Download PDF
Semin Reprod Med 2007; 25(6): 461-475
DOI: 10.1055/s-2007-991044
© Thieme Medical Publishers

Uterine Receptivity: Alterations Associated with Benign Gynecological Disease

Melissa Donaghay1 , Bruce A. Lessey2
  • 1Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia
  • 2Greenville Hospital System Department of Reproductive Endocrinology and Infertility, Greenville, South Carolina
Further Information

Publication History

Publication Date:
25 October 2007 (online)

    Permissions and Reprints

ABSTRACT

The role of the endometrium is to establish and maintain pregnancy. Endometrial receptivity is established during the mid-secretory phase, between cycle day (CD) 20 to 24, or 6 to 10 days after ovulation. In some cases of infertility or recurrent pregnancy loss, implantation failure is due to a lack of expression of specific critical participating proteins such as cell adhesion molecules. Numerous cell adhesion molecules (including integrins, selectins, and cadherins) are expressed by the endometrium and appear to be necessary for the successful interaction of the embryo with the endometrium. One of the best-characterized cell adhesion molecules are the integrins. Integrins are transmembrane glycoproteins that belong to a large family comprising α and β subunits, and are present on virtually all cells in the body. Women with various benign gynecologic disorders, including endometriosis, polycystic ovarian syndrome, hydrosalpinges, and luteal phase defect, appear to exhibit decreased uterine receptivity and abnormal expression of endometrial biomarkers. This review addresses proposed mechanisms of implantation and endocrine and paracrine signals responsible for the establishment of endometrial receptivity as well has the possible mechanisms of dysfunction in certain types of infertility in women with benign gynecologic disease.

KEYWORDS

Endometrium - polycystic ovary syndrome - integrins - endometriosis - infertility - hydrosalpinges

