Human Reproduction, Vol. 17, No. 11, 2967-2971,
November 2002
© 2002 European Society of Human Reproduction and Embryology
Operative morbidity and reproductive outcome in secondary myomectomy: a prospective cohort study
Department of Obstetrics, Gynaecology and Child Health, University Hospital of the West Indies, Kingston 7, Jamaica, W.I.
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Abstract |
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BACKGROUND: This prospective study was designed to evaluate the operative morbidity and reproductive outcome in patients who had secondary myomectomy for recurrent symptomatic uterine fibroids. METHODS: A total of 58 women were subjected to a secondary myomectomy via the abdominal route. The operative morbidity such as blood loss, presence of adhesions and febrile index were estimated and the pregnancy outcome over a 2–4 year period of follow-up. RESULTS: The mean age and standard deviation (± SD) of the women was 35 (± 2.4) years. Nineteen patients (33%) had a postoperative temperature
100°F and the estimated blood loss ranged from 159–2500 ml (median 700 ml). Seven patients (12%) required blood transfusion and one had a hysterectomy due to haemorrhage. Nine women (15.5%) became pregnant but only five (56%) had live births. Those with successful pregnancies tended to be younger with a mean age of 31.8 (± 2.6) years versus 35 (± 1.8) years, (P = 0.08, non-significant) and had fewer uterine leiomyomata; median with range values, 2 (1–6) versus 7 (6–15). The variables which best predicted the postoperative likelihood of pregnancy were; age, presence of tubal adhesions and the number of uterine fibroids. CONCLUSION: This prospective study showed a high operative morbidity and a poor fertility outcome after a repeat myomectomy. The factors affecting successful outcome in a logistic regression model were age, tubal adhesions and number of uterine fibroids.
Key words: operative morbidity/pregnancy outcome/secondary myomectomy/uterine fibroids
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Introduction |
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In Jamaica, where 90% of the population is of African descent, uterine fibroids are very common (Frederick et al., 1994
). Black women are three to nine times more likely to have fibroids than white women (Buttram and Reiter, 1981). A Jamaican woman undergoing primary myomectomy in her late twenties is not uncommon. Clinical reports on women with uterine fibroids who have had primary myomectomy have indicated that recurrence rates are between 15–45% within a 5–10 year period (Brown et al., 1956; Candiani et al., 1991).
Uterine fibroids are the most common female pelvic tumours occurring in about 15–30% of women in the reproductive age group (Zaloudek and Norris, 1987). Surgical intervention is often indicated when symptoms such as menorrhagia, congestive dysmenorrhoea, urinary frequency, infertility and recurrent pregnancy losses occur (Buttram and Reiter, 1981). The majority of studies on uterine fibroids have focused on primary myomectomy or interruption of blood supply by the abdominal approach (Berkeley et al., 1983; Frederick et al., 1994; Fletcher et al., 1996), laparoscopic removal (Hasson et al., 1992), hysteroscopic resection (Hallez, 1995), the vaginal approach (Magos et al., 1994), myolysis (Dubuisson et al., 1995) and arterial embolization (Spies et al., 2002).
Fertility after primary myomectomy using different techniques has been reported to be between 20–50% (Brown et al., 1956; Babaknia et al., 1978; Dubuisson and Chapron, 1996; Sudik et al., 1996) and up to 75% of these pregnancies will take place in the first year after surgery. These findings support the theory that fibroids have some association with infertility. Notwithstanding this, 50% of patients still remain infertile 5 years after primary myomectomy. Thus patients with recurrence of their symptomatic fibroids in their mid-thirties and who have not fulfilled their reproductive ambition are faced with a real dilemma.
Therefore the aim of this cohort study was to find a treatment modality to alleviate the symptoms of women with recurrence of their fibroids while conserving their reproductive potential. The principle was to perform a repeat myomectomy and assess: (i) the possible morbidity associated with the procedure, such as febrile index or blood loss, (ii) to assess the presence of adhesions caused by the first myomectomy, (iii) to evaluate the natural pregnancy outcome after the procedure and (iv) to improve the anatomy of the uterus in order to enhance implantation if assisted reproduction has to be employed.
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Materials and methods |
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This prospective cohort study analysed a total number of 58 women who had secondary myomectomy because of recurrence of their uterine fibroids and associated symptoms, at the University Hospital of the West Indies and Andrews Memorial Hospital Kingston, Jamaica, from January 1997–December 2000. A protocol sheet was designed to maintain uniformity for data entry. The subjects under study were between 30–41 years of age and had undergone further conservative surgery for relief of their symptoms, particularly preservation of their reproductive capabilities. The indications for surgery were patients with symptoms such as menorrhagia, infertility, chronic pelvic pain, and recurrent miscarriages. Exclusion criteria were patients who had endometriosis or those who were not desirous of further pregnancies or patients whose spouses had abnormal semen analyses.
