Myomectomy: a retrospective study to examine reproductive performance before and after surgery

Human Reproduction, Jul 1999

The aim of this retrospective study was to establish the impact of myomectomy on pregnancy outcome with particular reference to its effect on the incidence of pregnancy loss. Myomectomy was performed using microsurgical procedures upon 51 women who had intramural or subserosal fibroids and wished to conceive. Overall, the conception rate following myomectomy was 57%. Multiple regression analysis showed that age was the only factor which influenced conception rate: ⩽35 years, 74% (23/31); ⩾36 years, 30% (6/20; P < 0.005). The pregnancy loss rate prior to myomectomy was 60% (24/40), which was reduced to 24% (8/33) after myomectomy (P < 0.001). There was no instance of premature labour or scar rupture among 25 live births. This retrospective study suggests that myomectomy for intramural and subserosal fibroids may significantly improve the reproductive performance of women presenting with infertility or pregnancy loss.

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Myomectomy: a retrospective study to examine reproductive performance before and after surgery

T.C.Li 0 R.Mortimer 0 I.D.Cooke 0 0 Jessop Hospital for Women , Leavygreave Road, Sheffield S3 7RE , UK 1To whom correspondence should be addressed The aim of this retrospective study was to establish the impact of myomectomy on pregnancy outcome with particular reference to its effect on the incidence of pregnancy loss. Myomectomy was performed using microsurgical procedures upon 51 women who had intramural or subserosal fibroids and wished to conceive. Overall, the conception rate following myomectomy was 57%. Multiple regression analysis showed that age was the only factor which influenced conception rate: 35 years, 74% (23/31); 36 years, 30% (6/20; P , 0.005). The pregnancy loss rate prior to myomectomy was 60% (24/40), which was reduced to 24% (8/33) after myomectomy (P , 0.001). There was no instance of premature labour or scar rupture among 25 live births. This retrospective study suggests that myomectomy for intramural and subserosal fibroids may significantly improve the reproductive performance of women presenting with infertility or pregnancy loss. - Recent studies on uterine fibroids and myomectomy have focused primarily on the techniques of removing the fibroids, e.g. laparoscopic removal (Dubuisson and Chapron, 1995; Mettler et al., 1995), hysteroscopic resection (Hallez, 1995; Goldenberg et al., 1995), vaginal approach (Magos et al., 1994), myolysis (Patient et al., 1996), and arterial embolization (Goodwin et al., 1997) but very few have addressed the indications and the outcomes of myomectomy. Two important considerations involved in the decision to undertake surgery are the location of the fibroid, and whether or not the uterine cavity is distorted. It has been suggested that submucous fibroids (which invariably distort the uterine cavity) do result in subfertility and increase the risk of miscarriage, and so should be removed (Garcia and Tureck, 1984; Farhi et al., 1995). Moreover, in the majority of cases, submucous fibroids may be removed by simple, hysteroscopic techniques with very encouraging results (Goldenberg et al., 1995). In the case of intramural or subserosal fibroids, the situation is more controversial. There is considerable debate on whether these fibroids have adverse effects on reproductive outcome. Some investigators have claimed that they compromise assisted conception (Stovall et al., 1998) but others have reported that they do not affect the results (Ramzy et al., 1998). Many reports have considered intramural fibroids and subserosal fibroids as a single group, and little attempt has been made to analyse the two groups separately. However, it is possible that the impact of intramural fibroids on reproductive outcome is quite different to that of subserosal fibroids. The conception rate following myomectomy has been examined in a number of studies and ranged from 2570% (Table I). The presence of concomitant infertility factors appears to have an important effect on the conception rate. In a recent meta-analysis (Vercellini et al., 1998), the conception rate following myomectomy in women with otherwise unexplained infertility (61%) was higher than in those with other infertility factors (38%). However, few studies have considered the reproductive performance prior to myomectomy, including the presence of infertility and miscarriage, and hence have not examined how myomectomy alters the