Reproductive outcome after laparoscopic myomectomy for intramural myomas in infertile women with or without associated infertility factors

Abstract

Aims:   To evaluate reproductive outcome after laparoscopic myomectomy for intramural myomas in infertile women with or without associated infertility factors.

Methods:   A retrospective study was carried out in 30 infertile women with intramural myomas measuring ≥50 mm in diameter and treated using laparoscopy.

Results:   The overall rate of spontaneous intrauterine pregnancy was 50.0% (15 patients). Of 13 patients with infertility factors associated with the uterine myomas, three (23.1%) became pregnant, whereas 12 of 17 patients (70.6%) with no other associated infertility factor became pregnant. No uterine ruptures were observed. All pregnancies were spontaneous and 13 occurred within 1 year of the operation. In the 10 patients who gave birth by Cesarean section, no adhesions were found on the myomectomy scar.

Conclusions:   On the basis of these results, laparoscopic surgery for myomas appears to offer comparable results to laparotomy. In infertile patients with intramural myoma, pregnancy rates are affected by the presence of other infertility factors associated with the uterine myomas. (Reprod Med Biol 2006; 5: 31–35)

INTRODUCTION

UTERINE FIBROIDS ARE the most common tumors of the female genital tract. These benign neoplasms are estimated to occur in 20–50% of women, with increased frequency during later reproductive ages. ¹ Uterine fibroids are often asymptomatic, but in approximately 30% of cases they are associated with hypermenorrhea, pelvic pain and infertility. Surgery is still the principal method used to treat uterine myoma. Since the first reported myomectomy by Atlee, ² surgical treatment of uterine fibroids has used either a laparotomic approach or, less frequently, a vaginal route. The first report of laparoscopic myomectomy was published in 1979 by Semm and Mettler. ³ Since then several reports regarding laparoscopic myomectomy have been published and have confirmed both the feasibility and the safety of this method. ⁴ , ⁵ , ⁶ , ⁷ However, laparoscopic myomectomy has several drawbacks including, in particular, difficulty suturing the myometrium. Laparoscopic surgery has more limitations than laparotomy and various techniques are needed before surgery can be carried out safely.

The role of uterine myoma as a cause of infertility remains a matter of debate. ¹ , ⁸ , ⁹ , ¹⁰ Nevertheless, more than half of the women who have not previously given birth subsequently conceive following myomectomy for the treatment of recurrent pregnancy wastage or infertility. The long duration of infertility before surgery, the absence of other infertility factors, and the short time interval subsequent to surgery before conception occurs suggest that myomectomy is of benefit to infertile patients with leiomyomata. ¹¹ The aim of the present study was to assess the infertility results and pregnancy outcome in infertile patients with or without associated infertility factors who underwent laparoscopic myomectomy of large intramural myomas.

MATERIALS AND METHODS

Study population

THIRTY PATIENTS PRESENTING with intramural myomas measuring ≥50 mm in diameter who underwent laparoscopic myomectomy between January 1997 and December 2001 were included in the present study. Infertility was defined as the absence of all conception (whatever the outcome or location of the pregnancy) after at least 12 months of attempts. For 3 months prior to surgery, a gonadotrophin‐releasing hormone agonist was administrated to all patients to reduce the amount of intraoperative bleeding by decreasing uterine blood flow. ¹² All laparoscopic procedures were carried out by the same surgeon with the same team. Indications for laparoscopic myomectomy were a myoma measuring ≤10 cm for the largest myoma and the whole uterus the size of 14 weeks’ gestation or smaller. However, the position and number of myomas were not included among the exclusion criteria.

Laparoscopy was carried out under general anesthesia with endotracheal intubation. First, a 10‐mm port was placed through the umbilicus and a video laparoscope was introduced. Under direct laparoscopic vision, two 5‐mm ports were placed laterally on either side of the upper abdomen and one 12‐mm port was placed suprapubically.

