- Email: [email protected]
Motility of human myometrium in vivo
Motility of human myometrium in vivo: Intrarnural versus transcervical recording ELSIMAR
METZKER
LUSIA
NASCIMENTO,
HUGO
DA
MARIA
SILVA
Bahia,
M.D.
M.D. MAIA,
TERESA
Salvador,
COUTINHO, M.D.
R. GONCALVES,
M.D.
Brazil
Microballoons inserted into the thickness of the myometrium during laparotomy were used to record the motiliQ of the human uterus during the menstrual cycle. Except during menstruation when the myometrial contractions were similar to those recorded through intrauterine pressure recording, the pattern of localized myometrial activity bore no resemblance to the familiar intrauterine pressure tracings. Myometrial contractions of small amplitude, 5 to 20 mm Hg, were recorded during both the proliferative and luteal phases of the cycle. The contractions tended to occur in bursts at intervals of 5 minutes or longer. Uterine quiescence lasting several minutes was observed at all phases of the cycle with the exception of the menstrual period. Transcervical insertion of an open-end or balloon-tipped catheter provoked marked activation of myometrial motility at all phases of the menstrual cycle. Activation of the myometrium by transcervical insertion of the catheter during the estrogen-dominated proliferative phase was more marked and lasted longer than that during the progesterone-dominated luteal phase. The oxytocin response was recorded throughout the menstrual cycle but lasted longer during the preovulatory and early postovulatory phases than during the late luteal phase of the menstrual cycle. During the luteal phase activation of the myometrium following oxytocin injection failed to be translated into intrauterine pressure changes. (At&J. C)BSTET.GYNECOL. 134:801, 1979.)
INTRAUTERINE pressure recordings have been widely used in studies of uterine physiology and pharmacology. IT4 Fluid-filled balloons have been the favorite sensors of intrauterine pressure changes resulting from uterine contractions, and for this reason most of the data available on the motility of the nonpregnant human uterus are based mainly on studies conducted with balloons.5 Open-end and sponge-tipped catheters, proposed in the 1960’s as alternatives to the balloon, have met with limited success since the new techniques had no significant advantages over the balloon tech-
From the Department of Maternal Health and Child Care, Maternidadz Climerio de Oliveira, Federal University qf Bahia School of Medicine. Supported
by the Ford
Council, and the World Received
for
publication
Revised
.Vay
2, 1978.
Accepted
August
Foundation, The Population Health Organization. February
27, 1978.
2 I, 1978.
Reprint requests: Dr. E. M. Coutinho, Matemidade Climerio de Oliveira, Universidade Federal da Bahia, Salwdor, Bahia, Brazil. OOOZ-9378/79/15C1801+12$01.20/0
0
1979 The
C. V. Mosby
Co.
niques. 6, ’ However, open- end recordings reactivated an old controversy on the character of uterine contractility during the menstrual cycle as recorded by various investigators. Although all workers agree that menstruation is attended by contractions of high amplitude and high or low frequency and that at midcycle the frequency is higher and amplitude lower, recordings during the luteal phase with either open-end or closed systems show substantial differences. Pressure cycles of long duration and relatively high amplitude have been reported as typical of the luteal phase by some authors whereas others deny the occurrence of these cycles. The oxytocin response, which is another point of disagreement, has been reported variously as being suppressed throughout the menstrual cycle, during the luteal phase only, or not at all.“. 3, ’ Advocates of openend recording claim a more reliable technique because in their view the balloon tip is a greater irritant of uterine motility than the fine end of a catheter.‘j4 Propounders of the balloon method dismiss the open-end catheter technique as unreliable because it develops too many recording artifacts, and defend the balloon re801
802
Coutinho et al.
c’ep’or for its freedom from obstruction and reproducibilil~.2~ ‘j. ’ The controversy remains unresolved primarily because of’ individual differences in motilit!. patterns recorded by the same investigator with either open-end or closed systems. All the various techniques with open or closed systems require transcervical introduction of catheters which are held in place during the recording sessions. .i\lthough the possible influence of this transcervical catheter on uterine motility has been discounted as being negligible by most uterine physiologists, preliminary studies suggested that even minimal intrauterine stirriulation with an open-end catheter or very small balloon had a marked activating effect on u terinc motility. These findings may have implications in the interpretation of physiologic events and pharmacologic effects on the myotnetrium, since the assumed baseline of uterine motility as recorded through an intrauterine catherrr would become actually an artifact of the recording technique. Therefore in order to investigate the influence of transcervical recording on uterinr motilit), ir would seetn imperative to establish a basclint of’ uterine motility in uteri in which the cervical canal and rhe uterine cavity were left undisturbed during recordings. Microballoons inserted into rhe thickness of the myometrium have been used in studies of propagation in the human pregnant uterus.” The method allows recording of local contractions resulting from activit! of the muscle surrounding the balloon as well as passive rontractions originating elsewhere which propagate to the microballoon area. The presence of the balloon does not provoke generalized contractions and does not seem to interfere with normal uterine activity.” In the present study, the effect of intrauterine recordings on the motility of the nonpregnant uterus was investiSated in women whose myometrial activity was recorded through intramyometrial microballoons.
Methods ‘l‘he study was carried out in 16 women of reproductive age who had to undergo abdominal surgery for the following indications: tubal ligation (six), correction of‘ tubal occlusion (four), wedge ressection of the ovary (two), removal of periovarian tubal adhesions (two), or removal of ovarian cysts (two). All subjects volunteered for the study and have given full informed consent. Uterine motility was recorded through intramural microballoons for periods ranging frotn 1 to 8 weeks. In I2 women recordings lasting 1 to several hours were carried out every other day for at least one full menstrual cy< It?.