reproductive performance. In this retrospective study, we compared reproductive performance before and after myomectomy performed with the use of microsurgical techniques, with a view to a better understanding of the impact of myomectomy on reproductive outcome and of the extent to which myomectomy is able to improve reproductive performance. Materials and methods A total of 113 myomectomies were performed in women ,45 years of age between May 1991 and December 1996 at the Jessop Hospital for Women, Sheffield, UK. Patients were identified by computer search and by manually going through the operating theatre records. Among these 113 subjects, 51 fulfilled the following inclusion criteria: (i) they had laparotomy and myomectomy using microsurgical techniques, for intramural or subserosal fibroid(s); (ii) they wished to conceive shortly after surgery; (iii) they had no other significant infertility factors, i.e. tubal disease, abnormal semen analysis of the partner. The hospital records were analysed with the use of SPSSPC. The information retrieved included details and outcome of any pregnancy, either before or after surgery (including pregnancy loss and any obstetric complications), the location, number and size of the fibroid(s) and the indications for surgery. Pregnancy loss was considered to be the primary indication if there were 2 first trimester miscarriages or 1 mid-trimester or third trimester loss. Infertility was defined as failure to conceive after 1 year. In women with a history of infertility, the results of other infertility investigations, including tubal, male and ovulatory factors, were also recorded. None of the fibroids had involved or distorted the uterine cavity. (b) With various associated infertility factors (Berkeley et al., 1983) 19 (Verkauf, 1993) (Dubuisson et al., 1996) 12 (Gatti et al., 1989) 30 (Gehlbach et al., 1993) 28 (Smith and Uhlir, 1990) 32 (Darai et al., 1997) 15 aAll submucous fibroid. A fibroid was considered subserosal if .50% of the fibroid protruded out of the serosal surface of the uterus. The microsurgical techniques used have been previously described (Singhal et al., 1991) and included gentle tissue handling, constant irrigation of the tissue with a physiological solution which contained heparin (1000 m /l), and meticulous haemostasis. As the fibroids were enucleated, the vessels surrounding the fibroid were carefully identified, clamped and tied. The uterine defect was closed with 10 polyglactin (Vicryl; Ethicon, Edinburgh, UK), and the serosa was approximated with 20 polyglactin or 40 prolene. Afterwards, a portion of the omentum was removed, placed over the incision and secured in place with fine 40 non-absorbable prolene sutures. This acted as a form of barrier to prevent adhesion formation. In some cases (n 5 9), a piece of Interceed (Johnson & Johnson, New Brunswick, NJ, USA) absorbable adhesion barrier replaced the free omental graft. Finally, 750 mg of hydrocortisone acetate was instilled into the peritoneal cavity prior to abdominal closure with a view to further reducing adhesion formation (Swolin, 1967). Post-operatively, prophylactic antibiotics were given for 5 days. The duration of follow-up ranged from 360 months, and averaged 12.6 months. Statistics Results are expressed as means 6SD. Parameters before and after myomectomy were compared by Students t-test. Results were further analysed by 232 contingency table analysis and stepwise multiple regression analysis. Results Myomectomy was successfully performed in all the 51 women in the study. The mean (6SD) age of the subjects was 33.7 6 0.7 years (range, 2544 years). The characteristics of these 51 women including the indication for the surgery, reproductive history, location and number of fibroids are summarized in Table II. In calculating the size of the fibroids, 40 subjects had uterine Location of fibroid Number of fibroids present Diameter of fibroid/size of uterus 1 2 3 4 unspecified size 12 weeks or a diameter of the (largest) fibroid 5 cm: they were considered to have large fibroids. Ten subjects with uterine size 10 weeks and the diameter of the (largest) fibroid ,5 cm were considered to have small fibroids. In one subject, information was not available in the hospital record to enable classification. The diameters of the largest fibroid ranged from 117 cm, median 6 cm. The sizes of the uteri ranged from bulky to 20 weeks, median 14 weeks. In one subject, three intramural fibroids were of 1 cm diameter, and the size of the uterus was considered to be bulky. Apart from this particular subject, the