Jessop Hospital for Women, Leavygreave Road, Sheffield S3 7RE, UK
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Abstract |
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Key words: fibroids/infertility/myomectomy/reproductive out- come
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Introduction |
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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.
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Materials and methods |
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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. 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 µ/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 = 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 ±SD. Parameters before and after myomectomy were compared by Student's t-test. Results were further analysed by 2x2 contingency table analysis and stepwise multiple regression analysis.
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Results |
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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.
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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) (2x2 contingency table analysis, NS).
Age, infertility history, location, number and size of fibroids did not significantly affect the miscarriage rate following myomectomy (Table V).
Delivery
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.
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Discussion |
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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 mid-trimester 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.
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Notes |
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References |
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Submitted on January 1, 1999; accepted on March 9, 1999.