The balloon-tipped polyvinyl catheters were inserted in the uterine wall through a small incisio,, during laparotomy and held in place with a suture oic~hrotnic catgut. The microballoons, made of natur-al latex, measured I mm of external diameter and had a citpacitv of 0.3 ml. Iti some suhjecis two tnic-robaIloonc were itiserted in tlif-ferent parts of the ur<‘t.ttx. The effect of. transcervical insertion M;IX investigated during recording sessiorrs b! itttroducing a Teflon catheter deei) into tlw ulerus ,~rttl tworfling intrauterine and intramural pressure sil7i~tltaiicolisl~ li)r a few minutes to several hours. Both open-end and balloon-tipped catheter-s hal-e been used. In C~LC’I-Icase the tip of thr catheter touched the uterine fundus. Iti order to evaluate the influence of rransc.er\ical recording on the pharmacologic response of the rnrometrium, oxytocin (Syntocinon, Sando/) was injected intravenously before and during au intrauterine recording session. I tI order to datr 0\7rlation, htteiiiixing hormone (LH) and progcsteronr~ blood le\,els WIY measured bj radioimuno;tssa) in mos[ subjet tr.
Results Spontaneous activity. Contractions 01‘ small a mplitude developing approximately 5 co 20 mm of’ pressure were recorded during the early proliferative phase of’ the cycle from either the fundus or the isthmus. The frequency of these low-amplitude contractions v-aried from less than one pet- tninute to as many as 4 to .?I per minute. Periods of inactivity lasting 5 minutes or longer were common. Periods of’ quiescence lasting as long as 1 hour were recorded during this phase. Sudden spontaneous increases in frequency were recorded otcasionally. During the late proliferative and early luteal phases, the contractions occurred in bursts at intervals of5 to 10 minutes. Periods of quiescence lasting longer than 10 mimttes were nc\er seen during this phase in this group of patients. During the luteal phase, contractions developed a higher amplitude reaching sometimes 100 mm Hg or more. They still came in bursts which were more fiequent but of’ a shorter duration than those occurring during the late proliferative and early luteal phases of the cycle. As menstruation approached contracttons became more frequent, the groups of contractions fused together, and the burst pattern was lost. Fig. 1 illustrates the most common patterns recorded in all subjects who had ovulatory cycles. Synchrony between contractions occurring at different parts ot rhe utertrs was observed in all patients in whom two intramural balloons had been inserted. Synchronous contractions were recorded during menstruation and the rarlv proliferative phase of‘ the c\ cle.
Volume
134
Number
7
803
Motility of human myometrium in vivo
8
0
14
100
17
a’
,‘.
“’
20
Fig. 1, Patterns
of myometrial motility during the menstrual Note the high amplitude of the contractions recorded during activity developing during both the proliferative and luteal patient was detected on days 14 and 15.
cycle. In vivo intramural recording. menstruation. Note also the bursts of phases of the cycle. LH peak in this
t
i .: 10
Fig. 2. Response of the myometrium to transcervical introduction of a catheter. In viva intramut-al recording. Note the marked activation of myometrial motility following transcervical insertion of catheter (arrow pointing downward). Note also that following removal of the intrauterine catheter (arrow pointing upward) the burst pattern is re-established on days 2 1 and 27 but not on days 10 and IS. LH peak in this patient was detected on days 14 and 15.
Volume Number
Motility of human myometrium in vivo
134 7
Fig. 3. Response menstrual cycle. cervical insertion remains activated
of the myometrium to transcervical introduction of a catheter Intramural recording in vivo. Note the long period of quiescence and the prompt activation following insertion. Note also that long after removal of the intrauterine catheter.
on day 9 of the preceding transthe myometrium
805
806
Coutinho et al.
of the myometrium to transcervical introduction ot a balloon-tipped catheter Fig. 4. Response (balloon capacity 0.3 ml). Note that the intrauterine pressure records (IPi are typical for tht estrogen-dominated uterus on day 11 and for the progesterone-dominated uterus on day 26. Note also that in contrast with the marked activation of myometrial motility the intrauterine pressure record shows a quiescent uterus during the luteal phase. LH peak of this patient \\as detected on day 15.
During the late proliferative and early luteal phases, synchrony was lost. Simultaneous recordings carried out during the luteal phase from intramural microballoons placed at different parts of the uterus showed both contractions and bursts occurring completely independent from each other. Alterations in uterine motility following transcervital introduction of a catheter. Two to three minutes following the introduction of a transcervical catheter.
uterine motility was markedly activated. Activation occurred at all phases of the menstrual cycle but it was more marked during the proliferative phase than during the luteal phase of the cycle. During menstruation when spontaneous motility was greatest. activation following intrauterine insertion of the catheter was minimal. During the late proliferative and early luteal phases, uterine motility remained activated as long as rhe catheter was maintained in the uterine cavity. Dur-
Volume Number
Motility of human myometrium in vivo
134 7
807
Fig. 5. The
response of the nonpregnant human uterus to transcervical insertion of a catheter. Intramural recording. Note the marked increase in tonus and frequency.of contractions following insertion’ of the catheter. Note also that following indomethacin treatment (200 mg suppositories given three times) reinsertion of the catheter provokes only a moderate increase in tonus.
