1 Department of Obstetrics and Gynecology, School of Medicine and 2 Department of Radiology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran and 3 Department of Obstetrics and Gynecology, evang. Diakonie teaching hospital, Göttingen University, Bremen, Germany
4 To whom correspondence should be addressed at: PO Box 713451657, Shiraz, Iran. E.mail: parsame{at}sums.ac.ir
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Abstract |
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Key words: blood flow/cauterization/Doppler haemodynamics/polycystic ovary
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Introduction |
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Although a mechanism explaining the beneficial effects of LOD on PCOS has not yet been demonstrated (Al-Took, 1999), one possible explanation is that LOD reduces androgen production, which inhibits normal follicular development (Tulandi et al., 1997
). The ovarian stromal blood flow abnormalities in PCOS have been previously described (Battaglia et al., 1995
; Aleem et al., 1996
; Zaidi et al., 1998
; Vralacnik-Bokal and Meden-Vrtovec, 1998
), the possible effects of medical induction of ovulation on ovarian blood flow (Agrawal, 1998
; Zaidi et al., 1998
; Zaidi, 2000
), effects of LOD on ovarian steroidogenesis (Greenblatt and Casper, 1987
; Cohen, 1996
; Felemban et al., 2000
) and on ovarian stromal echogenecity (Al-Took et al., 1999
) in CC-resistant PCOS have been also described. The influence of LOD on the ovarian stromal blood flow has not as yet been studied. Evaluation of ovarian stromal blood flow before and after LOD may be considered a way to study the effects of this therapeutic intervention, or the mechanism by which the ovary may respond. The aims of this study were (i) to compare the ovarian stromal blood flow before and after LOD and (ii) to evaluate the value of these parameters in predicting the outcome of treatment.
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Materials and methods |
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After assessment of the pelvic structures and tubal patency, an insulated needle connected to a unipolar electrocautery unit was inserted through the operative channel of the optic. Eight to 10 cautery points 34 mm in diameter were created in each ovary with a current of 4 mA applied through the laparoscopic-insulated needle. Hormonal assay and blood flow assessment were performed 2 days after the operation and repeated 610 weeks thereafter (in the early follicular phase of the first post-operative menstruation). Folliculometry was performed on days 1517 and serum progesterone concentration was measured on days 1921 (mid-luteal phase) of the same cycle. This cycle was monitored to assess hormonal profile, ovarian stromal Doppler parameters and finally to detect ovulation. Ovulation was considered when the mean diameter of the leading follicle was ≥15 mm and serum progesterone level ≥5 ng/ml. A single radiologist performed all Doppler sonographies. Pulsatility index (PI), resistance index (RI), and peak systolic velocity (PSV) were measured in each scan. A colour Doppler ultrasound machine (Aloka Model SSD-1700) with a 5 MHz transvaginal transducer was used. Stromal blood flow of both ovaries was evaluated by colour and power Doppler ultrasonography. By means of colour and power Doppler flow imaging, colour signals were searched in the ovarian stroma away from the ovarian surface or near the wall of a follicle. By placing the colour Doppler gate over the ovarian stroma, areas of maximum colour intensity, representing the greatest Doppler frequency shifts, could be visualized, then selected for pulsed Doppler examination. Peak systolic blood flow velocity wave-forms were thus detected, and optimal flow velocity wave-forms were selected for analysis after angle correction. Then PI and RI were calculated in each selected Doppler wave. Both right and left ovaries were observed and analysed in each patient, revealing no statistical significance in Doppler parameters of ovarian stromal arteries. Therefore, the mean value for all ovarian blood flow parameters was calculated and used in the statistical analysis. The intra-ovarian blood flow of each ovary was assessed by studying blood vessels in the ovarian stroma (small arteries in the ovarian stroma not close to the surface of the ovary or near the wall of a follicle).
Statistical methods
The relationship between ovarian stromal blood flow indices and hormonal changes after LOD was examined by the Pearson correlation test. Paired t-test was used to compare mean values. In order to determine the correlation between Doppler indices and hormonal changes including ovulation, we used t-test and Pearson correla tion test. The data were first tested for normality using the KolmogrovSmirnov test. P < 0.05 was considered statistically significant.
