Objective:Understanding the physiology of the uterus and cervix during term and preterm parturition is crucial for developing methods to control their function and is essential to solving clinical problems related to labor. To date, only crude, inaccurate, and subjective methods are used to assess changes in uterine and cervical function in pregnancy.
Methods:In the past several years, we have developed noninvasive methods to quantitatively evaluate the uterus and cervix based on recording of uterine electrical signals from the abdominal surface (uterine electromyography) and measurement of light-induced fluorescence (LIF) of cervical collagen (Collascope), respectively. Both methods are rapid and allow immediate assessment of uterine contractility and cervical ripening.
Results:Studies in animals and humans indicated that uterine and cervical performance can be monitored successfully during pregnancy using those approaches and that these techniques can be used during labor to better define management in a variety of conditions associated with labor.
Conclusions:The potential benefits of the proposed instrumentation and methods include reducing the rate of preterm delivery, improving maternal and perinatal outcome, monitoring treatment, decreasing cesarean rate and providing research methods to understand uterine and cervical function.
1. Norwitz ER, Robinson J, Challis JRG. The control of labor. N Engl J Med1999;341:660-666.
2.
2. U.S. Preventive Services Task Force. Guide to clinical preventive services: An assessment of the effectiveness of 169 interventions. Baltimore: Williams & Wilkins, 1989.
3.
3. Ventura SJ, Martin JA, Curtin SC, Matthews TH. Report of final natality statistics. Monthly Vital Stat Rep1997;45:12-12.
4.
4. Brown ER, Epstein M. Immediate consequences of preterm birth. In: Fuchs F, Stubblefield PG, eds. Preterm birth: Causes, prevention, and management. New York: Macmillan Publishing, 1984:323-354.
5.
5. Goldenberg RL, Cliver SP, Bronstein J, Cutter GR, Andrews WW, Mennemeyer ST. bed rest in pregnancy. Obstet Gynecol1994;84:131-136.
6.
6. Mou Sm, Sunderji SG, Gall S, et al. Multicenter randomized clinical trial of home uterine activity monitoring for detection of preterm labor. Am J Obstet Gynecol1991;165:858-866.
7.
7. Wapner RJ, Cotton DB, Artal R, Librizzi RJ, Ross MG. A randomized multicenter trial assessing a home uterine activity monitoring device used in the absence of daily nursing contact. Am J Obstet Gynecol1995;172:1026-1034.
8.
8. The Collaborative Home Uterine Monitoring Study Group. A multicenter randomized controlled trial of home uterine monitoring: Active vs sham device. Am J Obstet Gynecol1995;173:1117-1120.
9.
9. Dyson DC, Dange KH, Bamber JA, et al. Monitoring women at risk for preterm labor. N Engl J Med1998;338:15-19.
10.
10. Andersen HF, Nugent CE, Wanty SD, Hayashi RH. Prediction of risk for preterm delivery by ultrasonographic measurement of cervical length. Am J Obstet Gynecol1990;163:859-867.
11.
11. Guzman ER, Houlihan C, Vintzileos A. Sonography and transfundal pressure in the evaluation of the cervix during pregnancy. Obstet Gynecol Survey1995;50:395-403.
12.
12. Chung TKH, Haines CJ, Kong D, Woo WK, Rogers MS. Transvaginal sonography in the diagnosis and management of cervical incompetence. Gynecol Obstet Invest1993;36:59-61.
13.
13. Iams JD, Goldenberg RL, Meis PJ, et al. The length of the cervix and the risk of spontaneous premature delivery. N Engl J Med1996;334:567-572.
14.
14. Cook CM, Ellwood DA. A longitudinal study of the cervix in pregnancy using transvaginal ultrasound. Br J Obstet Gynecol1996;103:16-18.
15.
15. Iams JD, Paraskos J, Landon MB, Teteris JN, Johnson FF. Cervical sonography in preterm labor. Obstet Gynecol1994;84:40-46.
16.
16. Lockwood CJ, Wein R, Lapinksi R, et al. The presence of cervical and vaginal fetal fibronectin predicts preterm delivery in an inner-city obstetric population. Am J Obstet Gynecol1993;169:798-804.
17.
17. Nageotte MP, Casal D, Senyei AE. Fetal fibronectic in patients at increased risk for premature birth. Am J Obstet Gynecol1994;170:20-25.