ing the luteal phase, the effect usually subsided soon after removal of the intrauterine probe. Fig. 2 illustrates the effects of insertion and removal of the intrauterine catheter during the menstrual cycle of the patient whose spontaneous uterine motility is shown in Fig. 1. The activating effect of the intrauterine catheter may last long after removal of ‘the catheter. During the luteal phase, the effect lasted only 10 to 20 minutes but during the late proliferative phase it could last several hours. Fig. :3 shows the long-lasting effect of catheter insertion and removal in a patient on day 9 of menstrual cycle. The patterns of uterine motility as recorded through the intramural balloon differ markedly from those recorded through the intrauterine balloon during both the proliferative and luteal phases. However, similarities developed when recordings were carried out simulataneously because activation of uterine motility induced by the intrauterine catheter affects equally intramyomettial and intrauterine pressure. Similarities developing during simultaneous recording are greater during the estrogen-dominated proliferative phase than during the early luteal phase of the cycle. During the late luteal phase, the motility patterns recorded through the intramural balloon bear almost no re-
semblance with the intrauterine pressure curves. Whereas the intrauterine pressure tracings reveal a lowered contractility suggestive of a quiescent uterus, the intramural recordings show an active myometrium with bursts of contractions occurring at intervals of 3 to 8 minutes (Fig. 4). The tracings again become similar as menstruation approaches and during menstruation there are almost no differences between the two tracings. Attempts to prevent or supress myometrial response to mechanical stimulation through transcervical insertion of the catheter by indomethacin treatment (200 mg suppositories used three times) were not successful. In some cases reactivatian of the uterus could not be achieved by reinsertion of the intrauterine probe following indomethacin administration, but in most cases indomethacin pretreatment failed to reduce the magnitude of the initial response of the uterus to insertion of the intrauterine probe. Fig. 5 illustrates the response of the uterus before and following indomethacin treatment in a patient on day 14 of the menstrual cycle. The response to oxytocin. The response of the nonpregnant uterus to oxytocin (1 unit intravenously) was recorded through the intramural balloon system throughout the menstrual cycle. The activating effect of oxytocin was more marked during the late pro-
808
Coutinho et al.
Fig. 6. The response of the nonpregnant human uterus Intramural recording. Note that the response lasts longer LH peaked on day 14.
to oxytocin during the menstrual qcle. on Days 10 and 17 than on days 5 and 23.
Volume Number
Motility of human myometrium in vivo
134 7
809
Fiig. 7. The effect of intrauterine catheter on the response of the nonpregnant human uterus to oxytocin. A: Response to oxytocin recorded through intramural microballoon. B and C: Response to oxytocin during the intrauterine recording. In B as recorded through the intramural microballoon, and in C as recorded through the intrauterine balloon-tipped catheter. Note that while frequency of the myometrial contractions increases markedly following oxytocin injection in E, simultaneous recordings of intrauterine pressure remain almost unaltered in C. liferative phase than during the early proliferative and late luteal phases of the cycle. During the late proliferative phase at midcycle, the response to a single oxytocin injection lasted 30 minutes or longer. During the late luteal phase, the response lasted 15 to 20 minutes and its intensity was less than that during the proliferative phase of the cycle (Fig. 6). In patients whose uteri were being recorded through transcervical recording, only a moderate increase in the frequency of contractions developed following oxytotin injections. ‘The response to oxytocin which could be recorded through the intramural recording system was almost imperceptible through the intrauterine pressure recordin,g. In fact in most cases no significant change in intrauterine pressure could be detected following oxytocj n injections during either the proliferative or luteal phases of the menstrual cycle. Moderate changes in intrauterine pressure following oxytocin in-
jections could be recorded only during the early proliferative and late luteal phases of the cycle. Marked changes of intrauterine pressure following oxytocin were restricted to the menstrual phase. Fig. 7 illustrates the recording of an oxytocin response through intramural recording before and during transcervical recording on day 5 of the cycle. Fig. 8 shows the oxytocin response during the early and late luteal phases as recorded simultaneously through intramural and intrauterine pressure recording.
Comment Uterine contractility recorded through the intramural balloon reveals a pattern of uterine motility which holds almost no resemblance to the familiar intrauterine pressure tracings. While intrauterine pressure records show marked differences in motility patterns throughout the menstrual cycle, localized myo-
810
Coutinho et al.
Fig. 8. The effect of an intrauterine balloon-tipped catheter on the response of the uterus to oxytocin during the luteal phase of the cycle. Simultaneous intramural and intrauterine recording. Note the slight increase in the frequency of myometrial contractions and the absence of any significant changes in the pattern of uterine contractility as recorded through the intrauterine pressure on day 19. Note also the differences in oxytocin response as recorded through rhe two systems on day 26. LH peaked on day IS. metrial contractility displays almost the same features during the proliferative and luteal phases of the cycle. The pattern of myometrial contractility changes markedly only during menstruation, when the tracings obtained through the intramural balloons become identical to the intrauterine pressure records. Unlike the pattern of “spontaneous” motility which may show periods of quiescence of relatively long du-
ration and which changes very little from the first to the second half of the menstrual cycle, the motility pattern of the uterus activated by the transcervical catheter displays features which may be considered typical for each phase of the cycle. During the estrogen-dominated proliferative phase of the cycle, the response to transcervical introduction of the catheter is prompt and lasts long after removal of the intrauterine probe.
Volume
Motility of human myometrium in vivo
134 7
Number
During the progesterone-dominated luteal phase the response is less marked than that recorded at midcycle and lasts a shorter period of time. Following removal of the
intrauterine
motility
returns
catheter
during
promptly
to
this
phase
uterine
preintroduction
levels.