They were all counselled and signed a consent form stating that a hysterectomy would be performed in the event of uncontrollable haemorrhage. Myomectomy was performed using vasopressin as the haemostatic agent and employing the technique previously described (Frederick et al., 1994). All fibroids were enucleated and large blood vessels were clamped and tied. The uterine defects were closed with 1–0 chromic catgut and the serosal surface closed with 2–0 chromic catgut (Ethicon, Brussels, Belgium). Pelvic lavage was carried out with warm normal saline solution prior to the application of Interceed® adhesion barrier (Johnson & Johnson, New Brunwick, NJ, USA). A prophylactic antibiotic Cefuroxime 1.5 g, (Glaxo Wellcome, Greenford, UK), was given i.v. prior to the procedure, by the anaesthetist.
Several parameters were determined pre-operatively, intra-operatively and post-operatively. The variables noted were: (i) pre-operative; age, parity, bulk symptoms (menorrhagia, infertility, pelvic pain and recurrent abortions), clinical uterine size, haemoglobin level, haematocrit and white cell count, (ii) intra-operative; the number of fibroids, number of incisions (anterior and or posterior), blood loss, presence of adhesions, cavity breached, and tubal occlusion, (iii) post-operative; a full blood count to determine the haemoglobin, haematocrit, white cell count difference, the highest temperature after the first 24 h post-operatively (to determine the febrile morbidity). The size of the largest leiomyoma was confirmed from the pathological report. Patients in the study were seen at monthly intervals for 2 months and 6 monthly intervals thereafter and were instructed to report in the event of a pregnancy. The number of patients who became pregnant and the outcome of the pregnancies such as miscarriages and the mode of delivery were recorded.
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Results |
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The mean age of the patients was 35.4 (± 2.4) years (range, 30–41). The mean duration of follow-up was 2 years. The characteristics of these 57 patients such as age, parity, size of the uterus, number and size of the largest fibroids, pre-operative haemoglobin and blood pressure are summarized in Table 1
. The uterine size ranged from 12–36 weeks (median 16 weeks), the number of fibroids ranged from 1–31 (median 10) and the median diameter of the largest fibroid was 7 cm (ranged from 4–18 cm) (Table I).
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In this series over 70% of the patients had the three main symptoms (menorrhagia, infertility and pelvic pain) associated with uterine fibroids as indications for surgical interventions. The majority of the patients (41/58) suffered from primary infertility compared to those with secondary infertility (17/58) (Table II
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Operative findings and morbidity.
Secondary myomectomy was successfully performed in 57 out of the 58 patients in this study as in one case a hysterectomy had to be performed as a result of postoperative bleeding and hypovolaemic shock. Abdomino-pelvic adhesions, possibly a reflection of the previous surgery, were the most significant finding (Table III
). Tubal adhesions were present in 34 (59%) patients, 30 (52%) and 22 (38%) patients had small and large bowel adhesions respectively. However, 39 (67%) patients had normal tubal patency despite the presence of adhesions. The cavity was breached in 37 (63%) patients to enucleate submucous fibroids that contributed to a high incidence of menorrhagia and infertility. Febrile morbidity occurred in 19 patients despite the administration of prophylactic antibiotics. Seventeen had a temperature of 100°F whilst two had a temperature of 102°F. The average intra-operative blood loss for all patients in the study ranged from 150–2500 ml (median 700 ml) but only seven (12%) of the patients received intra-operative and/or post-operative blood transfusions (Table III).
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Pregnancy outcome
Nine women became pregnant following secondary myomectomy. Out of the nine women who became pregnant, five (56%) carried the pregnancy to term and delivered a live infant. Compared with those women who became pregnant but had miscarriages, the patients with successful pregnancies tended to be younger [31.8 ± 2.6 year versus 35 ± 1.8 year (mean ± SD), P = 0.08, non-significant] and had fewer uterine leiomyomata; median with minimum and maximum values 2 (1–6) versus 7 (6–15). The relationship between the various predictors and subsequent pregnancy was explored with a series of logistic regression models. In these models a subsequent pregnancy outcome was coded as 1 while a code of zero was used if the women did not become pregnant post secondary myomectomy. Likelihood ratio tests were used to determine which of the following combination of variables (uterine size, number of uterine fibroids, breaching of uterine cavity, type of uterine incision, tubal adhesions, tubal patency and fimbrial adhesions) should be incorporated into a final regression model with age as a covariate and a subsequent pregnancy as the response variable. The results indicated that the absence of the variables such as uterine size, breaching of uterine cavity, type of uterine incision, tubal patency and fimbrial adhesions from the full model which included these variables along with age, number of uterine fibroids and the presence of tubal adhesions as predictors did not significantly reduce the log likelihood (
2 = 2.1, df : 5; P = 0.8, non-significant). On the other hand, the omission of either the variable, number of uterine fibroid or presence of tubal adhesions, from the reduced model significantly reduced the log likelihood. Thus the model which was the best predictor of positive pregnancy outcome from the data included the predictors, age OR 0.62 (95 % CI: 0.37, 1.02), presence of tubal adhesions OR 0.07 (95% CI: 0.01, 0.72), and number of uterine fibroids OR 0.81 (95% CI: 0.64,1.03) (Table IV).
