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A comparison of two adjunctive treatments for intrauterine adhesions following lysis
International Journal of Gynecology and Obstetrics 82 (2003) 49–56
Article
A comparison of two adjunctive treatments for intrauterine adhesions following lysis A.A.E. Orhue*, M.E. Aziken, J.O. Igbefoh Human Reproduction Research Programme, Unit Department of Obstetrics and Gynaecology, University of Benin Teaching Hospital, Benin City, Edo State, Nigeria Received 9 September 2002; received in revised form 9 December 2002; accepted 11 December 2002
Abstract Objectives: To assess which treatment modality has a better outcome: the use of an intrauterine contraceptive device or the Foley catheter balloon, for the adjunctive treatment of intrauterine adhesion (IUA) in patients presenting with infertility. Methods: In a 4-year initial period, patients with intrauterine adhesion were treated with the insertion of an intrauterine contraceptive device (IUCD) after adhesiolysis. In the next 4 years, a pediatric Foley catheter balloon was used after adhesiolysis instead of the IUCD. The postoperative treatment was the same throughout the 8 years. While the IUCD was removed after three consecutive withdrawal vaginal bleedings, the Foley catheter was removed after 10 days. Hysterosalpingography was repeated in all patients after the third withdrawal vaginal bleeding, and the procedure was repeated if the intrauterine adhesion still persisted. The x2 -test was used for analysis. Results: There were 51 cases of IUA treated with the IUCD and 59 cases treated with the Foley catheter balloon. In the Foley catheter group, 81.4% of the patients had restoration of normal menstruation compared with 62.7% in the IUCD group (P-0.05). Persistent posttreatment amenorrhea and hypomenorrhea occurred less frequently in the Foley catheter group (18.6%) than in the IUCD group (37.3%) (P-0.03), and the conception rate in the catheter group was 33.9% compared with 22.5% in the IUCD group. The need for repeated treatment was also significantly less in the Foley catheter group. Conclusion: The Foley Catheter is a safer and more effective adjunctive method of treatment of IUA compared with the IUCD. 䊚 2003 International Federation of Gynecology and Obstetrics. Published by Elsevier Science Ireland Ltd. All rights reserved. Keywords: Intrauterine adhesion; A comparison of two treatment methods
1. Introduction Intrauterine adhesion (IUA) was recognized as a factor contributing to infertility in women following a 1948 publication by Asherman w1x. In this *Corresponding author. E-mail address: [email protected] (A.A.E. Orhue).
article, IUA was described as a primary uterine disease often presenting as secondary amenorrhea, and arising from trauma to the recently pregnant uterus, such as repeated dilation and curettage (D&C) procedures. The etiology, pathology, and treatment evolved slowly from several other studies. Presently, IUA is known to be associated with
0020-7292/03/$30.00 䊚 2003 International Federation of Gynecology and Obstetrics. Published by Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S0020-7292Ž03.00030-4
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diverse non-traumatic factors, e.g. postabortal sepsis w2x, puerperal sepsis w3x, particulate infections such as tuberculous endometritis, and even normal delivery w4x. As adhesions may occur after a simple operation on the uterus like a cesarean section and a myomectomy w5,6x, the role of trauma other than D&C to a recently pregnant uterus has been emphasized. Even from these other sources, however, infection still plays a pivotal role in the etiology of the disease, as was emphasized originally by Asherman and corroborated by later studies w7x. The symptomatology is also now known to range from normal menstruation, through hypomenorrhea, to amenorrhea w5x, infertility, and obstetric complications w8x. Intrauterine adhesion has always been a disease difficult to diagnose and treat. Presently, its most effective means of diagnosis is hysteroscopy, which is also the most cost-effective means of classification and treatment w9–12x. However, in most developing countries, the diagnosis of IUA is usually achieved by hysterosalpingography (HSG), and treatment by the blind lysis of adhesions with uterine sound or curettage w13x, an antiquated method by today’s standards. The greatest revolutionary shift in IUA management lies in the principle of treatment. In the past, treatment was by direct abdominal approach, through laparotomy, to access the uterine cavity for surgical excision of the adhesions w14,15x; currently, lysis of adhesions, maintenance of the uterine cavity, and prevention of subsequent adhesions are mostly effected via the transcervical route w16x. The maintenance of the uterine cavity is an important step in the treatment of IUA because a well-maintained uterine cavity is the prerequisite for prevention of subsequent adhesion formation, while endometrial regrowth is usually facilitated by the use of sequential estrogen and progestogens w5x. The placement of an IUCD (a type made from an inert material and with a large surface area) in the uterine cavity for 3 months has been the standard method of maintaining the uterine cavity w2x. Although this method has always yielded good results, it can be associated with complications such as infection, uterine perforation, or misplacement of the IUCD, and IUA reoccurrence w9,13x. Overall, the idea of an IUCD (a device used for
contraception) used for the treatment of infertility is generally repulsive to the psyche and emotional wellbeing of the subfertile patient. The use of an inflated pediatric Foley catheter balloon in the uterine cavity instead of an IUCD to mechanically maintain the uterine cavity separated after adhesiolysis had been reported with equally good results but with much fewer complications w17–20x. In spite of the good results from published work with the Foley catheter balloon, and the particular attraction that the catheter is kept in situ for 10 days only, there are not many reports involving its use for the treatment of IUA. This study presents data from the treatment of consecutive infertile women with IUA as the only infertility factor in a first 4 years period in which after blind adhesiolysis, to recreate the uterine cavity, a size D Lippes loop IUCD was placed in situ for 3 months. In the last 4 years of the study, consecutive infertile women with IUA as the only infertility factor were treated with the placement of a size 8 pediatric Foley catheter with a 5-ml balloon in the uterine cavity for only 10 days, instead of the IUCD for 3 months. The other aspects of patient management during these 8 consecutive years remained the same. It was anticipated that the specific advantages or disadvantages of each method would be highlighted by comparing the data derived from the periods for which each method was used. 2. Materials and methods All patients with infertility and other endocrine problems were assessed at the Human Reproduction Research Programme Unit of our hospital. The protocol for management involved a detailed history, clinical examination, and other specific investigations such as a mid-luteal phase assay of reproductive hormones like FSH, LH, prolactin, progesterone, estradiol, and testosterone. An hysterosalpingography (HSG) was performed within the first 10 days of the menstrual cycle to assess the uterus and Fallopian tubes. For those who presented with secondary amenorrhea, and who had a negative pregnancy test, an initial history was taken and clinical examination performed, followed by a cervical mucus assessment (CMA)
