1 Department of Obstetrics and Gynaecology, Sahlgrenska University hospital, S-413 45 Göteborg, Sweden, 2 The Fertility Clinic, Copenhagen University hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark and 3 IVF Center Falun, Falu hospital, S-791 82 Falun, Sweden
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Abstract |
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Key words: hydrosalpinx/IVF/ovarian response/salpingectomy
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Introduction |
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Salpingectomy is often a consequence following ectopic pregnancy and the procedure itself is not questionable. However, prophylactic salpingectomy in women with large hydrosalpinges has recently been shown to be beneficial in terms of increased pregnancy and birth rates after IVF treatment (Strandell et al., 1999), and thus it seems important to determine whether or not the prophylactic procedure does harm the ovarian function. The aim of the present study was to examine the effect of prophylactic salpingectomy in patients with hydrosalpinges on ovarian function, assessed as the response to gonadotrophins in ovarian stimulation.
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Materials and methods |
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All patients were below 39 years of age at enrolment and had no prior IVF treatment. Two of them had delivered a child and another two had undergone a previous unilateral salpingectomy due to ectopic pregnancy. The ovarian stimulation protocol included pituitary desensitization with gonadotrophin releasing hormone (GnRH) analogue, stimulation with FSH or human menopausal gonadotrophin (HMG) and ovulation induction with human chorionic gonadotrophin (HCG). Male factor requiring intracytoplasmic sperm injection was present in one couple.
Laparoscopic salpingectomy was performed by using either bipolar diathermy and scissors or monopolar scissors directly. A bilateral procedure was performed in 17 cases and a unilateral procedure in nine cases, of which two only had one remaining tube before surgery. Among the seven patients with one remaining tube post-operatively, an alternate procedure of proximal ligation was performed on the contralateral side in three cases due to extensive adhesions, and the four remaining unilateral non-operated tubes were considered healthy.
Ovarian response was assessed as the need for FSH/HMG, measured as the total dose and duration of stimulation and the number of retrieved and fertilized oocytes. These four different outcome variables were analysed in four different group constellations, in which the first cycle(s) was compared with the subsequent cycle(s) after salpingectomy and thus, the patients acted as their own controls. The fifth group constituted two control groups with the same analysis design but without a surgical intervention between cycles.
In the primary analysis the outcome variables from the last cycle before surgery were compared with the first cycle after surgery.
The secondary analysis also included the additional cycles before and after surgery, by using the mean values for each individual, thereby minimizing the variance of individual cycles.
In a subgroup analysis including 13 patients who underwent two transfers post-operatively, a comparison between the last cycle before surgery to the second cycle after surgery was made, in an attempt to study the effect of increasing age and cycle number.
A subgroup analysis was undertaken, comparing the ovarian response in patients with bilateral and unilateral salpingectomy separately, as well as with each other. The last cycle before and the first cycle after surgery were included.
To examine the effect of increasing age between cycles, similar analyses were conducted on control groups retrieved from the original multicentre study. Ovarian response at first cycle was compared with subsequent cycles in two subsets of patients matched for age and number of retrieved oocytes at first cycle: those who underwent salpingectomy before IVF (n = 46) and those who never underwent surgery (n = 25). Mean values for each individual of the subsequent cycles were used.
Statistical analysis
Distribution of the variables are given as mean, SD and range. The sample size of 26 patients implied a power of 76% ( = 0.05) to detect a difference of 2.5 retrieved oocytes, which was considered to be of clinical significance. Changes over time were analysed by Wilcoxon's signed rank test for matched pairs. For comparison of continuous variables between groups, Mann-Whitney's U-test was used. All significance tests were two-tailed and conducted at the 5% significance level.
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Results |
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Analysis of last cycle before and first cycle after salpingectomy
The mean age increased 0.8 years (SD ± 0.4) from 32.7 (SD ± 3.6) to 33.6 years (SD ± 3.5) in the interval between the transfer cycles before and after surgery. Two hundred and thirteen units more of FSH/HMG were used at the same length of stimulation after salpingectomy (not significant). The number of retrieved and fertilized oocytes was not significantly reduced, 0.7 fewer oocytes were retrieved and 1.1 fewer oocytes were fertilized after salpingectomy. The results are presented in Table I.