During menstruation changes in myometrial activity induced by the insertion of the catheter are negligible. In addition to these variations in the character of the response during the menstrual cycle, the magnitude of the uterine response to intrauterine stimulation varies from
subject
to subject
mechanical
stimulation.
nique
to stimulate
used
cal recording region ever,
the of
even
uterus
to
the
catheter
with
minimum
and In
catheter
also the
uterus
required tip.
standardization
with repeated
these
with
the
present
This for
with
the with
transcerviassured
procedure. response the
tech-
the fundal
maneuver the
of
the
the
touching
precautions stimulation
intensity
study
a
Howof
the
transcervical
during the luteal phase varied substantially, suggesting that variations in the degree of pressure exerted against the uterine fundus could induce varying response. It should be pointed out, however, that these findings do not disqualify intrauterine recordings as a diagnostic method since the response of the uterus to mechanical sl:imulation is significantly changed from the estrogen-dominated preovulatory phase to the progesterone-dominated postovulatory phase of the cycle allowing therefore a precise evaluation of the endocrine status of the organ.” On the other hand, interpretation of pharmacologic effects on the uterus with intrauterine pressure measurements should be taken with ca.ution. Oxytocic compounds such as oxytocin may be wrongly considered weak stimulants because their effect is obscured by pre-existing exaggerated motility. I13 I2 By the same token inhibitory drugs are tested so’metimes on an overstimulated uterus, a condition which is far from representing the basal concatheter
REFERENCES 1. Coutinho, E. M.: Uterine activity in nonpregnant women, Proceedings of the Eighth International Conference of the International Planned Parenthood Federation, San-
tiago, Chile, 1967, pp. 432-439. C. A., Romeo-Salinas, and Mendez-Bauer, 2. Jaumendreu, C.: Action de la progesterona hidrosoluble intravenosa sobre a contractilidad de1 utero human0 no gravido in vivo, Proceedings of the Fourth Congress Uruguay Gincotocol. 1964, vol. 2, p. 394. 3. Csapo, A. I.: The d&gnostic significance of intrauterine oressure. Part I. Obstet. Gvnecol. Surv. 25:403. 1970a. 4. ksapo, A. I.: The diagnosiic significance of intrauterine pressure. Part II, Obstet. Gynecol. Surv. 25:515, 1970b. 5. Finn, C. A., and Porter, D. G.: The Uterus-Repro-
811
tractility of the myometrium.13 Unlike our own previous negative reports”, ‘* on the effects of oxytocin on the uterus during the menstrual cycle, the present investigation reveals the human myometrium to be capable of responding to oxytocin throughout the menstrual cycle. The lack of intrauterine pressure changes following oxytocin stimulation during the luteal phase suggests that under progesterone domination propagation is blocked, restricting the oxytocin response and causing erratic uncoordinated contractions which remain localized. The change in pattern of myometrial contractility which occurs following insertion of an intrauterine catheter reflects a physiologic response of the uterus to mechanical stimulation and cannot therefore be considered spontaneous activity. The response may result from either local release of oxytocic substances such as the prostaglandins or from reflex release of neurohypophyseal hormones. That the greatest responsiveness of the myometrium occurs at midcycle when the concentration of prostaglandins in the uterus is greatest14 speaks in favor of local release of prostaglandins. Also in favor of local prostaglandin activation is the observation that during the prostaglandin-rich, estrogen-dominated phase the response of the uterus is more pronounced and remains longer after removal of the catheter than during the luteal phase. The inability of indomethacin to supress the mechanical response does not rule out the prostaglandin hypothesis because the dose of indomethacin used in the present experiments may have been insufficient to block prostaglandins synthesis. Nevertheless the present study does not rule out the possible participation of reflex-released neurohypophyseal hormones or other myometrial stimulants such as norepinephrine which may in fact contribute to the response to mechanical stimulation.
ductive Biology Handbooks, Action Mass, ing Sciences Group, vol 1, pp. 134-236. 6. Braaksma, J. T., Janssens, J., Eskes, T.,
Hein, P. R.: Accurate pressure recording
1975,
Publish-
Arp,
A.,
and
in the non-
pregnant human uterus, Gynecol. Invest. 1:288, 1970. 7. Bengtsson, L. Ph.: The sponge tipped catheter. A modification of the open end catheter for the recording of myometrial activity in vivo, J. Reprod. Fertil. l&l 15, 1968. 8. Cibiis, L. A.: Contractility of the non-pregnant human uterus, Obstet. Gynecol. 30~441, 1967. 9. Caldeyro-Barcia, .R.: Function of the pregnant uterus, Proceedings of the Twentv-first Conmess of Physiological Science, B\enos Aires, Simposia a;d Special’Lectcres, 1959, pp. 7-13.
812
Coutinho
et al.
10. Caldeyro-Barcia, R.: Factors controlling the actions of the pr-egnant human uterus, in Kowlessar, M., editor: Physiology of Prematurity New York, 1961, Josiah Mac! Foundation, Publisher, pp. 11-l 12. 11. Coutinho, E. M.: Hormonal effects on the non-pregnant human uterus, in Gal, C., editor: Pogress in Endocrinology, Proceedings of the Third International Congress of Endocrinology Mexico City, Mexico, 1968, Excerpta Medica Foundation, International Congress Series 184, pp. 945951. 12. Coutinho, E. M., and Lopes, A. C. 11.: Response of the
nonpregnant human uterus to vasopressin as an rndcx ot ovarian function, AM. J. OBSTET. GYNECOI.. 102:.179. 1968.
1:3. Landesman, R., Coutinho, E. M., Wilson, K H.. .+rrd Vieira Lopes, A. C.: The relaxant effect of diazoxrtlr on non-gravid human myometrium in viva. .Ahf. J, 0~s1.r: I’. GYNECOL. 102: 1080, 1968. 14. Thorburn, G. D., Cox, R. I., Currie, W. B., Kestall. D. J., and Schweider. W.: Prostaglandin F concentration in tire rrtero-ovarian venous plasma of the ewe dun-ing oe\trtrs cycle. J. Reprod. Fertil. 53:325, 1972.
Copyright inf-tion The appearance of a code at the bottom of the first page of an original article in this indicates the copyright owner’s consent that copies of the article may be made for personal or internal use, or for the personal or internal use of specific clients. This consent is given on the condition, however, that the copier pay the stated per copy fee through the Copyright Clearance Center, Inc., P.O. Box 765, Schenectady, N. Y. 12301, (518) 374-4430, for copying beyond that permitted by Section 107 or 108 of the LT. S. Copyright Law. This consent does not extend to other kinds of copying, such as copying for general distribution, or advertising or promotional purposes, for creating new collective works, or for resa;.
