Long term safety of fluoroscopically guided selective salpingography and tubal catheterization

S. Papaioannou1,3, M. Afnan1, A. Coomarasamy1, B. Ola1, N. Hammadieh1, D.H. Temperton2, J.M. McHugo1 and K. Sharif1

1 Birmingham Women's Hospital, Metchley Park Road and 2 University Hospital Birmingham NHS Trust, Birmingham, UK


    Abstract
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 Abstract
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 Materials and methods
 Results
 Discussion
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BACKGROUND: The irradiation of the ovaries of reproductive age women during fluoroscopically guided selective salpingography and tubal catheterization has raised concern about the safety of the procedure. In addition to the risk of cancer induction, which exists with the irradiation of all tissues, with the gonads, the induction of hereditary disorders is possible. The objective of this study was to estimate these risks and present them in a clinically meaningful way. METHODS: Retrospective analysis was undertaken of 366 consecutive cases of selective salpingography and tubal catheterization performed at the Birmingham Women's Hospital, UK. The radiation doses of different types of procedure were compared with the background annual radiation dose. The risks of cancer and genetic disorders induction were calculated using conversion coefficients published by the International Commission on Radiological Protection. RESULTS: The radiation dose women were exposed to during selective salpingography and tubal catheterization under fluoroscopic guidance was a fraction of the background annual radiation dose. The excess lifetime risks of cancer and hereditary disorders were in the order of four to 13 and two to six per million procedures respectively. CONCLUSIONS: The long term risks of selective salpingography and tubal catheterization under fluoroscopic guidance are low.

Key words: infertility/proximal tubal obstruction/safety/selective salpingography/tubal catheterization


    Introduction
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Fluoroscopically guided selective salpingography and tubal catheterization (SS/TC) has raised concern about the risks associated with the irradiation of the ovaries. In addition to cancer induction, an inherent risk of the irradiation of any tissue, exposure of the gonads may also predispose to hereditary disorders in the offspring. Women undergoing these procedures are relatively young and actively trying to have children.

X-rays have been used to follow the course of contrast media injected in the uterine cavity for almost 90 years (Cary, 1914Go). Hysterosalpingography (HSG) is an established test of tubal patency and there are substantial data about the radiation dose delivered to the ovaries during this procedure (Shirley, 1971Go; Sheikh and Yussman, 1976Go; van der Weiden and van Zijl, 1989Go; Cregan et al., 1998Go). There is a paucity of such data in relation to SS/TC. As SS/TC involves longer screening times than HSG, radiation dose and safety information are important. Furthermore, discussion about radiation risks is usually fraught with terminology understandable only by radiology or physics experts. Quantification of such risks in a way meaningful to a wider professional audience is scarce.

The aim of this study was to present the risk of fatal cancer and the risk of hereditary disorders associated with SS/TC as cases per million procedures. The average annual background radiation dose was used as a reference radiation quantity for comparison.


    Materials and methods
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 Materials and methods
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Retrospective analysis of 366 consecutive SS/TC that were performed at the Birmingham Women's Hospital, UK, from April 1996 to December 1999 was undertaken. The patient's average age (± SD) was 32.5 (± 5.2) years. The different types (subsets) of SS/TC performed and their relative representation in this sample are shown in Table IGo.


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Table I. Types of SS/TC performed
 
The Fallopotorque® (Cook UK, Letchworth, Herts, UK) SS/TC catheter system was used. The fluoroscopic unit employed was the mobile Phillips Optimus BV29® (Phillips Corporation, Amsterdam, The Netherlands) with a C-arm system. The equipment utilizes `image capture' technology to obtain hard copies from stored digital images without the need for further patient exposure. The X-ray tube has a total beam filtration of 4 mm aluminium. Tube voltages of 70 kV (on average) were used. The radiation dose to the patient was recorded as the dose-area product (DAP) by a fitted calibrated meter (PTW, Freiburg, Germany). The DAP is a measure of the total energy imparted to the patient for the complete examination [units centiGray centimetre square (cGy cm2)].

The procedure was performed during the follicular phase of the cycle. The patient was placed on the radiology table in lithotomy. The vulvar region was cleaned with chlorexidine gluconate 0.05% sterile aqueous solution; the cervix was visualized with a Cusco's speculum and was then thoroughly cleaned with the same solution. After instillation of 2% Lignocaine gel (Instillagel Farco-Pharma, Cologne, Germany) into the cervical canal, a single-toothed tenaculum was applied at the 12 o'clock position of the cervix. The selective salpingography catheter was forwarded through the cervical canal and was advanced by tactile sensation to the tubal ostium. Its position was checked fluoroscopically and if satisfactory, dye was injected. If the obstruction was overcome the tubal contour was outlined with contrast. If it persisted a guidewire (roadrunner) was threaded through the inner cannula and was advanced towards the obstruction. A gentle push was applied to overcome it. The guidewire was then withdrawn and contrast medium was injected through the selective salpingography catheter to confirm patency. The process was repeated on the contralateral tube.

