Significance of uterine bleeding in early pregnancy

SIGNIFICANCE

OF UTERINE BLEEDING IN EARLY PREGNANCY * ALEX CULINER, M.D. Johannesburg, South Africa

I

T is generahy recognized that local lesions in the vagina and on the cervix may bIeed during earIy pregnancy and that such bIeeding is without significance as regards interruption of pregnancy. Vaginal bIeeding which, however, appears to arise from the uterine cavity is aImost invariabIy regarded as threatened abortion. This concept faiIs to take into consideration those reactions in the cavity of the uterus which are associated with the implantation and growth of the ovum and which are capable of initiating bleeding without disturbing the pregnancy or its attachments. Since the existence of such mechanisms is not bIeeding during early generaIIy recognized, of recognizable pregnancy in the absence pathoIogic disorder is usuaIIy treated as threatened abortion. WhiIe some writers consider Iower abdominal pain in addition to bleeding as a prerequisite to such a diagnosis,“j12 there is by no means any consistency in this respect.2 If bIeeding from the uterine cavity is usuaIIy regarded as an abortive process, the arrest of such bIeeding folIowing hormona1 therapy wouId possibly impIy some special merit in these measures. On the other hand, should it be possible for bIeeding to occur without danger of disrupting the pregnancy then onIy those cases in which some hormonal deficiency, altered uterine sensitivity or such other disturbed mechanism to which abortion can reasonabIy be ascribed should be seIected for specific forms of treatment and the assessment of efficacy based on these cases. Since the majority of patients with early pregnancy bIeeding do not have substantiation of the fact that their pregnancies are actuaIIy in the process of being dislodged from the implantation site or that such an event is imminent, it must be conceded that any treatment for such bIeeding is empirica1. It is the purpose of this communication to present evidence as to why bleeding may occur in early pregnancy without separation of the * From the Department

of Obstetrics and Gynecology,

ovum and that, consequently, uterine bleeding does not necessariIy connote threatened abortion. It is a common experience amongst obstetricians to have observed patients who, despite bleeding in earIy pregnancy, with no additional bed rest or medication of any kind, have continued their pregnancies without further troubIe. In some of these the patient volunteers the information that there was some irregularity in the last one or two menstrual periods and on examination the size of the pregnant uterus is found to be greater than was anticipated from the time Iapse since the Iast episode of bleeding. STATISTICAL

To determine the incidence of early pregnancy bIeeding in women who did not abort despite the Iack of adequate treatment a continuous series of 840 patients were questioned during their puerpera1 stay at the Queen Victoria Maternity Hospital, Johannesburg, concerning such bIeeding. Of these patients, eight-one gave a history of bIeeding during earIy pregnancy but because of inadequate data twelve of the Iatter were discarded. The incidence of bIeeding during earIy pregnancy, therefore, which could be attributed to an intra-uterine source was 8.2 per cent in this series. Other information which emerged from this study was as follows: $3.8 per cent did not get any additiona bed rest because of the bIeeding, 23.4 per cent had bed rest of not more than three days’ duration and the remainder received treatment which could by present standards be regarded as adequate for threatened abortion. These received bed rest, sedatives and hormonal therapy although the nature of the latter could not be accurately ascertained in each instance. Thus the number of patients without adequate treatment for threatened abortion who despite bleeding con-

University of the Witwatersrand,

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SURVEY

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tinued with their pregnancies to term was 65 per cent. In 36.1 per cent bleeding occurred at the time of at least one expected normal menstruat period and 14.4 per cent continued to have bleeding after fetal movements were felt. However, only one patient with early pregnancy bleeding was subsequently found to have a placenta previa. The incidence of bIeeding as between multipara and those with their first pregnancy was equal but of those with previous 45.8 per cent stated that full term pregnancies bleeding had occurred in the early months of pregnancy of at least one of such pregnancies. Whereas criticism may be offered that these observations are not based on objective findings but only on the historical accuracy of these patients we have observed that in our private practice in a comparabIy smaIIer series the incidence of bleeding is at Ieast twice as great as that stated previously. In private practice patients generally present themseIves for antenatal care much sooner than in hospita1 practice and the occurrence of bleeding is observed as a comphcation of early pregnancy. Since almost all private patients were confined to bed for five to seven days after cessation of bleeding, we did not feel justified in including these patients in the present statistica study. POTENTIAL

