- Email: [email protected]
Combined clinical and ultrasonographic work-up for the diagnosis of retained products of conception
Combined clinical and ultrasonographic work-up for the diagnosis of retained products of conception Igal Wolman, M.D., Eran Altman, M.D., Gidi Faith, M.D., Joseph Har-toov, M.D., Reuven Amster, M.D., Ilan Gull, M.D., and Ariel J. Jaffa, M.D. Ultrasound Unit in Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Tel-Aviv Medical Center, and The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Retained products of conception (RPOC) present a major clinical challenge. We assessed the accuracy of an evaluation protocol based on clinical management and transvaginal ultrasonographic evaluation for the detection of retained products of conception. This combined clinical and sonographic evaluation protocol offers a high sensitivity for the accurate diagnosis of RPOC. (Fertil Steril 2009;92:1162–4. 2009 by American Society for Reproductive Medicine.)
The diagnosis of retained products of conception (RPOC) presents a major clinical challenge. The primary aids to diagnosis are the clinical presentation of postpartum or postabortion abnormal bleeding, a dilated cervical canal, and the characteristic ultrasonographic findings of an intrauterine echogenic mass. Serum b human chorionic gonadotropin (b-hCG) levels also may be checked, but they often contribute little to the diagnosis in the immediate period after labor or abortions because b-hCG levels tend to remain high during this period. Retained products of conception are estimated to occur after approximately 1% of term pregnancies (1) and probably more often after termination of pregnancies. This condition is considered a possible cause for intrauterine adhesions and Asherman syndrome (1), so accurate diagnosis and treatment are mandatory. Two-dimensional ultrasound was believed to be a promising tool for the detection of RPOC, but several studies have shown that its sensitivity is insufficiently high (2–5). Although it would seem that hysteroscopy should be the ideal tool for diagnosing RPOC, it was shown to have a detection rate of less than 70%, as confirmed by histologic examination (6), thus hysteroscopy cannot accurately differentiate between RPOC and blood clots. We (7, 8), and others (9) have shown that sonohysterography is an excellent tool for the diagnosis of RPOC. Sonohysterography, however, requires special equipment and operator experience and is an invasive procedure. Ultrasonography has become an integral part of the gynecologic examination and is now widely applied. We designed a special protocol (Fig. 1) that combines assessment of the Received December 21, 2008; revised January 12, 2009; accepted January 16, 2009; published online February 26, 2009. I.W. has nothing to disclose. E.A. has nothing to disclose. G.F. has nothing to disclose. J.H. has nothing to disclose. R.A. has nothing to disclose. I.G. has nothing to disclose. A.J.J. has nothing to disclose. Reprint requests: Igal Wolman, M.D., Ultrasound Unit in Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Tel-Aviv Medical Center, 6 Weizman Street, Tel Aviv, Israel (FAX: 0097236911559; E-mail: [email protected]).
1162
clinical course, conservative treatment, and transvaginal sonographic (TVS) evaluation specifically for the detection of RPOC. Our study evaluated the sensitivity of this protocol. The present study is a retrospective chart review of an accepted protocol. Between October 2002 and March 2005, 339 patients were enrolled into this study. These patients had been referred to our unit because of abnormal bleeding, fever, abdominal pain, or a combination of these symptoms after labor or abortion. All patients were treated and observed according to an accepted protocol. On admission, the patients underwent a TVS evaluation (Allegra; Siemens, Malvern, PA) and were divided into two groups according to whether they had negative or positive results. A result was considered negative when TVS demonstrated a regular smooth endometrial cavity. A result was considered positive when the endometrial cavity appeared irregular and contained echogenic material. The echogenic content was measured and photographed. Patients with negative results were discharged and instructed to return to the hospital in the event that the bleeding, abdominal pain, or fever recurred. They were also instructed to return for further evaluation after the first menstrual period. Patients with positive results were treated conservatively with contracting agents (two 0.25 mg tablets of methyl ergometrine three times a day for 5 consecutive days), after which they were reexamined in the ultrasound unit. Those who had positive results in the second evaluation were referred for the surgical removal of the uterine content, which was sent for pathologic examination. The pathologic results were compared with the second TVS examination, and the sensitivity and positive predictive value were calculated. For ethics considerations, patients who were considered negative by TVS did not undergo any surgical procedure. They were all, however, reexamined after the first menstrual period: the sonographic appearance of a regular endometrial cavity after a regular period was, in our opinion, sufficient for confirmation of the diagnosis. Because we did not perform a different test such as hysteroscopy to ascertain the negative
Fertility and Sterility Vol. 92, No. 3, September 2009 Copyright ª2009 American Society for Reproductive Medicine, Published by Elsevier Inc.