18.
18. Lockwood CJ, Moscarelli RD, Wein R, Lynch L, Lapinski RH, Ghidini A. Low concentrations of vaginal fetal fibronectin as a predictor of deliveries occurring after 41 weeks. Am J Obstet Gynecol1994;171:1-4.
19.
19. Hellemans P, Gerris J, Verdonk P. Fetal fibronectin detection for prediction of preterm birth in low risk women. Br J Obstet Gynecol1995;102:207-212.
20.
20. Iams JD, Casal D, McGregor JA, et al. Fetal fibronectin improves the accuracy of diagnosis of preterm labor. Am J Obstet Gynecol1995;173:141-145.
21.
21. McGregor JA, Jackson GM, Lachelin GC, et al. Salivary estriol as risk assessment for preterm labor: A prospective trial. Am J Obstet Gynecol1995;173:1337-1342.
22.
22. Copper RL, Goldenberg RL, Dubard MB, Hauth JC, Cutter GR. Cervical examination and tocodynamometry at 28 weeks' gestation: Prediction of spontaneous preterm birth. Am J Obstet Gynecol1995;172:666-671.
23.
23. Heine RP, McGregor JA, Goodwin TM, et al. Serial salivary estriol to detect an increased risk of preterm birth. Obstet Gynecol2000;96:490-497.
24.
24. Kuriyama H. Recent studies of the electrophysiology of the uterus. In: Ciba Foundation Study Group Vol. 9. Progesterone and the defence mechanism of pregnancy. Boston: Little Brown1961:51-70.
25.
25. Csapo AI. Smooth muscle as a contractile unit. Physiol Rev1962;42:7-33.
26.
26. Marshall JM. Regulation of activity in uterine smooth muscle. Physiol Rev1962;42:213-227.
27.
27. Okawa H. Electrical and mechanical interaction between the muscle layers of rat uterus and different sensitivities to oxytocin. But Yamaguchi Med School1975;22:197-210.
28.
28. Kuriyama H, Suzuki H. Changes in electrical properties of rat myometrium during gestation and following hormonal treatments. J Physiol Lond1976;260:315-333.
29.
29. Kanda S, Kuriyama H. Specific features of smooth muscle cells recorded from the placental region of the myometrium of pregnant rats. J Physiol Lond1980;299:127-144.
30.
30. Osa T, Fujino T. Electrophysiological comparison between the longitudinal and circular muscles of the rat uterus during the estrous cycle and pregnancy. Jpn J Physiol1978;23:197-209.
31.
31. Osa T, Ogasawara T, Kato S. Effects of magnesium, oxytocin and prostaglandin F2 on the generation and propagation of excitation in the longitudinal muscle of rat myometrium during late pregnancy. Jpn J Physiol1983;33:51-67.
32.
32. Bengtsson B, Chow EMH, Marshall JM. Activity of circular muscle of rat uterus at different times in pregnancy. Am J Physiol1984;246:C216-C223.
33.
33. Kawarabayashi T, Marshall JM. Factors influencing circular muscle activity in the pregnant rat uterus. Biol Reprod1981;24:373-379.
34.
34. Anderson GF, Kawarabayashi T, Marshall JM. Effect of indomethacin and aspirin on uterine activity in pregnant rats: Comparison of circular and longitudinal muscle. Biol Reprod1981;24:359-372.
35.
35. Marshall JM. Effects of estrogen and progesterone on single uterine muscle fibers in the rat. Am J Physiol1959;197:935-942.
36.
36. Honnebier MB, Wentworth RA, Figueroa JP, Nathanielsz PW. Temporal structuring of delivery in the absence of a photoperiod: Preparturient myometrial activity of the rhesus monkey is related to maternal body temperature and depends on the maternal circadian system. Biol Reprod1991;45:617-625.
37.
37. Taverne MAM, Scheerboom J. Myometrial electrical activity during pregnancy and parturition in the pigmy goat. Res Vet Sci1985;38:120-123.
38.
38. Ducsay CA, McNutt CM. Circadian uterine activity in the pregnant rhesus macaque: Do prostaglandins play a role?Biol Reprod1989;40:988-993.
39.
39. Nathanielsz PW, Bayley A, Poore ER, Thorburn GD, Harding R. The relationship between myometrial activity and sleep state and breathing in fetal sheep throughout the last third of gestation. Am J Obstet Gynecol1980;138:653-659.