SOURCES

OF UTERINE

BLEEDING

IN

PREGNANCY

in tbe Decidua Vera. Vascular Changes There is littIe doubt that bleeding can occur from the uterus without interfering with feta1 So-called menstruation during deveIopment. pregnancy has been recorded by various au thors and Novak6 regards the incidence of menstruation in pregnancy as about 0.05 per cent. Various explanations have been suggested for such bleeding and it is assumed by some that inhibition of the cyclical menstrual rhythm has not been complete in these cases. It is an observed fact” that ovarian activity in the first trimester of pregnancy is far from static and the possibility that endocrine influences emanating from the ovaries and acting upon the decidua sufficient to provoke bleeding should not be disregarded. Follicle maturation, atresia and theta cell proIiferation continue to occur despite pregnancy and such changes in the ovary cannot be without hormonal effect. In some instances the bIeeding in pregnancy is cychcal and whether or not this can April,

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FIG. I. Vascular thrombosis and recanalization in decidua vera; (a) old and new blood vesse1; (b) decidua Vera.

be correIated with periodic fohicular growth has stiI1 to be estabhshed. Whatever the endocrine influences may be, it has been suitabIy demonstrated7x13 that profound reorganization of the vascular system occurs in the decidua during pregnancy before formation of the definitive placenta. Thrombosis and recanalization of vascular channeIs may be observed in endometria1 decidual tissue. (Fig. I.) It is improbable that gross alterations in the decidua and particularly its vessels even in areas removed from the pIacentaI site producing as they do a decrease in interglandular stroma, ballooning of the glands, intimal fibrosis of arteries and formation of mural arterial and venous systems designed for suppIy and drainage of the endometrial wall independentIy of the pIacenta1 circulation,’ can occur without the occasiona breakdown of so complex and rapid a mechanism. In fact, hemorrhages into the decidua are of extremely common occurrence and have been commented upon by other observers.g So long as such a break in the vascular system is sIight and of short duration it is unlikely to disturb the pregnancy and is, therefore, of little consequence as regards the

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in such a case. CIinicalIy, this phenomenon would J>e manifest as bleeding in the prcscnce of a normal pregnancy. Even when such vascular accidents occur in the region of the placental site they are not necessarily associated with disruption of the pregnancy. Minor degrees of hemorrhage from vessels beneath the pIacenta1 site with consequent bleeding into nearby gIands of the endometrium occurs with such regularity in rhesus monkeys and baboons that the term “placental sign” designed by Hartman to connote this phenomenon is a sign of pregnancy in these animals. The glands from which such bleeding occurs open into the cavity of the uterus at the margin of the placental areas and bleeding lasts in the rhesus from two to four weeks from about the twenty-ninth day of pregnancy. Since the endometria1 reorganization of early pregnancy in the human differs from the lower primate only with minor structura1 variances,* there is IittIe reason to doubt that bleeding may similarly occur into glands of human decidua vera and even from the sub- or paraplacental site without disruption of the pregnancy. When the decidua capsularis connects with the decidual Vera, a few glands may be seen with their ducts opening onto the outer surface of the membrane.r2 Bleeding into such glands would obviously have ready access to the vagina. Further evidence in support of the contention that bleeding may occur from the decidua vera may be gleaned from a consideration of the uterine bIeeding in the presence of a living ectopic pregnancy. That uterine bleeding indicates feta1 death or more specificaIIy death of chorionic tissue is not aIways true and numerous instances of bIeeding in the presence of a live tuba1 or abdominal pregnancy have been recorded. In a series of abdominal pregnancies described by Brady’ suppression of bleeding occurred in onIy haIf of the cases. Hoffman5 asserts that when pregnancy occurs in one horn of a uterus Didelphys, bIeeding from the other horn is a reIativeIy common symptom and Te Linde*O in discussing a paper by Brewer is of the opinion that breeding can occur from the decidua vera in the presence of a live tuba1 pregnancy. While the possibility of bIeeding occurring in the presence of an intra-uterine pregnancy without disturbing such a pregnancy has been suggested by others, this phenomenon is gen-