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by the Isler method, and the score was noted. Thereafter, a hormonal assay was performed and the patients were subjected to a progestogen challenge test with tablets of 10 mg of norethisterone acetate thrice daily for 5 days, anticipating a withdrawal bleeding per vagina as the positive response. Irrespective of the outcome of the progestogen challenge test in these amenorrheic patients, an HSG was also performed to detect any uterine and utero-tubal anomalies, and therefore IUA. The specific treatment was blind adhesiolysis with the uterine sound under general anesthesia. Since we do not have a hysteroscope at our institution, the IUA could not be classified before the treatment with blind lysis, as suggested in 1988 by Valle and Sciarra w21x. In the first 4 years of the study (June 1991 to June 1995), a size D Lippes loop IUCD was placed as the adjunctive treatment in the justseparated uterine. The IUCD was kept in the uterine cavity for three consecutive withdrawal vaginal bleedings and then was removed. In the last 4 years of the study (July 1995 to July 1999), after blind adhesiolysis with the uterine sound, a size 8 pediatric Foley catheter with a 5-ml balloon capacity was placed in the uterine cavity as the adjunctive treatment instead of the IUCD, and the balloon inflated. The device was strapped to the inner aspect of the thigh and left in situ for 10 days, after which it was removed. In all both the IUCD and Foley catheter patients, immediate postoperative treatment (among others) consisted of oral doxycycline (Vibramycin; Pfizer Neimeth International Pharm, Lagos, Nigeria), 200 mg as a first dose and 100 mg twice daily for 10 days; oral metronidazole (Flagyl; Mayer and Baker, Lagos, Nigeria), 400 mg thrice daily for 10 days; dexamethasone tablets (Organon Laboratories Ltd, Cambridge, England) was given in a tailed-down fashion as 1 mg 4 times daily for 3 days, 1 mg thrice daily for 3 days, 0.5 mg thrice daily for 3 days, 0.5 mg twice daily for 3 days, and finally 0.5 mg daily for 5 days. The regeneration of the endometrium was facilitated by sequential administration of natural estrogens and progestogens, as follows: estradiol valerate tablets (Progynova; Schering Health Care Ltd, Bungressttull, England), 4 mg thrice daily from the second
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postoperative day for 28 days, followed by norethisterone acetate tablets (Primolut; Schering AG, Germany) 10 mg thrice daily for 5 days. There was a maximum waiting period of 10 days from the completion of this sequential hormone treatment, during which a withdrawal vaginal bleeding was expected. If there was a withdrawal vaginal bleeding, an oral estrogen–progestogen regimen as described above was again begun on the fifth day of the withdrawal vaginal bleeding to secure another withdrawal bleeding. If there was no withdrawal bleeding after 10 days of waiting, a new estrogen– progestogen regimen was begun from the 11th day following the end of the last treatment. The estrogen–progestogen regimen was repeated for three consecutive cycles of withdrawal vaginal bleeding. The duration, volume of loss, and associated symptoms were noted with each withdrawal vaginal bleeding. The HSG was repeated after the third withdrawal vaginal bleeding and if the finding indicated the persistence of intrauterine adhesion, the entire treatment schedule, as described, was repeated again. The maximum number of treatments for persisting intrauterine adhesion detected by HSG was four. Patients included in this study were only those in whom IUA was the only factor of infertility identified in the couple. The study compared the age, menstrual disturbance and duration, and associated etiologic factors in the first 4 years (June 1991 to June 1995) when the Lippes loop IUCD was used, with the same parameters in the second 4 years (July 1995 to July 1999) when the Foley catheter balloon was used instead to mechanically maintain the uterine cavity separated. The outcome measures assessed were the restoration of normal menses and HSG; performed to assess the need for repeat treatment; the conception rates by the two methods, and the complication rate following each method of treatment. The statistical analysis was done using the t-test and the x2-test. The level of significance was set at P-0.05. 3. Results During the 8 years of the study (June 1991 to July 1999), a total of 2075 couples consulted for
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Table 1 Clinical data: uterine synechae treatment Total number ns110 (%)
P-value
Treatment methods Foley’s catheter ns59 (%)
IUCD ns51(%)
Age, years (mean"S.D.)
26.9"6.2
30.3"4.4
0.4532
Symptoms Amenorrhoea Oligomenorrhea Normal menses
57 (51.8) 46 (42.0) 7 (6.4)
31 (52.5) 24 (40.6) 4 (6.8)
26 (51.0) 22 (45.1) 3 (3.9)
0.8701 0.7943 0.8475
–
y3.8"4
3.34"4.3
0.5156
Duration menstrual symptoms (years) (mean"S.D.) Etiologic factors Induced abortion Missed abortion Spontaneous abortion CyS Myomectomy 20 Prev. PPH
59 18 13 9 4 7
(53.6) (16.4) (11.8) (8.2) (3.6) (6.4)
32 9 8 5 2 3
(54.2) (15.3) (13.6) (8.5) (3.4) (5.1)
27 9 5 4 2 4
(52.9) (17.6) (9.8) (7.8) (3.9) (7.8)
0.8919 0.7351 0.5429 0.9041 0.8819 0.5545
Last pregnancy outcome Induced abortion Missed abortion Spontaneous abortion Delivery (Vaginal) (CyS)
16 17 11 16 7 9
(60.0) (15.5) (10.0) (14.6) (6.4) (8.2)
36 9 6 8 3 5
(61.0) (15.3) (10.2) (13.6) (5.1) (8.5)
30 8 5 8 4 4
(58.9) (15.7) (9.8) (15.7) (7.8) (7.8)
0.8149 0.9502 0.9492 0.7524 0.5545 0.9041
infertility management at the Human Reproduction Research Programme Unit, out of which 131 consecutive women were confirmed to have uterine synechae, an incidence of 6.3%. During the first 4 years (June 1991 to June 1995), 1059 patients consulted for infertility and 60 had uterine synechae, out of whom 9, who had other infertility factors, were excluded from this study. Only 51 patients from this period who had only uterine synechae as the infertility factor were analyzed. In the second period (July 1995 to July 1999), 1016 patients were investigated and 71 had uterine synechae, out of whom 12, who had other infertility factors, were also excluded. In the second period, only 59 patients were analyzed. Thus, out of the of original 131 patients for both periods, a total of 110 was included in the study, and 21 were excluded because they had other infertility factors considered as confounding variables. Out of the 110 consecutive patients, 51 who were treated in the June 1991 to 1995 period had
adhesiolysis followed by the insertion of a Lippes loop IUCD in the uterine cavity to mechanically maintain it separated (IUCD group). The remaining 59 patients, who were treated in the period July 1995 to July 1999, had adhesiolysis followed by placement of a Foley catheter balloon in the uterine cavity to maintain it separated (Foley catheter group). The pretreatment characteristics were the same in the two groups. As shown in Table 1, the most common presentation was menstrual anomalies, especially secondary amenorrhea and hypomenorrhea (94%) in both groups. Normal menstruation occurred in only 6.4% of patients. The commonest etiological factor was previously induced abortion (53%) and missed abortion (16.4%), which were also the most common outcome of the penultimate pregnancies. Notably, previous uterine curettage in the pueperium for secondary postpartum hemorrhage (PPH) and previous myomectomy and cesarean section, were
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Table 2 Clinical summary of outcome Outcome
Total ns110 (%)
1. 2. 3. 4.