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Results |
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Discussion |
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The pathophysiology of abnormal ovarian blood flow in PCOS is not clearly understood. One possible explanation is that serum estradiol (E2) might have a role as the moderator of uterine and ovarian vascularity (Steer et al., 1990; de Ziegler et al., 1991
; Zaidi, 2000
). Greenblatt and Casper (1987
) showed a fall in E2 level starting the first day after LOD, reaching the minimum level by day 4 after operation and beginning to rise thereafter. Thus the hypothesis of any correlation between serum E2 levels and ovarian blood flow changes remains elusive. On the other hand, a significant decrease in vascular impedance to blood flow in the ovarian artery (Deutinger et al., 1989
), and in vessels around the follicles, in correlation with an increase in the number of follicles and serum E2 concentration (Weiner et al., 1993
), was observed after ovarian stimulation with gonadotrophins. As we demonstrated, ovarian blood flow decreased starting on day 2 following the operation and remained low for at least 2 months. Considering these observations and the data reported by Schurz et al. (1993
), it seems that some factors other than E2 could be the cause of increased ovarian stromal vascularity in PCOS. Dolz et al. (1999
) suggested that different mechanisms may be responsible for the haemodynamic anomalies that are uniformly observed in patients who do not undergo the type of luteal conversion occurring in normally cycling women. They suggested that the abnormal haemodynamic patterns may be due to an abnormal timing of LH-dependent prostaglandin release. Bourne and co-workers (1991
) described a direct correlation between LH levels, prostaglandin activity and blood flow changes in the ovary. An alteration in the finely tuned timing for release of specific prostaglandins is likely to interfere with ovulation in humans. Engmann et al. (1999b
) showed that ovarian stromal artery blood flow velocity declines after short term (23 weeks) treatment with GnRH agonist and increases significantly on the day of hCG administration. The decline in ovarian artery blood flow velocity after GnRH agonist therapy is unlikely to be due to a hypoestrogenic effect.
There is evidence that GnRH agonist therapy has a direct inhibitory effect on granulosa and luteal cell function and may play an important role in processes such as follicular atresia and luteal regression (Sharpe et al., 1982); therefore the ovaries are quiescent after GnRH agonist therapy. Primordial or smaller preantral follicles do not have any special vascular supply of their own and derive their blood supply from stromal blood vessels (Findaly, 1986
). Subsequent growth of primary follicles leads to development of a vascular network with increased follicular blood flow. Thus the stromal blood flow velocity in an inactive or quiescent ovary may reflect the baseline blood flow perfusion. Laparoscopic ovarian diathermy may result in the reduction in the number of small and intermediate follicles that usually seen in PCOS, it has the same effect on ovarian stromal tissue (Naether, 1993
; Liguri et al., 1996
). Regarding these effects and the above-mentioned mechanism by which ovarian stromal blood flow declined after GnRH agonist therapy (Findaly, 1986
), we can hypothesize that the decline in ovarian stromal blood flow velocity could be the result of the direct electrical and/or thermal effects of LOD. Considering the increased ovarian stromal blood flow velocity in PCOS (Battaglia et al., 1995
; Zaidi et al., 1995
) and its possible effects on ovarian steroidogenesis, there might be a possible beneficial effect of diminished ovarian stromal blood flow velocity on ovarian steroidogenesis in PCOS. Our data shed no light on these possibilities since we did not measure E2 or prostaglandins and no data regarding the direct effect of diminished ovarian stromal blood flow on ovarian steroidogenesis is available. In this study, we reported our preliminary findings regarding the effects of LOD on ovarian stromal blood flow. The results show that Doppler indices of ovarian stromal blood flow significantly changed after LOD and these changes are significantly correlated with hormonal changes and subsequent ovulation. Our results provide a potential new avenue for evaluation of ovarian stromal blood flow changes after LOD. These data also suggest that the measurement of ovarian stromal blood flow by colour Doppler may be of value in predicting the prognosis of PCOS related problems after LOD. However, we believe that further research on a larger sample size is needed to determine whether an interaction occurs between LOD, ovarian stromal blood flow and ovarian steroidogenesis.
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Acknowledgements |
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References |
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Submitted on December 5, 2002; accepted on February 21, 2003.