0015-0282/09/$36.00 doi:10.1016/j.fertnstert.2009.01.087
FIGURE 1 A flowchart of the evaluation protocol. US EVALUATION
POSITIVE
CONSERVATIVE TREATMENT
NEGATIVE
HOME
US EVALUATION
POSITIVE
NEGATIVE
SURGICAL REMOVAL
Wolman. Diagnosis of RPOC. Fertil Steril 2009.
diagnosis, we realize that the calculation of specificity and negative predictive value is of limited accuracy. Nevertheless, while acknowledging this limitation, we did calculate specificity and negative predictive value. Thus, sensitivity, specificity, and positive and negative predictive values were calculated for the entire patient cohort. The patients were further divided into five subgroups: after labor, after cesarean section, after late termination of pregnancy, after suction and curettage, and after mifepristone (Mifegyne; Exelgyn, Paris, France). The sensitivity and specificity for each group was calculated and compared among the groups. The statistical evaluation was performed using the Z test. P<.05 was considered statistically significant. Of the 339 patients referred to our unit, 269 (79.4%) were negative for RPOC and were discharged, and 70 (20.6%) were positive and received conservative treatment with methyl ergometrine and were reevaluated. Of the 70 originally positive patients, 33 (47.1%) had negative results at the second TVS, leaving 37 patients who remained positive and underwent surgical evacuation of the uterus. Of the 269 patients who were discharged, two (0.7%) returned due to recurrent bleeding. Both were reexamined, and both showed suspicious endometrial cavity tissue and were thus treated conservatively and reevaluated by TVS, which showed positive results. They were therefore referred for surgical evacuation of the uterine content. Thus, a total of 39 study participants (11.5%) underwent evacuation of the uterus. The calculated sensitivity was 94%, and the positive predictive value was 84%. Specificity was 98%, and the negative Fertility and Sterility
predictive value was 99%. The ability of TVS to accurately diagnose RPOC was calculated for the five different groups. Although the Z-test suggested differences among the five groups, these differences were not statistically significant, probably due to the limited sample size (n < 30). As this combined protocol allows for an accurate diagnosis of RPOC, the number of false-negative (n ¼ 2) and false-positive (n ¼ 6) results was too small for us to conclude that these five subgroups are distributed normally. Thus, a valid comparison among these groups could not be made. However, the largest difference in sensitivity was between patients after normal vaginal delivery (96%) and those after cesarean section (67%). The present series shows that the combined protocol we propose enables a highly sensitive accurate diagnosis of RPOC. Retained products of conception are a relatively common finding after normal vaginal delivery as well as after cesarean section and termination of pregnancy (1, 7, 9). But there has been a paucity of studies on the diagnosis and treatment of this condition. Although TVS enhances our ability to diagnose RPOC, the diagnosis is sometimes difficult because necrotic decidua and blood clots may be very difficult to differentiate from RPOC. Early ultrasonographic studies in the 1970s and 1980s (2–4) yielded only moderate success in diagnosing this condition. Furthermore, Achiron et al. (5) showed that the addition of Doppler studies to TVS does not dramatically improve our ability to diagnose RPOC. Even hysteroscopy was shown to have a detection rate of less than 70%, as confirmed by histologic examination (6). For the past few years, we and others have been using sonohysterography as an accurate tool to diagnose RPOC with a nearly 100% success rate (7–9). With accumulating experience and improved ultrasonographic technology, it has become apparent that our ability to diagnose RPOC by TVS has improved as well. This led to our designing a protocol of clinical treatment with contracting agents combined with TVS evaluation of the endometrial cavity (Fig. 1). This combined approach enables us to diagnose RPOC with greater accuracy: it allowed us to rule out nearly 50% of the patients (33 out of 70 patients) who presented with bleeding and an irregular endometrial cavity and were suspected as having RPOC. The sensitivity achieved by TVS was 94% with 98% specificity. When our results are compared with those of two historic cohort studies on the diagnosis of RPOC (7, 10), TVS emerges as being less accurate than sonohysterography, which is an extremely accurate tool in differentiating RPOC with a nearly 100% sensitivity and specificity. Sonohysterography, however, does require additional equipment and considerable experience on the part of the examiner. Furthermore, it is an invasive procedure and is more costly and time consuming than TVS, a device that is available in nearly every gynecologist’s office. Thus, a 94% sensitivity with a 98% specificity characterizes TVS as being a very efficient tool. The lowest sensitivity for TVS was in our patients who had undergone a cesarean section. The diagnosis of RPOC is
1163
ruled out once the examiner is able to demonstrate a regular endometrial wall. In this subgroup of patients, the sutures within the uterine wall and the blood clots are sometimes confusing, and it may be more difficult to arrive at the correct diagnosis because the endometrial wall may not seem smooth even though there is no residual tissue present. For these specific cases and in cases in which it is difficult to reach a definitive diagnosis, sonohysterography is recommended in addition to the TVS evaluation during the second examination after the completion of the conservative treatment. The combined protocol we describe appears to present an accurate and highly sensitive tool for the diagnosis of RPOC. Adaptation of this diagnostic protocol may help avoid unnecessary invasive procedures in patients after labor or abortion. REFERENCES 1. Romero R, Hsu YC, Athanassiadis AP, Hagay Z, Avila C, Nores J, et al. Preterm delivery: a risk for retained placenta. Am J Obstet Gynecol 1990;163:823–5.