REFERENCES

  • 1 Carson D D, Bagchi I, Dey S K et al.. Embryo implantation.  Dev Biol. 2000;  223 217-237
    CrossrefPubMedGoogle Scholar
  • 2 Aplin J D. Embryo implantation: the molecular mechanism remains elusive.  Reprod Biomed Online. 2006;  13 833-839
    CrossrefPubMedGoogle Scholar
  • 3 Horcajadas J A, Pellicer A, Simon C. Wide genomic analysis of human endometrial receptivity: new times, new opportunities.  Hum Reprod Update. 2007;  13 77-86
    CrossrefPubMedGoogle Scholar
  • 4 Margalioth E J, Ben-Chetrit A, Gal M, Eldar-Geva T. Investigation and treatment of repeated implantation failure following IVF-ET.  Hum Reprod. 2006;  21 3036-3043
    CrossrefPubMedGoogle Scholar
  • 5 Imakawa K, Imai M, Sakai A et al.. Regulation of conceptus adhesion by endometrial CXC chemokines during the implantation period in sheep.  Mol Reprod Dev. 2006;  73 850-858
    CrossrefPubMedGoogle Scholar
  • 6 Minas V, Loutradis D, Makrigiannakis A. Factors controlling blastocyst implantation.  Reprod Biomed Online. 2005;  10 205-216
    PubMedGoogle Scholar
  • 7 Yoshinaga K. Receptor concept in implantation research. In: Yoshinaga K, Mori T Development of Preimplantation Embryos and their Environment. New York; AR Liss 1989: 379-387
    Google Scholar
  • 8 Pope W F. Uterine asynchrony: a cause of embryonic loss.  Biol Reprod. 1988;  39 999-1003
    CrossrefPubMedGoogle Scholar
  • 9 Wilcox A J, Baird D D, Wenberg C R. Time of implantation of the conceptus and loss of pregnancy.  N Engl J Med. 1999;  340 1796-1799
    CrossrefPubMedGoogle Scholar
  • 10 Cowell T P. Implantation and development of mouse eggs transferred to the uterus of non-progestational mice.  J Reprod Fertil. 1969;  19 239-245
    PubMedGoogle Scholar
  • 11 Hertig A T, Rock J, Adams E C. A description of 34 human ova within the first 17 days of development.  Am J Anat. 1956;  98 435-493
    CrossrefPubMedGoogle Scholar
  • 12 Navot D, Bergh P A, Williams M et al.. An insight into early reproductive processes through the in vivo model of ovum donation.  J Clin Endocrinol Metab. 1991;  72 408-445
    CrossrefPubMedGoogle Scholar
  • 13 Navot D, Scott R T, Droesch K, Veeck L L, Liu H C, Rosenwaks Z. The window of embryo transfer and the efficiency of human conception in vitro.  Fertil Steril. 1991;  55 114-118
    PubMedGoogle Scholar
  • 14 Simon C, Moreno C, Remoh J, Pellicer A. Molecular interactions between embryo and uterus in the adhesion phase of human implantation.  Hum Reprod. 1998;  13(suppl 3) 219-232
    PubMedGoogle Scholar
  • 15 Giudice L C. Genes associated with embryonic attachment and implantation and the role of progesterone.  J Reprod Med. 1999;  44 165-171
    PubMedGoogle Scholar
  • 16 Lessey B A, Castelbaum A J. Integrins and implantation in the human.  Rev Endocr Metab Disord. 2002;  3 107-117
    CrossrefPubMedGoogle Scholar
  • 17 Stephenson M D. Frequency of factors associated with habitual abortion in 197 couples.  Fertil Steril. 1996;  66 24-29
    PubMedGoogle Scholar
  • 18 Lessey B A, Castelbaum A J, Buck C A, Lei Y, Yowell C W, Sun J. Further characterization of endometrial integrins during the menstrual cycle and in pregnancy.  Fertil Steril. 1994;  62 497-506
    PubMedGoogle Scholar
  • 19 Tabibzadeh S. Patterns of expression of integrin molecules in human endometrium throughout the menstrual cycle.  Hum Reprod. 1992;  7 876-882
    PubMedGoogle Scholar
  • 20 Genbacev O D, Prakobphol A, Foulk R A et al.. Trophoblast L-selectin-mediated adhesion at the maternal-fetal interface.  Science. 2003;  299 405-408
    CrossrefPubMedGoogle Scholar
  • 21 Fukuda M N, Sato T, Nakayama J et al.. Trophinin and tastin, a novel cell adhesion molecule complex with potential involvement in embryo implantation.  Genes Dev. 1995;  9 1199-1210
    CrossrefPubMedGoogle Scholar
  • 22 Paria B C, Elenius K, Klagsbrun M, Dey S K. Heparin-binding EGF-like growth factor interacts with mouse blastocysts independently of ErbB1: a possible role for heparan sulfate proteoglycans and ErbB4 in blastocyst implantation.  Development. 1999;  126 1997-2005
    PubMedGoogle Scholar
  • 23 Raab G, Kover K, Paria B C, Dey S K, Ezzell R M, Klagsbrun M. Mouse preimplantation blastocysts adhere to cells expressing the transmembrane form of heparin-binding EGF-like growth factor.  Development. 1996;  122 637-645
    PubMedGoogle Scholar
  • 24 Lessey B A. Integrins and uterine receptivity. In: Carson DD Embryo Implantation: Molecular, Cellular and Clinical Aspects. New York; Springer 1999: 210-222
    Google Scholar
  • 25 Yelian F D, Yang Y, Hirata J D, Schultz J F, Armant D R. Molecular interactions between fibronectin and integrins during mouse blastocyst outgrowth.  Mol Reprod Dev. 1995;  41 435-448
    CrossrefPubMedGoogle Scholar
  • 26 Aplin A E, Howe A K, Juliano R L. Cell adhesion molecules, signal transduction and cell growth.  Curr Opin Cell Biol. 1999;  11 737-744