41. Demianczuk N, Towell ME, Garfield RE. Myometrial electrophysiologic activity and gap junctions in the pregnant rabbit. Am J Obstet Gynecol1984;149:485-491.
42.
42. Verhoeff A, Garfield RE, Ramondt J, Wallenburg HC. Myometrial activity related to gap junction area in periparturient and in ovariectomized estrogen treated sheep. Acta Physiol Hung1986;67:117-129.
43.
43. Figureroa JP, Mahan S, Poore ER, Nathanielsz PW. Characteristics and analysis of uterine electromyographic activity in the pregnant sheep. Am J Obstet Gynecol1985;151:524-531.
44.
44. Sureau C. Etude de l'activité électrique de l'utérus au cours du travail. Gynecol Obstet1956;555:153-175.
45.
45. Wolfs GMJA, van Leeuwen M. Electromyographic observations on the human uterus during labor. Acta Obstet Gynecol Scand1979;90(Suppl):1-62.
46.
46. Wolfs GMJA, Rottinghuis H. Electrical and mechanical activity of the human uterus during labour. Arch Gynaekol1970;208:373-385.
47.
47. Lopes P, Germain G, Breart G, Reinatin S, Le Houezec R, Sureau C. Electromyographical study of uterine activity in the human during labor induced by prostaglandin. Gynecol Obstet Invest1984;17:96-105.
48.
48. Csapo A, Takeda H. Electrical activity of the parturient human uterus. Nature1963;200:68-68.
49.
49. Csapo AI. Force of labour. In: Iffy L, Kamientzky HA, eds. Principles and practice of obstetrics and perinatology. New York: John Wiley and Sons, 1981:761-799.
50.
50. Csapo A, Sauvage J. The evolution of uterine activity during human pregnancy. Acta Obstet Gynecol Scand1968;47:181-212.
51.
51. Buhimschi C, Garfield RE. Uterine contractility as assessed by abdominal surface recording of EMG activity in rats during pregnancy. Am J Obstet Gynecol1996;174:744-753.
52.
52. Buhimschi C, Boyle MB, Garfield RE. Electrical activity of the human uterus during pregnancy as recorded from the abdominal surface. Obstet Gynecol1997;90:102-111.
53.
53. Buhimschi C, Boyle MB, Saade GR, Garfield RE. Uterine activity during pregnancy and labor assessed by simultaneous recordings from the myometrium and abdominal surface in the rat. Am J Obstet Gynecol1998;178:811-822.
54.
54. Duchêne J, Devedeux D, Mansour S, Marque C. Analyzing uterine EMG: Tracking instantaneous burst frequency. IEEE Eng Med Biol1995;14:125-132.
55.
55. Marque C, Duchêne J, Lectercq S, Panczer G, Chaumont J. Uterine EMG processing for obstetrical monitoring. IEEE Trans Biomed Eng1986;33:1182-1187.
56.
56. Garfield RE, Yallampalli C. Structure and function of uterine muscle. In: Chard T, Grudzinskas JG, eds. The uterus. Cambridge Reviews in Human Reproduction, Cambridge University Press, 1995:54-93.
57.
57. Garfield RE. Role of cell-to-call coupling in control of myometrial contractility and labor. In: Grafield RE, Tabb TN, eds. Control of uterine contractility. Florida: CRC Press, 1994:40-81.
58.
58. Tezuka N, Ali M, Chwalisz K, Garfield RE. Changes in transcripts encoding calcium channel subunits of rat myometrium during pregnancy. Am J Physiol1995;269:C1008-C1017.
59.
59. Garfield RE, Yallampalli C. Control of myometrial contractility and labor. In: Chwalisz K, Garfield RE, eds. Basic mechanisms controlling term and preterm birth. New York: Springer-Verlag, 1993:1-28.
60.
60. Chwalisz K, Garfield RE. Regulation of the uterus and cervix during pregnancy and labor: Role of progesterone and nitric oxide. Ann N Y Acad Sci1997;828:238-253.
61.
61. Chwalisz K, Garfield RE. New molecular challenges in the induction of cervical ripening: Nitric oxide as the final metabolic mediator of cervical ripening. Hum Reprod1998;13:101-104.
62.
