1 Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, S-413 45, Göteborg, Sweden 2 The Fertility Clinic, Copenhagen University hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
Abstract
The result of the Scandinavian multicentre study on salpingectomy prior to IVF has promoted a discussion on whether there is a risk of unnecessary salpingectomies being performed. We agree that physicians have to discriminate carefully between a hydrosalpinx that should be removed and one that is suitable for surgical repair. Tubal endoscopy is the most advanced tool for that purpose, while transvaginal ultrasound is not appropriate in selecting patients to undergo either salpingectomy or salpingostomy. The Scandinavian study showed that patients with hydrosalpinges which are large enough to be visible on ultrasound before ovarian stimulation, benefit from salpingectomy in terms of improved fertility outcome after IVF. The result of the study does not interfere with the management of distal tubal infertility in general, since it was concluded that not every woman with a large hydrosalpinx should undergo salpingectomy. Hydrosalpinges with preserved mucosa may be better treated with reconstructive surgery as primary treatment instead of salpingectomy and IVF. The latter option may, however, be the secondary treatment after failed conception and re-occlusion of the tubes. Unnecessary salpingectomies should, of course, not be performed and they may easily be avoided by appropriate evaluation of the tubal mucosa at laparoscopy before any final decision of salpingectomy is made. We do not see a major conflict: functional surgery to the tubes with healthy mucosa and salpingectomy to the dilated tubes that are visible on ultrasound and have a severely damaged mucosa.
Key words: hydrosalpinx/salpingectomy/tubal mucosa/tubal surgery
Introduction
Since the first publication on the association between the presence of hydrosalpinx and poor IVF outcome in 1994 (Strandell et al., 1994), suggestions of surgical intervention have been proposed. Today there is no controversy about this association after the publication of numerous retrospective reports which also have been summarized in meta-analyses clearly demonstrating the negative effect of hydrosalpinges (Zeyneloglu et al., 1998
; Camus et al., 1999
). Pregnancy rates are reduced by half and the rates of spontaneous abortion are more than doubled according to the compiled data.
The debate today concerns the clinical management of patients with hydrosalpinges. Although we still do not know the exact mechanism through which a hydrosalpinx exerts its negative effects, treatment options have included surgical interventions to eliminate the hydrosalpingeal fluid. Transvaginal aspiration and distal salpingostomy have only been evaluated in retrospective case series and do not provide sufficient evidence to draw any conclusions from. Salpingectomy as the most radical treatment prior to IVF has now been evaluated in a randomized controlled trial (RCT) in Scandinavia and the results from the first cycle have recently been published (Strandell et al., 1999).
The study clearly showed that patients with hydrosalpinges large enough to be visible on ultrasound prior to IVF, benefit from salpingectomy in terms of increased pregnancy and delivery rates. This study raised a number of concerns and some authors (Puttemans et al., 2000) fear that tubes that are suitable for functional surgery could be sacrificed.
Is the sonographically visible hydrosalpinx a new clinical entity and is it suitable for functional surgery?
The latter question cannot be answered by a simple yes or no, since ultrasound is not yet a method used to evaluate the tubal mucosa. Transvaginal sonography using contrast agents is the main method used to detect tubal obstruction, but attempts have been made to evaluate distortion of the tube and the presence of pelvic adhesion (Hamilton et al., 1998). However, an endoscopic method with the possibility of direct inspection will probably always be superior to any indirect method, e.g. hysterosalpingography (HSG) or ultrasound, in terms of correct evaluation.
Puttemans et al. (2000) state that it was unfortunate that we did not correlate the sonographic findings with a systematic pathological study of the resected tubes. However, the aim of our study was to examine whether patients with hydrosalpinx would benefit from salpingectomy before IVF and not to establish the most appropriate treatment modality for patients with hydrosalpinx or to evaluate ultrasound as a method for selection of patients to surgery.
A pathological study will not help us in the decision making of salpingectomy or not, but can provide knowledge of whether ultrasound-visible hydrosalpinges have certain histo-pathological characteristics. Available data from 141 resected tubes in the Scandinavian RCT on salpingectomy, show that a thick tubal wall is as common as a thin wall among the ultrasound visible hydrosalpinges (40 versus 50%) and that fibrosis of the wall is a frequent occurrence (96%). The mucosa was severely damaged in 86% of the tubes without any correlation to the sonographic finding. Tubes with honeycomb appearance were never visible sonographically but intraluminal adhesions did not prevent the tube from dilation and subsequent detection on ultrasound. Of 18 tubes with documented mucosal adhesions, half of them were in tubes which were visible on ultrasound.
These data suggest, as expected, that ultrasound is not a good method for evaluating tubal status. It can be concluded that ultrasound visible hydrosalpinges are not a clinico- pathological entity per se, but vaginal sonography is a superior tool for detecting fluid in a diseased tube.