After intra‐abdominal observation confirmed the position and size of the uterine myomas, vasopressin diluted in physiologic saline was injected between the myometrium and the capsule of the myomas. The myomas were removed by making a horizontal incision directly above the lesions with the hook‐type probe of an ultrasonic incision and coagulation system (Harmonic Scalpel: Ethicon Endo‐Surgery, Cincinnati, OH, USA). Hemostasis at the myomectomy sites was achieved with bipolar forceps. ¹³ All suturing was carried out intracorporeally. According to the depth of the myomas, the myometrium was sutured one layer at a time with Z‐stitches using a curved needle and zero polyglycolic acid sutures.

The serosa was closed with figure‐of‐eight stitches using a curved needle and zero polyglycolic acid sutures. The suture sites of the myometrium were covered with Interceed (TC7: Johnson and Johnson Medical, Arlington, TX, USA) or TachoComb (Nycomed Pharma, Linz, Austria).

The mean (± SD) age of patients was 32.9 ± 3.0 years (range 26–39 years) and the mean duration of infertility was 36.4 ± 9.1 months (range 18–60 months). Infertility was primary in 27 cases (90%) and secondary in three cases (10%). For all women, associated infertility factors were evaluated using a complete work‐up, including ovulation studies, a spermocytogram, hysterosalpingography and a postcoital test.

Data analysis

All data were analyzed statistically using χ² and Mann–Whitney U‐tests. Differences with a probability less than 0.05 were regarded as statistically significant.

RESULTS

FOR THE 30 infertile patients who underwent laparoscopic myomectomy, the mean duration of the operation was 114.5 ± 26.0 min (range 70–180 min). No blood transfusions were required either pre or postoperatively. The mean estimated blood loss was 115.9 ± 64.6 mL (range 30–350 mL). The mean number of myomas removed was 1.8 ± 0.9 (range 1–4). The average size of the largest intramural myoma removed was 64.2 ± 13.4 mm (range 50–100 mm).

Thirteen of the 30 patients (43%) had associated infertility factors, including tubal factors in four patients (13.3%), mild endometriosis (Stage II, American Fertility Society [AFS] classification of endometriosis ¹⁴ ) in four patients (13.3%), and moderate endometriosis (Stage III) in five patients (16.7%). The characteristics of the 30 patients that underwent laparoscopic myomectomy are presented in Table 1.

Table 1.

Characteristics of the study population

Characteristics	n	Mean ± SD	%
Age (years)		32.9 ± 3.0
25–29	4		13
30–34	17		57
35–39	9		30
Duration of infertility (months)		36.4 ± 9.1
<36	13		43
≥36	17		57
Primary infertility
Yes	27		90
No	3		10
Associated infertility factor
Yes	13		43
With tubal factors	4
With mild endometriosis	4
With moderate endometriosis	5
No	17		57
No. myoma per patient		1.8 ± 0.9
Myoma diameter (mm)		64.2 ± 13.4
<70	18		60
≥70	12		40

With regard to the surgical procedures, all patients underwent intraperitoneal myomectomy. There were no conversions to laparotomy. Thirteen patients underwent associated procedures for infertility and these procedures included distal tuboplasty (with or without adhesiolysis) in four patients (13.3%) and surgery for endometriosis (adhesiolysis and cystectomy of ovarian endometriomas) in nine patients (30.0%).

Pregnancy outcomes after laparoscopic myomectomy are given in Table 2. In all patients, treatment using assisted reproduction technology was not done before or after the operation. The overall rate of spontaneous intrauterine pregnancy was 50.0% (15 patients). Of these 15 pregnancies in 15 women, 13 live newborn babies were delivered. Three of the 13 deliveries (23.1%) were vaginal. Cesarean sections were carried out in 10 cases (76.9%), eight of which were carried out as elective surgeries and two on the basis of obstetric indications during labor. There were no adhesions found on the myomectomy scars and no dehiscience of the uterine scars was observed.