JOURNAL
METZKER
LUSIA
NASCIMENTO,
HUGO
DA
MARIA
SILVA
Bahia,
M.D.
M.D. MAIA,
TERESA
Salvador,
COUTINHO, M.D.
R. GONCALVES,
M.D.
Brazil
Microballoons inserted into the thickness of the myometrium during laparotomy were used to record the motiliQ of the human uterus during the menstrual cycle. Except during menstruation when the myometrial contractions were similar to those recorded through intrauterine pressure recording, the pattern of localized myometrial activity bore no resemblance to the familiar intrauterine pressure tracings. Myometrial contractions of small amplitude, 5 to 20 mm Hg, were recorded during both the proliferative and luteal phases of the cycle. The contractions tended to occur in bursts at intervals of 5 minutes or longer. Uterine quiescence lasting several minutes was observed at all phases of the cycle with the exception of the menstrual period. Transcervical insertion of an open-end or balloon-tipped catheter provoked marked activation of myometrial motility at all phases of the menstrual cycle. Activation of the myometrium by transcervical insertion of the catheter during the estrogen-dominated proliferative phase was more marked and lasted longer than that during the progesterone-dominated luteal phase. The oxytocin response was recorded throughout the menstrual cycle but lasted longer during the preovulatory and early postovulatory phases than during the late luteal phase of the menstrual cycle. During the luteal phase activation of the myometrium following oxytocin injection failed to be translated into intrauterine pressure changes. (At&J. C)BSTET.GYNECOL. 134:801, 1979.)
INTRAUTERINE pressure recordings have been widely used in studies of uterine physiology and pharmacology. IT4 Fluid-filled balloons have been the favorite sensors of intrauterine pressure changes resulting from uterine contractions, and for this reason most of the data available on the motility of the nonpregnant human uterus are based mainly on studies conducted with balloons.5 Open-end and sponge-tipped catheters, proposed in the 1960’s as alternatives to the balloon, have met with limited success since the new techniques had no significant advantages over the balloon tech-
From the Department of Maternal Health and Child Care, Maternidadz Climerio de Oliveira, Federal University qf Bahia School of Medicine. Supported
by the Ford
Council, and the World Received
for
publication
Revised
.Vay
2, 1978.
Accepted
August
Foundation, The Population Health Organization. February
27, 1978.
2 I, 1978.
Reprint requests: Dr. E. M. Coutinho, Matemidade Climerio de Oliveira, Universidade Federal da Bahia, Salwdor, Bahia, Brazil. OOOZ-9378/79/15C1801+12$01.20/0
0
1979 The
C. V. Mosby
Co.
niques. 6, ’ However, open- end recordings reactivated an old controversy on the character of uterine contractility during the menstrual cycle as recorded by various investigators. Although all workers agree that menstruation is attended by contractions of high amplitude and high or low frequency and that at midcycle the frequency is higher and amplitude lower, recordings during the luteal phase with either open-end or closed systems show substantial differences. Pressure cycles of long duration and relatively high amplitude have been reported as typical of the luteal phase by some authors whereas others deny the occurrence of these cycles. The oxytocin response, which is another point of disagreement, has been reported variously as being suppressed throughout the menstrual cycle, during the luteal phase only, or not at all.“. 3, ’ Advocates of openend recording claim a more reliable technique because in their view the balloon tip is a greater irritant of uterine motility than the fine end of a catheter.‘j4 Propounders of the balloon method dismiss the open-end catheter technique as unreliable because it develops too many recording artifacts, and defend the balloon re801
802
Coutinho et al.
c’ep’or for its freedom from obstruction and reproducibilil~.2~ ‘j. ’ The controversy remains unresolved primarily because of’ individual differences in motilit!. patterns recorded by the same investigator with either open-end or closed systems. All the various techniques with open or closed systems require transcervical introduction of catheters which are held in place during the recording sessions. .i\lthough the possible influence of this transcervical catheter on uterine motility has been discounted as being negligible by most uterine physiologists, preliminary studies suggested that even minimal intrauterine stirriulation with an open-end catheter or very small balloon had a marked activating effect on u terinc motility. These findings may have implications in the interpretation of physiologic events and pharmacologic effects on the myotnetrium, since the assumed baseline of uterine motility as recorded through an intrauterine catherrr would become actually an artifact of the recording technique. Therefore in order to investigate the influence of transcervical recording on uterinr motilit), ir would seetn imperative to establish a basclint of’ uterine motility in uteri in which the cervical canal and rhe uterine cavity were left undisturbed during recordings. Microballoons inserted into rhe thickness of the myometrium have been used in studies of propagation in the human pregnant uterus.” The method allows recording of local contractions resulting from activit! of the muscle surrounding the balloon as well as passive rontractions originating elsewhere which propagate to the microballoon area. The presence of the balloon does not provoke generalized contractions and does not seem to interfere with normal uterine activity.” In the present study, the effect of intrauterine recordings on the motility of the nonpregnant uterus was investiSated in women whose myometrial activity was recorded through intramyometrial microballoons.
Methods ‘l‘he study was carried out in 16 women of reproductive age who had to undergo abdominal surgery for the following indications: tubal ligation (six), correction of‘ tubal occlusion (four), wedge ressection of the ovary (two), removal of periovarian tubal adhesions (two), or removal of ovarian cysts (two). All subjects volunteered for the study and have given full informed consent. Uterine motility was recorded through intramural microballoons for periods ranging frotn 1 to 8 weeks. In I2 women recordings lasting 1 to several hours were carried out every other day for at least one full menstrual cy< It?.
