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Keywords:

  • prostate brachytherapy;
  • fertility;
  • pregnancy

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

OBJECTIVES

To examine several cases of unusual and unexpected pregnancy in the female partners of men treated with brachytherapy for cancer of the prostate

PATIENTS AND METHODS

Self-reported pregnancy of partners of patients who had had prostate brachytherapy was assessed. The dosimetry to the testicles and sperm counts were used to examine the feasibility of pregnancy in the partners.

RESULTS

Three reported cases of pregnancy showed the men to have viable counts of within several or all of the parameters of the World Health Organisation criteria for normal semen analysis.

CONCLUSIONS

These cases provide a cautionary tale and suggest that all men being treated with prostate brachytherapy should be counselled about the possibility of continued fertility. Documentation of this ‘risk’ on the consent form will allow for proper discussion of this issue in a clinical and medicolegal context. The key to addressing this problem is to propagate much better patient information. The topic should be addressed clearly in information booklets for the patients. Prostate brachytherapy may allow for pregnancy to be achieved in the fertile partners of patients, even after full radiation treatment of the patient.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

Prostate brachytherapy has become a very popular procedure for treating localized prostate cancer. While it is still a preferred treatment for older patients, increasingly many younger men are now being managed with this method. Younger men may have even younger partners and thus consideration must be given to questions of fertility after treatment. After brachytherapy most men report a marked reduction in semen volume and altered viscosity. In addition, erectile dysfunction is also a common consequence. It is thus commonly assumed that these couples are infertile.

To date, only one evaluation of the fertility of men after prostate brachytherapy has been reported by Mydlo and Lebed [1]. In the present study we examined the fertility variables of three men whose partners became unintentionally pregnant, and found some of them to be within normal limits. We also simulated brachytherapy dosimetry to the testicles, and determined that the distance-dependent radiation may affect the germinal centres minimally to moderately.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

From July 1996 to June 2004, 485 cases of localized prostate cancer were treated at the Massachusetts General Hospital with either 125I- or 103Pd-brachytherapy, but fertility (as opposed to infertility) did not appear on the standard consent form. Because of the low scattered doses of radiation and the long period over which the radiation is released no attempt was made to shield the testicles. Advice on contraception was not routinely given, as the dialogue usually focused on erectile potency rather than fertility. Of these 485 men, three who continued to be sexually active reported that their female partner subsequently became pregnant. These men had standard semen analysis; genetic paternity testing was not desired by any of the men, and was not done in any of them. The radiation dose to the testicles was calculated using aggregate seed dosimetry, and was compared with that of doses that were known to reduce or eliminate germinal centre activity.

Calculations were made of the radiation doses received by the testicles of these three men, all of whom had been implanted with 125I-seeds. The model assumed a 40 mL prostate implanted with 96 sources of 11.1 MBq. At 2, 4, 6, 8, 10 and 12 cm from the apex of the prostate the point doses were 29.7, 7.5, 2.5, 0.9, 0.3 and 0.03 Gy (Fig. 1). The total dose received by each man cannot be known because of the naturally variable relationship between the prostate and the testes. However, it can be assumed to be 0.03–2.5 Gy, depending on the position of the testis and whether or not the distance is measured to the upper or lower pole of the testicles.

image

Figure 1. The radiation dose received as a function of the distance from the apex of a representative 40 mL prostate.

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RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

Two of the pregnancies were carried to term, and normal children were born; one pregnancy resulted in a first trimester spontaneous miscarriage. Semen analysis in the three men showed low semen volume and slightly decreased total sperm counts. Morphological variables were within WHO normal limits for the two conceptions carried to term. The radiation dose to the testicles, depending on distance to the prostate, was within limits to produce no or mild radiation decreases in sperm germinal centres.

