1 Ultrasound Unit in Obstetrics and Gynecology, Lis Maternity Hospital, Tel-Aviv Sourasky Medical Center, Tel-Aviv 64239, 2 Sara Racine IVF Unit, Lis Maternity Hospital, Tel-Aviv Sourasky Medical Center, Tel-Aviv 64239 and 3 Department of Biomedical Engineering, Faculty of Engineering, Tel-Aviv University, Tel-Aviv 69978, Israel
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Abstract |
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Key words: hydrosalpinx/pressure/reflux/simulation/uterine contractions
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Introduction |
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The hypothesis of the current study is that accumulation of tubal fluid in the Fallopian tube of a patient with hydrosalpinx increases tubal pressure and thereby induces a pressure gradient between the uterotubal junction and the uterine os. This pressure is in a direction opposite to cervix-to-fundus myometrial contractions which normally induce intrauterine peristaltic fluid motions that push the embryo to a fundal implantation site (Fanchin et al., 1998; Ijland et al., 1999
). This adverse pressure gradient may induce fluid reflux (Shapiro et al., 1969
) and create a mechanical obstacle to pre-implantation embryo motion towards the site of implantation in patients with hydrosalpinx.
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Materials and methods |
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In-vivo uterine motility
Patients
Five patients with hydrosalpinx (mean age 29.6 years, range 2635) on days 1017 of their menstrual cycle participated in the study. The hydrosalpinx was diagnosed and documented by hysterosalpingography, laparoscopy, and ultrasonography. Four patients had unilateral hydrosalpinx and one had bilateral hydrosalpinx. In this study only patients without fluid accumulation in the uterine cavity were included. The findings of this group were compared with a group of 25 healthy women who were evaluated in an earlier study (Eytan et al., 2001).
Data acquisition
TVUS images of sagittal cross-sections of a non-pregnant uterus were recorded with a digital ultrasound system (Sonoline Elegra, Siemens, Seattle, WA, USA). The sagittal cross-section near the fundus revealed a length of 34 cm from the fundus towards the cervix (Figure 1a). The images were recorded for 5 min while the patient was lying in a supine position and with the operator holding the probe steady. The images were digitized 1 s apart. The diameter of the Fallopian tube with the hydrosalpinx and the size of the follicles were measured prior to the recording.
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Data analysis
The boundaries of the intrauterine cavity in the sagittal cross-section were analysed by a custom-designed edge-detecting image processing technique (Eytan et al., 1999,2001
). The analysis was performed only in the region containing the uterine cavity, where the borders of the uterine cavity were detected in each image (Figure 1b
). The borders of the uterine cavity appeared as a narrow channel which changed over time due to myometrial motility. In order to analyse the characteristics of uterine peristalsis, we processed the geometry of the uterine cavity from all the images to evaluate the time variation of the width of the uterine cavity at fixed distances from the fundus.
The dynamic parameters of uterine activity were analysed from the time variations of the width (Figure 2). The geometry of the passive intrauterine cavity (i.e. absence of contractions) in the sagittal cross-section was computed by an arithmetic average of the time variations of the width of the uterine cavity at each fixed distance from the fundus. The amplitude was defined by the difference between the peaks and the passive width. The frequency of uterine wall motility at fixed distances from the fundus was derived by means of a fast Fourier transform.
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Results |
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Discussion |
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During myometrial contraction, the geometry of the uterine cavity changes and induces intrauterine flow. This flow may be visualized in the TVUS recordings of the sagittal cross-section of healthy women by the movements of fluid boluses. The movement of a fluid bolus was barely observable in the TVUS recording of patients with hydrosalpinx, although the uterine dynamics existed. These results mean that the absence of changes in spatial distribution of the echogenic fluid does not necessarily imply that uterine peristalsis is absent. The computational model demonstrates that visualization of a stationary fluid bolus is feasible under peristaltic contractions. It does not imply an impaired peristaltic motion, but rather the presence of adverse pressure. Hence, the paucity of bolus motion in patients with hydrosalpinx could be explained by the presence of adverse pressure having been applied on the uterine cavity.
It may be assumed that the baseline pressure within the uterine cavity and within the Fallopian tubes of healthy women is fairly constant, and that no flow is present in the absence of uterine or oviductal peristaltic activity, thus, P1 = P2 = P3 = P4 (Figure 3b). In this case, the intrauterine fluid flow is visible in a TVUS recording, and embryos would be pushed toward the site of implantation at the fundal area when they are transferred into the uterine cavity by IVF.
