Role of Surgery in Endometriosis-Associated Subfertility

Nicola Berlanda, MD; Paolo Vercellini, MD; Edgardo Somigliana, MD, PhD; Maria Pina Frattaruolo, MD; Laura Buggio, MD; Umberto Gattei, MD

Disclosures

Semin Reprod Med. 2013;31(2):133-143. 

In This Article

Ovarian Endometrioma

Pathophysiology

Ovarian endometriomas may cause infertility by reducing the number of follicles through either space-occupying effects with secondary compression atresia, local inflammatory reactions due to the very high iron concentration in chocolate fluid with related cytotoxic oxidative stress, or both. In addition to the direct effects of ovarian endometriomas, it has been reported that their surgical removal could paradoxically further reduce the amount of ovarian follicles. This may be caused by incidental follicles removal during cystectomy, by the insults of electrosurgical coagulation used to achieve hemostasis, and by a local inflammatory reaction resulting in damaged ovarian vascularization and subsequent ovarian fibrosis.[21]

Several techniques have been proposed for the assessment of the amount of the remaining ovarian follicles, which constitutes the so-called ovarian reserve. However, in patients with unilateral cysts, measurements such as day 3 serum follicle-stimulating hormone (FSH) or anti-müllerian hormone (AMH) levels are of limited value in evaluating the entity of reduction of ovarian reserve, either before or after surgical excision. In fact, despite a reduction in ovarian reserve of the affected ovary, in these patients a normal serum FSH or AMH value might be observed due to the compensatory function of the contralateral gonad. Thus in patients with unilateral cysts, the most informative tool in evaluating ovarian reserve is ovarian responsiveness to hyperstimulation because the contralateral unaffected gonad represents an optimal control.[22] Another technique that allows independent evaluation of the ovaries is the antral follicle count (AFC), that is, the sonographic assessment of the number of preantral follicles.

Preoperative Diagnosis

Unlike endometriotic pelvic implants, the preoperative diagnosis of ovarian endometrioma has been proven to be both accurate and reproducible. At bimanual examination, a painful or fixed adnexal mass can be palpated. However, sonography is the preferred nonsurgical diagnostic modality, due to the excellent test performance in terms of both sensitivity and specificity.[23] This generally renders computed tomography and magnetic resonance imaging superfluous. At transvaginal ultrasound, the typical characteristic of the endometriotic cysts are thick walls, regular margins, and homogeneous low echogenicity of fluid.[24,25]

Role of Surgery

No RCTs are available to evaluate the impact of surgical excision of ovarian endometriomas on fertility. Among uncontrolled studies, the overall mean pregnancy rate is ~50%; however, there is a great variability between studies, with conception rates ranging from 30%[26] to 67%[27] (Fig. 2). In our opinion, there seems to be a few tentative explanations to justify such inconsistent results between different series.[28] In women with unilateral cysts, the presence of the contralateral healthy gonad undoubtedly constitutes a confounding factor. In fact, when a pregnancy is achieved postoperatively, it is impossible to know whether the success was due to surgery or to the presence of the unoperated gonad. In this regard, it would be useful to know at least the proportion between unilateral and bilateral cysts in each reported series, but this information is rarely available. Moreover, many studies include women who did not try to conceive preoperatively (whose fertility status is therefore unknown), as well as patients who conceived postoperatively by means of in vitro fertilization (IVF). Excluding those women from the analysis would most probably result in lower pregnancy rates, but findings would be more reproducible and more adherent to the actual specific contribution that surgery per se may offer to infertile patients with ovarian endometriomas. In addition, due to the lack of controlled studies comparing reproductive performance in operated versus nonoperated patients, the background pregnancy rate in untreated women with ovarian endometriomas is almost unknown. To our knowledge, only Barri et al[29] has reported that expectant management of infertile women with endometriotic ovarian cysts is associated with a pregnancy rate of 12% (20 of 169). In the same series, surgery was followed by a conception rate of 54.2% (262 of 483).

Figure 2.

Pregnancy rates observed after laparoscopic excision of endometriomas. The diamonds represent percentage point estimates and the horizontal lines the 95% confidence intervals. (From Vercellini P, Somigliana E, Viganò P, Abbiati A, Barbara G, Crosignani PG. Surgery for endometriosis-associated infertility: a pragmatic approach. Hum Reprod 2009;24:254–269. Reprinted by permission.)

The standard technique for ovarian endometrioma removal has traditionally been cyst stripping, that is, the gentle traction and countertraction between the pseudocystic wall (ovarian cortex surrounding so-called chocolate fluid) and the residual ovarian parenchyma by means of atraumatic forceps. At laparoscopy, hemostasis of the pseudocystic bed is then achieved by pinpoint bipolar electrocoagulation. In recent years, several studies have demonstrated a reduction of the ovarian reserve associated with this technique including cases of postsurgical ovarian failure in patients operated on for bilateral endometriomas.[30,31] More specifically, it has been estimated that following the stripping of an endometrioma, follicular reserve is definitely impaired in ~13% of ovaries, and a reduced responsiveness to hyperstimulation is observed in ~50% of ovaries.[32,33] On the contrary, ovarian responsiveness is not affected in unoperated ovaries, thus suggesting that the presence of an endometrioma per se does not markedly affect the ovarian reserve.[34,35]

To minimize the gonadal damage associated with excision of endometriotic cysts, an alternative surgical technique has been proposed, consisting in the fenestration and drainage of the endometrioma followed by laser vaporization (or bipolar coagulation) of the internal endometriotic foci. Data from a RCT documented a less severe reduction of serum AMH levels as well as AFC in women who were operated using the fenestration-vaporization technique as compared with the stripping technique.[36] However, the results of two RCTs[37,38] demonstrated a substantial advantage of the stripping technique over the fenestration-vaporization technique for the spontaneous pregnancy rate, with an odds ratio of pregnancy of 5.1 (95% confidence interval, 2.0 to 12.8).[33,39] Moreover, the fenestration-vaporization technique has been associated with a significantly increased risk of endometrioma recurrence.[33]

In 2010, Donnez et al proposed a mixed technique consisting in the stripping of a large part of the cyst (80 to 90%), followed by laser vaporization of that part of the cyst (the remaining 10 to 20%) that is located close to the ovarian hilus, where the ovarian tissue is more vascularized and functional, and the cleavage plane less distinguishable.[40] Among 52 women treated by means of this partial cystectomy technique, the cumulative pregnancy and recurrence rates at 6-month-follow-up were 32% and 2%, respectively; postsurgical AFC resulted similar in the operated and nonoperated gonads.

Another follicular-sparing technique has been proposed, in which bipolar electrocoagulation following the stripping of the endometrioma was avoided and hemostasis was achieved by suturing the residual ovarian parenchyma.[41] In a comparative study including 47 women bearing a single ovary, lower levels of day 3 serum FSH were observed in the 26 women whose ovary was sutured when compared with the 21 who underwent electrocoagulation.

In conclusion, the optimal indications and technique for the surgical treatment of ovarian endometriomas are yet to be established. According to the authors of a literature review in which the issue of indications has been specifically addressed,[21] criteria in favor of surgical treatment were an intact ovarian reserve, no previous ovarian surgery, unilateral disease, and rapid cyst growth. Conversely, previous surgery, reduced ovarian reserve, and the presence of bilateral endometriomas favored surgical abstention. Surgery is also advisable when endometriomas are excessively large to undergo IVF (e.g., >4 cm according to the European Society for Human Reproduction guidelines[42]), associated with unbearable pelvic pain, or when doubts exist about the precise nature of the cyst.

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