Table 2.

Pregnancy outcome in women undergoing laparoscopic myomectomy

Characteristic	Data
No. patients who conceived	15
Mean delay in conception† (months)	8.6 ± 3.8 (4–18)
Ectopic pregnancy	0
First‐trimester abortion	2
Dehiscence of uterine scar	0
Live newborn	13
No. vaginal deliveries (%)	3 (23.1)

^† Data are the mean ± SD, with the range given in parentheses.

Fertility according to patient characteristics in women undergoing laparoscopic myomectomy for whom follow up was completed is reported in Table 3. Women without associated infertility factors had a higher pregnancy rate than the women with associated factors (P = 0.025). No statistically significant differences were observed between the two groups with respect to patient age, or the duration or type (primary or secondary) of infertility.

Table 3.

Factors influencing pregnancy rates after myomectomy

Patient characteristics	Patients who conceived (n = 15)†	Patients who did not conceive (n = 15)†	P‐value
Patient age (years)
≥35	3 (33.3)	6 (66.7)
<35	12 (57.1)	9 (42.9)	NS
Duration of infertility (months)
≥36	6 (46.8)	8 (53.2)
<36	9 (56.2)	7 (43.8)	NS
Type of infertility
Without associated factors	12 (70.5)	5 (29.5)
With associated factors	3 (23.0)	10 (77.0)	0.025
Primary	14 (53.8)	12 (46.2)
Secondary	1 (33.3)	3 (66.7)	NS

NS, not significant. †Percentage of patients in parentheses.

Fertility according to surgery results and to the fibroid characteristics in women undergoing laparoscopic myomectomy for whom follow up was completed is described in Table 4. No statistically significant differences were observed between the two groups with respect to the duration of the operation and estimated blood loss. Pregnancy rates did not differ according to the size of the largest fibroid, the number of fibroids or the location of the fibroid in the uterus.

Table 4.

Surgery results and fibroid characteristics according to fertility in women undergoing laparoscopic myomectomy

Patient characteristics	Patients who conceived (n = 15)†	Patients who did not conceive (n = 15)†	P‐value
Duration of operation (min)	113.5 ± 24.4	115.5 ± 28.4	NS
Estimated blood loss (mL)	115.9 ± 42.3	116.0 ± 82.8	NS
Size of fibroid (mm)	61.3 ± 11.1	67.0 ± 15.2	NS
At least one fibroid ≥70 mm	5 (41.7)	7 (58.3)	NS
No fibroids ≥70 mm	10 (55.6)	8 (44.4)
No. fibroids	1.9 ± 1.0	1.6 ± 0.7	NS
1	6 (42.9)	8 (57.1)	NS
≥2	9 (56.2)	7 (43.8)
Location of the largest fibroid
Posterior wall	7 (46.7)	8 (53.3)	NS
Other	8 (53.3)	7 (46.7)

NS, not significant. †Where appropriate, data are given as mean ± SD and the percentage of patients is in parentheses.

DISCUSSION

THE PRESENT STUDY confirms that laparoscopic myomectomy is feasible and safe in selected infertility patients. Almost half the women in the present study, including patients with a long duration of infertility, conceived after laparoscopic myomectomy. This is consistent with results from a series of reports on myomectomy treated surgically using laparotomy that showed pregnancy rates between 36% and 65% in previously infertile women. ¹ , ⁹ , ¹¹ , ¹⁵ Dubuisson et al. reported an overall rate of intrauterine pregnancy of 33% among 21 infertile women who underwent laparoscopic myomectomy. ¹⁶ No causal link between uterine fibroids and infertility has been established; ¹⁷ however, more than half the women that underwent surgical treatment for fibroids fell pregnant within 1 year after surgery, ¹ , ¹⁰ a figure much higher than that observed for women with untreated, unexplained infertility. ¹⁸ Myomectomy is a challenging procedure because it involves the reconstruction of an organ that can undergo remarkable structural changes, as it does during pregnancy. The literature documents the normal reproductive performance of uteri after laparotomic myomectomy. ¹⁹ , ²⁰ , ²¹ In the present study, the cumulative pregnancy rate for spontaneous intrauterine pregnancy was 50.0% 2 years after laparoscopic myomectomy for large intramural myoma. Moreover, the pregnancy rate was found to be 70.5% for women who had no other associated infertility factors and 23.0% in women with other infertility factors associated with the myomas. In the group of women with no associated infertility factors, this result is excellent.

