain;
-
41
Zhang X J, Moyse J, Jarari N, Confino E, Kazer R.
Pentraxin-3 gene expression in cumulus cells may be a molecular marker for egg quality.
Fertil Steril.
2003;
80(suppl 3)
S81
-
42
Grunwald K, Feldmann K, Melsheimer P, Rabe T, Neulen J, Runnebaum B.
Aneuploidy in human granulosa lutein cells obtained from gonadotrophin-stimulated follicles and its relation to intrafollicular hormone concentrations.
Hum Reprod.
1998;
13
2679-2687
-
43
Host E, Mikkelsen A L, Lindenberg S, Smidt-Jensen S.
Apoptosis in human cumulus cells in relation to maturation stage and cleavage of the corresponding oocyte.
Acta Obstet Gynecol Scand.
2000;
79
936-940
-
44
Moffatt O, Drury S, Tomlinson M, Afnan M, Sakkas D.
The apoptotic profile of human cumulus cells changes with patient age and after exposure to sperm but not in relation to oocyte maturity.
Fertil Steril.
2002;
77
1006-1011
-
45
Suh C S, Jee B C, Choi Y M et al..
Prognostic implication of apoptosis in human luteinized granulosa cells during IVF-ET.
J Assist Reprod Genet.
2002;
19
209-214
-
46
Artini P G, Battaglia C, D'Ambrogio G et al..
Relationship between human oocyte maturity, fertilization and follicular fluid growth factors.
Hum Reprod.
1994;
9
902-906
-
47
Friedman C I, Seifer D B, Kennard E A, Arbogast L, Alak B, Danforth D R.
Elevated level of follicular fluid vascular endothelial growth factor is a marker of diminished pregnancy potential.
Fertil Steril.
1998;
70
836-839
-
48
Saith R R, Srinivasan A, Michie D, Sargent I L.
Relationships between the developmental potential of human in-vitro fertilization embryos and features describing the embryo, oocyte and follicle.
Hum Reprod Update.
1998;
4
121-134
-
49
Kane M T, Morgan P M, Coonan C.
Peptide growth factors and preimplantation development.
Hum Reprod Update.
1997;
3
137-157
-
50
Hardy K, Spanos S.
Growth factor expression and function in the human and mouse preimplantation embryo.
J Endocrinol.
2002;
172
221-236
-
51
Krussel J S, Huang H Y, Hirchenhain J et al..
Is there a place for biochemical embryonic preimplantational screening?.
J Reprod Fertil Suppl.
2000;
55
147-159
-
52
Hemmings R, Langlais J, Falcone T, Granger L, Miron P, Guyda H.
Human embryos produce transforming growth factors alpha activity and insulin-like growth factors II.
Fertil Steril.
1992;
58
101-104
-
53
Baranao R I, Piazza A, Rumi L S, Polak de Fried E.
Determination of IL-1 and IL-6 levels in human embryo culture-conditioned media.
Am J Reprod Immunol.
1997;
37
191-194
-
54
Fuzzi B, Rizzo R, Criscuoli L et al..
HLA-G expression in early embryos is a fundamental prerequisite for the obtainment of pregnancy.
Eur J Immunol.
2002;
32
311-315
-
55
Roudebush W E, Wininger J D, Jones A E et al..
Embryonic platelet-activating factor: an indicator of embryo viability.
Hum Reprod.
2002;
17
1306-1310
-
56
Sher G, Keskintepe L, Nouriani M, Roussev R, Batzofin J.
Expression of sHLA-G in supernatants of individually cultured 46-h embryos: a potentially valuable indicator of ‘embryo competency’ and IVF outcome.
Reprod Biomed Online.
2004;
9
74-78
-
57
Retzloff M G, Combelles C MH, Bowman F P, Racowsky C, Schust D J.
Interleukin-10 levels in single human embryo conditioned media help predict implantation.
Reprod Biomed Online.
, In preparation
-
58
Merchant M, Weinberger S R.
Recent advancements in surface-enhanced laser desorption/ionization-time of flight-mass spectrometry.
Electrophoresis.
2000;
21
1164-1177
-
59
Rubin R B, Merchant M.
A rapid protein profiling system that speeds study of cancer and other diseases.
Am Clin Lab.
2000;
19
28-29
-
60
Issaq H J, Veenstra T D, Conrads T P, Felschow D.
The SELDI-TOF MS approach to proteomics: protein profiling and biomarker identification.
Biochem Biophys Res Commun.
2002;
292
587-592
-
61
Anahory T, Dechaud H, Bennes R, Marin P, Lamb N J, Laoudj D.
Identification of new proteins in follicular fluid of mature human follicles.
Electrophoresis.
2002;
23
1197-1202
-
62
Gosden R G, Yin H, Miller D, Platts A, Bell A, Boulay B.
Identification and class assignment proteins expressed during mouse oocyte development using proteomics strategy.
Fertil Steril.
2003;
80(suppl)
S39
-
63
Taft R A, Denegre J M, Pendola F L, Eppig J J.
Identification of genes encoding mouse oocyte secretory and transmembrane proteins by a signal sequence trap.
Biol Reprod.
2002;
67
953-960
-
64
Latham K E, Bautista F D, Hirao Y, O'Brien M J, Eppig J J.
Comparison of protein synthesis patterns in mouse cumulus cells and mural granulosa cells: effects of follicle-stimulating hormone and insulin on granulosa cell differentiation in vitro.
Biol Reprod.