80 20 10 34 8 8 18 2 16
Normal menses and HSG Hypomenorrhea Amenorrhea Pregnancy (Abortion) (Preterm delivery) (Term delivery) CyS Vaginal delivery
(72.7) (18.2) (22.9) (30.9) (7.2) (7.2) (16.4) (1.8) (14.5)
Foley’s catheter ns59 (%) 48 7 4 20 4 4 12 2 10
(81.4) (11.9) (6.8) (33.9) (6.8) (6.8) (20.3) (3.4) (16.9)
IUCD ns51(%)
P-value
(62.7) (25.5) (13.7) (27.5) (7.8) (7.8) (11.8)
0.0288* 0.3896 0.3644 0.4656 0.8304 0.8304 0.2254 0.1845 0.4418
32 13 6 14 4 4 6 – 6
(11.8)
*Statistically significant. HSG, hysterosalpingogram; CyS, cesarean delivery.
causal factors to the much lower extent of 6.4%, 3.6%, and 8.2%, respectively. Treatment outcomes by the two methods is shown in Table 2. Overall, posttreatment restoration of normal menses and normal HSG findings occurred in 72.7% of the entire study population. Importantly, the restoration of normal menses and HSG occurred in 81.4% (84) of cases in the group treated with the Foley catheter balloon, compared with the IUCD group, which was 62.7% (32 cases) (Ps0.023). Similarly, persistent posttreatment hypomenorrhea and secondary amenorrhea occurred less frequently in the Foley catheter group than in the IUCD Group (P-0.023). There were more pregnancies in the Foley catheter group 33.9% (20 cases) than in the IUCD group 27.5% (14 cases), and more of the pregnancies in the Foley catheter group achieved delivery at term—in 20.3% (12
cases) compared with the IUCD group 11.8% (six cases), although these differences were not statistically significant. The preterm delivery and spontaneous abortion rates were almost the same by the two methods, 6.8% and 7.8%, respectively. There were no third stage complications. Table 3 shows the need for repeated treatments for intrauterine adhesion and subsequent complication rates by the two methods. The need for repeated treatments occurred in 27.3% (30 cases) in the study; but it was significantly less in the Foley catheter group, in which repeated treatments were performed in 13.6% (8 cases), compared with 43.1% (22 cases) in the IUCD group (P0.005). Also, all the complications (five cases, 4.5%) except one occurred in the IUCD group. These complications were first genital tract sepsis, which developed in two patients treated with
Table 3 Complication and need for repeat treatment Repeat treatment cycles
Total ns110 (%)
1 2 3 Grand total Complications Genital sepsis Genital perforation U.T.I. Grand total
18 10 2 30 2 2 1 5
*Statistically significant.
Foley’s catheter ns59 (%)
IUCD ns51 (%)
(16.4) (9.1) (1.8) (27.3)
6 (10.2) 2 (3.4) – 8 (13.6)
12 8 2 22
(1.8) (1.8) (0.9) (4.5)
– – 1 (1.7) 1 (1.7)
2 (3.9) 2 (3.9) – 4 (7.8)
(23.5) (15.7) (3.9) (43.1)
P-value
0.0589 0.0253* 0.1247 0.0005*
0.1381
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IUCD. The symptoms consisted principally of fever, and an offensive vaginal discharge developed 5 days after adhesiolysis. The IUCD was removed in each case and the symptoms and signs abated with a course of doxycycline and metronidazole tablets. In the two patients who had genital perforation, suspicion began when the IUCD previously inserted could not be removed in the clinic after the third withdrawal PV bleeding. Subsequent ultrasound confirmed the partial perforation in each case. The IUCD was easily removed with crocodile forceps, with the patient under general anesthesia. The urinary tract infection was an incidental occurrence in a patient treated with the Foley catheter balloon. 4. Discussion Intrauterine adhesion is an important uterine factor in the etiology of infertility in our environment, with an incidence, in this study, of 6.3% of the infertile population. This is comparable to reports of (2–5%) by previous authors w9,12x. The study confirms that the main etiological factor in IUA is induced abortion or curettage following spontaneous or missed abortion (81.8%), especially if these were the outcome of the penultimate pregnancies. In most cases, pregnancy was the predisposing factor (96.4%), while myomectomy accounted for 3.6% of the cases. This is similar to the observation of various other authors w6,11,17x except Ozumba et al. who noted a high etiological association with previous CyS in his series w18x. It is curious that pregnancy should predispose to the occurrence of IUA in spite of the abundant hormone. In reality, it is the surgical manipulation of the recently pregnant uterus that provokes IUA formation, because the natural softness of the uterus at this time predisposes to an increased depth of curettage, which results in the denudation of the basal layer of the endometrium and the consequent loss of the regenerative mechanism. Alternatively, retained placenta remnants and villous element might facilitate the occurrence of infection and also promote increased fibroblastic activity and collagen formation before endometrial regeneration has taken place w3x.