The degree of involvement of myomas in the infertility of certain patients is the subject of considerable debate and a number of theories have been proposed. Fibroids may affect sperm migration by reducing uterine contractility and increasing the distance that the spermatozoa have to travel. ²² Fibroids may be responsible for vascular changes, ²³ which would have repercussions on the endometrium and may hinder implantation. ²² In a review of the literature, Buttram and Reiter ¹⁸ collected 1202 cases of myomectomy via laparotomy and reported an overall intrauterine pregnancy rate of 39.9% (480 patients). The results obtained in the present series are comparable with the results reported by Buttram and Reiter because 50.0% of patients who underwent laparoscopic myomectomy in the context of infertility managed to conceive following the surgery. ¹⁰ Pregnancy rates are affected by the presence of other infertility factors associated with uterine myomas. Although the intrauterine pregnancy rate in the analysis of Buttram and Reiter ¹⁸ was 39.0% (439 cases) for the 1126 patients presenting associated infertility factors, the pregnancy rate increased to 53.9% (n = 41) for the 76 patients who had no other infertility factors associated with the uterine myomas. ¹⁰ In the present study, the pregnancy rate was 23.0% when infertility factors were associated with the myomas, but increased to 70.5% when no infertility factors were found to be associated with the myomas. In the present study, we found that the main factor affecting fertility after myomectomy was the presence of additional infertility factors. Rosenfeld ¹¹ observed that adverse prognostic factors for fertility after laparoscopic myomectomy included increased patient age, a long duration of infertility and the size and number of fibroids removed. In contrast, we found that patient age and fibroid characteristics, including number, size and location, were not decisive. Our findings agree with those of the meta‐analysis by Vercellini et al., ¹⁵ who arrived at similar conclusions regarding abdominal meomectomy. However, in the present study there was no significant effect of patient age. This may be because the present sample is too small. In any event, patient characteristics may be the most important factor.

Some of the main concerns regarding laparoscopic myomectomy are obstetric complications, including uterine rupture during pregnancy and the need for an elective Cesarean section. There are a few published case reports of such complications occurring during the second trimester. ²⁴ , ²⁵ , ²⁶ , ²⁷ , ²⁸ , ²⁹ , ³⁰ , ³¹ Our policy for delivery after myomectomy of intramural myomas is by Cesarean section because there are no criteria for safe vaginal delivery after myomectomy. In the present study, Cesarean sections were carried out in 10 cases (76.9%) and no scar dehiscence or uterine ruptures were observed. This cannot be ascribed to the high incidence of Cesarean sections because all previous cases of uterine rupture in pregnant patients after laparoscopic myomectomy occurred during the second trimester (28–36 weeks gestational age), whereas in the present study all patients delivered after 36 weeks. In this study, three vaginal births occurred without complications. However, the present sample is too small to permit any definitive conclusions. The present study has some limitations, in that a control group was not included. Moreover, postoperative fertility data were collected retrospectively. However, the absence of any cases of uterine rupture demonstrates the reliability of the laparoscopic technique.

In conclusion, from this preliminary study, laparoscopic surgery for intramural myomas offers comparable results to those obtained using laparotomy. We believe that laparoscopic myomectomy is feasible and safe in selected infertility patients; however, further studies are necessary to establish whether there are any advantages in the long term with regard to adhesion formation and fertility restoration.