ART Outcome after Laproscopic Myomectomy

“It is apparent that little remains in the reproductive surgeon’s armamentarium that can’t be accomplished through the use of a laparoscope” Dr. Alan DeCherney. A role for laparoscopy is well supported in the treatment of Myoma associated subfertility.

Myomas and Assisted Reproduction

Uterine leiomyomas are present in 20-40% of reproductive-age women. Only 5% of fibroids are believed to be located in the submucosa where they can distort the endometrial cavity or cause abnormal bleeding patterns (Novak and Woodruff, 1979). Submucosal and intramural fibroids that protrude into the endometrial cavity have been associated with decreased pregnancy rate (PR) and implantation rate (IR) in patients undergoing IVF (Bernard et al., 2000).

Fibroids that distort the endometrial cavity may impair fertility by several mechanisms including the creation of an abnormal site for placental implantation and growth result­ing^ in infertility, an increased risk of spontaneous abortions, preterm labor and delivery. The acceptedstandard of care for patients with cavity-distorting submucosalfibroids is myomectomy before IVF.

Small intramural fibroids are associated with a significant reduction in the cumulative pregnancy, ongoing preg­nancy and live birth rates in women undergoing three cycles of IVF/ICSI compared with controls. This can have important implications, particularly for women failing to conceive after their first IVF cycle and considering further treatment attempts. (Stovall et al., 1998)

The mechanisms by which small intramural fibroids exert their adverse effect on the success rate of IVF are unclear but may include altered myometrial contractility, uterine vascular distortion (Ng et al., 2005)⁴, endometrial inflammation, thinning and atrophy (Verkauf, 1992)⁵ as well as exerting an adverse effect on gamete migration (Nishino et al., 2005)⁶. Recently, alterations in gene expression (particularly those regulating retinoid synthesis and insulin-like growth factors metabolism) were found in myoma tissue compared with adjacent normal myometrium.Because the same genes are involved in implantation (Tamura et al., 2004)⁷ and post-implantation embryonic development, these find­ings may provide a link between the presence of fibroids andadverse reproductive outcome (Surrev. 2003)⁸.

The reproductive performance of women with small intramural fibroids following myomectomy should also consider the influence of other factors, such as female age and duration of infertility, on reproductive outcome after surgery (Kumakiri et al., 2005⁹ Marchionnni et al., 2004¹⁰) Myoma size, location, number, age of patients, duration of infertility are key factors when discussing the outcomes after myomectomy. Unfortunately, these factors are not separable for an individual patient, and the surgeon must weigh the cu­mulative impact of all three factors when deciding how and when to perform a myomectomy. It is important to clarify this issue, as myomectomy for intramural fibroids has a risk of morbidity and adhesion formation, and surgery should not be considered unless the benefits outweigh the risks.

MYOMAS AND OBSTETRICAL OUTCOMES

Obstetrical outcomes are compromised by uterine fibroids, according to a Population-based retrospective study by Sheiner et al¹¹. Compared to controls, women with uterine myomas during pregnancy had a 3.5-fold increase in the incidence of intrauterine growth restriction (6.8% vs. 1.9%),a 4-fold increase in placental abruption (2.8% vs. 0.7%), a 5-fold increase in the incidence of transverse lie or breechpresentation (16.9% vs. 2.4%), a 5-fold increase in the cesarean section rate (57.7% vs. 10.8%), a 70% increase inpremature rupture of membranes (9.6% vs. 5.5%), and were three times more likely to receive transfusion (4.2% vs 1.4%). All of these outcomes were significant (P<0.001). Adjusting for maternal age, parity, gestational age, and malpresentation, pregnancies in the myoma group still had a 6.7-fold risk of cesarean section (95% confidence interval [CI] 5.5-8.1, P<0.01), 2.5-fold increase of placental abruption (95% CI 1.6-4.2, P<0.001), and a 40% increase in preterm deliveries compared to pregnancies without uterinefibroids (95% CI 1.1-1.7, P = 0.009). The size and location of the myomas were not described in this study, but otherstudies have shown that fibroids adjacent to the placenta increase the risk of bleeding and premature rupture of mem­branes¹². It would appear that myomectomy could be justified in some circumstances to reduce the risk of adverse pregnancy outcomes in some patients.

Laparoscopic vs. Abdominal Myomectomy

laparoscopic myomectomy is clearly associated with shorter hospitalization, faster recovery, less expense, less pain, less blood loss, less fever, and fewer surgical complica­tions compared to abdominal myomectomy. Pregnancy rates and recurrence rates appear to be comparable between laparoscopic and abdominal myomectomy. Surgical times may be longer than with open procedures, but the recovery time is shorter. In these studies, the conversion rate to laparotomy was typically less than 2% of cases, even large deep myomas were resected.

