Department of Obstetrics & Gynaecology, The University of Hong Kong, 102 Pokfulam Road, Hong Kong SAR, China
1 To whom correspondence should be addressed. e-mail: cwcchan{at}graduate.hku.hk
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Abstract |
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Key words: antral follicle count/ovarian function/salpingectomy/three-dimensional power Doppler ultrasonography
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Introduction |
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Various studies have attempted to evaluate the impact of salpingectomy on ovarian function. All these studies used the ovarian response after ovarian stimulation for IVF as the study model (Verhulst et al., 1994; Lass et al., 1998
; Dar et al., 2000
; Strandell et al., 2001
; Tal et al., 2002
), but the results were not consistent. Some of these operations were performed via laparoscopy (Dar et al., 2000
; Strandell et al., 2001
), others were either not specified (Verhulst et al., 1994
; Lass et al., 1998
) or mixed (Tal et al., 2002
). Furthermore, additional procedures including either contralateral salpingectomy or tubal cauterization were performed in some (Dar et al., 2000
; Strandell et al., 2001
) or all patients (Verhulst et al., 1994
); and some had pelvic adhesions or hydrosalpinx in the contralateral tube (Tal et al., 2002
). With the exception of the studies by Lass et al. (1998
) and Dar et al. (2000
) who compared the ovarian response of the operated and the non-operated sides after unilateral salpingectomy, all other studies reported the overall ovarian response in patients with unilateral or bilateral salpingectomy, or before and after salpingectomy.
Ovarian volume (Syrop et al., 1995; Lass et al., 1997
; Sharara et al., 1999
; Syrop et al., 1999
), antral follicle count (Tomás et al., 1997
; Chang et al., 1998
; Sharara et al., 1999
; Ng et al., 2000
) and ovarian stromal blood flow (Zaidi et al., 1996
; Bassil et al., 1997
; Engmann et al., 1999
; Kupesic and Kurjak, 2002
; Kupesic et al., 2003
) have been extensively used to predict ovarian response prior to stimulation for IVF. In particular, three-dimensional (3D) ultrasound power Doppler imaging has been shown to be well correlated with ovarian response and subsequent IVF outcome (Kupesic and Kurjak, 2002
). Since ovarian function cannot be measured directly, ovarian response to gonadotrophin stimulation can be considered as a surrogate measurement for ovarian function. In this study, these markers were used to assess the ovarian function. The objectives of the study were to compare ovarian function between the operated and the non-operated sides in the same individual who had unilateral salpingectomy for ectopic pregnancy through laparoscopy or laparotomy. The hypothesis was that ovarian function was impaired after salpingectomy.
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Materials and methods |
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Patients were asked to attend the clinic on the second day of the menstrual cycle, at around 08:00 to 10:00. All 3D ultrasound scan examinations were performed by C.C.W.C. using Voluson 730® (Kretz, Austria), after the patients had emptied the bladder. The assessor was blinded to the treatment the patients received. The antral follicle count was obtained using the same machine in the two-dimensional (2D) mode during the ultrasound examinations. Both ovaries were scanned with the power Doppler mode. The setting condition for this study was: Frequency: Mid, Dynamic set: 2; Balance: G>140; Smooth: 5/5; Ensemble: 12; Line Density: 7; power Doppler Map: 5; and the setting condition for the sub-power Doppler mode was: Gain: 6.0; Balance: 140; Quality: normal; Wall Motion Filter: low1; Velocity range: 0.9 kHz. The 3D ultrasound images were stored for later analysis by C.C.W.C., who was blinded as to what operation the patient had had and which side was operated on.
The built-in Vocal® (virtual organ computer-aided analysis) Imaging Program for the 3D power Doppler histogram analysis was used for analysis with computer algorithms to form indices of blood flow and vascularization and the ovarian volume. The vascularization index (VI) indicated the proportion of the volume showing a flow signal in the total volume of the ovary. The flow index (FI) was an average of the intensity of flow signal inside the ovary. The vascularization flow index (VFI) was a combination of the presence of vessel and the amount of flow made by multiplying the FI and VI (Pairleitner et al., 1999). During the analysis and calculation, the manual mode of the Vocal® Contour Editor was used to cover the whole 3D volume of the ovary with a 15° rotation step. Hence, 12 contour planes were analysed for each ovary to cover 180°. A completely reconstituted 3D view of the ovary is shown in Figure 1A. The VI, FI and VFI of this ovary are shown in the grey box in Figure 1B.
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Statistical analysis
Distributions of the variables were given as median (interquartile range). Continuous variables were compared using MannWhitney U-test, whereas categorical variables were compared using 2-test. In this study, ovarian function was assessed by the antral follicle count, the ovarian volume and the ovarian stromal blood flow indices including VI, FI and VFI. These parameters of the operated and the non-operated sides were compared using Wilson signed ranks test. Possible confounding factors included age of the patient, smoking and the interval from operation to ultrasound examination. P < 0.05 was considered significant. For the purpose of sample size calculation, FI was used as the primary outcome parameter. The FI of 64 fertile subjects was 28.26 ± 7.42 (mean ± SD) (unpublished data). The sample size of 14 patients should be able to detect a 20% reduction in FI of the operated side after salpingectomy as compared to the non-operated side with a power of 80% and P = 0.05. This reduction in FI was arbitrarily chosen and its clinical significance was undetermined.
