Uterine Receptivity: Alterations Associated with Benign Gynecological Disease

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
• 2 Aplin J D. Embryo implantation: the molecular mechanism remains elusive.  Reprod Biomed Online. 2006;  13 833-839
• 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
• 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
• 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
• 6 Minas V, Loutradis D, Makrigiannakis A. Factors controlling blastocyst implantation.  Reprod Biomed Online. 2005;  10 205-216
• 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
• 8 Pope W F. Uterine asynchrony: a cause of embryonic loss.  Biol Reprod. 1988;  39 999-1003
• 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
• 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
• 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
• 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
• 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
• 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
• 15 Giudice L C. Genes associated with embryonic attachment and implantation and the role of progesterone.  J Reprod Med. 1999;  44 165-171
• 16 Lessey B A, Castelbaum A J. Integrins and implantation in the human.  Rev Endocr Metab Disord. 2002;  3 107-117
• 17 Stephenson M D. Frequency of factors associated with habitual abortion in 197 couples.  Fertil Steril. 1996;  66 24-29
• 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
• 19 Tabibzadeh S. Patterns of expression of integrin molecules in human endometrium throughout the menstrual cycle.  Hum Reprod. 1992;  7 876-882
• 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
• 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
• 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
• 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
• 24 Lessey B A. Integrins and uterine receptivity. In: Carson DD Embryo Implantation: Molecular, Cellular and Clinical Aspects. New York; Springer 1999: 210-222
• 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
• 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
• 27 Aplin J D. The cell biology of human implantation.  Placenta. 1996;  17 269-275
• 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
• 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
• 30 Albelda S M, Buck C A. 1990 Integrins and other cell adhesion molecules.  FASEB J. 1990;  4 2868-2880
• 31 Hynes R O. Integrins: a family of cell surface receptors.  Cell. 1987;  48 549-554
• 32 Ruoslahti E, Pierschbacher M D. New perspectives in cell adhesion: RGD and integrins.  Science. 1987;  238 491-497
• 33 Lessey B A, Castelbaum A J. Integrins and implantation in the human.  Rev Endocr Metab Disord. 2002;  3 107-117
• 34 Getzenberg R H, Pienta K J, Coffey D S. The tissue matrix: cell dynamics and hormone action.  Endocr Rev. 1990;  11 399-417
• 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
• 36 Giancotti F G, Ruoslahti E. Integrin signaling.  Science. 1999;  285 1028-1032
• 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
• 38 Lessey B A. Endometrial Integrins.  Endocrinologist. 1995;  5 214-222
• 39 Zhao R, Pathak A S, Stouffer G A. beta(3)-Integrin cytoplasmic binding proteins.  Arch Immunol Ther Exp (Warsz). 2004;  52 348-355
• 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
• 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
• 42 Buck C A, Horwitz A F. Integrin, a transmembrane glycoprotein complex mediating cell-substratum adhesion.  J Cell Sci. 1987;  8(suppl) 231-250
• 43 Hynes R O. Integrins: versatility, modulation, and signaling in cell adhesion.  Cell. 1992;  69 11-25
• 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
• 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
• 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
• 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
• 48 Fazleabas A T, Kim J J. What makes an embryo stick?.  Science. 2003;  299 355-356
• 49 Noyes R W, Hertig A I, Rock J. Dating the endometrial biopsy.  Fertil Steril. 1950;  1 3-25
• 50 Jones G S. Luteal phase insufficiency.  Clin Obstet Gynecol. 1973;  16 255-273
• 51 Jones G S. The luteal phase defect.  Fertil Steril. 1976;  27 351-356
• 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
• 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
• 54 Anderson T L. Biomolecular markers for the window of uterine receptivity. In: Yoshinaga K Blastocyst Implantation. Boston MA; Adams Publishing 1993: 219-224
• 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
• 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
• 57 Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation.  Hum Reprod Update. 2006;  12 731-746
• 58 Lessey B A. The use of integrins for the assessment of uterine receptivity.  Fertil Steril. 1994;  61 812-814
• 59 Enders A C, Nelson D M. Pinocytotic activity of the uterus of the rat.  Am J Anat. 1973;  138 277-299
• 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
• 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
• 62 Psychoyos A, Nikas G. Uterine pinopodes as markers of uterine receptivity.  Assist Reprod Rev. 1994;  4 26-41