    CrossrefPubMedGoogle Scholar
  • 27 Aplin J D. The cell biology of human implantation.  Placenta. 1996;  17 269-275
    CrossrefPubMedGoogle Scholar
  • 28 Campbell S, Swann H R, Aplin J D, Seif M W, Kimber S J, Elstein M. CD44 is expressed throughout pre-implantation human embryo development.  Hum Reprod. 1995;  10 425-430
    PubMedGoogle Scholar
  • 29 Apparao K BC, Murray M J, Fritz M A et al.. Osteopontin and its receptor αvβ3 integrin are coexpressed in the human endometrium during the menstrual cycle but regulated differentially.  J Clin Endocrinol Metab. 2001;  86 4991-5000
    CrossrefPubMedGoogle Scholar
  • 30 Albelda S M, Buck C A. 1990 Integrins and other cell adhesion molecules.  FASEB J. 1990;  4 2868-2880
    PubMedGoogle Scholar
  • 31 Hynes R O. Integrins: a family of cell surface receptors.  Cell. 1987;  48 549-554
    CrossrefPubMedGoogle Scholar
  • 32 Ruoslahti E, Pierschbacher M D. New perspectives in cell adhesion: RGD and integrins.  Science. 1987;  238 491-497
    CrossrefPubMedGoogle Scholar
  • 33 Lessey B A, Castelbaum A J. Integrins and implantation in the human.  Rev Endocr Metab Disord. 2002;  3 107-117
    CrossrefPubMedGoogle Scholar
  • 34 Getzenberg R H, Pienta K J, Coffey D S. The tissue matrix: cell dynamics and hormone action.  Endocr Rev. 1990;  11 399-417
    PubMedGoogle Scholar
  • 35 Lessey B A, Damjanovich L, Coutifaris C, Castelbaum A, Albelda S M, Buck C A. Integrin adhesion molecules in the human endometrium. Correlation with the normal and abnormal menstrual cycle.  J Clin Invest. 1992;  90 188-195
    CrossrefPubMedGoogle Scholar
  • 36 Giancotti F G, Ruoslahti E. Integrin signaling.  Science. 1999;  285 1028-1032
    CrossrefPubMedGoogle Scholar
  • 37 Murray M J, Lessey B A. Embryo implantation and tumor metastasis: Common pathways of invasion and angiogenesis.  Semin Reprod Endocrinol. 1999;  17 275-290
    Article in Thieme ConnectPubMedGoogle Scholar
  • 38 Lessey B A. Endometrial Integrins.  Endocrinologist. 1995;  5 214-222
    PubMedGoogle Scholar
  • 39 Zhao R, Pathak A S, Stouffer G A. beta(3)-Integrin cytoplasmic binding proteins.  Arch Immunol Ther Exp (Warsz). 2004;  52 348-355
    PubMedGoogle Scholar
  • 40 Brooks P C, Clark R AF, Cheresh D A. Requirement of vascular integrin alpha v beta 3 for angiogenesis.  Science. 1994;  264 569-571
    CrossrefPubMedGoogle Scholar
  • 41 Friedlander M, Brooks P C, Shaffer R W, Kincaid C M, Varner J A, Cheresh D A. Definition of two angiogenic pathways by distinct alpha v integrins.  Science. 1995;  270 1500-1502
    PubMedGoogle Scholar
  • 42 Buck C A, Horwitz A F. Integrin, a transmembrane glycoprotein complex mediating cell-substratum adhesion.  J Cell Sci. 1987;  8(suppl) 231-250
    PubMedGoogle Scholar
  • 43 Hynes R O. Integrins: versatility, modulation, and signaling in cell adhesion.  Cell. 1992;  69 11-25
    CrossrefPubMedGoogle Scholar
  • 44 Brooks P C, Strimblad S, Sanders L C et al.. Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin αvβ3.  Cell. 1996;  85 683-693
    CrossrefPubMedGoogle Scholar
  • 45 Slayden O D, Brenner R M. Hormonal regulation and localization of estrogen, progestin and androgen receptors in the endometrium of nonhuman primates: effects of progesterone receptor antagonists.  Arch Histol Cytol. 2004;  67 393-409
    CrossrefPubMedGoogle Scholar
  • 46 Talbi S, Hamilton A E, Vo K C et al.. Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and underlying biological processes in normo-ovulatory women.  Endocrinology. 2006;  147 1097-1121
    CrossrefPubMedGoogle Scholar
  • 47 Lessey B A, Ilesanmi A O, Sun J, Lessey M A, Harris J, Chwalisz K. Luminal and glandular endometrial epithelium express integrins differentially throughout the menstrual cycle: Implications for implantation, contraception, and infertility.  Am J Reprod Immunol. 1996;  35 195-204
    PubMedGoogle Scholar
  • 48 Fazleabas A T, Kim J J. What makes an embryo stick?.  Science. 2003;  299 355-356
    CrossrefPubMedGoogle Scholar
  • 49 Noyes R W, Hertig A I, Rock J. Dating the endometrial biopsy.  Fertil Steril. 1950;  1 3-25
    PubMedGoogle Scholar
  • 50 Jones G S. Luteal phase insufficiency.  Clin Obstet Gynecol. 1973;  16 255-273
    PubMedGoogle Scholar
  • 51 Jones G S. The luteal phase defect.  Fertil Steril. 1976;  27 351-356
    PubMedGoogle Scholar
  • 52 Coutifaris C, Myers E R, Guzick D S et al.. Histological dating of timed endometrial biopsy tissue is not related to fertility status.  Fertil Steril. 2004;  82 1264-1272
    CrossrefPubMedGoogle Scholar
  • 53 Murray M J, Meyer W R, Zaino R J et al.. A critical analysis of the accuracy, reproducibility, and clinical utility of histologic endometrial dating in fertile women.  Fertil Steril. 2004;  81 1333-1343
    CrossrefPubMedGoogle Scholar
  • 54 Anderson T L. Biomolecular markers for the window of uterine receptivity. In: Yoshinaga K Blastocyst Implantation. Boston MA; Adams Publishing 1993: 219-224