62. Gerfield RE, Saade GR, Buhimschi C, et al. Control and assessment of the uterus and cervix during pregnancy and labor. Hum Reprod Update1998;4:673-695.
63.
63. Chwalisz K, Garfield RE. Antiprogestins in the induction of labor. Ann N Y Acad Sci1994;734:387-413.
64.
64. Challis JR, Lye SJ, Gibb W. Prostaglandins and parturition. Ann N Y Acad Sci1997;828:254-267.
65.
65. Casey ML, MacDonald PC. The endocrinology of pregnancy. Ann N Y Acad Sci1997;828:273-284.
66.
66. Danforth DN. The morphology of the human cervix. Clin Obstet Gynecol1983;26:7-13.
67.
67. Woessner JF, Brewer TH. Formation and breakdown of collagen and elastin in the human uterus during pregnancy and postpartum involution. Biochem J1963;89:75-82.
68.
68. Leppert PC, Keller S, Cerreta J, Mandl I. Conclusive evidence of elastin in the uterine cervix. Am J Obstet Gynecol1982;142:179-182.
69.
69. Danforth DN, Vies A, Breen M, Weinstein HG, Buckingham JC, Manalo P. The effect of pregnancy and labor on the human cervix: Changes in collagen, glycoprotein and glycosaminoglycans. Am J Obstet Gynecol1986;120:641-651.
70.
70. Liggins GC. Cervical ripening as an inflammatory reaction. In: Ellwood DA, Anderson ABM, eds. Cervix in pregnancy and labour: Clinical and biochemical investigation. New York: Churchill Livingstone, 1981:1-9.
71.
71. Bryant WM, Greenwell JE, Weeks PM. Alterations in collagen organization during dilatation of the cervix uteri. Surg Gynecol Obstet1968;126:27-39.
72.
72. Harkness MLR, Harkness RD. Changes in the physical properties of the uterine cervix of the rat during pregnancy. J Physiol Lond1959;148:524-547.
73.
73. Kokenyesi R, Woessner JF. Relationship between dilatation of the rat uterine cervix anda small dermatan sulfate proteoglycan. Biol Reprod1990;42:87-97.
74.
74. Rajabi MR, Dean DD, Beydoun SN, Woessner JF. Elevated tissue levels of collagenase during dilation of uterine cervix in human parturition. Am J Obstet Gynecol1988;139:971-976.
75.
75. Chwalisz K, Qing SS, Neef G, Elger W. The effect of the antigestagen ZK98.299 on the uterine cervix. Acta Endocrinol1987;114(Suppl):113-114.
76.
76. Chwalisz K, Qing SS, Esch A, Elger W. Cervical softening in non-pregnant guinea pigs. Acta Endocrinol1988;25(Suppl):1315-1315.
77.
77. Calder AA, Embrey MP, Tait T. Ripening of the cervix with extra-amniotic prostaglandin E2 in viscous gel before induction of labour. Br J Obstet Gynecol1977;84:264-268.
78.
78. Rath W, Osmers R, Adelmann-Grill BC, Stuhlsatz HW, Szevereny M, Kuhn W. Biochemical changes in the human cervical connective tissue after intracervical application of prostaglandin E2. Prostaglandins1993;45:375-384.
79.
79. Leppert PC. Anatomy and physiology of cervical ripening. Clin Obstet Gynecol1995;38:267-279.
80.
80. Leppert PC. The biochemistry and physiology of the uterine cervix during gestation and parturition. Prenat Neonat Med1998;3:103-105.
81.
81. Robinson G, Filshie GM, Cust M. Medical dilatation of the human cervix. In: Leppert PC, Woessner JF, eds. The extracellular matrix of the uterus, cervix and fetal membranes: Synthesis, degradation and hormonal regulation. New York: Perinatology Press, 1991:159-181.
82.
82. Ekman G, Almström H, Granström L, Malmström A, Norman M, Woessner JF. Connective tissue in human cervical ripening. In: Leppert PC, Woessner JF, eds. The extracellular matrix of the uterus, cervix and fetal membranes: Synthesis, degradation and hormonal regulation. New York: Perinatology Press, 1991:87-96.
83.
83. Mori Y, Ito A. Cervical ripening: Biochemical regulation. In: Leppert PC, Woessner JF, eds. The extracellular matrix of the uterus, cervix and fetal memberanes: Synthesis, degradation and hormonal regulation. New York: Perinatology Press, 1991:77-86.