The balloon-tipped polyvinyl catheters were inserted in the uterine wall through a small incisio,, during laparotomy and held in place with a suture oic~hrotnic catgut. The microballoons, made of natur-al latex, measured I mm of external diameter and had a citpacitv of 0.3 ml. Iti some suhjecis two tnic-robaIloonc were itiserted in tlif-ferent parts of the ur<‘t.ttx. The effect of. transcervical insertion M;IX investigated during recording sessiorrs b! itttroducing a Teflon catheter deei) into tlw ulerus ,~rttl tworfling intrauterine and intramural pressure sil7i~tltaiicolisl~ li)r a few minutes to several hours. Both open-end and balloon-tipped catheter-s hal-e been used. In C~LC’I-Icase the tip of thr catheter touched the uterine fundus. Iti order to evaluate the influence of rransc.er\ical recording on the pharmacologic response of the rnrometrium, oxytocin (Syntocinon, Sando/) was injected intravenously before and during au intrauterine recording session. I tI order to datr 0\7rlation, htteiiiixing hormone (LH) and progcsteronr~ blood le\,els WIY measured bj radioimuno;tssa) in mos[ subjet tr.
Results Spontaneous activity. Contractions 01‘ small a mplitude developing approximately 5 co 20 mm of’ pressure were recorded during the early proliferative phase of’ the cycle from either the fundus or the isthmus. The frequency of these low-amplitude contractions v-aried from less than one pet- tninute to as many as 4 to .?I per minute. Periods of inactivity lasting 5 minutes or longer were common. Periods of’ quiescence lasting as long as 1 hour were recorded during this phase. Sudden spontaneous increases in frequency were recorded otcasionally. During the late proliferative and early luteal phases, the contractions occurred in bursts at intervals of5 to 10 minutes. Periods of quiescence lasting longer than 10 mimttes were nc\er seen during this phase in this group of patients. During the luteal phase, contractions developed a higher amplitude reaching sometimes 100 mm Hg or more. They still came in bursts which were more fiequent but of’ a shorter duration than those occurring during the late proliferative and early luteal phases of the cycle. As menstruation approached contracttons became more frequent, the groups of contractions fused together, and the burst pattern was lost. Fig. 1 illustrates the most common patterns recorded in all subjects who had ovulatory cycles. Synchrony between contractions occurring at different parts ot rhe utertrs was observed in all patients in whom two intramural balloons had been inserted. Synchronous contractions were recorded during menstruation and the rarlv proliferative phase of‘ the c\ cle.
Volume
134
Number
7
803
Motility of human myometrium in vivo
8
0
14
100
17
a’
,‘.
“’
20
Fig. 1, Patterns
of myometrial motility during the menstrual Note the high amplitude of the contractions recorded during activity developing during both the proliferative and luteal patient was detected on days 14 and 15.
cycle. In vivo intramural recording. menstruation. Note also the bursts of phases of the cycle. LH peak in this
t
i .: 10
Fig. 2. Response of the myometrium to transcervical introduction of a catheter. In viva intramut-al recording. Note the marked activation of myometrial motility following transcervical insertion of catheter (arrow pointing downward). Note also that following removal of the intrauterine catheter (arrow pointing upward) the burst pattern is re-established on days 2 1 and 27 but not on days 10 and IS. LH peak in this patient was detected on days 14 and 15.
Volume Number
Motility of human myometrium in vivo
134 7
Fig. 3. Response menstrual cycle. cervical insertion remains activated
of the myometrium to transcervical introduction of a catheter Intramural recording in vivo. Note the long period of quiescence and the prompt activation following insertion. Note also that long after removal of the intrauterine catheter.
on day 9 of the preceding transthe myometrium
805
806
Coutinho et al.
of the myometrium to transcervical introduction ot a balloon-tipped catheter Fig. 4. Response (balloon capacity 0.3 ml). Note that the intrauterine pressure records (IPi are typical for tht estrogen-dominated uterus on day 11 and for the progesterone-dominated uterus on day 26. Note also that in contrast with the marked activation of myometrial motility the intrauterine pressure record shows a quiescent uterus during the luteal phase. LH peak of this patient \\as detected on day 15.
During the late proliferative and early luteal phases, synchrony was lost. Simultaneous recordings carried out during the luteal phase from intramural microballoons placed at different parts of the uterus showed both contractions and bursts occurring completely independent from each other. Alterations in uterine motility following transcervital introduction of a catheter. Two to three minutes following the introduction of a transcervical catheter.
uterine motility was markedly activated. Activation occurred at all phases of the menstrual cycle but it was more marked during the proliferative phase than during the luteal phase of the cycle. During menstruation when spontaneous motility was greatest. activation following intrauterine insertion of the catheter was minimal. During the late proliferative and early luteal phases, uterine motility remained activated as long as rhe catheter was maintained in the uterine cavity. Dur-
Volume Number
Motility of human myometrium in vivo
134 7
807
Fig. 5. The
response of the nonpregnant human uterus to transcervical insertion of a catheter. Intramural recording. Note the marked increase in tonus and frequency.of contractions following insertion’ of the catheter. Note also that following indomethacin treatment (200 mg suppositories given three times) reinsertion of the catheter provokes only a moderate increase in tonus.