    Google Scholar
  • 55 Ilesanmi A O, Hawkins D A, Lessey B A. Immunohistochemical markers of uterine receptivity in the human endometrium.  Microsc Res Tech. 1993;  25 208-222
    CrossrefPubMedGoogle Scholar
  • 56 Yaron Y, Botchan A, Amit A, Peyser M R, David M P, Lessing J B. Endometrial receptivity in the light of modern assisted reproductive technologies.  Fertil Steril. 1994;  62 225-232
    PubMedGoogle Scholar
  • 57 Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation.  Hum Reprod Update. 2006;  12 731-746
    CrossrefPubMedGoogle Scholar
  • 58 Lessey B A. The use of integrins for the assessment of uterine receptivity.  Fertil Steril. 1994;  61 812-814
    PubMedGoogle Scholar
  • 59 Enders A C, Nelson D M. Pinocytotic activity of the uterus of the rat.  Am J Anat. 1973;  138 277-299
    CrossrefPubMedGoogle Scholar
  • 60 Psychoyos A, Mandon P. Study of the surface of the uterine epithelium by scanning electron microscope. Observations in the rat at the 4th and 5th day of pregnancy (in French).  C R Acad Sci Hebd Seances Acad Sci D. 1971;  272(21) 2723-2725
    PubMedGoogle Scholar
  • 61 Nikas G, Drakakis P, Loutradis D et al.. Uterine pinopodes as markers of the `nidation window' in cycling women receiving exogenous oestradiol and progesterone.  Hum Reprod. 1995;  10 1208-1213
    PubMedGoogle Scholar
  • 62 Psychoyos A, Nikas G. Uterine pinopodes as markers of uterine receptivity.  Assist Reprod Rev. 1994;  4 26-41
    PubMedGoogle Scholar
  • 63 Martel D, Frydman R, Glissant M, Maggioni C, Roche D, Psychoyos A. Scanning electron microscopy of postovulatory human endometrium in spontaneous cycles and cycles stimulated by hormone treatment.  J Endocrinol. 1987;  114 319-324
    CrossrefPubMedGoogle Scholar
  • 64 Bentin-Ley U, Sjîgren A, Nilsson L, Hamberger L, Larsen J F, Horn T. Presence of uterine pinopodes at the embryo-endometrial interface during human implantation in vitro.  Hum Reprod. 1999;  14 515-520
    CrossrefPubMedGoogle Scholar
  • 65 Bentin-Ley U, Horn T, Sjîgren A, Sorensen S, Larsen J F, Hamberger L. Ultrastructure of human blastocyst-endometrial interactions in vitro.  J Reprod Fertil. 2000;  120 337-350
    PubMedGoogle Scholar
  • 66 Lessey B A. Two pathways of progesterone action in the human endometrium: implications for implantation and contraception.  Steroids. 2003;  68 809-815
    CrossrefPubMedGoogle Scholar
  • 67 Acosta A A, Elberger L, Borghi M et al.. Endometrial dating and determination of the window of implantation in healthy fertile women.  Fertil Steril. 2000;  73 788-798
    CrossrefPubMedGoogle Scholar
  • 68 Usadi R S, Murray M J, Bagnell R C et al.. Temporal and morphologic characteristics of pinopod expression across the secretory phase of the endometrial cycle in normally cycling women with proven fertility.  Fertil Steril. 2003;  79 970-974
    CrossrefPubMedGoogle Scholar
  • 69 Quinn C, Ryan E, Claessens E A et al.. The presence of pinopodes in the human endometrium does not delineate the implantation window.  Fertil Steril. 2007;  87 1015-1021
    CrossrefPubMedGoogle Scholar
  • 70 Clark G F, Oehninger S, Patankar M S et al.. A role for glycoconjugates in human development: The human feto-embryonic defence system hypothesis.  Hum Reprod. 1996;  11 467-473
    PubMedGoogle Scholar
  • 71 Oehninger S, Coddington C C, Hodgen G D, Seppala M. Factors affecting fertilization: endometrial placental protein 14 reduces the capacity of human spermatozoa to bind to the human zona pellucida.  Fertil Steril. 1995;  63 377-383
    PubMedGoogle Scholar
  • 72 Klentzeris L D, Bulmer J N, Seppala M, Li T C, Warren M A, Cooke I D. Placental protein 14 in cycles with normal and retarded endometrial differentiation.  Hum Reprod. 1994;  9 394-398
    PubMedGoogle Scholar
  • 73 Batista M C, Bravo N, Cartledge T P, Loriaux D L, Merriam G R, Nieman L K. Serum levels of placental protein 14 do not accurately reflect histologic maturation of the endometrium.  Obstet Gynecol. 1993;  81 439-443
    PubMedGoogle Scholar
  • 74 Kao L C, Germeyer A, Tulac S et al.. Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility.  Endocrinology. 2003;  144 2870-2881
    CrossrefPubMedGoogle Scholar
  • 75 Lindhard A, Bentin-Ley U, Ravn V et al.. Biochemical evaluation of endometrial function at the time of implantation.  Fertil Steril. 2002;  78 221-233
    CrossrefPubMedGoogle Scholar
  • 76 Bhatt H, Brunet L J, Stewart C L. Uterine expression of leukemia inhibitory factor coincides with the onset of blastocyst implantation.  Proc Natl Acad Sci USA. 1991;  88 11408-11412
    CrossrefPubMedGoogle Scholar
  • 77 Stewart C L, Kaspar P, Brunet L J et al.. Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor.  Nature. 1992;  359 76-79
    CrossrefPubMedGoogle Scholar
