Critical appraisal:Byrne J, Mulvihill JJ, Myers MH, Connelly RR, Naughton MD, Krauss MR, et al 1987

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Critical Appraisal

Article being appraised

Byrne J, Mulvihill JJ, Myers MH, Connelly RR, Naughton MD, Krauss MR, et al. Effects of treatment on fertility in long-term survivors of childhood or adolescent cancer. N Engl J Med 1987 Nov 19;317(21):1315-21 Available from: http://www.ncbi.nlm.nih.gov/pubmed/3683460.


Applicable clinical question

Key Facts

Study Design

cohort study

Study aims:

Aim to estimate risk of infertility in a "retrospective cohort study survivors" (though really a cross-sectional prevalence/incidence study) of childhood and adolescent cancer and controls

Number of Patients:

Not applicable

-2283 long term survivors of childhood and adolescent cancer (<20 yrs), Dx 1945-1975 across 5 cancer registries (clinics) in the US, who survives >5 years

-3270 sibling controls (quasi-matched)
-at age of majority (>21 yrs), and married after Dx. Also excluded pts who were sterile, voluntary infertility, or had a pregnancy before 1st marriage.

-interviews (91% response rate).
Reported outcome(s):

relative fertility = association between survivor and control and is equivalent to reltative risk

Results of outcome(s):

-in women, 15% survivors were post-menopausal at interview (vs 17% controls) - ave age of menopause 31 vs 36 years.
-survivors who were potentially fertile with sig less likely than controls to report a pregnancy (77% vs 86%; P<0.001)-> crude relative fertility was 0.88. Male survivors had greater fertility deficit than females (relative fertility=0.83 vs 0.94)
-age was not statistically sig factor
-Lower pregnancy rates in survivors - associated with age at marriage and decade of marriage. Those who married 25 or older had a relative fertility of 0.80 (vs 0.90 in those who married <25 years). Those who married <1970 had higher relative fertility (0.95) to >1970 (0.85). These were controlled for in later analyses.
-overall fertility of survivors 15% less than controls (0.85). Ater adjustment, the relative fertility in males slightly lower than crude estimate and remaing sig. in females, adjusted relative fertility was not sig difference to controls.
-differences in pregnancy rates among spouses of male survivors compared with controls apparent after 1 year of marriage. In females only slight differences which diminished over time.
-cancer site - adj relative fertility sig <1 seen in Hodgkin's and male genital system tumors
-least damaging Tx was surgery alone (9% reduction in fertility), RT below diaphragm reduced fertility in both sexes by ~25%, Tx with alkylating agents more harmful than radiation, most damaging was combined Tx with infradiaphragmatic radiation and alkylating agents almost 1/2 of that of controls (relative fertility 0.57). Non-alkylating agents = no deficit (RF=0.98).
-Chemo with alkylating agents, with or without radiation to sites below the diaphragm was assoc with fertility deficit ~60% in men: Alkylating agents along (RF=0.42) vs RT alone above diaphragm (RF=0.89) and below diaphragm (RF = 0.74). RT above diaphragm did not add sig to risk from alkylating agents in men, but in combination below the diaphragm RF=0.38.
-in women, no apparent effect of alkylating agents alone (RF =1.02) and moderate fertility deficit when alkylating agent combined with radiation below the diaphragm (RF=0.81).

Comments on results:

-no statistically sig differences between groups in respect to centre, sex or race. Survivors were slightly younger than sibling controls (32.4 yrs vs 33.8 yr
- proxy interviews for 10% survivors and 4% controls
-21% Hodgkin's
-37% soft tissue sarcomas, thyroid, and tumours of the brain and CNS (roughly equal numbers)
-result only for Tx receive within first 12 months after Dx
-age of Dx dichotomised at 15 years
-relative fertility no affected by income, educational attainment, race, center, self-reported health status, vital status, or other potentially confounding variables (e.g. freq of intercourse, #of marriages, current martial status, use of IUIs, endometriosis or PID, year of birth, or interview type [F2F or phone], proxy, infertility challenges).

Includes an economic evaluation

no

Evidence ratings

Level of evidence

III-3

Risk of bias
Moderate risk of bias Comments: Although the source of the populaiton was pretty good, they had some strange eligibility criteria which could result in bias (i.e. married, not had a prior pregnancy etc)
Result of appraisal

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Completed by

Dr Michelle Peate

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Article
Byrne J, Mulvihill JJ, Myers MH, Connelly RR, Naughton MD, Krauss MR, et al. Effects of treatment on fertility in long-term survivors of childhood or adolescent cancer. N Engl J Med 1987 Nov 19;317(21):1315-21 Available from: http://www.ncbi.nlm.nih.gov/pubmed/3683460.
Assigned to
User:Michelle.peate
Topic area
Guidelines:COSA:Cancer fertility preservation guidelines/Impact of cancer on fertility
Clinical question
Form
Form:Critical appraisal


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