The National Radiological Protection Board (NRPB) of the UK has published conversion coefficients (Hart et al., 1994Go), relating DAP values to effective radiation doses [measured in millisievert (mSv)]. The median DAP of each SS/TC subset was converted to the median effective radiation dose using the urinary bladder anterior-posterior projection conversion coefficient (which for the settings described above is 0.346 mSv Gy-1 cm-2). Ovarian equivalent doses were calculated using software produced by the NRPB (NRPB, 1994a,b). The average annual background effective radiation dose (from all sources) to the UK population was chosen as a reference radiation quantity. This is 2.6 mSv (Hughes, 1999Go). The median effective doses of the SS/TC subsets were divided by this factor to calculate a relative risk increase factor. International Commission on Radiological Protection (ICRP) recommendations were used to calculate the excess lifetime fatal cancer risk and the excess risk of hereditary effects per million procedures from the calculated effective doses (ICRP, 1991Go). According to the ICRP the lifetime risk of fatal cancer due to radiation exposure is 5x10-2 Sv-1, while the total risk of hereditary effects is 1.3x10-2 Sv-1 gonadal dose.


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 Materials and methods
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The dose distributions for the SS/TC subsets were invariably skewed and included a few extreme high-dose outliers. These distributions are shown in the form of box-whisker plots in Figure 1Go.



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Figure 1. Box-whisker plots of radiation doses for the different SS/TC types. The top and the bottom of the each box represent the 75th and the 25th centile respectively, while the central bar represents the 50th centile of each distribution. SS = selective salpingography; TC = tubal catheterization.

 
The median DAP and the median effective dose for the different SS/TC subsets are shown in Table IIGo. Ovarian equivalent doses, relative risk increase factors as well as the excess lifetime risk of fatal cancer and the excess risk of hereditary effects per million procedures are also shown in Table IIGo.


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Table II. Median dose-area product (DAP) values, median effective doses, ovary equivalent doses, relative risk increase factors in relation to the average background radiation dose and excess risks of fatal cancer and hereditary disorders due to SS/TC
 
The median DAP for all the procedures was 77.5 cGy cm2 (range 5–399 cGy cm2).


    Discussion
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 Abstract
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 Materials and methods
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This study shows that the radiation dose that patients receive, even during the most complicated cases of SS/TC, is a fraction of the average background radiation dose, to which people (at least in the UK) are exposed to per annum. The excess risks of fatal cancer and hereditary disorders due to SS/TC are in the order of four to 13 and two to six per million procedures respectively. Therefore SS/TC can be regarded as a low risk intervention.

For the individual patient, risk depends on age. The risk for a given effective dose decreases with increasing age at exposure, since somatic effects, being delayed for many years or even decades, will have a reduced opportunity for expression following X-ray examinations in older women. Fertility decreases with advancing age while hereditary effects are of no consequence for patients beyond their reproductive years.

It should not be forgotten, though, that a threshold for cancer induction is unlikely to exist. Muller, who won the 1946 Medicine Nobel prize (for his discovery of the production of mutations by X-rays), stated, in relation to irradiation of the gonads, that there is `no dose so small as to give no mutations at all; each individual ionization and probably each activation of an atom carries its definite chance of producing a mutation' (Muller, 1954Go). Furthermore, radiation damage is cumulative without regard to time. The probability of cancer induction can be expected to increase as the initial number of modified cells increases, i.e. with increasing radiation dose. The malignancies induced by radiation with or without a contribution from other agents are indistinguishable from cancers due to other causes.

Lack of a safety threshold is a concept that should apply to the hereditary effects of radiation as well. Studies on animals and plants have suggested that these can range from the undetectable to gross malformations (ICRP, 1991Go). They are believed to include both dominant and recessive conditions as well as multifactorial disorders, caused by the interaction of genetic and environmental factors. The risk estimates reported here include all of the above and are also weighted for years of life lost if harm occurs.

The ICRP accepts that its assessment of risk is based on studies (e.g. about the effects of the atomic bombs of Hiroshima and Nagasaki, accidents in the nuclear industry, effects on early radiologists), the conclusions of which are not directly transferable to low dose medical exposure settings (ICRP, 1991Go). Knowledge of specific organ sensitivities to the somatic or genetic effects of radiation is far from precise. Considerable interpretation of data was necessary for these conversion coefficients to be reached. However they are the best estimates of risk available.