  • 78 Sherwin J R, Smith S K, Wilson A, Sharkey A M. Soluble gp130 is up-regulated in the implantation window and shows altered secretion in patients with primary unexplained infertility.  J Clin Endocrinol Metab. 2002;  87 3953-3960
    CrossrefPubMedGoogle Scholar
  • 79 Cullinan E B, Abbondanzo S J, Anderson P S, Pollard J W, Lessey B A, Stewart C L. Leukemia inhibitory factor (LIF) and LIF receptor expression in human endometrium suggests a potential autocrine/paracrine function in regulating embryo implantation.  Proc Natl Acad Sci USA. 1996;  93 3115-3120
    CrossrefPubMedGoogle Scholar
  • 80 Mikolajczyk M, Wirstlein P, Skrzypczak J. Leukaemia inhibitory factor and interleukin 11 levels in uterine flushings of infertile patients with endometriosis.  Hum Reprod. 2006;  21 3054-3058
    CrossrefPubMedGoogle Scholar
  • 81 Zhu L J, Bagchi M K, Bagchi I C. Attenuation of calcitonin gene expression in pregnant rat uterus leads to a block in embryonic implantation.  Endocrinology. 1998;  139 330-339
    CrossrefPubMedGoogle Scholar
  • 82 Zhu L J, Cullinan-Bove K, Polihronis M, Bagchi M K, Bagchi I C. Calcitonin is a progesterone-regulated marker that forecasts the receptive state of endometrium during implantation.  Endocrinology. 1998;  139 3923-3934
    CrossrefPubMedGoogle Scholar
  • 83 Kumar S, Zhu L J, Polihronis M et al.. Progesterone induces calcitonin gene expression in human endometrium within the putative window of implantation.  J Clin Endocrinol Metab. 1998;  83 4443-4450
    CrossrefPubMedGoogle Scholar
  • 84 Illera M J, Cullinan E, Gui Y, Yuan L, Beyler S A, Lessey B A. Blockade of the alpha(v)beta(3) integrin adversely affects implantation in the mouse.  Biol Reprod. 2000;  62 1285-1290
    CrossrefPubMedGoogle Scholar
  • 85 Illera M J, Lorenzo P L, Gui Y T, Beyler S A, Apparao K B, Lessey B A. A role for alphavbeta3 integrin during implantation in the rabbit model.  Biol Reprod. 2003;  68 766-771
    PubMedGoogle Scholar
  • 86 Creus M, Balasch J, Ordi J et al.. Integrin expression in normal and out-of-phase endometria.  Hum Reprod. 1998;  13 3460-3468
    PubMedGoogle Scholar
  • 87 Lessey B A, Castelbaum A J, Sawin S W, Sun J. Integrins as markers of uterine receptivity in women with primary unexplained infertility.  Fertil Steril. 1995;  63 535-542
    PubMedGoogle Scholar
  • 88 Lessey B A, Castelbaum A J, Sawin S J et al.. Aberrant integrin expression in the endometrium of women with endometriosis.  J Clin Endocrinol Metab. 1994;  79 643-649
    CrossrefPubMedGoogle Scholar
  • 89 Meyer W R, Castelbaum A J, Somkuti S et al.. Hydrosalpinges adversely affect markers of endometrial receptivity.  Hum Reprod. 1997;  12 1393-1398
    CrossrefPubMedGoogle Scholar
  • 90 Apparao K BC, Lovely L P, Gui Y, Lininger R A, Lessey B A. Elevated endometrial androgen receptor expression in women with polycystic ovarian syndrome.  Biol Reprod. 2002;  66 297-304
    CrossrefPubMedGoogle Scholar
  • 91 Savaris R F, Pedrini J L, Flores R, Fabris G, Zettler C G. Expression of alpha 1 and beta 3 integrins subunits in the endometrium of patients with tubal phimosis or hydrosalpinx.  Fertil Steril. 2006;  85 188-192
    CrossrefPubMedGoogle Scholar
  • 92 Thomas K, Thomson A, Wood S, Kingsland C, Vince G, Lewis-Jones I. Endometrial integrin expression in women undergoing in vitro fertilization and the association with subsequent treatment outcome.  Fertil Steril. 2003;  80 502-507
    CrossrefPubMedGoogle Scholar
  • 93 Nardo L G, Bartoloni G, Di Mercurio S, Nardo F. Expression of the alpha(v)beta3 and alpha4beta1 integrins throughout the putative window of implantation in a cohort of healthy fertile women.  Acta Obstet Gynecol Scand. 2002;  81 753-758
    CrossrefPubMedGoogle Scholar
  • 94 Bildirici I, Bukulmez O, Ensari A, Yarali H, Gurgan T. A prospective evaluation of the effect of salpingectomy on endometrial receptivity in cases of women with communicating hydrosalpinges.  Hum Reprod. 2001;  16 2422-2426
    PubMedGoogle Scholar
  • 95 von Wolff M, Strowitzki T, Becker V, Zepf C, Tabibzadeh S, Thaler C J. Endometrial osteopontin, a ligand of beta 3-integrin, is maximally expressed around the time of the “implantation” window.  Fertil Steril. 2001;  76 775-781
    CrossrefPubMedGoogle Scholar
  • 96 Mosher W D, Pratt W F. Fecundity and infertility in the United States: incidence and trends.  Fertil Steril. 1991;  56 192-193
    CrossrefPubMedGoogle Scholar
  • 97 Mosher W D, Pratt W F. Fecundity and infertility in the United States: incidence and trends.  Fertil Steril. 1991;  56 192-193
    CrossrefPubMedGoogle Scholar
  • 98 Abma J C, Chandra A, Mosher W D, Peterson L, Piccinino L. Fertility, family planning, and women's health: new data from the 1995 National Survey of Family Growth.  Vital Health Stat. 1997;  23 1-114
    PubMedGoogle Scholar
  • 99 Blacker C M, Ginsburg K A, Leach R E, Randolph J, Moghissi K S. Unexplained infertility: evaluation of the luteal phase; results of the National Center for Infertility Research at Michigan.  Fertil Steril. 1997;  67 437-442
