Critical appraisal:Barton SE, Najita JS, Ginsburg ES, Leisenring WM, Stovall M, Weathers RE, et al 2013

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Critical Appraisal

Article being appraised

Barton SE, Najita JS, Ginsburg ES, Leisenring WM, Stovall M, Weathers RE, et al. Infertility, infertility treatment, and achievement of pregnancy in female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol 2013 Aug;14(9):873-81 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23856401.


Applicable clinical question

Key Facts

Study Design

cohort study

Study aims:

infertility and time to pregnancy among female childhood cancer survivors, and analyzes treatment characteristics associated with infertility and subsequent pregnancy.

Number of Patients:

4897

-3,531 survivors from Childhood Cancer Survivor Study (CCSS) cohort study that includes five-year cancer survivors from 26 institutions who were <21 years old at the time of diagnosis between January 1, 1970, and December 31, 1986

-1,366 female sibling control

-females ages 18–39 years reporting they had ever been sexually active
Reported outcome(s):

-Self-reported infertility (‘clinical infertility’ - anyone who responded yes to: “Was there ever a period in your life when you and a partner tried for one year or more to become pregnant, without success?” AND ‘total infertility’ included women with ‘clinical infertility’ as well as those who reported ovarian failure [never having had a menstrual period or menstrual periods stopping five years or more from time of baseline], inclusive of both those women who attempted to become pregnant for one year or more).
-pregnancy (including time to first pregnancy)
-risk of infertility

Results of outcome(s):

-still menstruating at the time of the baseline questionnaire (82·0%[2894/3531] of survivors and 86·8% [1186/1366] of siblings).
-Survivors had an increased risk of clinical infertility (>1 year of attempts at conception without success) compared to siblings:
~including ovarian failure group - RR =1.48 95% CI 1·23–1·78 (adj for sociodemographic and behavioral risk factors)
~was most pronounced at early reproductive ages (≤24 years RR=2·92, 95%CI 1·18–7·20; 25–29 years RR=1·61, 95% CI 1·05–2·48; 30–39 years RR=1·37, 95% CI 1·11–1·69).
-In adjusted models, older age (>29 vs. 24–29) at the time of the baseline questionnaire (RR=1·68, 95% CI 1·26–2·24), marital status (RR=7·91, 95% CI 4·58–13·68 if currently married), and BMI >30 kg/m2 (RR=1·71, 95% CI 1·30–2·26) were associated with clinical infertility
-association between age at primary diagnosis and infertility was not observed after adjustment
-In adjusted models, uterine RT doses >5 Gy (RR=2·48, [95% CI 1·54–4·01] for 5·1–10 Gy; RR=2·02, [95% CI 1·27–3·23] for
10·1–20 Gy; RR=1·95, [95% CI 1·19–3·19] for >20 Gy) and the alkylating agent (AA) score of 3 (RR=1·48, 95% CI 1·10–1·99) remained significant.
-704 participants who reported a planned first pregnancy
-survivors had an increased time to pregnancy interval (p=0·032):
~13.0% (55/423) of survivors required more than twelve months of attempts to achieve pregnancy, compared to 8·3% (21/253) of siblings
~When grouped by Tx - abdominal RT significantly longer to become pregnant (than no abom RT), RT to the brain or head had a significantly decreased time to pregnancy compared to other survivors
~64·2% (292/455) with infertility achieved a pregnancy
~In adjusted analyses, infertile survivors who received >10 Gy of uterine RT were less likely to become pregnant (RR=0·33, 95% CI 0·14–0·75 for 10·1–20 Gy and RR=0·21, 95% CI 0·08–0·60 for >20 Gy) than those who were not exposed to uterine RT. Additionally, those with AA scores of 2 (RR=0·59, 95% CI 0·43–0·82) or 3 (RR=0·77, 95% CI 0·62–0·97) were less likely to become pregnant

Comments on results:

-median age 27.6 years in survivors and 33.6 years in controls
-also collected medical treatment for infertility (which is listed as exclusion criteria above, but I am assuming this is not what is meant for exclusion of the paper) - Despite being equally likely to seek treatment for infertility, survivors were less likely to be prescribed medication for treatment of infertility (RR=0·57, 95% CI 0·46–0·70).

Includes an economic evaluation

no

Evidence ratings

Level of evidence

III-3

Risk of bias
Low risk of bias Comments: Questionnaire based - selection bais, recall bias etc
Result of appraisal

Jutta's tick icon.png Included




Completed by

Dr Jessica Harris

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Article
Barton SE, Najita JS, Ginsburg ES, Leisenring WM, Stovall M, Weathers RE, et al. Infertility, infertility treatment, and achievement of pregnancy in female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol 2013 Aug;14(9):873-81 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23856401.
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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