The Fertility Clinic, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
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Abstract |
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Key words: delivery rates/hydrosalpinges/in-vitro fertilization/salpingectomy/tubal disease
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Introduction |
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One clinical approach in order to overcome the negative effect of hydrosalpinges includes surgical drainage of the hydrosalpinx fluid at the time of oocyte retrieval. Meanwhile, this procedure seems of no (Sowter et al., 1997) or doubtful (Voorhis et al., 1998
) benefit. Aspiration of the hydrosalpinx fluid may even induce complications (Bloechle et al., 1997
). It has therefore been suggested to perform salpingectomy prior to IVF (Shelton et al., 1996
; Andersen et al., 1996
), although this radical approach has been questioned and discussed (Puttemans and Brosens., 1996
). A small number of studies based on 1533 patients have demonstrated apparently normal pregnancy rates after salpingectomy or salpingoplasty (Vandromme et al., 1995
; Shelton et al., 1996
; Freeman et al., 1998
; Murray et al., 1998
).
The purpose of the present retrospective case-controlled study was to assess the impact of bilateral salpingectomy on the outcome of IVF in a large consecutive group of patients who had bilateral salpingectomy due to uni-or bilateral hydrosalpinges.
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Materials and methods |
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Study group
The study group included a consecutive series of 139 women undergoing a total number of 263 IVF cycles after surgical intervention of the tubes due to unilateral (21%) or bilateral (79%) hydrosalpinges. Bilateral salpingectomy (128 women) was performed on patients with unilateral hydrosalpinx mostly due to an ectopic pregnancy in one of the tubes, and a contralateral hydrosalpinx with surgery. Due to technical reasons, 11 patients underwent partial salpingectomy by medial sterilization and distal fenestration of the tubes.
The women had either surgical treatment between 1.5 and 5 years prior to their first IVF treatment (n = 92 patients) or in the interval between IVF cycles (n = 47 patients).
Before IVF treatment, tubal patency was evaluated either by hysterosalpingography, laparoscopy with chromopertubation, laparotomy, and/or by ultrasonography. All had surgically verified hydrosalpinges.
Control group
A total of 139 patients with tubal infertility without a history of hydrosalpinges was included and underwent 296 IVF cycles. The controls were identified as the next following patient in the IVF programme group who was of similar age (±2 years) and had oocyte retrieval. The tubal status was evaluated by hysterosalpingography and/or laparoscopy with chromopertubation or laparotomy prior to IVF. Furthermore, ultrasonography during the IVF treatments was consistent with the absence of hydrosalpinges. The control group included patients with previous ectopic pregnancies treated conservatively or by unilateral salpingectomy but without demonstration of a contralateral hydrosalpinx, patients with adhesions and patients with medial occlusions.
IVF treatment
Ovarian stimulation was performed using a gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG) or recombinant follicle stimulation hormone (r-FSH). In the majority of cases, ovarian stimulation with HMG or r-FSH was used in the long protocol using down-regulation from day 21 of the cycle. A small proportion of patients was treated with the ultrashort protocol, using the flare-up effect of GnRHa. The cycle was monitored by vaginal sonographic measurements of follicles and endometrial thickness. HCG was given 36 h before oocyte retrieval. Embryo replacement was performed after 48 h culture. Progesterone was given as luteal phase support. Routinely, a maximum of two embryos was transferred, but a limited number of cases had three embryos transferred.
An ongoing pregnancy was defined as the presence of an intrauterine gestational sac with a living fetus on ultrasound beyond 7 weeks of gestation. The implantation rate was defined as the number of gestational sacs per embryos transferred. The embryos were evaluated for cleavage stage and scored for morphology prior to transfer in accordance with previously described criteria (Ziebe et al., 1997). Briefly, the scoring system was: (i) morphology score 1.0: equally sized symmetrical blastomeres; (ii) morphology score 2.0: uneven sized blastomeres; (iii) 2.1: embryos with <10% fragmentation; (iv) 3.0: 2050% blastomeric fragmentation; (v) 4.0: >50% blastomeric fragmentation.
Statistics
Statistical analyses were carried out with 2 test. Differences were considered significant when P < 0.5.
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Results |
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Discussion |
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Proposed mechanisms exerting a negative effect on the implantation rate due to hydrosalpinges have been recently discussed in a review by Nackley and Muasher (1998) and include: mechanical factors caused by reflux of hydrosalpinx fluid into the uterine cavity (Mansour et al., 1991), and release of intrauterine cytokines, prostaglandins and other inflammatory compounds directly to the endometrium (Ben-Rafael and Orvieto., 1992
). Other suggestions include embryotoxic substances in the hydrosalpinx fluid (Mukherjee et al., 1996
; Rawe et al., 1997
), lipophilic embryotoxic factors in hydrosalpinx fluid (Beyler et al., 1997
), or the presence of Chlamydia infections causing inflammatory reactions within the endometrial cavity (Sharara et al., 1996
). Alterations in the endometrial adhesion molecules have been shown by Meyer et al. (1997), who found an altered endometrial histology and expression of integrins in the endometrium of patients with hydrosalpinges. Endometrial receptivity was found to be reversible in most, but not all patients after surgical correction.