    CrossrefPubMedGoogle Scholar
  • 100 Strathy J H, Molgaard C A, Coulam C B, Melton L J. Endometriosis and infertility: a laparoscopic study of endometriosis among fertile and infertile women.  Fertil Steril. 1982;  38 667-672
    PubMedGoogle Scholar
  • 101 Verkauf B S. Incidence, symptoms, and signs of endometriosis in fertile and infertile women.  J Fla Med Assoc. 1987;  74 671-675
    PubMedGoogle Scholar
  • 102 Schenken R S, Guzick D S. Revised endometriosis classification: 1996.  Fertil Steril. 1997;  67 815-816
    CrossrefPubMedGoogle Scholar
  • 103 Bancroft K, Vaughan Williams C A, Elstein M. Minimal/mild endometriosis and infertility. A review.  Br J Obstet Gynaecol. 1989;  96 454-460
    PubMedGoogle Scholar
  • 104 Arici A, Oral E, Bukulmez O, Duleba A, Olive D L, Jones E E. The effect of endometriosis on implantation: results from the Yale University in vitro fertilization and embryo transfer program.  Fertil Steril. 1996;  65 603-607
    PubMedGoogle Scholar
  • 105 Matson P L, Yovich J L. The treatment of infertility associated with endometriosis by in vitro fertilization.  Fertil Steril. 1986;  46 432-434
    PubMedGoogle Scholar
  • 106 Surrey E S, Silverberg K M, Surrey M W, Schoolcraft W B. Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis.  Fertil Steril. 2002;  78 699-704
    CrossrefPubMedGoogle Scholar
  • 107 Yovich J L, Matson P L, Richardson P A, Hilliard C. Hormonal profiles and embryo quality in women with severe endometriosis treated by in vitro fertilization and embryo transfer.  Fertil Steril. 1988;  50 308-313
    PubMedGoogle Scholar
  • 108 Mahadevan M M, Trounson A, Leeton J. The relationship of tubal blockage, infertility of unknown cause, suspected male infertility, and endometriosis to success of in vitro fertilization and embryo transfer.  Fertil Steril. 1983;  40 755-762
    PubMedGoogle Scholar
  • 109 Wardle P G, McLauglin E A, McDermott A, Mitchell J D, Ray B D, Hull M GR. Endometriosis and ovulatory disorder: reduced fertilization in vitro compared with tubal and unexplained infertility.  Lancet. 1985;  2 236-239
    PubMedGoogle Scholar
  • 110 Yovich J L, Yovich J M, Tuvik A I. In vitro fertilization for endometriosis.  Lancet. 1985;  2 552
    PubMedGoogle Scholar
  • 111 O'Shea R T, Chen C, Weiss T, Jones W R. Endometriosis and in vitro fertilization.  Lancet. 1985;  2 723
    PubMedGoogle Scholar
  • 112 Barnhart K, Dunsmoor R, Coutifaris C. The effect of endometriosis on IVF outcome.  Fertil Steril. 2002;  77 1148-1155
    CrossrefPubMedGoogle Scholar
  • 113 Jones Jr H W, Acosta A A, Andrews M C et al.. Three years of in vitro fertilization at Norfolk.  Fertil Steril. 1984;  42 826-834
    PubMedGoogle Scholar
  • 114 Oehninger S, Brzyski R G, Muasher S J, Acosta A A, Jones G S. In-vitro fertilization and embryo transfer in patients with endometriosis: impact of a gonadotrophin releasing hormone agonist.  Hum Reprod. 1989;  4 541-544
    PubMedGoogle Scholar
  • 115 Alsalili M, Yuzpe A, Tummons I et al.. Cumulative pregnancy rates and pregnancy outcome after in-vitro fertilization: > 5000 cycles at one centre.  Hum Reprod. 1995;  10 470-474
    PubMedGoogle Scholar
  • 116 Dmowski W P, Rana N, Michalowska J, Friberg J, Papierniak C, el-Roeiy A. The effect of endometriosis, its stage and activity, and of autoantibodies on in vitro fertilization and embryo transfer success rates.  Fertil Steril. 1995;  63 555-562
    PubMedGoogle Scholar
  • 117 Inoue M, Kobayashi Y, Honda I, Awaji H, Fujii A. The impact of endometriosis on the reproductive outcome of infertile patients.  Am J Obstet Gynecol. 1992;  167 278-282
    PubMedGoogle Scholar
  • 118 Gerber S, Paraschos T, Atkinson G, Margara R, Winston R M. Results of IVF in patients with endometriosis: the severity of the disease does not affect outcome, or the incidence of miscarriage.  Hum Reprod. 1995;  10 1507-1511
    CrossrefPubMedGoogle Scholar
  • 119 Tanbo T, Omland A, Dale P O, Abyholm T. In vitro fertilization/embryo transfer in unexplained infertility and minimal peritoneall endometriosis.  Acta Obstet Gynecol Scand. 1995;  74 539-543
    CrossrefPubMedGoogle Scholar
  • 120 Lessey B A. Integrins and the endometrium: new markers of uterine receptivity.  Ann N Y Acad Sci. 1997;  828 111-122
    CrossrefPubMedGoogle Scholar
  • 121 Taylor H S, Arici A, Olive D, Igarashi P. HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium.  J Clin Invest. 1998;  101 1379-1384
    CrossrefPubMedGoogle Scholar
  • 122 Ma L, Benson G V, Lim H J, Dey S K, Maas R L. Abdominal B (AbdB) Hoxa genes: regulation in adult uterus by estrogen and progesterone and repression in Mullerian duct by the synthetic estrogen diethylstilbestrol (DES).  Dev Biol. 1998;  197 141-154
    CrossrefPubMedGoogle Scholar
