Endometrioma and oocyte retrieval–induced pelvic abscess: a clinical concern or an exceptional complication? The authors evaluated the risk of developing a pelvic abscess in a series of 214 in vitro fertilization cycles that were performed in women with endometriomas. This complication was never recorded, indicating that its risk is very low (0.0; 95% confidence interval, 0.0–1.7%). (Fertil Steril 2008;89:1263–6. 2008 by American Society for Reproductive Medicine.)
In vitro fertilization currently is considered an effective treatment in women with endometriosis. There is a general consensus that in vitro fertilization should be recommended in infertile women who have failed to get pregnant after surgical treatment (1, 2). A debated and still-unsolved topic in this context is whether or not endometriomas should be treated before undergoing IVF cycles (3–7). There currently is cumulative evidence supporting the view that surgical treatment does not improve ovarian responsiveness to gonadotropins (7–9). However, a possible concern in this field is the risk of causing the infection of the endometrioma after oocyte retrieval. It is noteworthy that the bloody content of the cyst may serve as an excellent culture medium and may facilitate the spread of infection (10). The development of pelvic abscess after oocyte retrieval has been reported by seven independent investigators (11–17). Overall, nine cases were described. Prophylactic antibiotics have been administered in at least eight cases. The endometrioma was punctured at the time of oocyte retrieval in at least six cases. Case reports that document complications of a technique generally are of utmost interest. Physicians who are aware of a specific risk may adapt their clinical attitude to prevent it and/or to promptly identify patients affected. However, because case reports do not indicate the frequency of a complication, this may pose significant concerns in everyday clinical practice. For instance, the knowledge that the presence of an endometrioma may favor the development of a pelvic abscess after oocyte retrieval prompts the need to consider the removal of the cyst before initiation of an IVF cycle. In the decision-making process, the frequency of the complication represents a crucial point. To provide insights into this field, we set up an active follow-up of patients with endometriomas who under-
Received April 19, 2007; revised and accepted May 29, 2007. Reprint requests: Laura Benaglia, M.D., Infertility Unit, Department of Obstetrics and Gynecology, Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Via M. Fanti, 6, 20122, Milan, Italy (FAX: 39-02-55034302; E-mail:
[email protected]).
0015-0282/08/$34.00 doi:10.1016/j.fertnstert.2007.05.038
went oocyte retrieval. The primary aim of the study was to estimate the frequency of pelvic abscess in these women. Patients who underwent oocyte retrieval between January 2004 and December 2006 in the Infertility Unit of the Fondazione Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, were considered for study entry. Women were selected if they were diagnosed with one or more ovarian endometriomas at the time of IVF. Selected women were contacted by phone between October 2006 and February 2007 for follow-up. Patients who could not be contacted were excluded. The local institutional review board approved the study. Patients selected for IVF were monitored and managed according to a standardized clinical protocol, as reported elsewhere (18). Patients routinely underwent transvaginal ultrasound (with an EUB 6000 Hitachi [Hitachi, Genova, Italy], equipped with a 6-MHz curvilinear color Doppler probe) on day 8 of the cycle before ovarian stimulation. The presence of ovarian cysts is recorded systematically at this time, and their presence is confirmed during the stimulation. Ovarian endometrioma was diagnosed when a roundshaped cystic mass with a minimum diameter of 1 cm, with thick walls, regular margins, and homogeneous low-echogenic fluid content with scattered internal echoes and without papillary proliferations was observed (19). Only women who were diagnosed persistently with lesions, in at least two evaluations performed at least two menstrual cycles apart, were included. The dimension of the cysts was recorded before each treatment cycle. Oocyte retrieval was performed under sedation with midazolam (Midazolam Mayne, 2 mg; Mayne Pharma Italia, Napoli, Italy) and fentanyl citrate (Fentanest, 0.05 mg; Pfizer, Milano, Italy). The vagina was disinfected with povidone-iodine (Betadine; Beiersdorf, Milano, Italy) and subsequently was repeatedly soaked with a sterile isotonic saline solution. The patient was covered with sterile surgical sheets, and the gynecologist wore sterile surgical gloves. The ultrasound transducer was covered with a sterile surgical glove.
Fertility and Sterility Vol. 89, No. 5, May 2008 Copyright ª2008 American Society for Reproductive Medicine, Published by Elsevier Inc.