diameter of the largest fibroid ranged from 3 17 cm, with the size of the uterus ranging from 620 weeks. Prior to surgery, there was a total of 40 pregnancies among the 51 subjects. The outcome of these pregnancies is summarized in Table III. Prior to myomectomy, a total of 24 pregnancies were lost among 19 women. Three women experienced degeneration of a fibroid in previous pregnancies, of which two resulted in mid-trimester loss and the third progressed to term delivery by Caesarean section. Following myomectomy, there were 33 spontaneous pregnancies among 29 of the 51 subjects. Comparison of reproductive outcomes before and after myomectomy Two by two contingency table analysis showed that the rate of pregnancy loss following myomectomy (24%) was significantly lower (P , 0.001) than that before myomectomy (60%). The reproductive outcomes of a subgroup of patients (n 5 11) in whom the primary indication for surgery was pregnancy loss are shown in Table IV. In this subgroup, the rate of pregnancy loss following myomectomy (33%) was significantly lower (P , 0.001) than that prior to surgery (79%). Factors affecting conception after myomectomy Overall, 29 of 51 (57%) subjects conceived after myomectomy. The possible impact of age (35 or 36 years), infertility, location and number of fibroids on the outcome was further analysed by contingency table analysis (Table V). Women aResults were analysed by 232 contingency table analysis, pregnant versus not pregnant. bn 5 50, the size was uncertain in one case. cn 5 48, the number was uncertain in three cases. NS 5 not significant. Total pregnant Not pregnant aged 35 years had a significantly (P , 0.005) higher chance of conception (74%) than women 36 years (30%). A history of infertility also influenced the chance of conception after myomectomy: those without a history were significantly more likely to conceive (76%) than those with a history of infertility (43%). The location, number and size of fibroids and the size of the uterus did not appear to have any significant impact on the conception rate. Among the 30 subjects who had a history of infertility, the mean (6SD) duration of infertility prior to surgery was 5.9 6 5.2 years. Nineteen women had primary infertility whereas 11 women had secondary infertility. Thirteen (43%) conceived following myomectomy, five suffered pregnancy loss, whilst the remaining eight progressed to live delivery. All women who conceived in this group were ,40 years of age. Of the 17 subjects who did not conceive, seven were 40 years of age. Consequently, the conception rate for women ,40 years was 57% (13/23). The duration of infertility did not appear to have a significant impact on conception rate following myomectomy, which was 33% (3/9) for infertility 2 years and 48% (10/21) for infertility .2 years (NS). Stepwise multiple regression analysis showed that the chance of conception following myomectomy was primarily influenced by age; a history of infertility did not significantly influence the chance of conception after the age factor had been taken into consideration. Pregnancy loss Myomectomy appeared to significantly reduce the occurrence of miscarriage associated with fibroids (Tables III and IV). The pre-operative rate of pregnancy loss (60%) was reduced post-operatively to 24%; subgroup analysis showed that in women in whom the main indication was pregnancy loss the miscarriage rate was 33% (3/9), whereas in women in whom the indication for surgery was not pregnancy loss, the miscarriage rate was 21% (5/24) (232 contingency table analysis, NS). Age, infertility history, location, number and size of fibroids did not significantly affect the miscarriage rate following myomectomy (Table V). Among the 21 pregnancies which resulted in live births, 8 (38%) were delivered by Caesarean Section (one case because of fetal distress, two cases because of delay in progress of labour, three cases because the uterine incision involved the whole thickness of the uterine wall, and two cases due to patient request), and the remaining 13 (62%) had vaginal delivery. There were no instances of premature labour (,37 weeks), preterm rupture of membranes, placental abruption, intrauterine growth retardation, scar rupture or post-partum haemorrhage. Fibroids and infertility The role of fibroids as a possible cause of infertility has been the subject of considerable debate. While many women with fibroids conceive easily, some have problems conceiving. The anatomical location of the fibroid is highly relevant, submucous, intramural and subserosal fibroids being