  • 123 Gui Y, Zhang J, Yuan L, Lessey B A. Regulation of Hoxa-10 and its expression in normal and abnormal endometrium.  Mol Hum Reprod. 1999;  5 866-873
    CrossrefPubMedGoogle Scholar
  • 124 Daftary G S, Troy P J, Bagot C N, Young S L, Taylor H S. Direct regulation of beta3-integrin subunit gene expression by HOXA10 in endometrial cells.  Mol Endocrinol. 2002;  16 571-579
    CrossrefPubMedGoogle Scholar
  • 125 Taylor H S, Bagot C, Kardana A, Olive D, Arici A. HOX gene expression is altered in the endometrium of women with endometriosis.  Hum Reprod. 1999;  14 1328-1331
    CrossrefPubMedGoogle Scholar
  • 126 Wu Y, Halverson G, Basir Z, Strawn E, Yan P, Guo S W. Aberrant methylation at HOXA10 may be responsible for its aberrant expression in the endometrium of patients with endometriosis.  Am J Obstet Gynecol. 2005;  193 371-380
    CrossrefPubMedGoogle Scholar
  • 127 Lessey B A, Killam A P, Metzger D A, Haney A F, Greene G L, McCarty Jr K S. Immunohistochemical analysis of human uterine estrogen and progesterone receptors throughout the menstrual cycle.  J Clin Endocrinol Metab. 1988;  67 334-340
    CrossrefPubMedGoogle Scholar
  • 128 Lessey B A, Palomino W A, Apparao K B, Young S L, Lininger R A. Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women.  Reprod Biol Endocrinol. 2006;  4(suppl 1) S9
    CrossrefPubMedGoogle Scholar
  • 129 Fazleabas A T, Brudney A, Chai D, Langoi D, Bulun S E. Steroid receptor and aromatase expression in baboon endometriotic lesions.  Fertil Steril. 2003;  80(suppl 2) 820-827
    CrossrefPubMedGoogle Scholar
  • 130 Igarashi T M, Bruner-Tran K L, Yeaman G R et al.. Reduced expression of progesterone receptor-B in the endometrium of women with endometriosis and in cocultures of endometrial cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.  Fertil Steril. 2005;  84 67-74
    CrossrefPubMedGoogle Scholar
  • 131 Burney R O, Talbi S, Hamilton A E et al.. Gene expression analysis of endometrium reveals progesterone resistance and candidate genetic loci in women with endometriosis.  Endocrinology. 2007;  148 3814-3826
    CrossrefPubMedGoogle Scholar
  • 132 Kitawaki J, Kusuki I, Koshiba H, Tsukamoto K, Honjo H. Expression of aromatase cytochrome P450 in eutopic endometrium and its application as a diagnostic test for endometriosis.  Gynecol Obstet Invest. 1999;  48(suppl 1) 21-28
    CrossrefPubMedGoogle Scholar
  • 133 Zeitoun K M, Bulun S E. Aromatase: a key molecule in the pathophysiology of endometriosis and a therapeutic target.  Fertil Steril. 1999;  72 961-969
    CrossrefPubMedGoogle Scholar
  • 134 Lessey B A, Young S L. Integrins and other cell adhesion molecules in endometrium and endometriosis.  Semin Reprod Endocrinol. 1997;  15 291-299
    PubMedGoogle Scholar
  • 135 Lessey B A. Medical management of endometriosis and infertility.  Fertil Steril. 2000;  73 1089-1096
    CrossrefPubMedGoogle Scholar
  • 136 Matsuzaki S, Canis M, Vaurs-Barriere C, Boespflug-Tanguy O, Dastugue B, Mage G. DNA microarray analysis of gene expression in eutopic endometrium from patients with deep endometriosis using laser capture microdissection.  Fertil Steril. 2005;  84(suppl 2) 1180-1190
    CrossrefPubMedGoogle Scholar
  • 137 Strandell A, Lindhard A. Hydrosalpinx and ART: salpingectomy prior to IVF can be recommended to a well-defined subgroup of patients.  Hum Reprod. 2000;  15 2072
    CrossrefPubMedGoogle Scholar
  • 138 Cohen M A, Lindheim S R, Sauer M V. Hydrosalpinges adversely affect implantation in donor oocyte cycles.  Hum Reprod. 1999;  14 1087-1089
    CrossrefPubMedGoogle Scholar
  • 139 Strandell A, Lindhard A, Waldenstrim U, Thorburn J, Janson P O, Hamberger L. Hydrosalpinx and IVF outcome: a prospective, randomized multicentre trial in Scandinavia on salpingectomy prior to IVF.  Hum Reprod. 1999;  14 2762-2769
    CrossrefPubMedGoogle Scholar
  • 140 Nackley A C, Muasher S J. The significance of hydrosalpinx in in vitro fertilization.  Fertil Steril. 1998;  69 373-384
    CrossrefPubMedGoogle Scholar
  • 141 Akman M A, Garcia J E, Damewood M D, Watts L D, Katz E. Hydrosalpinx affects the implantation of previously cryopreserved embryos.  Hum Reprod. 1996;  11 1013-1014
    PubMedGoogle Scholar
  • 142 Katz E, Akman M A, Damewood M D, Garcia J E. Deleterious effect of the presence of hydrosalpinx on implantation and pregnancy rates with in vitro fertilization.  Fertil Steril. 1996;  66 122-125
    PubMedGoogle Scholar
  • 143 Mukherjee T, Copperman A B, McCaffrey C, Cook C A, Bustillo M, Obasaju M F. Hydrosalpinx fluid has embryotoxic effects on murine embryogenesis: a case for prophylactic salpingectomy.  Fertil Steril. 1996;  66 851-853
    PubMedGoogle Scholar
  • 144 Puttamens P J, Brosens I. Preventive salpingectomy of hydrosalpinx prior to IVF - salpingectomy improves in-vitro fertilization outcome in patients with a hydrosalpinx: Blind victimization of the fallopian tube?.  Hum Reprod. 1996;  11 2079-2081