Whatever the cause of the reduced pregnancy and implantation rates in patients with hydrosalpinges, our study provides firm clinical evidence that it is reversible after salpingectomy. A normalization of the delivery rates after IVF treatment can also be achieved post-surgery in cases with repeated IVF failure.
It has been shown in several studies based on fewer than 35 patients with bilateral salpingectomy due to hydrosalpinges that pregnancy as well as implantation rates are improved compared to controls with hydrosalpinges (Kassabji et al., 1994; Verhulst et al., 1994
; Vandromme et al., 1995
; Shelton et al., 1996
; Freeman et al., 1998
; Murray et al. 1998
). Recently Dechaud et al. (1998) in a prospective, randomized pilot study enrolled 30 patients with severe tubal infertility who were undergoing salpingectomy before IVF treatment and another 30 patients who had not undergone salpingectomy prior to IVF. The outcome after IVF was not significantly different, but there was a trend towards increased pregnancy as well as implantation rates after surgery. A similar Nordic study is in progress. Only Verhulst et al. (1994), Murray et al. (1998) and Freeman et al. (1998), based on 33 patients, compared the post-surgery outcome to a control group with tubal infertility without hydrosalpinges. Our data confirm their results.
One novel finding from the present study was that the live birth rate in patients who had bilateral salpingectomy between 1.5 and 5 years prior to their first IVF treatment was similar to the outcome in patients who had surgery in the interval between IVF attempts (22.5 versus 20.5%). IVF attempts before surgery do not reduce the chances of achieving a pregnancy subsequently. Clinically, this is important as uni- or bilateral hydrosalpinges are often recognized for the first time by ultrasonography during hormone stimulation (Schiller and Tsuchiyama, 1995). The decision of whether or not to perform bilateral salpingectomy prior to the first IVF cycle or after failed IVF attempts is always difficult. Seen from the patient's point of view, bilateral salpingectomy sterilizes her, excluding her chance of achieving a spontaneous pregnancy. On the other hand, the risk of recurrence of hydrosalpinges following less radical tubal surgery by salpingostomy, as well as the risk of ectopic pregnancy even during IVF treatment has to be considered. Our results show that after repeated IVF failures the chance of achieving a pregnancy remains high at least for the first three cycles subsequent to salpingectomy.
In a controlled study, Sowter et al. (1997) demonstrated that a non-surgical option such as ultrasonographically guided drainage of the hydrosalpinx at the time of oocyte collection did not restore the implantation rate in 30 patients. On the other hand, Voorhis et al. (1998) recently, in a study based on 23 patients, suggested that combining antibiotics and aspiration of the hydrosalpinx fluid at the time of oocyte retrieval improved the pregnancy rates.
There is evidence that bilateral salpingectomy does not compromise ovarian stimulation in an IVF programme (Kassabji et al., 1994; Verhulst et al., 1994
; Vandromme et al., 1995
; Shelton et al., 1996
), although Csemiczky et al. (1996) demonstrated a lower ovarian response in women with tubal damage grade IV. Our study confirms the earlier findings, that the number of oocytes, the cleavage rates and the morphology score are unaffected by bilateral salpingectomy. The ovarian response was unaffected even in 11 patients likely to have the most damaged tubes as they had, for technical reasons, medial sterilization and distal fenestration of the tubes. Recently, Freeman et al. (1998) in 30 patients followed the development of untransferred embryos for 7 days in 30 patients to determine whether hydrosalpinges affect oocyte quality or embryo development. Their results showed that hydrosalpinges might have a permanent negative influence on oocyte quality and embryo development despite surgical treatment of the hydrosalpinges accomplished by salpingectomy or neosalpingostomy. Transfer in our study was carried out 4850 h after oocyte retrieval and might be the reason why we did not find decreased oocyte quality or embryo development in the patients who underwent salpingectomy due to hydrosalpinges.
Although the number of patients is small, none of those who had medial sterilization and distal fenestration of the tubes achieved an ongoing pregnancy. This finding should be confirmed in a larger series.
The trend world-wide is moving towards transfer of no more than two embryos. It is therefore of tremendous importance to improve the implantation as well as delivery rates as much as possible by different approaches, including patients with hydrosalpinges. As discussed by Puttemans and Brosens (1996), salpingectomy in patients with hydrosalpinges should not be indiscriminately recommended without careful evaluation of the tubal mucosa and a search for the presence of chronic inflammation. Our findings (Andersen et al., 1996) support the supposition that at least in younger patients with thin-walled hydrosalpinges, it may be worthwhile to perform one or two IVF treatments before salpingectomy.
In summary, it is concluded that bilateral salpingectomy due to hydrosalpinges restores a normal delivery as well as implantation rate after IVF treatment compared to controls. A favourable outcome is also found in patients with salpingectomy after repeated IVF failures. Furthermore, a normal live birth rate as well as a high implantation rate is maintained for at least three IVF cycles subsequent to surgical treatment.
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Notes |
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References |
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Submitted on August 14, 1998; accepted on October 6, 1998.