in decreasing order of importance or likelihood to cause infertility. A number of mechanisms have been proposed to explain the possible adverse effect of fibroids on fertility. Fibroids may obstruct the tubal ostia, affecting gamete transport. The anatomical enlargement of the uterus and alteration of uterine contour may adversely affect implantation. It has been suggested (Farhi et al., 1995) that implantation is likely to be impaired if the uterine cavity is distorted. Overall, uterine fibroids may be associated with 510% of cases of infertility (The American Fertility Society Guideline for Practice, 1992) but uterine fibroid as the sole factor occurs in only 23% of all infertility cases (Buttram and Reiter, 1981). Overall, among the 51 subjects studied, 29 (57%) conceived and produced 33 pregnancies. In women 40 years of age the pregnancy rate in infertile subjects following myomectomy was similar to that of subjects without a history of infertility (75%). Our results confirm earlier findings (Garcia and Tureck, 1984; Rosenfeld, 1986; Gehlbach et al., 1993) which have suggested an improvement in conception rates following myomectomy. A recent meta-analysis (Vercellini et al., 1998) also showed that the conception rate among three studies involving only intramural and/or subserosal fibroids ranged from 5865%. However, previous infertility investigations have been incomplete and, as infertility is often multifactorial, the precise role of myomectomy is difficult to establish. In our series, thorough pre-operative infertility investigations were carried out which enabled identification of a subgroup of subjects without significant tubal or male factors. Following myomectomy, the conception rate in subjects with a history of infertility became similar to that of subjects of equivalent age without a history of infertility. Fibroids and pregnancy loss The association between fibroids and pregnancy loss is also controversial. It has been observed (Vollenhoven et al., 1990) that miscarriage rates are high if implantation occurs over a submucous fibroid. However, there are no prospective data to suggest whether or not intramural or subserosal fibroids increase the rate of pregnancy loss, and to what extent they are the cause of recurrent miscarriage. This study shows that uterine fibroids are associated with a high rate of overall pregnancy loss (60%) which was reduced following myomectomy. A reduction of miscarriage rate from 41% pre-myomectomy to 19% post-myomectomy has been reported (Buttram and Reiter, 1981). Further analysis (Table III) suggested that uterine fibroids are associated not only with a high rate of mid-trimester loss (17%), but also with a high rate of first trimester loss (40%), both of which were reduced following surgery. The results suggest that myomectomy should be considered in women with a history of pregnancy loss, especially midtrimester loss or after 2 first trimester losses. When there is only one first trimester miscarriage, the pros and cons of surgery should be carefully discussed with the patient and the treatment defined by other factors including age, infertility, and other gynaecological symptoms such as menorrhagia (Friedman and Haas, 1993). The possible risks of operation including adhesion formation, intrauterine synechiae, blood transfusion and unexpected hysterectomy should be balanced against the potential benefits. In women with recurrent first trimester loss, thorough investigation should exclude other possible underlying causes (Li, 1998). Obstetric outcomes Uterine fibroids may cause a number of complications in the third trimester, including pain due to tumour degeneration, premature labour, preterm rupture of membranes, placental abruption particularly in women with large fibroid volume, retained placenta, intrauterine growth retardation, malpresentation, outlet obstruction, post-partum haemorrhage and puerperal sepsis. Large fibroids may be more likely to cause pain (due to tumour degeneration) and premature labour; placentation over the fibroid may result in pregnancy loss, abruption and post-partum haemorrhage (Muram et al., 1980; Buttram and Reiter, 1981; Winer-Muram et al., 1984; Rice et al., 1989; Exacoustos and Rosati, 1993). In our series of 33 pregnancies following myomectomy, there were few obstetric complications, and no cases of premature labour, preterm rupture of membranes, placental abruption, intrauterine growth retardation and post-partum haemorrhage. There was no case of scar rupture. Risk factors for uterine rupture include post-operative haematoma