• 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
• 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
• 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
• 66 Lessey B A. Two pathways of progesterone action in the human endometrium: implications for implantation and contraception.  Steroids. 2003;  68 809-815
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 86 Creus M, Balasch J, Ordi J et al.. Integrin expression in normal and out-of-phase endometria.  Hum Reprod. 1998;  13 3460-3468
• 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
• 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
• 89 Meyer W R, Castelbaum A J, Somkuti S et al.. Hydrosalpinges adversely affect markers of endometrial receptivity.  Hum Reprod. 1997;  12 1393-1398
• 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
• 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
• 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
• 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
• 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
• 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
• 96 Mosher W D, Pratt W F. Fecundity and infertility in the United States: incidence and trends.  Fertil Steril. 1991;  56 192-193
• 97 Mosher W D, Pratt W F. Fecundity and infertility in the United States: incidence and trends.  Fertil Steril. 1991;  56 192-193
• 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
• 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
• 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
• 101 Verkauf B S. Incidence, symptoms, and signs of endometriosis in fertile and infertile women.  J Fla Med Assoc. 1987;  74 671-675
• 102 Schenken R S, Guzick D S. Revised endometriosis classification: 1996.  Fertil Steril. 1997;  67 815-816
• 103 Bancroft K, Vaughan Williams C A, Elstein M. Minimal/mild endometriosis and infertility. A review.  Br J Obstet Gynaecol. 1989;  96 454-460
• 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
• 105 Matson P L, Yovich J L. The treatment of infertility associated with endometriosis by in vitro fertilization.  Fertil Steril. 1986;  46 432-434
• 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
• 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
• 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
• 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
• 110 Yovich J L, Yovich J M, Tuvik A I. In vitro fertilization for endometriosis.  Lancet. 1985;  2 552
• 111 O'Shea R T, Chen C, Weiss T, Jones W R. Endometriosis and in vitro fertilization.  Lancet. 1985;  2 723
• 112 Barnhart K, Dunsmoor R, Coutifaris C. The effect of endometriosis on IVF outcome.  Fertil Steril. 2002;  77 1148-1155
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 120 Lessey B A. Integrins and the endometrium: new markers of uterine receptivity.  Ann N Y Acad Sci. 1997;  828 111-122
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 134 Lessey B A, Young S L. Integrins and other cell adhesion molecules in endometrium and endometriosis.  Semin Reprod Endocrinol. 1997;  15 291-299
• 135 Lessey B A. Medical management of endometriosis and infertility.  Fertil Steril. 2000;  73 1089-1096
• 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
• 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
• 138 Cohen M A, Lindheim S R, Sauer M V. Hydrosalpinges adversely affect implantation in donor oocyte cycles.  Hum Reprod. 1999;  14 1087-1089
• 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
• 140 Nackley A C, Muasher S J. The significance of hydrosalpinx in in vitro fertilization.  Fertil Steril. 1998;  69 373-384
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 148 Strandell A, Waldenstrom U, Nilsson L, Hamberger L. Hydrosalpinx reduces in-vitro fertilization/embryo transfer pregnancy rates.  Hum Reprod. 1994;  9 861-863
• 149 Granot I, Dekel N, Segal I, Fieldust S, Shoham Z, Barash A. Is hydrosalpinx fluid cytotoxic?.  Hum Reprod. 1998;  13 1620-1624
• 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
• 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
• 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
• 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
• 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
• 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
• 156 Doldi N, Gessi A, Destefani A, Calzi F, Ferrari A. Polycystic ovary syndrome: anomalies in progesterone production.  Hum Reprod. 1998;  13 290-293
• 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
• 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
• 159 Hardiman P, Pillay O C, Atiomo W. Polycystic ovary syndrome and endometrial carcinoma.  Lancet. 2003;  361 1810-1812
• 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
• 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
• 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
• 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)
• 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
• 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
• 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