 

ADHESIONS

Laparoscopic vs. Abdominal Myomectomy

Dubuisson et al¹⁵ performed second-look laparoscopy in 45 women after laparoscopic myomectomy and assessed 72 myomectomy sites. Adhesions were found in 36% of patients and at 17% of each myomectomy site. The adhesion rate was highest with posterior incisions, but the rate of adhesion formation was only 33% at this site. The sigmoid colon was the leading site for uterine adhesions, followed by the bladder, adnexa, small bowel, and peritoneum. Of those who had adnexal adhesions, most had preexisting adnexal adhesions, another surgical procedure carried out at the same time as myomectomy, or a posterior myomectomy site. The investigators concluded that the rate of adhesions after lapa­roscopic myomectomy was low and rarely involved the adnexa.

 

Adhesion rate with laparoscopic myomectomy is consistently lower than the rate expected with abdominal myomectomy, Oxygenized regenerated cellulose and autocrosslinked hyaluronic acid gel both appear to reduce adhesions, and GnRH-a therapy may also be effective for this purpose.

PREGNANCY AFTER LAPAROSCOPIC MYOMECTOMY

Overall pregnancy rates and spontaneous abortion (SAB) rates with laparoscopic myomectomy are comparable to abdominal myomectomy (Table 1). This appears to be true for patients who require laparoscopic repair of the endometrial cavity^14,15have large myomas¹⁶, and for those who require IVF¹⁷

Table 1

Pregnancy outcomes after laparoscopic myomectomy (patients attempting pregnancy).
Study	Number pregnant	Pregnancy rate	SAB	Live birth rate	C/S rate	Uterine rupture
RCTs	30 L/S	54%	20%	77%	65%	0
Seracchioli, 2000 (23)	33 abd	56%	12%	88%	78%	0
Case control	44 L/S	42%	7%	93%		0
Bulletti, 1999 (64)	12 No Tx	11%	45%	55%		0
	27 Unexpl	25%	7%	93%		0
Case series
Ribeiro, 1999 (68)	18	64%	12%	78%	57%	0
Landi, 2003 (69)	72		17%	79%	46%	0
Campo, 1999 (37)	13	54%	15%	85%	45%	0
Malzoni, 2003 (31)	21	55%	15%	81%	57%	0
Seracchioli, 2003 (61)	9	39%	22%	78%		0
DiGregorio, 2002 (52)	65	44%	11%	86%	92%	0
Dubuisson, 2000 (76, 77)	100	53%	31%	69%	42%	1 surgical site
Seinera, 1997, 2000 (33, 63)	64		12%	86%	80%	0
Stringer, 1997, 2001 (26, 60)	7		28%	72%	57%	0
Rossetti, 2001 (73)	21	66%	22%	78%	71%	0
Dessolle, 2001 (74)	44	41%	14%	82%	32%	0
Darai, 1997 (70)	17	39%	23%	58%	33%	0
Nezhat, 1999 (71)	42		20%	75%	78%	0
Dubuisson, 1996 (62)	7	33%	0%	100%	57%	0
Miller, 1996 (72)	30	75%	13%	87%		0
Campo, 2003 (65)	22	61%	14%	86%	40%	0
Total L/S (n)	626					1
Hurst. Laparoscopic myomeclomy. Ferlil Sleril 2005.

 

The only prospective randomized study to evaluate preg­nancy rates after laparoscopic and abdominal myomectomy was published in 2000 by Seracchioli et al.¹⁸and there was no difference in pregnancy rates or outcomes. The study included 56 women who attempted to conceive after lapa­roscopic myomectomy, and 59 after abdominal myomec­tomy. All women were instructed to delay pregnancy for 6 months postoperatively. The pregnancy rate was 54% with laparoscopic myomectomy, not different compared to 56% with abdominal myomectomy. The cumulative pregnancyrates by Kaplan-Meier analysis was approximately 26% by 12 months in both groups, approximately 45% by 2 years, and approximately 50% by 3 years. The abortion rate was 20% in the laparoscopic myomectomy group and 12% with open myomectomy, but this difference was not significant. There was no difference in the incidence of preterm deliveries. The cesarean section rate was 78% in the abdominal myomectomy group, and 65% with laparoscopic myomectomy corresponding to a vaginal delivery rate of 22% and 35%, respectively.