1999;
61
482-492
-
65
Leese H J.
Non-invasive methods for assessing embryos.
Hum Reprod.
1987;
2
435-438
-
66
Leese H J, Conaghan J, Martin K L, Hardy K.
Early human embryo metabolism.
Bioessays.
1993;
15
259-264
-
67
Gardner D K, Lane M, Stevens J, Schoolcraft W B.
Noninvasive assessment of human embryo nutrient consumption as a measure of developmental potential.
Fertil Steril.
2001;
76
1175-1180
-
68
Houghton F D, Hawkhead J A, Humpherson P G et al..
Non-invasive amino acid turnover predicts human embryo developmental capacity.
Hum Reprod.
2002;
17
999-1005
-
69
Downs S M, Humpherson P G, Leese H J.
Pyruvate utilization by mouse oocytes is influenced by meiotic status and the cumulus oophorus.
Mol Reprod Dev.
2002;
62
113-123
-
70
Roberts R, Franks S, Hardy K.
Culture environment modulates maturation and metabolism of human oocytes.
Hum Reprod.
2002;
17
2950-2956
-
71
Trimarchi J R, Liu L, Porterfield D M, Smith P J, Keefe D L.
A non-invasive method for measuring preimplantation embryo physiology.
Zygote.
2000;
8
15-24
-
72
Krisher R L, Bavister B D.
Enhanced glycolysis after maturation of bovine oocytes in vitro is associated with increased developmental competence.
Mol Reprod Dev.
1999;
53
19-26
-
73
Spindler R E, Pukazhenthi B S, Wildt D E.
Oocyte metabolism predicts the development of cat embryos to blastocyst in vitro.
Mol Reprod Dev.
2000;
56
163-171
-
74
Sutton M L, Gilchrist R B, Thompson J G.
Effects of in-vivo and in-vitro environments on the metabolism of the cumulus-oocyte complex and its influence on oocyte developmental capacity.
Hum Reprod Update.
2003;
9
35-48
-
75
Trimarchi J R, Liu L, Smith P J, Keefe D L.
Noninvasive measurement of potassium efflux as an early indicator of cell death in mouse embryos.
Biol Reprod.
2000;
63
851-857
-
76
Ebner T, Moser M, Sommergruber M, Tews G.
Selection based on morphological assessment of oocytes and embryos at different stages of preimplantation development: a review.
Hum Reprod Update.
2003;
9
251-262
-
77
Combelles C M, Albertini D F, Racowsky C.
Distinct microtubule and chromatin characteristics of human oocytes after failed in-vivo and in-vitro meiotic maturation.
Hum Reprod.
2003;
18
2124-2130
-
78
Blondin P, Coenen K, Guilbault L A, Sirard M-A.
Superovulation can reduce the developmental competence of bovine embryos.
Theriogenology.
1996;
46
1191-1203
-
79
Moor R M, Dai Y, Lee C, Fulka Jr J.
Oocyte maturation and embryonic failure.
Hum Reprod Update.
1998;
4
223-236
-
80
Takagi M, Kim I H, Izadyar F et al..
Impaired final follicular maturation in heifers after superovulation with recombinant human FSH.
Reproduction.
2001;
121
941-951
-
81
Diedrich K, Felberbaum R.
New approaches to ovarian stimulation.
Hum Reprod.
1998;
13(suppl 3)
1-17
-
82
Fauser B C, Bouchard P, Coelingh Bennink H J et al..
Alternative approaches in IVF.
Hum Reprod Update.
2002;
8
1-9
-
83
Racowsky C, Hinrichsen M J, Ginsburg E G.
Embryo quality based on ovulation induction stimulation: defining the differences.
Reprod Biomed Online.
2005;
11
, In press
-
84
Chen D, Burmeister L, Goldschlag D, Rosenwaks Z.
Ovarian hyperstimulation syndrome: strategies for prevention.
Reprod Biomed Online.
2003;
7
43-49
-
85
Merton J S, de Roos A P, Mullaart E et al..
Factors affecting oocyte quality and quantity in commercial application of embryo technologies in the cattle breeding industry.
Theriogenology.
2003;
59
651-674
-
86
Summers M C, Biggers J D.
Chemically defined media and the culture of mammalian preimplantation embryos: historical perspective and current issues.
Hum Reprod Update.
2003;
9
557-582
-
87
Hendriksen P J, Vos P L, Steenweg W N, Bevers M M, Dieleman S J.
Bovine follicular development and its effect on the in vitro competence of oocytes.
Theriogenology.
2000;
53
11-20
-
88
Catt J W, Henman M.
Toxic effects of oxygen on human embryo development.
Hum Reprod.
2000;
15(suppl 2)
199-206
-
89
Suh R S, Phadke N, Ohl D A, Takayama S, Smith G D.
Rethinking gamete/embryo isolation and culture with microfluidics.
Hum Reprod Update.
2003;
9
451-461
-
90
Moor R, Dai Y.
Maturation of pig oocytes in vivo and in vitro.
Reprod Suppl.
2001;
58
91-104
-
91
Sanfins A, Lee G Y, Plancha C E, Overstrom E W, Albertini D F.
Distinctions in meiotic spindle structure and assembly during in vitro and in vivo maturation of mouse oocytes.
Biol Reprod.
2003;
69
2059-2067
Catherine M. H CombellesPh.D.
Biology Department, Bicentennial Hall 350, Middlebury College
Middlebury, VT 05753
Email: ccombell@middlebury.edu