We postulated that in both unilateral and bilateral hydrosalpinx the pressure in the Fallopian tube (P3 and/or P4) is larger than the intrauterine pressure (P1 = P2). For example, in unilateral hydrosalpinx P1 = P2 = P3 < P4. This adverse pressure is in the opposite direction to that of the peristaltic pumping and may cause reflux (Figure 5,b and c). Thus, the boluses of fluid containing the embryos that are transferred into the uterus by an IVF procedure will not be conveyed toward the fundus in the direction of contractions, but will instead be pushed toward the cervix and implantation will not occur. The calculated values of the adverse pressure which hold the bolus in place (34 mmHg) should be higher within the uterus since the embryo has weight and volume. Nevertheless, the calculated adverse pressure is of the order of the pressure found in the uterine cavity (525 mmHg) during the proliferative and secretory phases (Hendricks, 1966
).
The hypothesis that hydrosalpinx induces internal pressure within the Fallopian tube and thus affects the normal pressure within the uterus can explain the reported observations in the literature. The reflux phenomenon would satisfactorily explain the associated reduced implantation rate (Andersen et al., 1994; Strandell et al., 1994
; Fleming and Hull, 1996
; Katz et al., 1996
; Sharara et al., 1996
; Wainer et al., 1997
; De Wit et al., 1998
; Strandell et al., 1999
) since the embryos would be pushed towards the cervix. The increasing size and extent (unilateral or bilateral) of hydrosalpinx are inversely correlated to the implantation rate (Wainer et al., 1997
; De Wit et al., 1998
; Nackley and Muasher, 1998
): we contend that they probably increase the adverse pressure gradient and thereby increase the refluxed volume of the intrauterine fluid. In cases where the adverse pressure exceeds the pressure created by the uterine peristaltic pump, peristaltic pumping is not effective (Eytan and Elad, 1999
). This finding may explain the direction of the flow of hydrosalpinx fluid from the Fallopian tube to the uterus and the accumulation of fluid within the uterine cavity during ovarian stimulation and hydrorrhea (Andersen et al., 1996
; Sharara and McClamrock, 1997
; Sawin, 1998
; Strandell et al., 1998
; Sharara, 1999
).
The mathematical model used in the current study illustrates that deletion of the adverse pressure removes reflux. Thus, it would be reasonable that the performance of salpingectomy in patients with bilateral hydrosalpinx yielded double the implantation rates of those patients who had no surgical intervention (Strandell et al., 1999). Temporary removal of the pressure by surgical fluid drainage prior to IVF was only slightly beneficial to implantation (Sowter et al., 1997
), probably due to the re-accumulation of the fluid since the pathology remained unchanged. The mechanical effects of hydrosalpinx on implantation warrant further investigation to refine our understanding of them and thus contribute valuable lines of evidence for both resolving the controversial issue of whether to surgically remove Fallopian tubes with hydrosalpinx and for providing new directions in enhancing IVF/embryo transfer pregnancy rates.
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Acknowledgements |
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Notes |
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References |
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Andersen, A.N., Lindhard, A., Loft, A. et al. (1996) The infertile with hydrosalpinges-IVF with or without salpingectomy? Hum. Reprod., 11, 20812084.[ISI][Medline]
Bredkjaer, H.E., Zeibe, S., Hamid, B. et al. (1999) Delivery rates after in-vitro fertilization following bilateral salpingectomy due to hydrosalpinges: a case control study. Hum. Reprod., 14, 101105.
De Wit, W., Gowrising, C.J., Kuik, D.J. et al. (1998) Only hydrosalpines visible on ultrasound are associated with reduced implantation and pregnancy rates after in-vitro fertilization. Hum. Reprod., 13, 16961701.[Abstract]
Dechaud, H, Daures, J.P., Arnal, F. et al. (1998) Does previous salpingectomy improve implantation and pregnancy rates in patients with severe tubal factor infertility who are undergoing in-vitro fertilization? A pilot prospective randomized study. Fertil. Steril., 69, 10201025.[ISI][Medline]
Eytan, O. and Elad, D. (1999) Analysis of intra-uterine fluid motion induced by uterine contractions. Bull. Math. Biol., 61, 221238.[ISI]
Eytan, O., Jaffa, A.J., Har-Toov, J. et al. (1999) Dynamics of the intrauterine fluid-wall interface. Ann. Biomed. Eng., 27, 372379.[ISI][Medline]
Eytan, O., Halevi, I., Har-Toov, J. et al. (2001) Characteristics of uterine peristalsis in spontaneous and induced cycles. Fertil. Steril., 76, 337341.[ISI][Medline]
Fanchin, R., Righini, C., Olivennes, F. et al. (1998) Uterine contractions at the time of embryo transfer alter pregnancy rates after in-vitro fertilization. Hum. Reprod., 13, 19681974.[Abstract]
Fleming, C. and Hull, M.G.R. (1996) Impaired implantation after in-vitro fertilization treatment associated with hydrosalpinx. Br. J. Obstet. Gynaecol., 103, 268272.[ISI][Medline]
Granot, I., Dekel, N., Segal, I. et al. (1998) Is hydrosalpinx fluid cytotoxic? Hum. Reprod., 13, 16201624.[Abstract]
Harper, M.J.K. (1994) Gamete and zygote transport. In Knobile, E. and Neil, J.D. (eds), The Physiology of Reproduction. Raven Press, New York, pp. 123187.