ing the luteal phase, the effect usually subsided soon after removal of the intrauterine probe. Fig. 2 illustrates the effects of insertion and removal of the intrauterine catheter during the menstrual cycle of the patient whose spontaneous uterine motility is shown in Fig. 1. The activating effect of the intrauterine catheter may last long after removal of ‘the catheter. During the luteal phase, the effect lasted only 10 to 20 minutes but during the late proliferative phase it could last several hours. Fig. :3 shows the long-lasting effect of catheter insertion and removal in a patient on day 9 of menstrual cycle. The patterns of uterine motility as recorded through the intramural balloon differ markedly from those recorded through the intrauterine balloon during both the proliferative and luteal phases. However, similarities developed when recordings were carried out simulataneously because activation of uterine motility induced by the intrauterine catheter affects equally intramyomettial and intrauterine pressure. Similarities developing during simultaneous recording are greater during the estrogen-dominated proliferative phase than during the early luteal phase of the cycle. During the late luteal phase, the motility patterns recorded through the intramural balloon bear almost no re-
semblance with the intrauterine pressure curves. Whereas the intrauterine pressure tracings reveal a lowered contractility suggestive of a quiescent uterus, the intramural recordings show an active myometrium with bursts of contractions occurring at intervals of 3 to 8 minutes (Fig. 4). The tracings again become similar as menstruation approaches and during menstruation there are almost no differences between the two tracings. Attempts to prevent or supress myometrial response to mechanical stimulation through transcervical insertion of the catheter by indomethacin treatment (200 mg suppositories used three times) were not successful. In some cases reactivatian of the uterus could not be achieved by reinsertion of the intrauterine probe following indomethacin administration, but in most cases indomethacin pretreatment failed to reduce the magnitude of the initial response of the uterus to insertion of the intrauterine probe. Fig. 5 illustrates the response of the uterus before and following indomethacin treatment in a patient on day 14 of the menstrual cycle. The response to oxytocin. The response of the nonpregnant uterus to oxytocin (1 unit intravenously) was recorded through the intramural balloon system throughout the menstrual cycle. The activating effect of oxytocin was more marked during the late pro-
808
Coutinho et al.
Fig. 6. The response of the nonpregnant human uterus Intramural recording. Note that the response lasts longer LH peaked on day 14.
to oxytocin during the menstrual qcle. on Days 10 and 17 than on days 5 and 23.
Volume Number
Motility of human myometrium in vivo
134 7
809
Fiig. 7. The effect of intrauterine catheter on the response of the nonpregnant human uterus to oxytocin. A: Response to oxytocin recorded through intramural microballoon. B and C: Response to oxytocin during the intrauterine recording. In B as recorded through the intramural microballoon, and in C as recorded through the intrauterine balloon-tipped catheter. Note that while frequency of the myometrial contractions increases markedly following oxytocin injection in E, simultaneous recordings of intrauterine pressure remain almost unaltered in C. liferative phase than during the early proliferative and late luteal phases of the cycle. During the late proliferative phase at midcycle, the response to a single oxytocin injection lasted 30 minutes or longer. During the late luteal phase, the response lasted 15 to 20 minutes and its intensity was less than that during the proliferative phase of the cycle (Fig. 6). In patients whose uteri were being recorded through transcervical recording, only a moderate increase in the frequency of contractions developed following oxytotin injections. ‘The response to oxytocin which could be recorded through the intramural recording system was almost imperceptible through the intrauterine pressure recordin,g. In fact in most cases no significant change in intrauterine pressure could be detected following oxytocj n injections during either the proliferative or luteal phases of the menstrual cycle. Moderate changes in intrauterine pressure following oxytocin in-
jections could be recorded only during the early proliferative and late luteal phases of the cycle. Marked changes of intrauterine pressure following oxytocin were restricted to the menstrual phase. Fig. 7 illustrates the recording of an oxytocin response through intramural recording before and during transcervical recording on day 5 of the cycle. Fig. 8 shows the oxytocin response during the early and late luteal phases as recorded simultaneously through intramural and intrauterine pressure recording.
Comment Uterine contractility recorded through the intramural balloon reveals a pattern of uterine motility which holds almost no resemblance to the familiar intrauterine pressure tracings. While intrauterine pressure records show marked differences in motility patterns throughout the menstrual cycle, localized myo-
810
Coutinho et al.
Fig. 8. The effect of an intrauterine balloon-tipped catheter on the response of the uterus to oxytocin during the luteal phase of the cycle. Simultaneous intramural and intrauterine recording. Note the slight increase in the frequency of myometrial contractions and the absence of any significant changes in the pattern of uterine contractility as recorded through the intrauterine pressure on day 19. Note also the differences in oxytocin response as recorded through rhe two systems on day 26. LH peaked on day IS. metrial contractility displays almost the same features during the proliferative and luteal phases of the cycle. The pattern of myometrial contractility changes markedly only during menstruation, when the tracings obtained through the intramural balloons become identical to the intrauterine pressure records. Unlike the pattern of “spontaneous” motility which may show periods of quiescence of relatively long du-
ration and which changes very little from the first to the second half of the menstrual cycle, the motility pattern of the uterus activated by the transcervical catheter displays features which may be considered typical for each phase of the cycle. During the estrogen-dominated proliferative phase of the cycle, the response to transcervical introduction of the catheter is prompt and lasts long after removal of the intrauterine probe.
Volume
Motility of human myometrium in vivo
134 7
Number
During the progesterone-dominated luteal phase the response is less marked than that recorded at midcycle and lasts a shorter period of time. Following removal of the
intrauterine
motility
returns
catheter
during
promptly
to
this
phase
uterine
preintroduction
levels.
During menstruation changes in myometrial activity induced by the insertion of the catheter are negligible. In addition to these variations in the character of the response during the menstrual cycle, the magnitude of the uterine response to intrauterine stimulation varies from
subject
to subject
mechanical
stimulation.
nique
to stimulate
used
cal recording region ever,
the of
even
uterus
to
the
catheter
with
minimum
and In
catheter
also the
uterus
required tip.