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According to the policy of our institution regarding the management of women with endometriomas who have been selected for IVF, surgical excision of the cysts before initiation of the cycle is not recommended. Moreover, the women are prescribed Ceftriaxone (1 g IM per d for 4 d), starting 2 hours before oocyte retrieval. Finally, during the procedure, every effort is made to avoid puncture of the endometrioma. Data regarding baseline clinical characteristics, cycle outcome, and complications were extracted from the patients’ chart. An active follow-up was performed by telephone to investigate infective complications that may have been omitted from the patients’ charts. In particular, the following five items were investigated: [1] pelvic pain, [2] fever, [3] antibiotic use, [4] hospitalization, and [5] independent causes of fever (such as flu, pneumonia, or other). These points related to the 2-month period after oocyte retrieval. The patients also were invited to report any other health-related complications that occurred during this period. A binomial distribution model was used to calculate the 95% confidence interval (CI) of the risk of pelvic abscess. One hundred nineteen patients satisfied our selection criteria. The mean ( SD) age and duration of infertility were 34.6 4.0 years and 3.5 2.1 years, respectively. Fourteen (12%) women had had previous pregnancies. Ninety-one (77%) patients previously had undergone surgery for endometriosis. The American Society for Reproductive Medicine classifications for these women were as follows: stage I–II in 9 cases (10%), stage III in 40 cases (44%), and stage IV in the remainder (n ¼ 42, 46%). Twenty-two women underwent more than one operation for endometriosis. The selected women underwent 214 retrieval cycles. Characteristics of the endometriomas and IVF cycle outcomes are shown in Table 1. In 25 cycles (12%), oocyte retrieval was performed without puncturing the affected ovaries. The endometrioma was accidentally punctured in six cases (3%). Complications related to the IVF cycle were recorded in three cases. In two cases, patients were admitted to the hospital as a result of a moderate ovarian hyperstimulation syndrome. The third woman reported unexplained fever, occurring 7 days after oocyte retrieval. She was not hospitalized. She was treated with paracetamol and did not receive antibiotics. She recovered within 2 days. Overall, none of the recruited women complained of a pelvic abscess. The frequency (95% CI) of this complication in women with endometriomas undergoing oocyte retrieval was thus 0.0 (0.0–1.7%). When considering only women whose affected ovaries were punctured (n ¼ 189), the frequency (95% CI) was 0.0 (0.0–1.9%). Finally, none of the women whose endometriomas were accidentally punctured (n ¼ 6) developed a pelvic abscess (0.0, 95% CI: 0.0–45.9%). 1264
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TABLE 1 Characteristics of the oocyte retrieval cycles. Characteristic No. of endometriomas 1 2 R3 Diameter, in mm, of the endometriomaa 3 oocytes per cycle. Benaglia. Endometriomas, IVF, and pelvic abscess. Fertil Steril 2008.
Some limits of the present study should be considered. To begin with, histological confirmation of the diagnosis of endometriosis was lacking. However, even if we cannot totally exclude some misdiagnosis, we believe that this may be an exceptional event for at least two reasons. First, many studies have validated the nonsurgical diagnosis of these cysts with transvaginal ultrasound. Because of their characteristic echogenic appearance, endometriomas usually can be distinguished easily from other ovarian cysts. Sensitivity and specificity of transvaginal ultrasound have been reported to be 84%–100% and 90%–100%, respectively (19–22). Second, we included only women who were diagnosed with lesions persistently, in at least two evaluations, performed at least two menstrual cycles apart. On this basis, it is unlikely that we included functional ovarian cysts. Vol. 89, No. 5, May 2008
The main outcome considered in the present study is pelvic abscess. It may be argued that the frequency of pelvic inflammatory disease (PID) in general would have been a more suitable outcome. Unfortunately, the diagnosis of PID remains a challenging task (23). The concomitant presence of hyperstimulated ovaries may even further increase the diagnostic difficulties. Overall, we estimated that a diagnosis of PID through retrospective investigation was not sufficiently reliable. In particular, mild cases may be underreported. In contrast, pelvic abscess is a challenging clinical situation and possibly a life-threatening condition. It is implausible that these cases may be underreported. Even if firm conclusions regarding the frequency of PID in our series cannot be drawn because of the above-mentioned concerns, it is noteworthy that none of the women recruited in the present study was diagnosed with severe PID. A further possible concern about our study is related to the extremely small number of women (n ¼ 6) whose endometrioma was accidentally punctured during oocyte retrieval. Of note is that this event occurred