The commonest modes of presentation were secondary amenorrhea and hypomenorrhea in 51.8% and 42.0% of patients, respectively; only 6.4% had normal menstruation. Diagnosis in all cases in this study was reached by HSG, which showed a consistent intrauterine filling defect. Hysteroscopy which is the Gold standard in making the diagnosis classification, and treatment of IUA w10,11x was not available in our institution. Efforts are on presently to acquire a hysteroscope for the institution. The ideal treatment of IUA consists not only of physically removing the adhesion but also preventing the formation of new ones by the use of other adjunctive measures. The prevention of adhesion formation is commonly done by the dual approach of maintenance of the freshly separated uterine cavity by some physical means and enhancement of endometrial growth, which is often facilitated by a cyclical estrogen and progestogen treatment regimen w12x. In general, the placement of IUCD or pediatric Foley catheter balloon in the freshly separated uterine cavity is the common adjunctive approach for the maintenance of the separated uterine cavity for subsequent endometrial regeneration w19–23x and there are good reports on the use of either in IUA treatment. However, the efficiency and effectiveness of the IUCD and Foley catheter balloon has not been comparatively tested in the same patient population, over a specific period in the same clinical setting. This is what has been performed in this study, assessing outcome measures such as restoration of normal menses and HSG, pregnancy rate, and pregnancy outcome. The overall outcome of treatment using the two methods, the IUCD and Foley catheter balloon, to maintain the uterine cavity separated was good as evidenced by the attainment of a 72.7% return of normal menstruation and a pregnancy rate of 30.9%. This is comparable but slightly better than those of previous authors w5,6,9,11–13x. In all assessed parameters, patients treated with the Foley catheter balloon had a better outcome than patients treated with the IUCD. However, the differences in treatment outcome only reached statistical significance with outcomes such as restoration of normal menstruation, HSG, and persistent post-
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treatment secondary amenorrhea and hypomenorrhea. The need for repeated treatments was also significantly lower in patients treated with the Foley catheter balloon. The complication rate was higher for patients treated with the IUCD but this was not statistically significant. This finding agrees with similar observations by various other authors w17–23x. The findings in this comparative study are noteworthy, especially for the developing countries where induced and unsafe abortion rate is high w24,25x and there will be increasing incidence of IUA complicating these abortion cases. For the developing countries the choice in the treatment of IUA will usually be between the IUCD and the Foley catheter balloon as the other adjunctive treatment after lysis of adhesion with the uterine sound or curette, which is not very effective in removing the adhesions, unlike in the developed countries where the hysteroscope can be effectively used to remove the adhesions. However, the Foley catheter balloon has been shown in this study to be a more effective and efficient option than the IUCD for IUA treatment. The obvious advantages are immense. It is cheap and accessible which is a special advantage in the developing countries with poor resources and appears to be more acceptable to the patients who view the IUCD as a psychological barrier in itself to conception. Furthermore, the Foley catheter balloon appears to achieve a greater and more effective separation of the uterine cavity because of the larger surface area, which enable it to maintain the separated uterine cavity while the endometrial regeneration is going on w17,19x. In conclusion, the result of this study, which spanned eight consecutive years, has confirmed that in the treatment of IUA, the placement of a pediatric Foley catheter balloon to maintain the uterine cavity separated is safer and more effective than the IUCD in ensuring return of normal menstruation and later pregnancies with minimal complications. References w1x Asherman J. Amenorrhoea traumatic (atretical). J Obstet Gynaecol Br Empire 1948;55:23 –27.
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w2x Louros NC, Danezis JM, Pontifix G. Use of intrauterine devices in the treatment of intra-uterine adhesions. Fertil Steril 1968;19:509 –528. w3x Polishuk WZ, Anteby SO, Weinstein D. Puerperal endometritis and intrauterine adhesions. Int Surg 1975;60:418 –420. w4x Zondek R, Rozin S. Filling defect in the hysterogram simulating intrauterine synechae which disappear after denervation. Am J Obstet Gynecol 1964;88:123 –127. w5x Schenker JG, Margalioth EJ. Intrauterine adhesions; an update appraisal. Fertil Steril 1982;37:593 –610. w6x Sugimoso O. Diagnostic and therapeutic hysteroscopy for traumatic intrauterine adhesions. Am J Obstet Gynecol 1978;131:539 –547. w7x Rabau E, David A. Intrauterine adhesions: aetiology, prevention and treatment. Obstet Gynecol 1963;22:626 – 629. w8x Forssman L. Post traumatic intrauterine synaechae and pregnancy. Obstet Gynecol 1965;26:710 –718. w9x Otubu JAM, Olarewoju RS. Hysteroscopy in infertile Nigerian women. Afr J Med Sci 1989;18:117 –125. w10x Dicker D, Ashekenazi T, Deker A, Eastenon AF, Kategmon DT, Bucknan SD, et al. The value of hysteroscopic evaluation in patients with pre-clinical in vitro fertilisation abortion. Hum Reprod 1996;11:730 –731. w11x Katz Z, Bon Arie A, Lurie S, Manor M, Luster V. Reproductive outcome following hysteroscopic adhesiolysis in Asherman syndrome. Int J Fertil 1996;41(5):462 –467. w12x Chen F-P, Yung K, Yu-long H. Successful treatment of severe uterine synechae with transcervical resectoscopy combined with aminriatent. Hum Reprod 1997;12:943 – 949. w13x Ogedegbe OK, Giwa-Osagie OFA, Ayodeji JDF, Oyeyinka O. Intrauterine adhesions in Lagos, Nigeria. J Obstet Gynecol 1991;11:134 –135. w14x Bergman P. Traumatic intrauterine lesion. Acta Obstet Gynaecol Scand 1961;40:1 –8. w15x Moyer D. Endrometrial diseases in infertility. In: Benrmans X, editor. Progress in Infertility. Berton: Little Brown and Co, 1975. p. 3 –10. w16x March C, Israel R. Intrauterine adhesions secondary to elective abortion. Hysteroscopic diagnosis and management. Obstet Gynecol 1976;48:422 –429. w17x Wallach E. Evaluation and management of uterine causes of infertility. Chin Obstet Gynecol 1979;18:126 – 132. w18x Ozumba BC, Ezegorui H. Intrauterine adhesions in an African population. Int J Gynecol Obstet 2002;77:37 – 38. w19x Doody KM, Carr BR. Ammenorrhoea in child. In: London HJ, editor. Menstrual cycle disorders. 1990. p. 361 –387. w20x Speroff L, Robert HG, Nathan GK. Asherman syndrome. In: Speroff L, Robert HG, Nathan GK, editors.