The first case of pregnancy was reported by a 42-year-old man 13 months after brachytherapy, in a female domestic partner in her 20s. Pregnancy had not been desired and the man consented to a sperm count; there were 95 million viable sperm within an ejaculate volume of 1.4 mL. The morphological variables were within WHO criteria. A healthy child was born and this couple did not wish to pursue paternity issues further.

The second patient, aged 60 years, had been married shortly before brachytherapy and he and his wife wished to conceive children. He banked sperm before his brachytherapy procedure but the banked sperm was never required. He and his wife reported no other sexual partners in the 9 months after brachytherapy and before conception. A healthy child was subsequently delivered. Semen analysis showed 76 million sperm in a low ejaculatory volume of 0.5 mL.

The third man (55 years old) reported an unexpected pregnancy, with conception 22 months after brachytherapy. Both man and partner are Jehovah's Witnesses and reported no other sexual partners. A sperm count showed 95 million sperm with normal morphology, and a low ejaculatory volume of 1.4 mL.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

When localized prostate cancer is treated by radiation infertility can occur in several ways: direct damage to the sperm while in the seminal vesicles; damage to the testicular germinal centres and hormonal supporting cells from scattered radiation; fibrotic obstruction of ducts for sperm transportation; and from the development of erectile dysfunction. As treatment commonly induces at least one of these problems, and because patients tend to be older, with older partners, fertility as an issue is rarely considered. Indeed, it is usually assumed that brachytherapy will inevitably cause infertility.

This small series shows convincingly that pregnancy is possible after prostate brachytherapy. While none of the three couples consented to genetic testing to prove paternity, all three men produced semen samples. The morphology of the sperm was within normal limits, although sperm counts were normal and semen volumes low.

It has been long recognized that external radiation to the testes can induce azoospermia. In adults Leydig cell dysfunction requires doses of >20 Gy but spermatogonia are far more sensitive [2]. Single direct doses of just 4–6 Gy may produce azoospermia lasting ≥ 5 years [3]. Scattered doses have been calculated for the remaining testis of men being treated for seminoma. Two-thirds develop oligo- or azoospermia after doses of 0.2–1.3 Gy [4]. However, recovery occurs in most of these men [5]. There are few data on teratogenesis among the progeny of children born to men who have received previous testicular irradiation.

There is much uncertainty about the radiation doses that the present patients received, due to variability in testicular position, but they can be estimated to be 0.03–2.5 Gy. These are doses that might be expected to induce oligospermia but not necessarily permanent azoospermia. There is probably a lesser biological effect on the testis from low-dose rate brachytherapy than there is from published values for pulsed external beam radiation.

These three cases provide a cautionary tale and suggest that all men being treated with prostate brachytherapy should be counselled about possible continued fertility. Documentation of this ‘risk’ on the consent form will allow for proper discussion of this issue in a clinical and medicolegal context. The key to addressing this problem is to propagate much better patient information. The topic should be addressed clearly in information booklets provided for the patient. Prostatic brachytherapy may allow for pregnancy in the fertile female partners of patients, even after the patient has received the full radiation treatment.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES
  • 1
    Mydlo JH, Lebed B. Does brachytherapy of the prostate affect sperm quality and/or fertility in younger men? Scand J Urol Nephrol 2004; 38: 2214
  • 2
    Brauner R, Czernichow P, Cramer P, Schaison G, Rappaport R. Leydig-cell function in children after direct testicular radiation for acute lymphoblastic leukemia. N Eng J Med 1983; 309: 258
  • 3
    Clifton DK, Bremner WJ. The effect of testicular X-irradiation on spermatogenesis in man. A comparison with the mouse. J Androl 1983; 4: 38792
  • 4
    Berthelsen JG. Sperm counts and serum follicle-stimulating hormone levels before and after radiotherapy and chemotherapy in men with testicular germ cell cancer. Fertil Steril 1984; 41: 2816
  • 5
    Ohl DA, Sonksen J. What are the chances of fertility and should sperm be banked? Semin Urol Oncol 1996; 14: 3644