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Discussion |
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This is the first study, to our knowledge, addressing both alleviation of symptoms and conserving the reproductive potential in women with recurrence of fibroids by performing a repeat myomectomy. The mean age of women in this study was 35 ± 2.4 years, with recurrence of symptomatic fibroids which justified the need for a conservative treatment particularly in those who were childless.
The median blood loss was 700 ml intra-operatively in this study despite the use of vasopressin as a haemostatic agent compared with 200–400 ml in other reported series of primary myomectomy (LaMorte et al., 1993; Fletcher et al., 1996). Seven patients (12%) required blood transfusions. This compared favourably with other reported series of the primary myomectomies (Smith and Uhlir, 1990; Frederick et al., 1994). Only one patient had a hysterectomy as a result of intractable post-operative haemorrhage, however, this is acceptable for such a difficult procedure.
Febrile morbidity in this study was higher, compared with the primary myomectomy and hysterectomy in other reported series. (Gambone et al., 1990; LaMorte et al., 1993). However, our definition of the fever was a temperature 
100°F (excluding the first 24 h) compared with the criteria of 100.4°F used in the above series.
Adnexal adhesions occurred in 59% of the cases in this series and could have been associated with the infertility in this group. This is said to be mainly due to posterior adhesions in patients with posterior incisions on the uterus during myomectomy. (Tulandi et al., 1993; Ugur et al., 1996). Second look laparoscopy performed 6 weeks post primary myomectomy revealed a high incidence of adhesions particularly adnexal with posterior uterine incisions in two series (Tulandi et al., 1993; Dubuisson et al., 1998). They also showed that lysis of adhesions at laparoscopy increased the pregnancy rate post myomectomy.
Most studies have reported pregnancy successes between 20–50% post primary myomectomy (Rosenfield 1986; Li et al., 1999; Solitt and Issa, 2000) but no studies have been reported on the natural pregnancy outcome in secondary myomectomy. Firstly, this study clearly demonstrates that the natural pregnancy outcome (15%) is significantly lower than most reported series of primary myomectomy. Secondly, there was a high incidence of dense vascular adhesions present during the secondary myomectomies which despite adhesiolysis left the potential for tubal occlusion particularly in posterior incisions (Fauconnier et al., 2000).
In light of the operative morbidity and poor fertility results reported in this series, assisted reproduction may be a valid alternative form of treatment. One study found no significant difference in the total pregnancy rates between patients with uterine fibroids and all IVF patients (Seoud et al., 1992). Another study reported similar findings and that implantation rate was impaired only in cases in which the fibroids caused intracavitary deformity (Farhi et al., 1995). In a third series, which excluded multiple large uterine fibroids causing deformity of the cavity, comparable results were found with those with uterine myomas and those without (Ramzy et al., 1998).
This series has shown that primary myomectomy is associated with adhesions, which can compromise fertility, and a secondary procedure also has a poor fertility outcome. Most of the studies on the effects of uterine fibroids on patients undergoing IVF excluded patients with large leiomyomata and those causing deformity of the uterine cavity. The ultimate aim of our study was to alleviate symptoms and to preserve the reproductive potential, therefore large sizes and site were not part of our exclusion criteria as compared with the three studies reported in assisted reproduction.
The miscarriage rate was 40% in this series but the numbers are too small to compare with other series with reduction rates post primary myomectomy from 60–19% (Buttram and Reiter, 1981; Li et al., 1999). Other modalities of treatment such as GnRH analogues (Friedman et al., 1994) and uterine artery embolization (Spies et al., 2002) have been used effectively to improve symptoms but have not addressed the fertility outcome as in this study.
In conclusion, a repeat myomectomy is a difficult procedure with risk of complications and a pregnancy rate that appears to be lower than that of the primary procedure. However, the evolution of assisted reproduction affords women another option of improving their fertility following a repeat myomectomy.
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Acknowledgements |
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We would like to thank Dr. W.Gardner, Dr. S.Shah, Y.McDonald, D.Bailey, D.Jones, V.Gabbadon, E.Rhoden, O.Charles, R.Shaw, G.Campbell, R.Kerr and S.Livingston for their help in this study.
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Notes |
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1 To whom correspondence should be addressed. E-mail: jfrederick{at}jamweb.net
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References |
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Submitted on March 11, 2002; accepted on July 18, 2002.
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