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Article
A comparison of two adjunctive treatments for intrauterine adhesions following lysis A.A.E. Orhue*, M.E. Aziken, J.O. Igbefoh Human Reproduction Research Programme, Unit Department of Obstetrics and Gynaecology, University of Benin Teaching Hospital, Benin City, Edo State, Nigeria Received 9 September 2002; received in revised form 9 December 2002; accepted 11 December 2002
Abstract Objectives: To assess which treatment modality has a better outcome: the use of an intrauterine contraceptive device or the Foley catheter balloon, for the adjunctive treatment of intrauterine adhesion (IUA) in patients presenting with infertility. Methods: In a 4-year initial period, patients with intrauterine adhesion were treated with the insertion of an intrauterine contraceptive device (IUCD) after adhesiolysis. In the next 4 years, a pediatric Foley catheter balloon was used after adhesiolysis instead of the IUCD. The postoperative treatment was the same throughout the 8 years. While the IUCD was removed after three consecutive withdrawal vaginal bleedings, the Foley catheter was removed after 10 days. Hysterosalpingography was repeated in all patients after the third withdrawal vaginal bleeding, and the procedure was repeated if the intrauterine adhesion still persisted. The x2 -test was used for analysis. Results: There were 51 cases of IUA treated with the IUCD and 59 cases treated with the Foley catheter balloon. In the Foley catheter group, 81.4% of the patients had restoration of normal menstruation compared with 62.7% in the IUCD group (P-0.05). Persistent posttreatment amenorrhea and hypomenorrhea occurred less frequently in the Foley catheter group (18.6%) than in the IUCD group (37.3%) (P-0.03), and the conception rate in the catheter group was 33.9% compared with 22.5% in the IUCD group. The need for repeated treatment was also significantly less in the Foley catheter group. Conclusion: The Foley Catheter is a safer and more effective adjunctive method of treatment of IUA compared with the IUCD. 䊚 2003 International Federation of Gynecology and Obstetrics. Published by Elsevier Science Ireland Ltd. All rights reserved. Keywords: Intrauterine adhesion; A comparison of two treatment methods
1. Introduction Intrauterine adhesion (IUA) was recognized as a factor contributing to infertility in women following a 1948 publication by Asherman w1x. In this *Corresponding author. E-mail address: [email protected] (A.A.E. Orhue).
article, IUA was described as a primary uterine disease often presenting as secondary amenorrhea, and arising from trauma to the recently pregnant uterus, such as repeated dilation and curettage (D&C) procedures. The etiology, pathology, and treatment evolved slowly from several other studies. Presently, IUA is known to be associated with
0020-7292/03/$30.00 䊚 2003 International Federation of Gynecology and Obstetrics. Published by Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S0020-7292Ž03.00030-4
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diverse non-traumatic factors, e.g. postabortal sepsis w2x, puerperal sepsis w3x, particulate infections such as tuberculous endometritis, and even normal delivery w4x. As adhesions may occur after a simple operation on the uterus like a cesarean section and a myomectomy w5,6x, the role of trauma other than D&C to a recently pregnant uterus has been emphasized. Even from these other sources, however, infection still plays a pivotal role in the etiology of the disease, as was emphasized originally by Asherman and corroborated by later studies w7x. The symptomatology is also now known to range from normal menstruation, through hypomenorrhea, to amenorrhea w5x, infertility, and obstetric complications w8x. Intrauterine adhesion has always been a disease difficult to diagnose and treat. Presently, its most effective means of diagnosis is hysteroscopy, which is also the most cost-effective means of classification and treatment w9–12x. However, in most developing countries, the diagnosis of IUA is usually achieved by hysterosalpingography (HSG), and treatment by the blind lysis of adhesions with uterine sound or curettage w13x, an antiquated method by today’s standards. The greatest revolutionary shift in IUA management lies in the principle of treatment. In the past, treatment was by direct abdominal approach, through laparotomy, to access the uterine cavity for surgical excision of the adhesions w14,15x; currently, lysis of adhesions, maintenance of the uterine cavity, and prevention of subsequent adhesions are mostly effected via the transcervical route w16x. The maintenance of the uterine cavity is an important step in the treatment of IUA because a well-maintained uterine cavity is the prerequisite for prevention of subsequent adhesion formation, while endometrial regrowth is usually facilitated by the use of sequential estrogen and progestogens w5x. The placement of an IUCD (a type made from an inert material and with a large surface area) in the uterine cavity for 3 months has been the standard method of maintaining the uterine cavity w2x. Although this method has always yielded good results, it can be associated with complications such as infection, uterine perforation, or misplacement of the IUCD, and IUA reoccurrence w9,13x. Overall, the idea of an IUCD (a device used for
contraception) used for the treatment of infertility is generally repulsive to the psyche and emotional wellbeing of the subfertile patient. The use of an inflated pediatric Foley catheter balloon in the uterine cavity instead of an IUCD to mechanically maintain the uterine cavity separated after adhesiolysis had been reported with equally good results but with much fewer complications w17–20x. In spite of the good results from published work with the Foley catheter balloon, and the particular attraction that the catheter is kept in situ for 10 days only, there are not many reports involving its use for the treatment of IUA. This study presents data from the treatment of consecutive infertile women with IUA as the only infertility factor in a first 4 years period in which after blind adhesiolysis, to recreate the uterine cavity, a size D Lippes loop IUCD was placed in situ for 3 months. In the last 4 years of the study, consecutive infertile women with IUA as the only infertility factor were treated with the placement of a size 8 pediatric Foley catheter with a 5-ml balloon in the uterine cavity for only 10 days, instead of the IUCD for 3 months. The other aspects of patient management during these 8 consecutive years remained the same. It was anticipated that the specific advantages or disadvantages of each method would be highlighted by comparing the data derived from the periods for which each method was used. 2. Materials and methods All patients with infertility and other endocrine problems were assessed at the Human Reproduction Research Programme Unit of our hospital. The protocol for management involved a detailed history, clinical examination, and other specific investigations such as a mid-luteal phase assay of reproductive hormones like FSH, LH, prolactin, progesterone, estradiol, and testosterone. An hysterosalpingography (HSG) was performed within the first 10 days of the menstrual cycle to assess the uterus and Fallopian tubes. For those who presented with secondary amenorrhea, and who had a negative pregnancy test, an initial history was taken and clinical examination performed, followed by a cervical mucus assessment (CMA)