1164
Wolman et al.
Diagnosis of RPOC
2. Lee CY, Madrazo BH. Ultrasonic evaluation of the postpartum uterus in the management of postpartum bleeding. Obstet Gynecol 1981;58: 227–32. 3. Robinson HP. Sonar in the puerperium. A means of diagnosing retained products of conception. Scott Med J 1972;17:364–7. 4. Malvern J, Campbell S, May P. Ultrasonic scanning of the puerperal uterus following secondary postpartum hemorrhage. J Obstet Gynecol Br Commonw 1973;80:320–4. 5. Achiron R, Goldenberg M, Lipitz S, Mashiach S. Transvaginal duplex ultrasonography in bleeding patients suspected of having residual trophoblastic tissue. Obstet Gynecol 1993;81:507–11. 6. Zakut H, Achiron R. Intrauterine balloon catheter for ultrasound evaluation of pelvic masses. Enhancement of uterine localization. Gynecol Obstet Invest 1987;24:68–72. 7. Wolman I, Hartoov J, Pauzner D, Grutz A, Amit A, David MP, et al. Transvaginal sonohysterography for the early diagnosis of residual trophoblastic tissue. J Ultrasound Med 1997;16:257–61. 8. Wolman I, Jaffa AJ, Pauzner D, Hartoov J, David MP, Amit A. Transvaginal sonohysterography: a new aid in the diagnosis of residual trophoblastic tissue. J Clin Ultrasound 1996;24:257–61. 9. Zalel Y, Cohen SB, Oren M, Seidman DS, Zolti M, Achiron R, et al. Sonohysterography for the diagnosis of residual trophoblastic tissue. J Ultrasound Med 2001;20:877–81.
Vol. 92, No. 3, September 2009
Retained products of conception (RPOC) present a major clinical challenge. We assessed the accuracy of an evaluation protocol based on clinical management and transvaginal ultrasonographic evaluation for the detection of retained products of conception. This combined clinical and sonographic evaluation protocol offers a high sensitivity for the accurate diagnosis of RPOC. (Fertil Steril 2009;92:1162–4. 2009 by American Society for Reproductive Medicine.)
The diagnosis of retained products of conception (RPOC) presents a major clinical challenge. The primary aids to diagnosis are the clinical presentation of postpartum or postabortion abnormal bleeding, a dilated cervical canal, and the characteristic ultrasonographic findings of an intrauterine echogenic mass. Serum b human chorionic gonadotropin (b-hCG) levels also may be checked, but they often contribute little to the diagnosis in the immediate period after labor or abortions because b-hCG levels tend to remain high during this period. Retained products of conception are estimated to occur after approximately 1% of term pregnancies (1) and probably more often after termination of pregnancies. This condition is considered a possible cause for intrauterine adhesions and Asherman syndrome (1), so accurate diagnosis and treatment are mandatory. Two-dimensional ultrasound was believed to be a promising tool for the detection of RPOC, but several studies have shown that its sensitivity is insufficiently high (2–5). Although it would seem that hysteroscopy should be the ideal tool for diagnosing RPOC, it was shown to have a detection rate of less than 70%, as confirmed by histologic examination (6), thus hysteroscopy cannot accurately differentiate between RPOC and blood clots. We (7, 8), and others (9) have shown that sonohysterography is an excellent tool for the diagnosis of RPOC. Sonohysterography, however, requires special equipment and operator experience and is an invasive procedure. Ultrasonography has become an integral part of the gynecologic examination and is now widely applied. We designed a special protocol (Fig. 1) that combines assessment of the Received December 21, 2008; revised January 12, 2009; accepted January 16, 2009; published online February 26, 2009. I.W. has nothing to disclose. E.A. has nothing to disclose. G.F. has nothing to disclose. J.H. has nothing to disclose. R.A. has nothing to disclose. I.G. has nothing to disclose. A.J.J. has nothing to disclose. Reprint requests: Igal Wolman, M.D., Ultrasound Unit in Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Tel-Aviv Medical Center, 6 Weizman Street, Tel Aviv, Israel (FAX: 0097236911559; E-mail: [email protected]).