    PubMedGoogle Scholar
  • 145 Shelton K E, Butler L, Toner J P, Oehninger S, Muasher S J. Salpingectomy improves the pregnancy rate in in-vitro fertilization patients with hydrosalpinx.  Hum Reprod. 1996;  11 523-525
    PubMedGoogle Scholar
  • 146 Vandromme J, Chasse E, Lejeune B, Van Rysselberge M, Delvigne A, Leroy F. Hydrosalpinges in in-vitro fertilization: an unfavourable prognostic feature.  Hum Reprod. 1995;  10 576-579
    PubMedGoogle Scholar
  • 147 Andersen A N, Yue Z, Meng F J, Petersen K. Low implantation rate after in-vitro fertilization in patients with hydrosalpinges diagnosed by ultrasonography.  Hum Reprod. 1994;  9 1935-1938
    PubMedGoogle Scholar
  • 148 Strandell A, Waldenstrom U, Nilsson L, Hamberger L. Hydrosalpinx reduces in-vitro fertilization/embryo transfer pregnancy rates.  Hum Reprod. 1994;  9 861-863
    PubMedGoogle Scholar
  • 149 Granot I, Dekel N, Segal I, Fieldust S, Shoham Z, Barash A. Is hydrosalpinx fluid cytotoxic?.  Hum Reprod. 1998;  13 1620-1624
    CrossrefPubMedGoogle Scholar
  • 150 Sachdev R, Kemmann E, Bohrer M K, El-Danasouri I. Detrimental effect of hydrosalpinx fluid on the development and blastulation of mouse embryos in vitro.  Fertil Steril. 1997;  68 531-533
    CrossrefPubMedGoogle Scholar
  • 151 Sawin S W, De Mola J RL, Monzon-Bordonaba F, Wang C L, Feinberg R F. Hydrosalpinx fluid enhances human trophoblast viability and function in vitro: Implications for embryonic implantation in assisted reproduction.  Fertil Steril. 1997;  68 65-71
    CrossrefPubMedGoogle Scholar
  • 152 Strandell A, Sjogren A, Bentin-Ley U, Thorburn J, Hamberger L, Brannstrom M. Hydrosalpinx fluid does not adversely affect the normal development of human embryos and implantation in vitro.  Hum Reprod. 1998;  13 2921-2925
    PubMedGoogle Scholar
  • 153 Ng E HY, Ajonuma L C, Lau E YL, Yeung W SB, Ho P C. Adverse effects of hydrosalpinx fluid on sperm motility and survival.  Hum Reprod. 2000;  15 772-777
    CrossrefPubMedGoogle Scholar
  • 154 Sagoskin A W, Lessey B A, Mottla G L et al.. Salpingectomy or proximal tubal occlusion of unilateral hydrosalpinx increases the potential for spontaneous pregnancy.  Hum Reprod. 2003;  18 2634-2637
    CrossrefPubMedGoogle Scholar
  • 155 Dor J, Itzkowic D J, Mashiach S, Lunenfeld B, Serr D M. Cumulative conception rates following gonadotropin therapy.  Am J Obstet Gynecol. 1980;  136 102-105
    PubMedGoogle Scholar
  • 156 Doldi N, Gessi A, Destefani A, Calzi F, Ferrari A. Polycystic ovary syndrome: anomalies in progesterone production.  Hum Reprod. 1998;  13 290-293
    CrossrefPubMedGoogle Scholar
  • 157 Pillay O C, Te Fong L F, Crow J C et al.. The association between polycystic ovaries and endometrial cancer.  Hum Reprod. 2006;  21 924-929
    PubMedGoogle Scholar
  • 158 Niwa K, Imai A, Hashimoto M et al.. A case-control study of uterine endometrial cancer of pre- and post-menopausal women.  Oncol Rep. 2000;  7 89-93
    PubMedGoogle Scholar
  • 159 Hardiman P, Pillay O C, Atiomo W. Polycystic ovary syndrome and endometrial carcinoma.  Lancet. 2003;  361 1810-1812
    CrossrefPubMedGoogle Scholar
  • 160 Apparao K B, Lovely L P, Gui Y, Lininger R A, Lessey B A. Elevated endometrial androgen receptor expression in women with polycystic ovarian syndrome.  Biol Reprod. 2002;  66 297-304
    CrossrefPubMedGoogle Scholar
  • 161 Gregory C W, Wilson E M, Apparao K B et al.. Steroid receptor coactivator expression throughout the menstrual cycle in normal and abnormal endometrium.  J Clin Endocrinol Metab. 2002;  87 2960-2966
    CrossrefPubMedGoogle Scholar
  • 162 MacLaughlan S D, Palomino W A, Mo B, Lessey B A. Endometrial expression of Cyr61: A marker of estrogen activity and normal and abnormal endometrium.  Obstet Gynecol. 2007;  110 146-154
    CrossrefPubMedGoogle Scholar
  • 163 Groll J M, Vendrov A E, Marshal J C, Evans W S, Giudice L C, Lessey B A. Endometrial gene profiling in women with polycystic ovarian syndrome compared to normal women.  J Soc Gyn Invest. 2003;  (suppl 10) 178A , (abst 266)
    PubMedGoogle Scholar
  • 164 Kumar A, Woods K S, Bartolucci A A, Azziz R. Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS).  Clin Endocrinol (Oxf). 2005;  62 644-649
    CrossrefPubMedGoogle Scholar
  • 165 Suikkari A M, Ruutiainen K, Erkkola R, Seppala M. Low levels of low molecular weight insulin-like growth factor-binding protein in patients with polycystic ovarian disease.  Hum Reprod. 1989;  4 136-139
    PubMedGoogle Scholar
  • 166 Irwin J C, Suen L F, Martina N A, Mark S P, Giudice L C. Role of the IGF system in trophoblast invasion and pre-eclampsia.  Hum Reprod. 1999;  14(suppl 2) 90-96
    CrossrefPubMedGoogle Scholar

Bruce A LesseyM.D. 

Eastern Virginia Medical School, CONRAD - Intramural Preclinical Lab

601 Colley Ave., Jones Institute Building, Room 322, Norfolk, VA 23507

Email: blessey@ghs.org

      >