in Early

Pregnanq

erally regarded as being of infrequent occurrence. As has been shown More, the incitlencc of such I~Iccding is actually greater than gcnerally supposed and it is probable that many instances of what is generally assumed to be threatened abortion is merely an example of bleeding analagous to the pIacenta1 sign or that which occurs as a result of the vascular reorganization in the decidua vera during the predefrnitive stage of placental deveJopment regardless of whether the pregnancy is intraor extra-uterine. The apparently lowered incidence of bleeding from the uterus when the pregnancy is intrauterine as compared with extra-uterine pregnancies may we11 be related to the mechanical tamponade effect of the amniotic sac. The pressure of the expanding amniotic sac against the decidua vera could easily prevent the escape of any mild degree of blood loss associated with the re-establishment of new blood vessels. The uterine cavity is not wholly occupied by the amniotic sac until the third month and any bleeding tendency occurring in the decidua before this time wouJd thus not be compIeteIy inhibited by this slowly expanding tampon. Actual proof of such a device is Jacking but presumptive evidence of this may be drawn from the foIlowing history: A married woman, age thirty-four, had cyclical bleeding unti1 the fifth month of her pregnancy at about thirtyday intervals. This was unrelated to coitus. Whereas her menses were normally of three to four days’ duration, during her pregnancy the Ioss was very slight and did not Iast for more than a day on each of these particuIar occasions. She was observed to have a pIaque of endometriosis on the Iateral vaginal waI1 which was excised and found histologicaIIy to contain decidua. There was no further bleeding and her pregnancy proceeded uneventfully. The factors responsible for the bIeeding in this instance must obviously have been acting on the uterine decidua as we11 as upon this ectopic endometrial decidua. Since there was no evidence of bleeding from the uterine cavity and bleeding ceased after removaJ of this plaque of tissue, it is suggested that the pressure effect of the feta1 amniotic sac may have been a factor in the prevention of bIeeding from the cavity of the uterus. ObviousIy in those instances of bleeding in ectopic pregnancies, tuba1 or abdomina1, or those in double uteri, such a mechanical device American

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Bleeding

for the prevention of bleeding is absent and one would expect the incidence of bleeding from the uterus to be greater in these instances. Such generally is the case. Should there be an excess of endometrial decidua1 tissue in an area within the uterus inaccessibIe to the expanding amniotic sac then a similar state of affairs may prevail in that, the packing effect of the fetal sac cannot exert any pressure against vascuIar loss in the superficiaI Iayers of the decidua Vera. In a recent patient profuse bleeding was occurring in the early months of pregnancy from a smooth tongue-Iike projection about I l/4 inches in Iength extending through the cervix. Histologically, this was shown to be an endometria1 poIyp with deciduaI reaction and without viIli. Despite its removal pregnancy continued. Had this endometrial tissue not presented through the cervix but remained inconspicuously above the external cervica1 OS then treatment in this patient would have been that commonly employed for threatened abortion and credit for salvage of the pregnancy faIseIy given to whatever therapeutic measures were used. In Figure 2 the type of decidual hypertrophy which can occur in such circumstances is observed at the IeveI of the interna OS. This area which is a potentia1 source of bleeding has been designated by Johnstone as the “bleeding triangle” aIthough he considers the mechanism to be one of poorIy devefoped decidua vera inaccessibIe to decidua reffexa. This illustration shows well developed decidua with marked hypertrophy. In the presence of uterine fibromyomas distortion of the uterine cavity may occur with the result that the amniotic sac and decidua reflexa may not come in juxtaposition with the decidua Vera. ConsequentIy their effectiveness in preventing escape of blood from superficia1 vascuIar hemorrhages is Iimited. Certainly the incidence of bfeeding in early pregnancy associated with myomas appears to be refatively high and the unfortunate embarrassment of the surgeon who removes a uterus with fibromyoma and finds an earIy pregnancy is generally due to the irregular bleeding which occurs in these cases. The usua1 mechanisms which give rise to menorrhagia when fibromyomas are present do not usua1Iy pertain when there is an intra-uterine pregnancy. Extraplacental Villus Activity. In considering the phenomenon of early feta1 growth and April,

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Pregnancy

the formation of amniotic and chorionic structures it is apparent that the villi on the antiplacental surface of the sac, instead of undergoing atrophy as is customary, may persist until such time as the expanding sac strikes the opposing uterine waI1 and its decidua. Evidence of such persistence can be observed even at term; and while these viIIi commonly undergo degeneration, they do not completely disappear.i2 There are many instances of inhibition of such degeneration with actual persistence of function. These are cIinicaIIy recognizabIe as succenturiate Iobes of pIacenta and the much rarer pIacenta membranacea. Should the degeneration of such viIIi be but delayed and not form gross placenta1 tissue recognizabIe at term, then it is conceivabIe that the Iytic activity of the trophobIast may give rise to bIeeding by destruction of the stroma and bIood vesseIs of the decidua Vera. Since such bIeeding occurs in an area removed from the vital placental areas, in the earIy stages the decidua basalis, the danger of disruption of the fetus is remote, particularly if there is free access for such bleeding to the endocervical cana and vagina. If such bleeding accumulates in the uterine cavity and there is no free egress, then a stimuhrs for uterine contractions is provided and the possibiIity of expulsion of a norma fetus arises. Any bIeeding less than this critica amount is of little consequence. Provided that there is no obstruction to the blood which is Iost in this way then even severe bIeeding may not induce abortion. About a year ago a private patient, para I, was admitted to the hospitaI for termination of what appeared to be an inevitable abortion of about fourteen weeks’ duration. She had Iost I 1.5 pints of bIood over the preceding two days and this loss had been accompanied with rower abdominal pain which six hours before admission was sufficiently severe to warrant morphia for its alleviation. However, vagina1 examination indicated no diIatation of the cervix and the size of the uterus as normal for the duration of the pregnancy. The patient was consequently left without surgica1 interference; and while slight bleeding dicI continue for a further ten days, it gradually subsided. Subsequent delivery at term was uneventful but the placenta was of the circumvaflate type. While the pathoIogic nature of this placenta is of IittIe consequence in the present discussion,

