1 Leuven Institute for Fertility and Embryology, Tiensevest 168, B-3000 Leuven, 2 Department of Obstetrics and Gynaecology, St Elisabeth Hospital, Avenue De Fré 206, B-1180 Brussels, and 3 Unit for Reproductive Medicine, H.Hart Hospital, Naamsestraat 205, B-3000 Leuven, Belgium
Abstract
The debate on the effect of the hydrosalpinx on medically-assisted reproduction has demonstrated the importance of understanding the complex pathophysiology of the hydrosalpinx in outlining the principles of its clinical management, whether it is by functional surgery or IVF, preceded or not by salpingectomy. New endoscopic techniques are available to accurately assess, both in the operating room and the office, the quality of the tubal mucosa. The direct endoscopic evaluation of the tubal mucosa in hydrosalpinges is at present the most reliable technique to select between functional surgery and preventive salpingectomy. In future, prospective randomized studies on salpingectomy will benefit greatly from accurate clinicopathological data.
Key words: hydrosalpinx/mucosal adhesions/salpingectomy/tubal surgery/tubal mucosa
Introduction
The results of prospective randomized studies on salpingectomy in patients with hydrosalpinges are now forthcoming and greatly assist the debate on whether or not IVF will benefit from salpingectomy. A prospective randomized study (Dechaud et al., 1998a) did not demonstrate that patients with severe tubal damage, as defined by the presence of proximal nodes or an inflammatory and thick-walled hydrosalpinx, benefited from bilateral salpingectomy. The study indicated that in each group (i.e. one with and one without salpingectomy before IVF treatment), 322 patients would have to be included to reach statistical significance. A study started in 1994 in nine Nordic IVF centres (Strandell et al., 1999
) had recruited 204 (of the originally planned 300) patients by 1998, 116 of which were randomized to undergo laparoscopic salpingectomy and 88 to undergo IVF without salpingectomy. The diagnosis of hydrosalpinx was made by a previous hysterosalpingography (HSG) or diagnostic laparoscopy, at which time reconstructive surgery had been rejected. The authors recently reported on the outcome of the first IVF cycle and concluded that salpingectomy can be recommended for patients with hydrosalpinges enlarged enough to be visible on ultrasound and in particular for those affected bilaterally.
Is the sonographically visible hydrosalpinx suitable for functional surgery?
The study of Dechaud et al. (1998a) indicates that the removal of thick-walled hydrosalpinges could improve the outcome of IVF. However, the study of Strandell et al. (1999) suggests that IVF results would benefit from the removal of sonographically visible hydrosalpinges. Such hydrosalpinges constituted 33% of the salpingectomy group and 50% of the control group. Unfortunately, the authors did not correlate their sonographic findings with a systematic pathological study of the 166 resected tubes. The sonographically visible hydrosalpinx is likely to be a thin-walled hydrosalpinx. Thick-walled hydrosalpinges with a mean diameter of 12 cm, a wall thickness of 210 mm and a frequently obliterated lumen (Vasquez et al., 1995a), are not likely to distend during ovarian stimulation and are, or become, visible at ultrasound.
If those in favour of salpingectomy before IVF and those who promote functional surgery are competing for the sonographically visible, thin-walled hydrosalpinges, the first question to answer is whether functional surgery has a place in this subgroup of hydrosalpinges? One group (Boer-Meisel et al., 1986) used criteria based on inspection with the operating microscope and identified a subgroup of 27 (25%) patients in which the hydrosalpinx was thin-walled and showed a well-preserved mucosa. They found that reconstructive surgery in this subgroup resulted in an intra-uterine pregnancy rate of 77% and a tubal pregnancy rate of 4%. A prospective study (Vasquez et al., 1995a
) found that amongst the different lesions of thin-walled hydrosalpinges, the mucosal adhesions are the most important factor in determining fertility outcome. Thin-walled hydrosalpinges, with a normal or flattened mucosa but without mucosal adhesions, are associated with a 58% pregnancy rate and a low risk of tubal pregnancy; thin-walled hydrosalpinges with mucosal adhesions have a statistically significantly lower intra-uterine pregnancy rate, and thick-walled hydrosalpinges with fibrosis of the wall are incompatible with a normal pregnancy. In addition, the pregnancy rate is not influenced by the presence or extent of peritubal adhesions (Vasquez et al., 1995b
).