formation at the incision site, defective scarring secondary to tissue necrosis and fistula formation on the scar. Uterine rupture in subsequent pregnancy is a possible complication of myomectomy. Considering that many of the women in our study had a poor obstetric history, it is likely that there was heightened awareness in patients, obstetricians and midwives of the need to optimize the chance of delivering a live infant. It is therefore not surprising that an apparently high proportion of babies was born by Caesarean section (41%) in this series. Factors affecting the outcome A number of factors have been reported to influence the reproductive outcome following myomectomy: size, number and location of the fibroid, age, pre-existing infertility or miscarriage history, and co-existing infertility factors. It has been reported (Sudik et al., 1996) that pregnancy rate was significantly lower in women with more than five fibroids removed (2/13, 15.4%) compared with those with 15 fibroids removed (37/54, 65.5%). Age .30 years, infertility .3 years and multiple fibroids also appeared to negatively affect pregnancy rate following myomectomy (Acien and Quereda, 1996). In our study, age appeared to have a clinically significant impact on pregnancy rate. A history of infertility also influenced the outcome: women with no history of infertility were more likely to conceive than those with a history of infertility. However, multiple, stepwise regression analysis showed age to be the only factor which significantly influenced the pregnancy rate. After adjusting for the impact of age, a previous history of infertility did not significantly affect the outcome. The nature of the fibroid did not appear to affect pregnancy rates, for two possible reasons. Firstly, successful removal of the fibroid(s) restores normal reproductive performance, regardless of its nature and presentation prior to surgery. It has been suggested (Verkauf, 1992) that with appropriate surgical care, pre-operative distortion of the uterine cavity, the number or size of fibroids removed, the number of incisions made, or entry into the uterine cavity should not influence the likelihood of subsequent conception. Secondly, the study involved a small number of patients and it is possible that a larger population will show that the nature of the fibroid may have an impact on outcome. The value of myomectomy for subserosal fibroid is a particularly controversial issue. Our series included 10 cases whose outcome appeared encouraging (conception rate, 80%). However, its effect upon the rate of pregnancy loss requires a much larger observational or randomized control study. A recent study (Eldar-Geva et al., 1998) suggested that intramural or submucosal fibroids were associated with a significantly impaired implantation rate (6.4 and 4.3% respectively) compared with subserosal fibroids (15.1%) and those without fibroids (15.7%) in women undergoing assisted conception. The site of uterine incision during myomectomy has been shown to influence adhesion formation (Tulandi et al., 1993): posterior uterine incisions resulted in more adnexal adhesions than anterior or fundal incision. However, it is unclear if the pregnancy rate following myomectomy is also influenced by the site of uterine incision. In our study the reproductive outcomes before and after myomectomy were compared and the subjects did not undergo myomectomy as part of a prospective randomized controlled trial. So far, no such trial has examined reproductive outcome following myomectomy. Until a multicentre study has been carried out, the only available, retrospective, data suggest that myomectomy may improve reproductive outcome. American Fertility Society (1992) Guideline for Practice. Myomas and Reproductive Dysfunction. The American Fertility Society, Alabama, USA. Acien, P. and Quereda, F. (1996) Abdominal myomectomy: results of a simple operative technique. Fertil. Steril., 65, 4151. Berkeley, A.S., De Cherney, A.H. and Polan, M.L. (1983) Abdominal myomectomy and subsequent fertility. Surg. Gynecol. Obstet., 156, 319322. Brown, A.B., Chamberlaine, R. and TeLinde, R.W. (1956) Myomectomy. Am. J. Obstet. Gynaecol., 71, 759763. Buttram, V.C. Jr and Reiter, R.C. (1981) Uterine leiomyomata: etiology, symptomatology and management. Fertil. Steril., 36, 433445.


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T.C. Li, R. Mortimer, I.D. Cooke. Myomectomy: a retrospective study to examine reproductive performance before and after surgery, Human Reproduction, 1999, 1735-1740, DOI: 10.1093/humrep/14.7.1735