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by the Isler method, and the score was noted. Thereafter, a hormonal assay was performed and the patients were subjected to a progestogen challenge test with tablets of 10 mg of norethisterone acetate thrice daily for 5 days, anticipating a withdrawal bleeding per vagina as the positive response. Irrespective of the outcome of the progestogen challenge test in these amenorrheic patients, an HSG was also performed to detect any uterine and utero-tubal anomalies, and therefore IUA. The specific treatment was blind adhesiolysis with the uterine sound under general anesthesia. Since we do not have a hysteroscope at our institution, the IUA could not be classified before the treatment with blind lysis, as suggested in 1988 by Valle and Sciarra w21x. In the first 4 years of the study (June 1991 to June 1995), a size D Lippes loop IUCD was placed as the adjunctive treatment in the justseparated uterine. The IUCD was kept in the uterine cavity for three consecutive withdrawal vaginal bleedings and then was removed. In the last 4 years of the study (July 1995 to July 1999), after blind adhesiolysis with the uterine sound, a size 8 pediatric Foley catheter with a 5-ml balloon capacity was placed in the uterine cavity as the adjunctive treatment instead of the IUCD, and the balloon inflated. The device was strapped to the inner aspect of the thigh and left in situ for 10 days, after which it was removed. In all both the IUCD and Foley catheter patients, immediate postoperative treatment (among others) consisted of oral doxycycline (Vibramycin; Pfizer Neimeth International Pharm, Lagos, Nigeria), 200 mg as a first dose and 100 mg twice daily for 10 days; oral metronidazole (Flagyl; Mayer and Baker, Lagos, Nigeria), 400 mg thrice daily for 10 days; dexamethasone tablets (Organon Laboratories Ltd, Cambridge, England) was given in a tailed-down fashion as 1 mg 4 times daily for 3 days, 1 mg thrice daily for 3 days, 0.5 mg thrice daily for 3 days, 0.5 mg twice daily for 3 days, and finally 0.5 mg daily for 5 days. The regeneration of the endometrium was facilitated by sequential administration of natural estrogens and progestogens, as follows: estradiol valerate tablets (Progynova; Schering Health Care Ltd, Bungressttull, England), 4 mg thrice daily from the second
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postoperative day for 28 days, followed by norethisterone acetate tablets (Primolut; Schering AG, Germany) 10 mg thrice daily for 5 days. There was a maximum waiting period of 10 days from the completion of this sequential hormone treatment, during which a withdrawal vaginal bleeding was expected. If there was a withdrawal vaginal bleeding, an oral estrogen–progestogen regimen as described above was again begun on the fifth day of the withdrawal vaginal bleeding to secure another withdrawal bleeding. If there was no withdrawal bleeding after 10 days of waiting, a new estrogen– progestogen regimen was begun from the 11th day following the end of the last treatment. The estrogen–progestogen regimen was repeated for three consecutive cycles of withdrawal vaginal bleeding. The duration, volume of loss, and associated symptoms were noted with each withdrawal vaginal bleeding. The HSG was repeated after the third withdrawal vaginal bleeding and if the finding indicated the persistence of intrauterine adhesion, the entire treatment schedule, as described, was repeated again. The maximum number of treatments for persisting intrauterine adhesion detected by HSG was four. Patients included in this study were only those in whom IUA was the only factor of infertility identified in the couple. The study compared the age, menstrual disturbance and duration, and associated etiologic factors in the first 4 years (June 1991 to June 1995) when the Lippes loop IUCD was used, with the same parameters in the second 4 years (July 1995 to July 1999) when the Foley catheter balloon was used instead to mechanically maintain the uterine cavity separated. The outcome measures assessed were the restoration of normal menses and HSG; performed to assess the need for repeat treatment; the conception rates by the two methods, and the complication rate following each method of treatment. The statistical analysis was done using the t-test and the x2-test. The level of significance was set at P-0.05. 3. Results During the 8 years of the study (June 1991 to July 1999), a total of 2075 couples consulted for
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Table 1 Clinical data: uterine synechae treatment Total number ns110 (%)
P-value
Treatment methods Foley’s catheter ns59 (%)
IUCD ns51(%)
Age, years (mean"S.D.)
26.9"6.2
30.3"4.4
0.4532
Symptoms Amenorrhoea Oligomenorrhea Normal menses
57 (51.8) 46 (42.0) 7 (6.4)
31 (52.5) 24 (40.6) 4 (6.8)
26 (51.0) 22 (45.1) 3 (3.9)
0.8701 0.7943 0.8475
–
y3.8"4
3.34"4.3
0.5156
Duration menstrual symptoms (years) (mean"S.D.) Etiologic factors Induced abortion Missed abortion Spontaneous abortion CyS Myomectomy 20 Prev. PPH
59 18 13 9 4 7
(53.6) (16.4) (11.8) (8.2) (3.6) (6.4)
32 9 8 5 2 3
(54.2) (15.3) (13.6) (8.5) (3.4) (5.1)
27 9 5 4 2 4
(52.9) (17.6) (9.8) (7.8) (3.9) (7.8)
0.8919 0.7351 0.5429 0.9041 0.8819 0.5545
Last pregnancy outcome Induced abortion Missed abortion Spontaneous abortion Delivery (Vaginal) (CyS)
16 17 11 16 7 9
(60.0) (15.5) (10.0) (14.6) (6.4) (8.2)
36 9 6 8 3 5
(61.0) (15.3) (10.2) (13.6) (5.1) (8.5)
30 8 5 8 4 4
(58.9) (15.7) (9.8) (15.7) (7.8) (7.8)
0.8149 0.9502 0.9492 0.7524 0.5545 0.9041
infertility management at the Human Reproduction Research Programme Unit, out of which 131 consecutive women were confirmed to have uterine synechae, an incidence of 6.3%. During the first 4 years (June 1991 to June 1995), 1059 patients consulted for infertility and 60 had uterine synechae, out of whom 9, who had other infertility factors, were excluded from this study. Only 51 patients from this period who had only uterine synechae as the infertility factor were analyzed. In the second period (July 1995 to July 1999), 1016 patients were investigated and 71 had uterine synechae, out of whom 12, who had other infertility factors, were also excluded. In the second period, only 59 patients were analyzed. Thus, out of the of original 131 patients for both periods, a total of 110 was included in the study, and 21 were excluded because they had other infertility factors considered as confounding variables. Out of the 110 consecutive patients, 51 who were treated in the June 1991 to 1995 period had
adhesiolysis followed by the insertion of a Lippes loop IUCD in the uterine cavity to mechanically maintain it separated (IUCD group). The remaining 59 patients, who were treated in the period July 1995 to July 1999, had adhesiolysis followed by placement of a Foley catheter balloon in the uterine cavity to maintain it separated (Foley catheter group). The pretreatment characteristics were the same in the two groups. As shown in Table 1, the most common presentation was menstrual anomalies, especially secondary amenorrhea and hypomenorrhea (94%) in both groups. Normal menstruation occurred in only 6.4% of patients. The commonest etiological factor was previously induced abortion (53%) and missed abortion (16.4%), which were also the most common outcome of the penultimate pregnancies. Notably, previous uterine curettage in the pueperium for secondary postpartum hemorrhage (PPH) and previous myomectomy and cesarean section, were
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Table 2 Clinical summary of outcome Outcome
Total ns110 (%)
1. 2. 3. 4.