1162
clinical course, conservative treatment, and transvaginal sonographic (TVS) evaluation specifically for the detection of RPOC. Our study evaluated the sensitivity of this protocol. The present study is a retrospective chart review of an accepted protocol. Between October 2002 and March 2005, 339 patients were enrolled into this study. These patients had been referred to our unit because of abnormal bleeding, fever, abdominal pain, or a combination of these symptoms after labor or abortion. All patients were treated and observed according to an accepted protocol. On admission, the patients underwent a TVS evaluation (Allegra; Siemens, Malvern, PA) and were divided into two groups according to whether they had negative or positive results. A result was considered negative when TVS demonstrated a regular smooth endometrial cavity. A result was considered positive when the endometrial cavity appeared irregular and contained echogenic material. The echogenic content was measured and photographed. Patients with negative results were discharged and instructed to return to the hospital in the event that the bleeding, abdominal pain, or fever recurred. They were also instructed to return for further evaluation after the first menstrual period. Patients with positive results were treated conservatively with contracting agents (two 0.25 mg tablets of methyl ergometrine three times a day for 5 consecutive days), after which they were reexamined in the ultrasound unit. Those who had positive results in the second evaluation were referred for the surgical removal of the uterine content, which was sent for pathologic examination. The pathologic results were compared with the second TVS examination, and the sensitivity and positive predictive value were calculated. For ethics considerations, patients who were considered negative by TVS did not undergo any surgical procedure. They were all, however, reexamined after the first menstrual period: the sonographic appearance of a regular endometrial cavity after a regular period was, in our opinion, sufficient for confirmation of the diagnosis. Because we did not perform a different test such as hysteroscopy to ascertain the negative
Fertility and Sterility Vol. 92, No. 3, September 2009 Copyright ª2009 American Society for Reproductive Medicine, Published by Elsevier Inc.
0015-0282/09/$36.00 doi:10.1016/j.fertnstert.2009.01.087
FIGURE 1 A flowchart of the evaluation protocol. US EVALUATION
POSITIVE
CONSERVATIVE TREATMENT
NEGATIVE
HOME
US EVALUATION
POSITIVE
NEGATIVE
SURGICAL REMOVAL
Wolman. Diagnosis of RPOC. Fertil Steril 2009.
diagnosis, we realize that the calculation of specificity and negative predictive value is of limited accuracy. Nevertheless, while acknowledging this limitation, we did calculate specificity and negative predictive value. Thus, sensitivity, specificity, and positive and negative predictive values were calculated for the entire patient cohort. The patients were further divided into five subgroups: after labor, after cesarean section, after late termination of pregnancy, after suction and curettage, and after mifepristone (Mifegyne; Exelgyn, Paris, France). The sensitivity and specificity for each group was calculated and compared among the groups. The statistical evaluation was performed using the Z test. P<.05 was considered statistically significant. Of the 339 patients referred to our unit, 269 (79.4%) were negative for RPOC and were discharged, and 70 (20.6%) were positive and received conservative treatment with methyl ergometrine and were reevaluated. Of the 70 originally positive patients, 33 (47.1%) had negative results at the second TVS, leaving 37 patients who remained positive and underwent surgical evacuation of the uterus. Of the 269 patients who were discharged, two (0.7%) returned due to recurrent bleeding. Both were reexamined, and both showed suspicious endometrial cavity tissue and were thus treated conservatively and reevaluated by TVS, which showed positive results. They were therefore referred for surgical evacuation of the uterine content. Thus, a total of 39 study participants (11.5%) underwent evacuation of the uterus. The calculated sensitivity was 94%, and the positive predictive value was 84%. Specificity was 98%, and the negative Fertility and Sterility