Both retrospective and prospective clinical data suggest that the presence of hydrosalpingeal fluid is harmful to embryo implantation, and culture experiments on human embryos reject the theory of the content itself being toxic (Granot et al., 1998; Strandell et al., 1998
). It is believed that the leakage of fluid, rather than the content, is deleterious to embryo implantation in the endometrial environment (Meyer et al., 1997
). It is thus an important finding if fluid is detected before initiating ovarian stimulation. It certainly provides the information that the patient has a reduced chance of pregnancy and childbirth with IVF and a discussion of possible interventions should be brought up. The Scandinavian RCT provided evidence for the benefit of salpingectomy in cases with hydrosalpinges that are large enough to be visible on ultrasound and in particular in those with bilateral affection. However, this very clear-cut result does not imply that all large hydrosalpinges should be removed. Patients starting IVF have often waited a long time, sometimes years, for their first treatment and tubal repair has in some cases been rejected at the diagnostic laparoscopy. Other patients have already undergone distal salpingostomy but failed to conceive due to re-occlusion of the tubes or other functional disturbances. Such patients are probably unsuitable for functional surgery, but patients who did not have a proper evaluation of their tubal status certainly need to have their tubes opened and inspected before any removal.
Selection of patients for functional surgery
The literature is consistent in the findings of tubal endoscopic methods being superior to more traditional methods, e.g. HSG and/or laparoscopy (see Puttemans et al., 2000). The reasons that tubal endoscopy has not gained widespread clinical acceptance are probably mainly economical but the method is also difficult to learn and requires additional equipment.
There is, however, a possibility to evaluate the mucosa by using a more available method. Dubuisson et al. (1994) showed that the mucosal appearance at laparoscopy was as good as a more complicated scoring system using HSG and laparoscopy, in terms of predicting intrauterine pregnancy (Dubuisson et al., 1994). Even if no other endoscopic technique than laparoscopy is available, the mucosal status can still be evaluated.
The selection of patients suitable for surgical repair has to be based on the evaluation of the tubal mucosa, preferably through an endoscopic technique, and tubes with more than half of the mucosa in a good condition may have a fair chance of spontaneous conception (Vasquez et al., 1995; Marana et al., 1999
). As well as the risk of ectopic pregnancy, which is as high as 718%, the overall fertility prognosis, both with and without IVF, should be considered (Mosgaard et al., 1996
). As seen from the histo-pathological examination of the resected tubes and the types of surgery performed in the Scandinavian study, there are very few patients that are suitable for functional surgery when they finally come for IVF, often after failure of other treatment options.
Of course these scenarios of infertility work-up and therapy tradition differ greatly both between and within countries, and also the availability of IVF differs. In countries and separate centres where IVF can be offered without delay, it is even more important to recognize those patients, who have not been through a complete infertility examination and who may benefit from tubal surgery, before salpingectomy is performed. There is a massive load of information on all these treatment modalities, prognoses, risks etc. available to the patient but it is crucial that she and her husband are well informed.
Natural cycles
It has been suggested that patients with tubal infertility would perform better in a natural cycle than in a stimulated cycle (Lindheim et al., 1997), since hydrosalpinges often enlarge during controlled ovarian hyperstimulation (Hill et al., 1986
; Andersen et al., 1996
).
In the Scandinavian study we recognized patients who had ultrasound-visible hydrosalpinges prior to ovarian stimulation to have a poor prognosis. They would certainly not benefit from a natural cycle instead of a stimulated cycle, since they already had fluid-filled tubes. A meta-analysis including two studies has shown an adverse effect also in natural cycles with transfer of frozen-thawed embryos. The first study (Strandell et al., 1994) included patients with and without ultrasound-visible hydrosalpinges and no controlled ovarian hyperstimulation cycles were present. In one study (Akman et al., 1996
), all patients had their hydrosalpinges diagnosed by ultrasound prior to stimulation, implying that they had a bad prognosis also in a natural cycle.
Obviously, the meta-analysis did not only include patients who developed fluid during the ovarian stimulation. That is a group which, theoretically, could benefit from natural cycles. Lindheim et al. (1997) undertook a retrospective study of the difference in pregnancy outcome in patients having natural cycles rather than controlled ovarian hyperstimulation. The diagnosis of hydrosalpinx was made by HSG or laparoscopy, indicating that also hydrosalpinges non-visible at ultrasound were present. The lower ongoing pregnancy rate after stimulated cycles (6.7%) was not significantly different from that after natural cycles (18.1%), but the miscarriage rate was significantly higher (76.9 versus 38.8%). The option of performing natural cycles in selected patients needs to be properly studied, taking into account the lower success rate and the risk of cancellations. It may be an option for patients who are reluctant to undergo any type of surgical intervention.