80 20 10 34 8 8 18 2 16
Normal menses and HSG Hypomenorrhea Amenorrhea Pregnancy (Abortion) (Preterm delivery) (Term delivery) CyS Vaginal delivery
(72.7) (18.2) (22.9) (30.9) (7.2) (7.2) (16.4) (1.8) (14.5)
Foley’s catheter ns59 (%) 48 7 4 20 4 4 12 2 10
(81.4) (11.9) (6.8) (33.9) (6.8) (6.8) (20.3) (3.4) (16.9)
IUCD ns51(%)
P-value
(62.7) (25.5) (13.7) (27.5) (7.8) (7.8) (11.8)
0.0288* 0.3896 0.3644 0.4656 0.8304 0.8304 0.2254 0.1845 0.4418
32 13 6 14 4 4 6 – 6
(11.8)
*Statistically significant. HSG, hysterosalpingogram; CyS, cesarean delivery.
causal factors to the much lower extent of 6.4%, 3.6%, and 8.2%, respectively. Treatment outcomes by the two methods is shown in Table 2. Overall, posttreatment restoration of normal menses and normal HSG findings occurred in 72.7% of the entire study population. Importantly, the restoration of normal menses and HSG occurred in 81.4% (84) of cases in the group treated with the Foley catheter balloon, compared with the IUCD group, which was 62.7% (32 cases) (Ps0.023). Similarly, persistent posttreatment hypomenorrhea and secondary amenorrhea occurred less frequently in the Foley catheter group than in the IUCD Group (P-0.023). There were more pregnancies in the Foley catheter group 33.9% (20 cases) than in the IUCD group 27.5% (14 cases), and more of the pregnancies in the Foley catheter group achieved delivery at term—in 20.3% (12
cases) compared with the IUCD group 11.8% (six cases), although these differences were not statistically significant. The preterm delivery and spontaneous abortion rates were almost the same by the two methods, 6.8% and 7.8%, respectively. There were no third stage complications. Table 3 shows the need for repeated treatments for intrauterine adhesion and subsequent complication rates by the two methods. The need for repeated treatments occurred in 27.3% (30 cases) in the study; but it was significantly less in the Foley catheter group, in which repeated treatments were performed in 13.6% (8 cases), compared with 43.1% (22 cases) in the IUCD group (P0.005). Also, all the complications (five cases, 4.5%) except one occurred in the IUCD group. These complications were first genital tract sepsis, which developed in two patients treated with
Table 3 Complication and need for repeat treatment Repeat treatment cycles
Total ns110 (%)
1 2 3 Grand total Complications Genital sepsis Genital perforation U.T.I. Grand total
18 10 2 30 2 2 1 5
*Statistically significant.
Foley’s catheter ns59 (%)
IUCD ns51 (%)
(16.4) (9.1) (1.8) (27.3)
6 (10.2) 2 (3.4) – 8 (13.6)
12 8 2 22
(1.8) (1.8) (0.9) (4.5)
– – 1 (1.7) 1 (1.7)
2 (3.9) 2 (3.9) – 4 (7.8)
(23.5) (15.7) (3.9) (43.1)
P-value
0.0589 0.0253* 0.1247 0.0005*
0.1381
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IUCD. The symptoms consisted principally of fever, and an offensive vaginal discharge developed 5 days after adhesiolysis. The IUCD was removed in each case and the symptoms and signs abated with a course of doxycycline and metronidazole tablets. In the two patients who had genital perforation, suspicion began when the IUCD previously inserted could not be removed in the clinic after the third withdrawal PV bleeding. Subsequent ultrasound confirmed the partial perforation in each case. The IUCD was easily removed with crocodile forceps, with the patient under general anesthesia. The urinary tract infection was an incidental occurrence in a patient treated with the Foley catheter balloon. 4. Discussion Intrauterine adhesion is an important uterine factor in the etiology of infertility in our environment, with an incidence, in this study, of 6.3% of the infertile population. This is comparable to reports of (2–5%) by previous authors w9,12x. The study confirms that the main etiological factor in IUA is induced abortion or curettage following spontaneous or missed abortion (81.8%), especially if these were the outcome of the penultimate pregnancies. In most cases, pregnancy was the predisposing factor (96.4%), while myomectomy accounted for 3.6% of the cases. This is similar to the observation of various other authors w6,11,17x except Ozumba et al. who noted a high etiological association with previous CyS in his series w18x. It is curious that pregnancy should predispose to the occurrence of IUA in spite of the abundant hormone. In reality, it is the surgical manipulation of the recently pregnant uterus that provokes IUA formation, because the natural softness of the uterus at this time predisposes to an increased depth of curettage, which results in the denudation of the basal layer of the endometrium and the consequent loss of the regenerative mechanism. Alternatively, retained placenta remnants and villous element might facilitate the occurrence of infection and also promote increased fibroblastic activity and collagen formation before endometrial regeneration has taken place w3x.