predictive value was 99%. The ability of TVS to accurately diagnose RPOC was calculated for the five different groups. Although the Z-test suggested differences among the five groups, these differences were not statistically significant, probably due to the limited sample size (n < 30). As this combined protocol allows for an accurate diagnosis of RPOC, the number of false-negative (n ¼ 2) and false-positive (n ¼ 6) results was too small for us to conclude that these five subgroups are distributed normally. Thus, a valid comparison among these groups could not be made. However, the largest difference in sensitivity was between patients after normal vaginal delivery (96%) and those after cesarean section (67%). The present series shows that the combined protocol we propose enables a highly sensitive accurate diagnosis of RPOC. Retained products of conception are a relatively common finding after normal vaginal delivery as well as after cesarean section and termination of pregnancy (1, 7, 9). But there has been a paucity of studies on the diagnosis and treatment of this condition. Although TVS enhances our ability to diagnose RPOC, the diagnosis is sometimes difficult because necrotic decidua and blood clots may be very difficult to differentiate from RPOC. Early ultrasonographic studies in the 1970s and 1980s (2–4) yielded only moderate success in diagnosing this condition. Furthermore, Achiron et al. (5) showed that the addition of Doppler studies to TVS does not dramatically improve our ability to diagnose RPOC. Even hysteroscopy was shown to have a detection rate of less than 70%, as confirmed by histologic examination (6). For the past few years, we and others have been using sonohysterography as an accurate tool to diagnose RPOC with a nearly 100% success rate (7–9). With accumulating experience and improved ultrasonographic technology, it has become apparent that our ability to diagnose RPOC by TVS has improved as well. This led to our designing a protocol of clinical treatment with contracting agents combined with TVS evaluation of the endometrial cavity (Fig. 1). This combined approach enables us to diagnose RPOC with greater accuracy: it allowed us to rule out nearly 50% of the patients (33 out of 70 patients) who presented with bleeding and an irregular endometrial cavity and were suspected as having RPOC. The sensitivity achieved by TVS was 94% with 98% specificity. When our results are compared with those of two historic cohort studies on the diagnosis of RPOC (7, 10), TVS emerges as being less accurate than sonohysterography, which is an extremely accurate tool in differentiating RPOC with a nearly 100% sensitivity and specificity. Sonohysterography, however, does require additional equipment and considerable experience on the part of the examiner. Furthermore, it is an invasive procedure and is more costly and time consuming than TVS, a device that is available in nearly every gynecologist’s office. Thus, a 94% sensitivity with a 98% specificity characterizes TVS as being a very efficient tool. The lowest sensitivity for TVS was in our patients who had undergone a cesarean section. The diagnosis of RPOC is
1163
ruled out once the examiner is able to demonstrate a regular endometrial wall. In this subgroup of patients, the sutures within the uterine wall and the blood clots are sometimes confusing, and it may be more difficult to arrive at the correct diagnosis because the endometrial wall may not seem smooth even though there is no residual tissue present. For these specific cases and in cases in which it is difficult to reach a definitive diagnosis, sonohysterography is recommended in addition to the TVS evaluation during the second examination after the completion of the conservative treatment. The combined protocol we describe appears to present an accurate and highly sensitive tool for the diagnosis of RPOC. Adaptation of this diagnostic protocol may help avoid unnecessary invasive procedures in patients after labor or abortion. REFERENCES 1. Romero R, Hsu YC, Athanassiadis AP, Hagay Z, Avila C, Nores J, et al. Preterm delivery: a risk for retained placenta. Am J Obstet Gynecol 1990;163:823–5.
1164
Wolman et al.
Diagnosis of RPOC
2. Lee CY, Madrazo BH. Ultrasonic evaluation of the postpartum uterus in the management of postpartum bleeding. Obstet Gynecol 1981;58: 227–32. 3. Robinson HP. Sonar in the puerperium. A means of diagnosing retained products of conception. Scott Med J 1972;17:364–7. 4. Malvern J, Campbell S, May P. Ultrasonic scanning of the puerperal uterus following secondary postpartum hemorrhage. J Obstet Gynecol Br Commonw 1973;80:320–4. 5. Achiron R, Goldenberg M, Lipitz S, Mashiach S. Transvaginal duplex ultrasonography in bleeding patients suspected of having residual trophoblastic tissue. Obstet Gynecol 1993;81:507–11. 6. Zakut H, Achiron R. Intrauterine balloon catheter for ultrasound evaluation of pelvic masses. Enhancement of uterine localization. Gynecol Obstet Invest 1987;24:68–72. 7. Wolman I, Hartoov J, Pauzner D, Grutz A, Amit A, David MP, et al. Transvaginal sonohysterography for the early diagnosis of residual trophoblastic tissue. J Ultrasound Med 1997;16:257–61. 8. Wolman I, Jaffa AJ, Pauzner D, Hartoov J, David MP, Amit A. Transvaginal sonohysterography: a new aid in the diagnosis of residual trophoblastic tissue. J Clin Ultrasound 1996;24:257–61. 9. Zalel Y, Cohen SB, Oren M, Seidman DS, Zolti M, Achiron R, et al. Sonohysterography for the diagnosis of residual trophoblastic tissue. J Ultrasound Med 2001;20:877–81.
Vol. 92, No. 3, September 2009