in at least six of the nine cases of pelvic abscess after oocyte retrieval that have been reported elsewhere. Even if we failed to detect such a case in these six women, the calculated 95% CI (0.0–45.9%) is too imprecise to draw any meaningful conclusion. However, it has to be emphasized that the present study was not designed to determine the risk of pelvic abscess in women who have an endometrioma punctured. Our aim was to assess this risk in women with endometriomas who are selected for an IVF cycle. In other words, we aimed to estimate the risk of pelvic abscess before perform oocyte retrieval. From a clinical point of view, our results can be used to counsel patients before initiation of the cycle. Of relevance here is that in our unit, every effort was made to avoid puncture of the endometrioma. We indeed assumed that this event plays a critical role in the development of pelvic abscess after oocyte retrieval. Nevertheless, endometrioma puncture occurred in six cases in our series (3%), thus suggesting that this incident cannot be totally prevented. A further aspect of our policy in women with endometriomas who are undergoing oocyte retrieval is related to the use of antibiotics. A 4-day prophylaxis with ceftriaxone was systematically prescribed, even if available information does not support the view that antibiotic prophylaxis is totally effective in preventing pelvic abscess in these women. At least, eight of the nine reported cases received antibiotics during oocyte retrieval. Of note, the benefits of an antibiotic prophylaxis using a single 1-g IM ceftriaxone administration at the time of oocyte retrieval are well known (24). On the basis of the increased risk of infection in women carrying ovarian endometriomas, we decided to pursue the prophylaxis for 3 days after the day of oocyte retrieval. We are aware, however, that a scientific rationale to support this strategy currently is lacking. In conclusion, in women with endometriomas who are selected for IVF, the risk of developing pelvic abscess after Fertility and Sterility
oocyte retrieval is very low. Fear about this complication should not play a role in the decision-making process regarding the opportunity to remove the cyst before initiating the cycle. Laura Benaglia, M.D.a,b Edgardo Somigliana, M.D., Ph.D.a Roberta Iemmello, M.D.a,b Elisabetta Colpi, M.D.c Anna Elisa Nicolosi, M.D.a,b Guido Ragni, M.D.a a Infertility Unit, Department of Obstetrics and Gynecology, Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Milan; b Universita` degli Studi di Milano, Milan; and c Department of Obstetrics and Gynecology, Ospedale Filippo del Ponte, Varese, Italy REFERENCES 1. Kennedy S, Bergqvist A, Chapron C, D’Hooghe T, Dunselman G, Greb R, et al. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod 2005;20:2698–704. 2. Practice Committee of the American Society for Reproductive Medicine. Endometriosis and infertility. Fertil Steril 2006;86(Suppl): S156–60. 3. Brosens I. Endometriosis and the outcome of in vitro fertilization. Fertil Steril 2004;81:1198–200. 4. Garcia-Velasco JA, Arici A. Surgery for the removal of endometriomas before in vitro fertilization does not increase implantation and pregnancy rates. Fertil Steril 2004;81:1206. 5. Gibbons WE. Management of endometriosis in fertility patients. Fertil Steril 2004;81:1204–5. 6. Sharpe-Timms KL, Young SL. Understanding endometriosis is the key to successful therapeutic management. Fertil Steril 2004;81:1201–3. 7. Somigliana E, Vercellini P, Vigano P, Ragni G, Crosignani PG. Should endometriomas be treated before IVF-ICSI cycles? Hum Reprod Update 2006;12:57–64. 8. Garcia-Velasco JA, Mahutte NG, Corona J, Zuniga V, Giles J, Arici A, et al. Removal of endometriomas before in vitro fertilization does not improve fertility outcomes: a matched, case-control study. Fertil Steril 2004;81:1194–7. 9. Demirol A, Guven S, Baykal C, Gurgan T. Effect of endometrioma cystectomy on IVF outcome: a prospective randomized study. Reprod Biomed Online 2006;12:639–43. 10. Chen MJ, Yang JH, Yang YS, Ho HN. Increased occurrence of tuboovarian abscesses in women with stage III and IV endometriosis. Fertil Steril 2004;82:498–9. 11. Padilla SL. Ovarian abscess following puncture of an endometrioma during ultrasound-guided oocyte retrieval. Hum Reprod 1993;8:1282–3. 12. Yaron Y, Peyser MR, Samuel D, Amit A, Lessing JB. Infected endometriotic cysts secondary to oocyte aspiration for in-vitro fertilization. Hum Reprod 1994;9:1759–60. 13. Younis JS, Ezra Y, Laufer N, Ohel G. Late manifestation of pelvic abscess following oocyte retrieval, for in vitro fertilization, in patients with severe endometriosis and ovarian endometriomata. J Assist Reprod Genet 1997;14:343–6. 14. Den Boon J, Kimmel CEJM, Nagel HTC, Van Roosmalen J. Pelvic abscess in the second half of pregnancy after oocyte retrieval for in-vitro fertilization. Hum Reprod 1999;14:2402–3. 15. Matsunaga Y, Fukushima K, Nozaki M, Nakanami N, Kawano Y, Shigematsu T, et al. A case of pregnancy complicated by the development of a tubo-ovarian abscess following in vitro fertilization and embryo transfer. Am J Perinatol 2003;20:277–82.
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