standardization
with repeated
these
with
the
present
This for
with
the with
transcerviassured
procedure. response the
tech-
the fundal
maneuver the
of
the
the
touching
precautions stimulation
intensity
study
a
Howof
the
transcervical
during the luteal phase varied substantially, suggesting that variations in the degree of pressure exerted against the uterine fundus could induce varying response. It should be pointed out, however, that these findings do not disqualify intrauterine recordings as a diagnostic method since the response of the uterus to mechanical sl:imulation is significantly changed from the estrogen-dominated preovulatory phase to the progesterone-dominated postovulatory phase of the cycle allowing therefore a precise evaluation of the endocrine status of the organ.” On the other hand, interpretation of pharmacologic effects on the uterus with intrauterine pressure measurements should be taken with ca.ution. Oxytocic compounds such as oxytocin may be wrongly considered weak stimulants because their effect is obscured by pre-existing exaggerated motility. I13 I2 By the same token inhibitory drugs are tested so’metimes on an overstimulated uterus, a condition which is far from representing the basal concatheter
REFERENCES 1. Coutinho, E. M.: Uterine activity in nonpregnant women, Proceedings of the Eighth International Conference of the International Planned Parenthood Federation, San-
tiago, Chile, 1967, pp. 432-439. C. A., Romeo-Salinas, and Mendez-Bauer, 2. Jaumendreu, C.: Action de la progesterona hidrosoluble intravenosa sobre a contractilidad de1 utero human0 no gravido in vivo, Proceedings of the Fourth Congress Uruguay Gincotocol. 1964, vol. 2, p. 394. 3. Csapo, A. I.: The d&gnostic significance of intrauterine oressure. Part I. Obstet. Gvnecol. Surv. 25:403. 1970a. 4. ksapo, A. I.: The diagnosiic significance of intrauterine pressure. Part II, Obstet. Gynecol. Surv. 25:515, 1970b. 5. Finn, C. A., and Porter, D. G.: The Uterus-Repro-
811
tractility of the myometrium.13 Unlike our own previous negative reports”, ‘* on the effects of oxytocin on the uterus during the menstrual cycle, the present investigation reveals the human myometrium to be capable of responding to oxytocin throughout the menstrual cycle. The lack of intrauterine pressure changes following oxytocin stimulation during the luteal phase suggests that under progesterone domination propagation is blocked, restricting the oxytocin response and causing erratic uncoordinated contractions which remain localized. The change in pattern of myometrial contractility which occurs following insertion of an intrauterine catheter reflects a physiologic response of the uterus to mechanical stimulation and cannot therefore be considered spontaneous activity. The response may result from either local release of oxytocic substances such as the prostaglandins or from reflex release of neurohypophyseal hormones. That the greatest responsiveness of the myometrium occurs at midcycle when the concentration of prostaglandins in the uterus is greatest14 speaks in favor of local release of prostaglandins. Also in favor of local prostaglandin activation is the observation that during the prostaglandin-rich, estrogen-dominated phase the response of the uterus is more pronounced and remains longer after removal of the catheter than during the luteal phase. The inability of indomethacin to supress the mechanical response does not rule out the prostaglandin hypothesis because the dose of indomethacin used in the present experiments may have been insufficient to block prostaglandins synthesis. Nevertheless the present study does not rule out the possible participation of reflex-released neurohypophyseal hormones or other myometrial stimulants such as norepinephrine which may in fact contribute to the response to mechanical stimulation.
ductive Biology Handbooks, Action Mass, ing Sciences Group, vol 1, pp. 134-236. 6. Braaksma, J. T., Janssens, J., Eskes, T.,
Hein, P. R.: Accurate pressure recording
1975,
Publish-
Arp,
A.,
and
in the non-
pregnant human uterus, Gynecol. Invest. 1:288, 1970. 7. Bengtsson, L. Ph.: The sponge tipped catheter. A modification of the open end catheter for the recording of myometrial activity in vivo, J. Reprod. Fertil. l&l 15, 1968. 8. Cibiis, L. A.: Contractility of the non-pregnant human uterus, Obstet. Gynecol. 30~441, 1967. 9. Caldeyro-Barcia, .R.: Function of the pregnant uterus, Proceedings of the Twentv-first Conmess of Physiological Science, B\enos Aires, Simposia a;d Special’Lectcres, 1959, pp. 7-13.
812
Coutinho
et al.
10. Caldeyro-Barcia, R.: Factors controlling the actions of the pr-egnant human uterus, in Kowlessar, M., editor: Physiology of Prematurity New York, 1961, Josiah Mac! Foundation, Publisher, pp. 11-l 12. 11. Coutinho, E. M.: Hormonal effects on the non-pregnant human uterus, in Gal, C., editor: Pogress in Endocrinology, Proceedings of the Third International Congress of Endocrinology Mexico City, Mexico, 1968, Excerpta Medica Foundation, International Congress Series 184, pp. 945951. 12. Coutinho, E. M., and Lopes, A. C. 11.: Response of the
nonpregnant human uterus to vasopressin as an rndcx ot ovarian function, AM. J. OBSTET. GYNECOI.. 102:.179. 1968.
1:3. Landesman, R., Coutinho, E. M., Wilson, K H.. .+rrd Vieira Lopes, A. C.: The relaxant effect of diazoxrtlr on non-gravid human myometrium in viva. .Ahf. J, 0~s1.r: I’. GYNECOL. 102: 1080, 1968. 14. Thorburn, G. D., Cox, R. I., Currie, W. B., Kestall. D. J., and Schweider. W.: Prostaglandin F concentration in tire rrtero-ovarian venous plasma of the ewe dun-ing oe\trtrs cycle. J. Reprod. Fertil. 53:325, 1972.
Copyright inf-tion The appearance of a code at the bottom of the first page of an original article in this indicates the copyright owner’s consent that copies of the article may be made for personal or internal use, or for the personal or internal use of specific clients. This consent is given on the condition, however, that the copier pay the stated per copy fee through the Copyright Clearance Center, Inc., P.O. Box 765, Schenectady, N. Y. 12301, (518) 374-4430, for copying beyond that permitted by Section 107 or 108 of the LT. S. Copyright Law. This consent does not extend to other kinds of copying, such as copying for general distribution, or advertising or promotional purposes, for creating new collective works, or for resa;.
JOURNAL