 

Three case control studies have evaluated pregnancy outcomes after laparoscopic myomectomy. Bulletti et al¹⁹retrospectively compared pregnancy outcomes in threegroups of infertile women: [1] women with uterine fibroids and no surgery, [2] laparoscopic myomectomy, and [3] unexplained infertility. Delivery rates were significantly higher with laparoscopic myomectomy (42%) compared to untreated women with fibroids (11%) and women with unex­plained infertility (25%). The spontaneous abortion rate was higher in the untreated myoma group compared to either the laparoscopic myomectomy group or those with unexplained infertility, although the difference did not meet statisticalsignificance.

Stringer and colleagues' retrospective case-control study compared 49 women with abdominal myomectomy and 49 women with laparoscopic myomectomy²⁰. Seven pregnancies were reported in the laparoscopic group, including three who had delivered by the time of publication. All three were delivered by elective cesarean section at term, and no evidence of uterine dehiscence was found.

 

Campo and co-investigators⁽²¹⁾ retrospectively studied 41 women with infertility attributed to uterine fibroids, in­cluding 22 treated with laparoscopic myomectomy, and 19 abdominal myomectomy patients. Postoperative outcomes were similar in both groups. Overall the pregnancy rate was 61%, and included a live birth rate of 86% and a spontaneous abortion rate of 14%. Patients who conceived were younger, had larger myomas resected, and the myomas tended to be intramural. There were no cases of uterine rupture.

 

Goldberg et al.⁽²²⁾ valuated published series and found more pregnancy complications in 53 pregnancies after uter­ine artery embolization compared to 139 pregnancies afterlaparoscopic myomectomy. Pregnancies after uterine artery embolization had significantly higher preterm delivery (oddsratio 6.2, 95% CI 1.4-27.7) and malpresentation rates (odds ratio 4.3, 95% CI 1.0-20.5). Postpartum hemorrhage and spontaneous abortion rates tended to be higher after embo­lization, but the sample size was too small to be conclusive.

 

These combined studies indicate that laparoscopic myo­mectomy is a feasible option for infertile women. The best prognosis for future fertility is found in young women with otherwise unexplained infertility when a myoma distorts the endometrial cavity.

 

Comparison of pregnancy outcome betweenwomen undergoing laparoscopy and those undergoing laparo-conversion. Delivery rate insignificantly higher after laparoscopic myomectomy than after laparoconversion. This difference may be explained by the smaller number and size of myomata removed by laparoscopy. (Nezhat et al. 1996)²³

 

 

Uterine Rupture After Laparoscopic Myomectomy

Uterine rupture appears to be a rare occurrence in large clinical series. Based on the clinical trials and case series, it would appear that the risk of uterine rupture during pregnancy is no higher than 1% when the myometrial incision is appropriately repaired¹⁶. Laparo-scopically-assisted myomectomy LAM may be performed if correct closure of the myometrium cannot be obtained by laparoscopy¹³.

Cesarean section should be routinely advised for delivery after resecting large, deep or multiple leiomyomata.

 

ENTRY INTO THE CAVITY

Entry into the endometrial cavity presents another technical challenge during laparoscopic myomectomy. Small series show that the cavity can be adequately repaired and the prognosis for future pregnancy is good in these circum­stances. Delivery by cesarean section is generally recommended in these cases.

Seracchioli et al.¹⁵ reported on laparoscopic myomectomy in 34 women with uterine fibroids penetrating the uterine cavity. Of the 23 women who attempted pregnancy, 9 conceived within 1 year, and 7delivered at term without complications. They concluded that laparoscopic myomectomy for fibroids penetrating into the uterine cavity was safe and provided the advantages of minimal access surgery.

Laparoscopy provides a mechanism to diagnose and treat underlying pelvic pathology that may be causative for infertility as well as other symptoms, thereby optimizing both spontaneous and assisted PRs. Assisted reproductive technology and laparoscopy are not mutually exclusive, but coexisting and potentially complimentary treatments.

 

 

REFERENCES

1.  Novak ER and Woodruff JD (1979) Myoma and Other Benign Tumors of the Uterus. Gynecologic and Obstetric Pathology,8th edn. W.B. Saunders Co, Philadelphia, London, Toronto, p. 260.

 

2.  Bernard G, Darai E, Poncelet C, Benifla JL and Madelenat P (2000) Fertility after hysteroscopic myomectomy: effect of intramural myomas associated. Eur J Obstet Gynecol Reprod Biol 88, 85-90.

 

3.  Stovall DW, Parrish SB, Van Voorhis BJ, Hahn Sj, Sparks AET and SyropCH (1998) Uterine leiomyomas reduce the efficacy of assisted reproduction cycles. Hum Reprod 13, 192-197.