Culiner-Uterine

Bleeding

FIG. 2. (a) Hypertrophy of decidua over intern:11OSin a pregnant uterus; (b) fibromyoma.

the point that emerges from this case is that despite gross and profuse intra-uterine hemorrhage accompanied with uterine contractions, a pregnancy was stil1 able to continue without interruption. It is extremely diIhcuIt to obtain direct evidence of hemorrhage occurring from the decidua vera with continuation of the pregnancy, but we have observed and studied severat oId museum specimens of uteri harboring early pregnancies which provide some information in the elucidation of the phenomena under discussion. Two of these showed evidence of bleeding into endometria1 gIands and in areas removed from the pIacenta1 sites. (Figs. 3 and 4.) The placentas, while incompIeteIy deveIoped, showed no evidence of separation. (Fig. 2.) Figure 5 shows viIIous structures in regions well removed from the site of the de nitive placenta; and whiIe there was no microscopic evidence of vascuIar destruction, the mere presence of villi in this area is sufficient to suggest that a mechanism exists in this case for the production of inconsequentia1 bIeeding. Figure 6 illustrates the presence of villi over cervical gIand epithebum. This was obtained with a biopsy curette from a patient who was not suspected of being pregnant

in EarIy

Pregnancy

hecause of long periods of amenorrhea ant occasional menses of variable duration. TJris specimen was obtained six days following a two-day episode of bleeding. Yet despite its removal the pregnancy continued undisturbed. Viability of viIIi and their capacity to induce vascuJar destruction are not directty dependent upon a Jiving fetus as is apparent in hydatidiform moles and chorionepitheIiomas. Therefore, it must be anticipated that bIeeding might occur from extrapIacenta1 areas so long as viIIi continue to exist in these Iocalities. It is impossibIe to estimate the extent of bleeding upon which wil1 hinge the probabiIity of abortion provided that the hemorrhage is occurring in a region which wiIl not disrupt the pregnancy directly. In these circumstances in which the actua1 site of the dehnitive placenta is detached the prognosis is obviousIy extremely poor. On summary, al1 that can be said at this time is that there is histopathologic evidence supported by clinical observations that bleeding from the uterine cavity does not necessarily connote impending separation of the fetus. On theoretic grounds only it is conceivable that other conditions could give rise to bleeding from the uterus without interfering with further fetal development but IittIe can be said of these at this time. COMMENTS

Because of the Iarge number of women who despite bIeeding in earIy pregnancy continue with their pregnancies undisturbed it must be accepted that such bIeeding is frequently a norma phenomenon or a minor variation from the normaI. The histophysioIogic metamorphosis which takes pIace in the endometrium during pregnancy is associated with an extensive vascuIar reorganization and it is indeed surprising that bIeeding does not occur from the decidua more often than is normally encountered. Compared to the macacus and baboon, the human fares we11 in this respect. When one considers the high fetal Ioss resulting from abnormahties in the formation and deveIopment of fertilized ova and the implantation process in the decidua, then the occasiona breakdown in the vascuIarization of parts of the decidua must be regarded as but a sIight variance from the normal in this concerning earIy fetal complex mechanism deveIopment. It is aIso possible that actual

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FIG. 3. Decidua with normal endometrial gIand showing vascular extravasation into the Iumen of the gland. FIG. 4. As Figure 3; note proximity of blood vessel to endometrial gland. FIG. 5. Pregnant myomatous uterus with well deveIoped placenta (b) and persistent villous structures (a); (c) cervix; (d) myoma. FIG. 6. Norma1 vilii over cervica1 epithelium.