Hendricks, C.H. (1966) Inherent motility patterns and response characteristics of the non-pregnant human uterus. Am. J. Obstet. Gynecol., 96, 824843.[ISI][Medline]
Ijland, M.M., Hoogland, H.J., Dunselman, A.J. et al. (1999) Endometrial wave direction switch and the outcome of in-vitro fertilization. Fertil. Steril., 71, 476481.[ISI][Medline]
Kassabji, M., Sims, J.A., Butler, L. and Muasher, S.J. (1994) Reduced pregnancy outcome in patients with unilateral or bilateral hydrosalpinx after in-vitro fertilization. Eur. J. Obstet. Gynecol. Reprod. Biol., 56, 129132.[ISI][Medline]
Katz, E., Akman, M.A., Damewood, M.D. and Garcia, J.E. (1996) Deleterious effect of the presence of hydrosalpinx on implantation and pregnancy rates with in-vitro fertilization. Fertil. Steril., 66, 122125.[ISI][Medline]
Murray, D.L., Sagoskin, A.W., Widra, E.A. and Levy, M.J. (1998) The adverse effect of hydrosalpinges on in-vitro fertilization pregnancy rates and the benefit of surgical correction. Fertil. Steril., 69, 4145.[ISI][Medline]
Nackley, A.C. and Muasher, S.J. (1998) The significance of hydrosalpinx in in-vitro fertilization. Fertil. Steril., 69, 373384.[ISI][Medline]
Pozrikidis, C. (1987) A study of peristaltic flow. J. Fluid Mech., 180, 515527.[ISI]
Sawin, S.W. (1998) The management of hydrosalpinx before in-vitro fertilization and embryo transfer. Curr. Opin. Obstet. Gynecol., 10, 233238.[ISI][Medline]
Sawin, S.W., deMola, J.R.L., Monzon-Bordonaba, F. et al. (1997) Hydrosalpinx fluid enhances human trophoblast viability and function in vitro: implication for embryonic implantation in assisted reproduction. Fertil. Steril., 68, 6571.[ISI][Medline]
Shapiro, A.H., Jaffrin, M.Y. and Weinberg, S.L. (1969) Peristaltic pumping with long wavelength at low Reynolds number. J. Fluid Mech., 37, 799825.[ISI]
Sharara, F.I. (1999) What effect does hydrosalpinx have on assisted reproduction? The role of hydrosalpinx in IVF: simply mechanical? Hum. Reprod., 14, 577578.
Sharara, F.I. and McClamrock, H.D. (1997) Endometrial fluid collection in women with hydrosalpinx after human chorionic gonadotrophin administration: a report of two cases and implications for management. Hum. Reprod., 12, 28162819.[Abstract]
Sharara, F.I., Scott, R.T.Jr, Marut, E.L. and Queenan, J.T.Jr. (1996) In-vitro fertilization outcome in women with hydrosalpinx. Hum. Reprod., 11, 526530.[Abstract]
Sowter, M.C., Akande, V.A., Williams, J.A.C. and Hull, M.G.R. (1997) Is the outcome of in-vitro fertilization and embryo transfer treatment improved by spontaneous or surgical drainage of a hydrosalpinx? Hum. Reprod., 12, 21472150.[Abstract]
Spandorfer, S.D., Liu, H., Neuer, A. et al. (1999) The embryo toxicity of hydrosalpinx fluid is only apparent at high concentrations: an in-vitro model that simulates in-vivo events. Fertil. Steril., 71, 619626.[ISI][Medline]
Strandell, A., Waldenstorm, U., Nilsson, L. and Hamberger, L. (1994) Hydrosalpinx reduces in-vitro fertilization/embryo transfer pregnancy rates. Hum. Reprod., 5, 861863.
Strandell, A., Sjogren, A., Bentin-ley, U. et al. (1998) Hydrosalpinx fluid does not adversely affect the normal development of human embryos and implantation in vitro. Hum. Reprod., 13, 29212925.
Strandell, A., Lindhard, A., Waldenstrom, U. et al. (1999) Hydrosalpinx and IVF outcome: a prospective, randomized multicentre trial in Scandinavia on salpingectomy prior to IVF. Hum. Reprod., 14, 27622769.
Wainer, R.W., Martin, C., Camus, E. et al. (1997) Does hydrosalpinx reduce the pregnancy rate after in-vitro fertilization? Fertil. Steril., 68, 10221026.[ISI][Medline]
Submitted on April 26, 2001; accepted on September 6, 2001.