 

4.  Ng EH, Chan CC, Tang OS, Yeung WS and Ho PC(2005) Endometrial and subendometrial blood flow measured by three-dimensional power Doppler ultrasound in patients with small intramural uterine fibroids during IVF treatment. Hum Reprod 20, 501-506.

 

5.  Verkauf BS (1992) Myomectomy for fertility enhancement and preservation. Fertil Steril 58, 1-15.

 

6.  Nishino M, Togashi K, Nakai A, Hayakawa K, Kanao S, Iwasaku K and Fujii S (2005) Uterine contractions evaluated on cine MR imaging in patients with uterine leiomyomata. Eur J Radiol 53, 142-146.

 

7.  Tamura K, Hara T, Kutsukake M, Iwatsuki K, Yanagida M, Yoshie M and Kogo H (2004) Expression and the biological activities of insulin-like growth factor-binding protein related protein 1 in rat uterus during the peri-implantation period. Endocrinology 145, 5243-5251.

 

8.  Surrey ES (2003) Impact of intramural leiomyomata on in-vitro fertilisation-embryo transfer cycle outcome. Curr Opin Obstet Gynecol 1 5,239-242.

 

9.  Kumakiri J, Takeuchi H, Kitade M, Kikuchi I, Shimanuki H, Itoh S and Kinoshita K (2005) Pregnancy and delivery after laparoscopic myomectomy. J Minim Invasive Gynecol 12(3), 241-246.

 

10. Marchioni M, Fambrini M, Zambelli V, Scarselli G and Susini T (2004) Reproductive performance before and after abdominal myomectomy : a retrospective analysis. Fertil Steril 82, 154-159.

 

11. Sheiner E, Bashiri A, Levy A, Hershkovitz R, Katz M, Mazor M.Obstetric characteristics and perinatal outcome of pregnancies with uterine leiomyornas. J Reprod Med 2004:49:182-6.

 

12. Muram D, Gillieson M, Walters JH. Myomas of the uterus in pregnancy: ultrasonographic follow-up. Am J Obstet Gynecol 1980:138:16-9.

 

13. Dubuisson JB, Fauconnier A. Chapron C, Kreiker G. Norgaard C. Second look after laparoscopic myomectomy. Hum Reprod 1998:13:

 

14. Stringer NH, Strassner HT, Lawson L, et al. Pregnancy outcomes after laparoscopic myomectomy with ultrasonic energy and laparoscopic suturing of the endometrial cavity. J Am Assoc Gynecol Laparosc 2001;8:129-36.

 

15. Seracchioli R, Colombo FM, Bagnoli A, Govoni F, Missiroli S, Venturoli S. Laparoscopic myomectomy for fibroids penetrating the uterine cavity: is it a safe procedure? Br J Obstet Gynaecol 2003;110: 236-40.

 

16. Dubuisson JB, Chapron C, Chavet X, Gregorakis SS. Fertility after laparoscopic myomectomy of large intramural myomas: preliminary results. Hum Reprod 1996; 11:518-22.

 

17. Seinera P, Farina C, Todros T. Laparoscopic myomectomy and sub­ sequent pregnancy: results in 54 patients. Hum Reprod 2000:15: 1993-6.

 

18. Seraccmoli R, Rossi S, Govoni F, et al. Fertility and obstetric outcome after laparoscopic myomectomy of large myomata: a randomized comparison with abdominal myomectomy. Hum Reprod 2000; 15:2663-8.

 

19. Bulletti C, DeZiegler D, Polli V, Flamigni C. The role of leiomyomas in infertility. J Am Assoc Gynecol Laparosc 1999;6:441-5.

 

20. Stringer NH, Walker JC, Meyer PM. Comparison of 49 laparoscopic myomectomies with 49 open myomectomies. J Am Assoc Gynecol Laparosc 1997:4:457-64.

 

21. Campo S, Campo V, Gambadauro P. Reproductive outcomes before and after laparoscopic or abdominal myomectomy for subserous or intramural myomas. Eur J Obstet Gynecol Reprod Biol 2003;110: 215-9.

 

22. Goldberg J, Pereira L, Berghella V. et al. Pregnancy outcomes after treatment for fibromyomata: uterine artery embolization versus lapa­roscopic myomectomy. Am J Obstet Gynecol 2004;191:18-21.

 

23. Nezhat, F.D., Seidman, S., Nezhat, C. et al. (1996) Laparoscopic myomectomy today - why, when and for whom? Hum. Reprod, 11, 933-934.