The concept of effective dose was introduced to take account of the distribution of radiation amongst organs with different relative sensitivity to radiation induced somatic or genetic effects (ICRP, 1991Go). It is a measure of harm (or health detriment) rather than true dose and is more closely associated with radiation risks. Effective doses are unlikely to be calculated routinely in the X-ray room. The DAP on the other hand is a measurable quantity which is closely related to the effective dose (Hart et al., 1994Go). Our study, in addition to reporting specific risk estimates, suggests a system by which departments with an interest in SS/TC, or indeed any radiological investigation, can obtain figures closely related to potential harm to their patients, which would be useful in counselling them as well as in communicating with others.

Two previous papers (Hedgpeth et al., 1991Go; Karande et al., 1997Go) have discussed radiation doses in relation to SS/TC. These used a technique different from that used in the current study and results were expressed in units of radiation only.

The need to minimize the radiation dose that women are exposed to during SS/TC remains. The procedure does not have a place in the presence of distal tubal disease. The screening time should be kept to a minimum by obtaining pictures that would add to the diagnostic information provided by the procedure. Radiographs that show the guidewire in the recanalized tube add little information about the Fallopian tube. If adjustments to the radiographic parameters are to be made, it is preferable to increase the X-ray tube voltage rather than the tube current. Effective co-ordination of staff involved can reduce radiation doses. Hysteroscopic (Das et al., 1995Go) or ultrasound (Hughes et al., 1988Go) guidance have been used as alternatives.

In conclusion, radiation risks associated with SS/TC are low. The margin of safety is adequately wide to allow for repeat procedures in women with infertility if indicated. Nevertheless one should recognize that no radiation dose, however small, can be regarded as completely safe and employ good clinical judgement as well as good radiological technique to minimize radiation doses and the consequent risks to which these women are exposed.


    Notes
 
3 To whom correspondence should be addressed at: The Assisted Conception Unit, Birmingham Women's Hospital, Metchley Park Road, Birmingham B15 2TG, UK. E-mail: Spyrospap{at}talk21.com Back

Submitted on June 6, 2001; resubmitted on July 23, 2001


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Cary, W.H. (1914) Note on determination of patency of fallopian tubes by the use of Collargol and x-ray shadow. Am. J. Obstet. Dis. Women Child., 69, 462.

Cregan, A.C., Peach, D. and McHugo, J.M. (1998) Patient dosimetry in hysterosalpingography: a comparative study. Brit. J. Radiol., 71, 1058–1061.[Abstract/Free Full Text]

Das, K., Nagel, T.C. and Malo, J.W. (1995) Hysteroscopic cannulation for proximal tubal obstruction: a change for the better? Fertil. Steril., 63, 1009–1015.[ISI][Medline]

Hart, D., Jones, D.G. and Wall, B.F. (1994) Estimation of effective dose in diagnostic radiology from entrance surface dose and dose-area product measurements. HMSO, London, NRPB-R262.

Hedgpeth, P.L., Thurmond, A.S., Fry, R., Schmidgall, J.R. and Rösch, J. (1991) Radiographic Fallopian tube recanalization: absorbed ovarian dose. Radiology, 180, 121–122.[Abstract]

Hughes, E.G., Shekelton, P., Leonie, M. and Leeton, J. (1988) Ultrasound-guided fallopian tube catheterization per vaginum: a feasibility study with the use of laparoscopic control. Fertil. Steril., 50, 986–989.[ISI][Medline]

Hughes, J.S. (1999) Ionising radiation exposure of the UK population: 1999. HMSO, London, NRPB-R311.

ICRP (1991) Recommendations of the International Commission on Radiological Protection. Pergamon Press, Oxford, ICRP publication 60.

Karande, V.C., Pratt, D.E., Balin, M.S., Levrant, S.G., Morris, R.S. and Gleicher, N. (1997) What is the radiation exposure to patients during a gynecoradiologic procedure? Fertil. Steril., 67, 401–403.[ISI][Medline]

Muller, H.J. (1954) Damage to posterity caused by irradiation of the gonads. Am. J. Obstet. Gynecol., 67, 467–483.[ISI][Medline]

National Radiological Protection Board (1994a) Normalised organ doses for x-ray examinations calculated using the Monte Carlo techniques. NRPB, Didcot, Oxon, NRPB-SR262 (software).

National Radiological Protection Board (1994b) Estimation of effective doses in diagnostic radiology from entrance surface doses and dose-area product measurements. NRPB, Didcot, Oxon, NRPB Report-R262.

Sheikh, H.H. and Yussman, M.A. (1976) Radiation exposure of ovaries during hysterosalpingography. Am. J. Obstet. Gynecol., 124, 307–310.[ISI][Medline]

Shirley, R.L. (1971) Ovarian radiation dosage during hysterosalpingography. Fertil. Steril., 22, 83–85.[ISI][Medline]

Van der Weiden, R.M. and Van Zijl, J. (1989) Radiation exposure of the ovaries during hysterosalpingography. Is radionuclide hysterosalpingography justified? Br. J. Obstet. Gynaecol., 96, 471–472.[ISI][Medline]

accepted on October 8, 2001.