The second question to address is how the patients that are most suitable for functional surgery can be selected? As noted by Strandell et al. (1999), the initial exclusion of certain cases from reconstructive surgery at the time of HSG or diagnostic laparoscopy, proved to be wrong later on, i.e. at the time of salpingectomy where it became obvious that some tubes were more suitable for reconstruction than removal or that, as in some cases, no tubal pathology could be found. It is well known that a normal, yet tortuous tube can simulate a hydrosalpinx at HSG or chromopertubation, while a patent tube can be more severely damaged than a hydrosalpinx. A recent prospective study (Dechaud et al., 1998b) demonstrated that the combination of HSG and laparoscopy is less accurate for the diagnosis of tubal infertility than the endoscopic inspection of the tubal mucosa. Several studies on hydrosalpinges have shown that when salpingoscopy can exclude the presence of mucosal adhesions it thereby identifies the subgroup with a >50% intra-uterine and a <5% tubal pregnancy rate following reconstructive surgery (Puttemans et al., 1987
; De Bruyne et al., 1989
; Marana et al., 1995
, 1999
; Surrey, 1999
). However, tubal endoscopy has not yet gained widespread clinical acceptance (Puttemans et al., 1998
). Further development of endoscopic office techniques, e.g. transvaginal salpingoscopy and fertiloscopy, may permit more routine use in clinical practice (Gordts et al., 1998
; Watrelot et al., 1999
). The use of micro-endoscopic needle techniques also avoids the necessity of opening the tube and risking a tubal pregnancy in case of a damaged mucosa (Dubuisson et al., 1991
).
Functional surgery is, therefore, indicated in patients with thin-walled hydrosalpinges with minimal or no mucosal adhesions. It is, however, unclear whether these patients represent the same subgroup as the patients with sonographically visible hydrosalpinx.
Is the sonographically visible hydrosalpinx a new clinical entity?
The hydrosalpinx that is visible on transvaginal sonography is proposed as a new clinical entity (de Wit et al., 1998), although the diagnostic and pathophysiological features of this subgroup are poorly defined. Several authors describe the enlargement of hydrosalpinges during ovarian stimulation for IVF (Hill et al., 1986
; Andersen et al., 1996
; Bloechle et al., 1997
; Sharara and McClamrock, 1997
). However, one group (Atri et al., 1994
) found that endovaginal ultrasound prior to HSG only identified 34% of the patients with a hydrosalpinx diagnosed at HSG, while another group (Swayne et al., 1984
) concluded after correlation with pathology that ultrasound may suggest the diagnosis of hydrosalpinx but that the obtained images are not pathognomonic.
The mechanism of enlargement of hydrosalpinges during ovarian stimulation is unknown. In experimental conditions, distal occlusion results in a very slow distension of the mechanically induced hydrosalpinx, taking >12 weeks, while the combination of a distal and proximal block results in a significant distension within 2 weeks (Boeckx, 1982). It can be speculated that uterine junctional zone contractions play a fundamental role in the movements of both uterine and tubal fluids (Kunz et al., 1996
; Leyendecker et al., 1996
). The wave frequency of junctional zone contractions is higher in IVF cycles than in the spontaneous cycle (Fanchin et al., 1998
; IJland et al., 1999
). Interestingly, more waves with a fundalcervical orientation persist until administration of human chorionic gonadotrophin (HCG) in those IVF cycles in which patients conceived (IJland et al., 1999
). The altered fluid movements caused by junctional zone contractions during ovarian stimulation in the presence of a thin-walled hydrosalpinx could be responsible for an adverse effect, e.g. by acting as a mechanical barrier to embryo implantation (Mansour et al., 1991
; Edwards, 1992
). The fluid composition itself has apparently no cytotoxic or adverse effect on the normal development of human embryos and their implantation in vitro (Ng et al., 1997
; Granot et al., 1998
; Strandell et al., 1998
; Spandorfer et al., 1999
). Only a long exposition to a high concentration of hydrosalpinx fluid influences sperm motility and survival (Ng et al., 2000
).