84.
84. Leppert PC, Yeh Yu S. Elastin and collagen in the human uterus and cervix: Biochemical and histological correlation. In: Leppert PC, Woessner JF, eds. The extracellular matrix of the uterus, cervix and fetal membranes: Synthesis, degradation and hormonal regulation. New York: Perinatology Press, 1991:59-67.
85.
85. Yeh Yu S, Leppert PC. The collagenous tissues of the cervix during pregnancy and delivery. In: Leppert PC, Woessner JF, es. The extracellular matrix of the uterus, cervix and fetal membranes: Synthesis, degradation and hormonal regulation. New York: Perinatology Press, 1991:68-76.
86.
86. Kline SB, Meng H, Munsick RA. Cervical dilation from laminaria tents and synthetic osmotic dilators used for 6 hours before abortion. Obstet Gynecol1995;86:931-935.
87.
87. Bokström H, Wiqvist N. Prostaglanin release from human cervical tissue in the first trimester of pregnancy after preoperative dilatation with hygroscopic tents. Prostaglandins1995;50:179-188.
88.
88. Rouben D, Arias F. A randomized trial of extra-amniotic saline infusion plus intracervical Foley catheter balloon versus prostaglandin E2 vaginal gel for ripening the cervix and inducing labor in patients with unfavorable cervices. Obstet Gynecol1993;82:290-294.
89.
89. Porreco RP, Thorp JA. The cearean birth epidemic: Trends, causes, and solutions. Am J Obstet Gynecol1996;175:369-374.
90.
90. Undenfriend S. Fluorescence assay in biology and medicine. Vol. I. New York: Academic Press, 1962.
91.
91. Cantor Cr, Schimmel PR. Biophysical chemistry. New York: WH Freeman and Company, 1980.
92.
92. Lakowicz JR. Principles of fluorescence spectroscopy. New York: Plenum Press, 1986.
93.
93. Ramanujam N, Mitchell MF, Mahadevan A, Thomsen S, Silva E, Richards-Kortum R. Fluorescence spectroscopy: A diagnostic tool for cervical intrepithelial neoplasia (CIN). Gynecol Oncol1994;52:31-38.
94.
94. Lam S, Hung JYC, Kennedy SM, et al. Detection of dysplasia and carcinoma in situ by ratio fluorometry. Am Rev Respir Dis1992;146:1458-1461.
95.
95. Cothren RM, Richards-Kortum RR, Sivak MV, et al. Gatrointestinal tissue diagnosis by laser induced fluorescence spectroscopy at endoscopy. Gastrontest Endosc1990;36:105-111.
96.
96. Schomaker KT, Frisoli JK, Compton CC, et al. Ultraviolet laser-induced fluorescence of colonic tissue: Basic biology and diagnostic potential. Lasers Surg Med1992;12:63-78.
97.
97. Glassman W, Byam-Smith M, Garfield RE. Changes in rat cervical collagen during gestation and following antiprogesterone treatment as measured in vivo with light induced autofluorescence. Am J Obstet Gynecol1995;173:1550-1556.
98.
98. Fujimoto D. Isolation and characterization of a fluorescent material in bovine achilles tendon collagen. Biochem Biophysics Res Commun1977;76:1124-1129.
99.
99. Glassman WS, Liao QP, Shi SQ, et al. Fluorescence probe for cervical examination during various reproductive states. Proceedings of SPIE -Advances in Fluorescence Sensing Technology III, 1997;2980:286-292.
100.
100. Fittkow CT, Shi SQ, Bytautiene E, Olson G, Saade GR, Garfield RE. Changes in light-induced fluorescence of cervical collagen in guinea pigs during gestation and after sodium nitroprusside treatment. J Perinat Med2001;29:535-543.
101.
101. Olson G, Goodrum L, Martin E, Saade GR, Garfield RE. Noninvasive measurement of cervical collagen content in women approaching delivery (abstract). Am J Obstet Gynecol1998;178:S91-S91.
102.
102. Garfield RE, Maner W, Martin E, Saade GR. Prediction of parturition in humans using transabdominal uterine electromyographic activity recording (abstract). Am J Obstet Gynecol2000;182:S53-S53.