The commonest modes of presentation were secondary amenorrhea and hypomenorrhea in 51.8% and 42.0% of patients, respectively; only 6.4% had normal menstruation. Diagnosis in all cases in this study was reached by HSG, which showed a consistent intrauterine filling defect. Hysteroscopy which is the Gold standard in making the diagnosis classification, and treatment of IUA w10,11x was not available in our institution. Efforts are on presently to acquire a hysteroscope for the institution. The ideal treatment of IUA consists not only of physically removing the adhesion but also preventing the formation of new ones by the use of other adjunctive measures. The prevention of adhesion formation is commonly done by the dual approach of maintenance of the freshly separated uterine cavity by some physical means and enhancement of endometrial growth, which is often facilitated by a cyclical estrogen and progestogen treatment regimen w12x. In general, the placement of IUCD or pediatric Foley catheter balloon in the freshly separated uterine cavity is the common adjunctive approach for the maintenance of the separated uterine cavity for subsequent endometrial regeneration w19–23x and there are good reports on the use of either in IUA treatment. However, the efficiency and effectiveness of the IUCD and Foley catheter balloon has not been comparatively tested in the same patient population, over a specific period in the same clinical setting. This is what has been performed in this study, assessing outcome measures such as restoration of normal menses and HSG, pregnancy rate, and pregnancy outcome. The overall outcome of treatment using the two methods, the IUCD and Foley catheter balloon, to maintain the uterine cavity separated was good as evidenced by the attainment of a 72.7% return of normal menstruation and a pregnancy rate of 30.9%. This is comparable but slightly better than those of previous authors w5,6,9,11–13x. In all assessed parameters, patients treated with the Foley catheter balloon had a better outcome than patients treated with the IUCD. However, the differences in treatment outcome only reached statistical significance with outcomes such as restoration of normal menstruation, HSG, and persistent post-
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treatment secondary amenorrhea and hypomenorrhea. The need for repeated treatments was also significantly lower in patients treated with the Foley catheter balloon. The complication rate was higher for patients treated with the IUCD but this was not statistically significant. This finding agrees with similar observations by various other authors w17–23x. The findings in this comparative study are noteworthy, especially for the developing countries where induced and unsafe abortion rate is high w24,25x and there will be increasing incidence of IUA complicating these abortion cases. For the developing countries the choice in the treatment of IUA will usually be between the IUCD and the Foley catheter balloon as the other adjunctive treatment after lysis of adhesion with the uterine sound or curette, which is not very effective in removing the adhesions, unlike in the developed countries where the hysteroscope can be effectively used to remove the adhesions. However, the Foley catheter balloon has been shown in this study to be a more effective and efficient option than the IUCD for IUA treatment. The obvious advantages are immense. It is cheap and accessible which is a special advantage in the developing countries with poor resources and appears to be more acceptable to the patients who view the IUCD as a psychological barrier in itself to conception. Furthermore, the Foley catheter balloon appears to achieve a greater and more effective separation of the uterine cavity because of the larger surface area, which enable it to maintain the separated uterine cavity while the endometrial regeneration is going on w17,19x. In conclusion, the result of this study, which spanned eight consecutive years, has confirmed that in the treatment of IUA, the placement of a pediatric Foley catheter balloon to maintain the uterine cavity separated is safer and more effective than the IUCD in ensuring return of normal menstruation and later pregnancies with minimal complications. References w1x Asherman J. Amenorrhoea traumatic (atretical). J Obstet Gynaecol Br Empire 1948;55:23 –27.
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w2x Louros NC, Danezis JM, Pontifix G. Use of intrauterine devices in the treatment of intra-uterine adhesions. Fertil Steril 1968;19:509 –528. w3x Polishuk WZ, Anteby SO, Weinstein D. Puerperal endometritis and intrauterine adhesions. Int Surg 1975;60:418 –420. w4x Zondek R, Rozin S. Filling defect in the hysterogram simulating intrauterine synechae which disappear after denervation. Am J Obstet Gynecol 1964;88:123 –127. w5x Schenker JG, Margalioth EJ. Intrauterine adhesions; an update appraisal. Fertil Steril 1982;37:593 –610. w6x Sugimoso O. Diagnostic and therapeutic hysteroscopy for traumatic intrauterine adhesions. Am J Obstet Gynecol 1978;131:539 –547. w7x Rabau E, David A. Intrauterine adhesions: aetiology, prevention and treatment. Obstet Gynecol 1963;22:626 – 629. w8x Forssman L. Post traumatic intrauterine synaechae and pregnancy. Obstet Gynecol 1965;26:710 –718. w9x Otubu JAM, Olarewoju RS. Hysteroscopy in infertile Nigerian women. Afr J Med Sci 1989;18:117 –125. w10x Dicker D, Ashekenazi T, Deker A, Eastenon AF, Kategmon DT, Bucknan SD, et al. The value of hysteroscopic evaluation in patients with pre-clinical in vitro fertilisation abortion. Hum Reprod 1996;11:730 –731. w11x Katz Z, Bon Arie A, Lurie S, Manor M, Luster V. Reproductive outcome following hysteroscopic adhesiolysis in Asherman syndrome. Int J Fertil 1996;41(5):462 –467. w12x Chen F-P, Yung K, Yu-long H. Successful treatment of severe uterine synechae with transcervical resectoscopy combined with aminriatent. Hum Reprod 1997;12:943 – 949. w13x Ogedegbe OK, Giwa-Osagie OFA, Ayodeji JDF, Oyeyinka O. Intrauterine adhesions in Lagos, Nigeria. J Obstet Gynecol 1991;11:134 –135. w14x Bergman P. Traumatic intrauterine lesion. Acta Obstet Gynaecol Scand 1961;40:1 –8. w15x Moyer D. Endrometrial diseases in infertility. In: Benrmans X, editor. Progress in Infertility. Berton: Little Brown and Co, 1975. p. 3 –10. w16x March C, Israel R. Intrauterine adhesions secondary to elective abortion. Hysteroscopic diagnosis and management. Obstet Gynecol 1976;48:422 –429. w17x Wallach E. Evaluation and management of uterine causes of infertility. Chin Obstet Gynecol 1979;18:126 – 132. w18x Ozumba BC, Ezegorui H. Intrauterine adhesions in an African population. Int J Gynecol Obstet 2002;77:37 – 38. w19x Doody KM, Carr BR. Ammenorrhoea in child. In: London HJ, editor. Menstrual cycle disorders. 1990. p. 361 –387. w20x Speroff L, Robert HG, Nathan GK. Asherman syndrome. In: Speroff L, Robert HG, Nathan GK, editors.
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