Hydrosalpinges in the natural cycle
The effect of a hydrosalpinx on IVF during the natural cycle has been poorly documented. A meta-analysis of two retrospective studies was performed (Zeyneloglu et al., 1998) to assess whether the hydrosalpinx had any impact on the transfer cycle with frozenthawed embryos and concluded that the adverse effect was also present in such cycles. However, one study (Akman et al., 1996
) was based on a small number of only sonographically identified hydrosalpinges and the other (Strandell et al., 1994
) may have included controlled ovarian stimulation during transfer cycles. Another group (Monks et al., 1993
) compared the development of embryos from natural cycle IVF with the pregnancy rates, and they found that although only `good' quality embryos from patients with non-tubal (or `unexplained') infertility were able to implant, embryos from patients with tubal infertility implanted and formed viable pregnancies irrespective of their morphological appearance. In addition, Fahy et al. observed a trend for higher success rates during IVF in the natural cycle in women with tubal disease in comparison with unexplained infertility (Fahy et al., 1995
). The suggestion made by Janssens et al. that a prospective, randomized study comparing natural and stimulated cycle IVF is required to establish whether it makes sense to offer natural cycle IVF to infertile patients with isolated tubal pathology as a regular treatment, is more than welcome (Janssens et al., 1999
). Meanwhile, these authors recently published the results of 75 natural cycle IVF in 50 women with tubal infertility in a prospective study (Janssens et al., 2000
). Successful oocyte recovery rate was 67% per started cycle and 82% per oocyte retrieval. In all, 35 embryos were transferred and resulted in four ongoing pregnancies (5.3% per cycle, 6.5% per oocyte retrieval, 11.4% per embryo transfer and 11.4% per embryo). Six patients who participated in the study made a second attempt with natural cycle IVF. Five of them conceived of which four were ongoing. Cumulative ongoing pregnancy rates were 9.8% per cycle, 11.9% per oocyte retrieval, 19.5% per embryo transfer and 19.5% per embryo. These data correspond with our own findings (P.Puttemans, unpublished data) in a series of 83 natural cycle IVF attempts in 37 couples with a mean duration of infertility of 4.2 years. The pregnancy rate was very low because of the inclusion of a too high incidence of male infertility at the time and without the use of any gamete micromanipulation, but all four clinical pregnancies developed in patients with tubal infertility that failed to conceive during earlier stimulated IVF, while no pregnancies occurred in the endometriosis group or in couples with unexplained infertility. Apparently, the time has not yet arrived to recommend indiscriminate preventive salpingectomy for the hydrosalpinx (Puttemans and Brosens, 1996
).
On the other hand, it is also important to mention that patients with a visible hydrosalpinx present significantly more cycle disturbances than patients with a hydrosalpinx that is invisible at ultrasound (de Wit et al., 1998), suggesting that thin-walled hydrosalpinges can be associated with ovarian dysfunction. Ultrasound monitoring of the natural cycle in patients with hydrosalpinges (Hamilton et al., 1986
) revealed that in 52% of the patients the dominant follicle failed to rupture in one or more cycles and that the unruptured follicle could persist in the early phase of the subsequent cycle. On the other hand, salpingectomy before IVF may jeopardize the blood supply to the ovaries and reduce the ovarian reserve (Lass, 1999
).
Notes
4 To whom correspondence should be addressed at: Leuven Institute for Fertility and Embryology, Tiensevest 168, B-3000 Leuven, Belgium. E-mail: ivo.brosens{at}med.kuleuven.ac.be
This debate was previously published on Webtrack, May 3, 2000
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