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Discussion |
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All other recent clinical studies have used patients with previous salpingectomy due to ectopic pregnancy as a study group. Naturally, the surgical procedure is then curative and not prophylactic and thus without any controversy. However, it is possible that a salpingectomy for an ectopic pregnancy is different from a prophylactic salpingectomy, since the pregnant tube may be haemorrhagic and oedematous, rendering the surgery more imprecise and difficult. Nevertheless, the patient group can be used to study the effect of salpingectomy per se. In a study of a similar size and design to the current study, but including almost exclusively patients who were unilaterally salpingectomized due to ectopic pregnancy after IVF, no negative effect of surgery on response parameters was seen, nor was the operated side more affected (Dar et al., 2000). However, any pregnancy obtained after IVF is carefully monitored and presumably the ectopic pregnancies were treated at an early gestation when the damage to the tube was limited. Hitherto, only one recent study has shown an adverse effect on the ovary ipsilateral to a salpingectomy, due to ectopic pregnancy presumably after a spontaneous conception (Lass et al., 1998
). It is possible that the surgery was more extensive than a salpingectomy performed in an early ectopic pregnancy obtained after IVF. Furthermore, there was no difference in the overall performance when the sides were not separated, which may suggest a compensatory mechanism in the contralateral adnex. In another retrospective study, 26 women with a previous bilateral salpingectomy expressed the same ovarian response as their controls (Verhulst et al., 1994
).
The current study did not allow for analysis of separate sides, since the majority of cases had undergone bilateral salpingectomy. The analysis of unilateral versus bilateral salpingectomy and the comparison of the subsequent ovarian response rather implied a better response after a bilateral salpingectomy, contradictory to the result of Lass et al. (1998), although the sample size was then too small for a statistical analysis.
The main result of the current study clearly states that laparoscopic salpingectomy does not compromise ovarian function. However, an appropriate question is whether there is a group in which salpingectomy should be avoided. It is not clear if a patient with a diminished ovarian reserve has a higher risk of poor response and cancellation of cycles subsequent to salpingectomy. The present study cannot answer that question, since there were only five patients who were in the lower range of retrieved oocytes before surgery (35) and they did not perform worse post-operatively, which illustrates the difficulties in predicting the ovarian response. Without a previous cycle, the prediction is even more difficult. Age, regularity of periods and basal serum FSH are not reliable predictors of ovarian reserve. Measurement of day 3 serum oestradiol in addition to a normal FSH, the clomiphene challenge test and a sonographic measurement of the ovarian volume are claimed to be better predictors (Navot et al., 1989; Buyalos et al., 1997
; Lass et al., 1997
). Recent studies have shown that inhibin B concentrations may reflect ovarian function, but an absolute cut-off point has not yet been found (Hall et al., 1999
; Peñarrubia et al., 2000
).
The effect of increasing age and higher rank of cycle are obviously closely related. The current study found an increased total dose of FSH in higher rank cycles after salpingectomy while the number of retrieved oocytes was not significantly affected. This result is in agreement with a previous report on the FSH dosage effect on the ovarian response (Out et al., 2000). Their data suggested that the linear relationship between the dose of FSH and the ovarian response disappears with age (>33 years).
From the current results it cannot be concluded that patients with a low ovarian reserve are at greater risk of suffering from poor response after salpingectomy. However, theoretically it seems important to be very careful not to damage the vascular and nervous supply when performing a salpingectomy. In our opinion, a laparoscopic salpingectomy should be performed with cautious use of electrocautery, no unnecessary excision of the mesosalpinx but resection very close to the actual tube to avoid damage to the medial tubal artery and rather leave a portion of an adherent tube on the ovary than to perform an unnecessarily radical salpingectomy. The risk of dehiscence in the uterine wall and subsequent protrusion of the fetus has been described, suggesting a recommendation of resection not too close to the uterus (Inovay et al., 1999).
In conclusion, a prophylactic laparoscopic salpingectomy prior to IVF in patients with hydrosalpinges can be performed without risk of impairing the ovarian function.
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Notes |
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References |
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Submitted on November 3, 2000; accepted on March 7, 2001.