Concluding remarks
It is our firm belief that there is no competition for the hydrosalpinges between those in favour of salpingectomy in IVF and those who promote functional surgery, as described by Puttemans et al. Within the group of hydrosalpinges visible on ultrasound, there can still be tubes which are suitable for functional surgery and the main rule must be that tubes with healthy looking mucosa should not be removed. However, patients who have undergone reconstructive tubal surgery, should be given a long enough post-operative period to achieve spontaneous conception, which declines after 12 months (Canis et al., 1991). After a post-operative period without spontaneous conception, the patient can be offered IVF (Audibert et al., 1991
). This is the reason why we do not see any conflict. Patients suitable for functional surgery should not have IVF as primary treatment, contrary to patients with severely damaged tubes. On the other hand, patients with large hydrosalpinges and with no prospect of spontaneous conception should not be denied a salpingectomy, which truly increases their chances of a successful IVF treatment.
Notes
3 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, S-413 45, Göteborg, Sweden. E-mail: annika.strandell{at}medfak.gu.se
This debate was previously published on Webtrack, July 19, 2000
References
Akman, M.A., Garcia, J.E., Damewood, M.D. et al. (1996) Hydrosalpinx affects the implantation of previously cryopreserved embryos. Hum. Reprod., 11, 10131014.[Abstract]
Andersen, A.N., Lindhard, A., Loft, A. et al. (1996) The infertile patient with hydrosalpinges-IVF with or without salpingectomy. Hum. Reprod., 11, 20812084.[ISI][Medline]
Audibert, F., Hédon, B., Arnal, F. et al. (1991) Therapeutic strategies in tubal infertility with distal pathology. Hum. Reprod., 6, 14391442.-[Abstract]
Camus, E., Poncelet, C., Goffinet, F. et al. (1999) Pregnancy rates after IVF in cases of tubal infertility with and without hydrosalpinx: meta-analysis of published comparative studies. Hum. Reprod., 14, 12431249.
Canis, M., Mage, G., Pouly, J.L. et al. (1991) Laparoscopic distal tuboplasty: report of 87 cases and a 4-year experience. Fertil. Steril., 56, 616621.[ISI][Medline]
Dubuisson, J.B., Chapron, C., Morice, P. et al. (1994) Laparoscopic salpingostomy: fertility results according to the mucosal appearance. Hum. Reprod., 9, 334339.[Abstract]
Granot, I., Dekel, N., Segal, I. et al. (1998) Is hydrosalpinx fluid cytotoxic? Hum. Reprod., 13, 16201624.[Abstract]
Hamilton,J.A., Larson,A.J., Lower,A.M., et al. (1998) Evaluation of the performance of hysterosalpingo contrast sonography in 500 consecutive, unselected, infertile women. Hum. Reprod., 13, 15191526.[Abstract]
Hill,G.A., Herbert,C.M., Fleischer,A.C. et al. (1986) Enlargement of hydrosalpinges during ovarian stimulation protocols for in vitro fertilization and embryo replacement. Fertil. Steril., 45, 883885.[ISI][Medline]
Lindheim, S.R., Hellner, D., Ditkoff, E.C. and Sauer, M.V. (1997) Ovarian hyperstimulation compounds the deleterious effect of hydrosalpinx on outcome during IVF-ET. Assist. Reprod. Rev., 7, 6466.
Marana, R., Catalano, G.F., Muzii, M. et al. (1999) The prognostic role of salpingoscopy in laparoscopic tubal surgery. Hum. Reprod., 14, 29912995.
Meyer, W.R., Castelbaum, A.J., Somkuti, S. et al. (1997) Hydrosalpinges adversely affect markers of endometrial receptivity. Hum. Reprod., 12, 13931398.[Abstract]
Mosgaard, B., Hertz, J., Steenstrup, B.R. et al. (1996) Surgical management of tubal infertility, a regional study. Acta Obstet. Gynecol., 75, 469474.[ISI]
Puttemans,P., Campo,R., Gordts,S. and Brosens,I. (2000) Hydrosalpinx and ART: Hydrosalpinxfunctional surgery or salpingectomy. Hum. Reprod., 15, 14271430.
Strandell, A., Waldenström, U., Nilsson, L. et al. (1994) Hydrosalpinx reduces in-vitro fertilization/embryo transfer rates. Hum. Reprod., 9, 861863.[Abstract]
Strandell, A., Sjögren, A., Bentin-Ley, U. et al. (1998) Hydrosalpinx fluid does not adversely affect the normal development of human embryos and implantation in vitro. Hum. Reprod., 13,29212925.
Strandell, A., Lindhard, A., Waldenström, U. et al. (1999) Hydrosalpinx and IVF outcome: a prospective, randomized multicentre trial in Scandinavia on salpingectomy prior to IVF. Hum. Reprod., 14, 27622769.
Vasquez, H.B., Arici, A., Olive, D. et al. (1995) Prospective study of tubal mucosal lesions and fertility in hydrosalpinges. Hum. Reprod., 10, 10751078.[Abstract]
Zeyneloglu, H.B., Arici, A. and Olive, D.L. (1998) Adverse effects of hydrosalpinx on pregnancy rates after in vitro fertilizationembryo transfer. Fertil. Steril., 70, 492499.[ISI][Medline]