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bleeding occurs from the decidua Jllllc~l more often than is hvitnessed but that the mcchanisms preventing the cscapc of’ minor blood Iosses are adequate in the human. There is no doubt that bIeeding even from the extraplacental areas of the decidua may resuIt in abortion provided that it is of suffrcient magnitude to induce uterine contractions. ConsequentIy the long accepted practice of bed rest for patients with bleeding in early pregnancy is a rationa procedure since it might tend to minimize such blood loss. The fact that many women do not abort despite ambulation indicates that this type of bIeeding is in actual fact of little consequence in many instances. While the use of hormonal therapy is of definite value in selected cases of earIy pregnancy bleeding, it appears generaIIy to be an empirical procedure since the number of physicians using estrogens, progesterones and vitamin E for threatened abortion is far in excess of the number who have adequate faciIities for the accurate determination or assessment of deficiencies in their pregnancy bIeeders. In the face of those potentia1 sources of inconsequential bleeding as have been indicated in this presentation and in view of the relatively large numbers of individuaIs who do bIeed from such sources the efficacy of the routine use of endocrine substances becomes suspect. For correct evaluation of such therapy, therefore, any statistica data purporting to show the specific vaIue of hormona1 therapy in the prevention of abortion must eIiminate vaginal or cervical sources of bIeeding, intrauterine bIeeding of a quasi-physioIogic nature and must also establish the existence of a deficiency or imbaIance of hormones suficient to imply that abortion will occur unIess specific therapy is instituted. The earlier successes cIaimed for progesterones, subsequently questioned then superceded by estrogens aIone or with progesterones, can be reconciIed by the fact that some of the patients who continued with their pregnancies with each type of treatment would possibly not have aborted regardIess of treatment. Since few medical inen would aIIow their patients with bIeeding in earIy pregnancy to remain ambuIatory, such patients invariabIy get the benefit of bed rest, sedation with or without additional hormonal or vitamin therapy. The apparent resuIts of such treatment

in Early

Pregnancy

bvill then depend upon \vhcther or not such ;I patient \vould have aborted in any cast, \z,hether bed rest \vas sufficient to prevent the amount of bleeding ncccssary to incite uterine contractions or whether there was in fact a deficiency corrected by adequate medicinal therapy. UnIess each of these can be adequately assessed, treatment remains specuIative; and until cases of early pregnancy bleeding can be definitely assessed as potential aborters by endocrine assays or whatever other method suffices, it is pointIess to regard any form of medicinal treatment as anything but empirical. Certainly until such time as it is possible to discriminate between inconsequentia1 bIeeding and threatened abortion it behoves us to regard and treat a11 bleeding from the uterine cavity in early pregnancy as potentia1 aborters but to propound cIaims for success with particular remedia1 measures without precise evidence of threatening abortion other than bleeding is unquestionabIy presumptuous at this time. Acknowledgments: I wish to express my sincere thanks to Professor 0. S. Heyns for his continued interest and cooperation and to the Resident Staff of the Queen Victoria Maternity Hospital for their aid in the statistica survey. I wish also to acknowledge Professor J. GiIIman’s va1uabIe suggestions. REFERENCES BRADY, Bull. Johns Hopkins Hosp., 34: 152, 1923. 2. DE LEE, J. and GREENHILL, J. P. Principles and Practice of Obstetrics, 8th ed. Philadelphia, 1943. W. B. Saunders Co. El. B. Surg., Cynec. 6~ 3. GILLMAN, J. and STEIN, I.

Obst., 72:

129, rgq.1.

4. HARTMAN, C. G. Bull. Johns Hopkins Hasp., ‘55, ‘929. 51: 5. HOFFMAN, E. S. Am. J. Obst. TV cynec.,

44:

6gz,

1946.

6. NOVAK, E. Menstruation

and Its Disorders. New York, 1921. D. Appleton-Century Co. to embryology. 7. RAMSAY, E. M. Contributions _. 33: 113, 1949. 8. SPANNER, R. Quoted by Ramsay, E. M. In: Contributions to embryology. 33: I 13, 1949. 9. TEACHER, J. H. Obstetrical and Gynaecological Pathology. London, 1935. Oxford University Press. IO. TE LINDE, R. W. In discussion of paper by Jones, H. 0. and Brewer, J. I. Am. J. Obst. I’d Gvnec., 38: 839. 1939. II. TITUS. P. Management of Obstetrical Diffxculties. 3rd’ed. St. Lo&, 1945. C. V. Mosby Co. 12. WILLIAMS, J. D. Obstetrics, 8th ed. New York, D. Appleton-Century Co. ‘3. WISLOCKI, G. B. and STREETER, G. L. Contributions to embryology. 160: 1938.

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