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Results |
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There were no significant differences in the antral follicle count, the ovarian volume, and 3D ovarian stromal indices (VI, FI and VFI) between the operated and the non-operated sides in the whole group (data not shown) and in the laparotomy group (Table I). However, when the analysis was restricted to those in the laparoscopy group, the antral follicle count and 3D ovarian stromal indices of the operated side were significantly reduced when compared to the non-operated side. The ovarian volume was not affected (Table II).
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Discussion |
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In this study, we evaluated ovarian stromal blood flow using 3D power Doppler ultrasonography in patients who had had unilateral salpingectomy for 3 months. Two other markers of ovarian function, the antral follicle count and the ovarian volume, were evaluated at the same time. There was no difference in all these markers on the ipsilateral side of salpingectomy when compared to the non-operated side. However, when only those with laparoscopic salpingectomy were analysed, the antral follicle count and the ovarian blood flow were significantly reduced. Our findings were in fact similar to those of Sumiala et al. (1995
). If the mechanism of reduced ovarian blood flow after sterilization is due to the interruption of blood supply, the same mechanism applies in salpingectomy which involves more extensive surgery than sterilization. Furthermore, the decreased antral follicle count was further evidence that vascular supply was jeopardized. In fact, Lass et al. (1998
) reported a reduction in the ovarian response after gonadotrophin stimulation during IVF treatment on the side with salpingectomy performed while the ovarian volume remained unchanged. Ovarian volume is generally viewed as an insensitive marker in this respect, as it may require years for such a difference to be clinically evident.
It is interesting to find that such a reduction in antral follicle count and ovarian blood flow were not seen in those in the laparotomy group. We are cautious about the difference between the laparotomy and laparoscopy groups, which may be related to uneven distribution of patients as this was not a randomized study. However, it is possible that during open surgery, it was easy to place the surgical clamp very close to the mesenteric border of the affected Fallopian tube and hence limit any damage to blood vessels in the mesosalpinx. In contrast, during laparoscopic salpingectomy, bipolar diathermy was the method employed in cauterizing the mesosalpinx in our hospital. This procedure was sometimes made difficult by the angle of access. Moreover, the heat damage could be more extensive with diathermy as the depth of damage was not limited to the excision site. It is therefore imperative that meticulous surgical skills be employed and surgical excision of the Fallopian tube be performed as close to the tube as possible. Since the laparotomy group had significantly longer interval between the date of the operation and the ultrasound scan assessment than the laparoscopy group, the differences in these ovarian markers could be accounted for in terms of this different interval rather than the mode of surgery. If the impaired ovarian blood flow was related to a disruption in blood supply, it was possible that the effect might be short term only as no such reduction in ovarian blood flow could be observed in the laparotomy group after a longer gap between operation and the assessment. Further long-term follow-up studies will be necessary to address this issue.
Ovarian response to gonadotrophin during IVF treatment is commonly used to evaluate ovarian function after salpingectomy. In two retrospective case-controlled studies (Verhulst et al., 1994; Tal et al., 2002
), no difference in ovarian response after gonadotrophin stimulation during IVF treatment could be found between patients with and without salpingectomy. In order to limit bias introduced by the control group, Dar et al. (2000
) and Strandell et al. (2001
) used the patients themselves as the controls, and compared the ovarian response to gonadotrophin during IVF treatment before and after salpingectomy. There was again no difference demonstrated. However, Lass et al. (1998
) showed a reduction in the number of follicles >10 mm in mean diameter on the day of the hCG administration and the number of oocytes recovered from the operated side compared with the non-operated side. When the ovarian response was compared between patients with and without salpingectomy, the difference was not evident.
These controversial findings probably indicated that the difference in ovarian response after gonadotrophin stimulation was modest, even if it was present. Such observations did not contradict with our findings in this study because the models employed were different. We believe that if ovarian function is affected by salpingectomy through disruption of arterial blood supply, the ovarian blood flow is the first parameter to be affected. The use of 3D power Doppler ultrasonography is therefore the best method to study such a subtle and early change. The antral follicle count may also be affected early by disrupted blood supply to the ovaries. Ovarian response after gonadotrophin stimulation, like ovarian volume, is a late phenomenon and can only be shown years after salpingectomy. Any subtle reduction in ovarian blood flow and antral follicle count may be overcome by the hyperstimulation induced by high dose gonadotrophin given during IVF treatment. This postulation helps to explain the observation that ovarian response was not altered even after bilateral salpingectomy (Strandell et al., 2001). However, the long-term implication of impaired ovarian function cannot be overlooked. Not addressed in this study is the possibility of early menopause as a result of these changes especially if the procedure is performed on both sides. Furthermore, the effect on ovarian function may differ with the initial indication for salpingectomy. While these parameters were impaired after laparoscopic salpingectomy for ectopic pregnancy, such observations might not present after laparoscopic salpingectomy for hydrosalpinx.
In conclusion, we have demonstrated impaired ovarian blood flow and reduced antral follicle count on the operated side shortly after laparoscopic unilateral salpingectomy. This may imply an adverse sub-clinical short-term effect on the ovary after salpingectomy. Whether such an effect persists in the long term will need further evaluation. However, during the operation, care should be undertaken not to disrupt the blood vessels in the mesosalpinx as far as possible.
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Acknowledgements |
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References |
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Submitted on April 1, 2003; resubmitted on May 13, 2003; accepted on June 26, 2003.