Hum. Reprod. Advance Access originally published online on November 16, 2007
Human Reproduction 2008 23(1):178-186; doi:10.1093/humrep/dem362
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Parenthood probability and pregnancy outcome in patients with a cancer diagnosis during adolescence and young adulthood
1 Rikshospitalet-Radiumhospitalet Medical Center, Department of Clinical Cancer Research, University of Oslo, Montebello, 0310 Oslo, Norway 2 Medical Faculty, University of Oslo, Montebello, 0310 Oslo, Norway 3 The Medical Birth Registry of Norway, National Institute of Public Health, Oslo, Norway 4 Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway
5 Correspondence address. E-mail: henriette.magelssen{at}radiumhospitalet.no Tel: +47-22935791; Fax: +47-22934553
 |
Abstract |
|---|
 Top Abstract IntroductionMaterial and MethodsResultsDiscussionFundingReferences |
|---|
BACKGROUND: To compare first-time parenthood probability and pregnancy outcome between cancer patients and the general population.
METHODS: Data from a hospital registry on cancer patients aged 15–35 years at diagnosis, including date/type of diagnosis, treatment and date of death, were merged with data from the Cancer Registry and the Medical Birth Registry, providing date of childbirth, IVF, pregnancy outcomes and demographics.
RESULTS: The first-time parenthood probability at the age of 35 years was 63% in male patients (n = 463) and 64% in the male general population (n = 367 068). Figures in female patients were 66% (n = 284) compared with 79% in the female general population (n = 349 576) (P = 0.007). A total of 487 male and 251 female cancer patients were childless pre-diagnosis, and 130 male and 104 female cancer patients had one child before diagnosis and at least one birth post-diagnosis. Congenital anomalies were more frequent in first-borns to previously childless male patients [adjusted odds ratio (ORadj): 1.5; 95% confidence interval (CI): 1.1–2.3]. The risk of low birth weight and preterm delivery after cancer was increased in infants born to female patients, as was perinatal mortality (ORadj 2.3; 95% CI: 1.1–5.0) among post-diagnosis first births.
CONCLUSIONS: The first-time parenthood probability in 35-year old cancer patients is 
60%, which in female patients is significantly reduced compared with the general population. Post-diagnosis pregnancies to female patients are high-risk pregnancies.
Key words: parenthood probability/pregnancy outcome/cancer/general population/adolescence
|
Introduction |
|---|
|
TopAbstractIntroductionMaterial and MethodsResultsDiscussionFundingReferences |
|---|
A 5-year survival of
80% in today’s young cancer patients (Stiller et al., 2006
; Pritchard-Jones et al., 2006) has led to an increased interest of late sequelae among long-term cancer survivors, with infertility as a major concern. Several institutions have reported their experience with long-term gonadal function in specific cancer groups, such as childhood cancer, Hodgkin’s lymphoma, testicular cancer and choriocarcinoma (Rustin, et al., 1984; Ben Arush et al., 2000; Huddart et al., 2005; Ishikawa et al., 2004). Limitations of these studies are their small patient numbers, short follow-up time, selection bias and lack of comparative fertility rates from the general population.
Linkage between hospital and population registries reduces these limitations (Fossa and Kravdal, 2000; Curwen et al., 2005). Preliminary results from linkage between the 13 817 patients from the Rikshospitalet-Radiumhospitalet Medical Center (RRMC) and the Medical Birth Registry of Norway (MBRN) with data from 1967 to 1998 showed that gender, age at diagnosis, previous parenthood and type of cancer influenced the probability of post-diagnosis parenthood in young patients with an adult-onset cancer diagnosis (Fossa et al., 2005). No direct comparison with the general population was done for parenthood probability. No increased risk of birth defects in post-diagnosis offspring was demonstrated. However, in this preliminary study we did not consider the sibling-related associations in perinatal outcomes (Skjaerven et al., 1988, 1999). Therefore, with more recent data from the MBRN, new analyses were done that (i) considered first-time parenthood also in the general population and (ii) used sibship files for the evaluation of pregnancy outcomes. The present analyses thus had two aims.
- To establish cumulative first-time parenthood probabilities of at least one child in adult-onset cancer patients at the age of 35 years compared with the general population.
- To evaluate pregnancy outcomes, including congenital anomalies, among cancer patients compared with the general population using sibship files.
|
Material and Methods |
|---|
|
TopAbstractIntroductionMaterial and MethodsResultsDiscussionFundingReferences |
|---|
Data sources
By means of the unique national identification numbers, given to each citizen in Norway, the records from the RRMC patient registry were merged with data from The Cancer Registry in Norway (CRN) for additional information on the cancer diagnosis, and the MBRN for data on reproduction and pregnancy outcomes (Fig. 1).
|
The CRN
Cancer reporting to this registry has been compulsory in Norway since 1953, recording date and type of diagnosis, initial extent of the disease (localized, regional, distant), histology, date of death and initial treatment (except hormonal treatment). No information is recorded on recurrence and its treatment. We traced the records of the CRN for information on medical data not available in the records from the RRMC.
The MBRN
Since its start in 1967 this population-based registry collects, with compulsory notification, information on all childbirths in Norway, live or still, of at least 16-week gestation. Registered information includes demographic data of the parents, their previous reproductive history, use of assisted reproductive techniques (ARTs) (in vivo fertilization or IVF, registered since 1988), maternal health before and during pregnancy, complications during delivery and the results of the medical examination of the new-born (including congenital anomalies). Since 1999, the Registry also receives notification from neonatal intensive care units for infants transferred to such units after birth. Individuals born before 1967 without parenthood in this year or later are not registered in the MBRN, whereas all individuals born in Norway in 1967 or later are covered in the Registry. Individuals born in the early period of the MBRN can thus be followed for their own reproduction. For the present study data were available for the observation period from 1 January 1967 through 30 June 2004 (cut-off date of the study).
Patient registry of the RRMC
The RRMC functions as a referral hospital for patients needing multidisciplinary oncological treatment. An electronic patient registry contains information on each patient’s cancer diagnosis hospitalized since 1971, including treatment given at the RRMC, but excluding hormone manipulation.
On the basis of information from the hospital registry and the CRN, four categories of overall treatment [surgery alone, radiotherapy (±surgery), chemotherapy (±surgery) and radiotherapy and chemotherapy (±surgery)] were defined.
We conducted two independent substudies in cancer patients (cases) and their controls, identified in the general population. Cases had to fulfil all of the following eligibility criteria: (i) born from 1945 through 1982; (ii) 15–35 years old at the time of diagnosis of their first invasive cancer (all invasive cancers, except basal cell carcinoma, are included) and (iii) referral to the RRMC from 1980 throughout 1997. For each substudy, appropriate control groups were provided by the MBRN.
(i) Substudy I: First-time parenthood probability.
Among the individuals born from 1945–1982 we identified all individuals born in Norway from 1967 to 1978, and followed them for their first childbirth (yes/no) until June 2004. This selection was done since only individuals born after 1967 would be registered in the MBRN also if they did not reproduce during the observation period. Within this population we identified our cases, who had to fulfil criteria 2 and 3.
First-time parenthood probability takes into account the individuals’ first childbirth during the observation period (
16-week gestation), without considering whether the pregnancy was initiated prior or after the cancer diagnosis. For the most frequent cancer types, we also calculated the post-diagnosis parenthood probability defined as first-time parenthood after cancer in patients who were childless when their malignancy was diagnosed.
(ii) Substudy II: Obstetric and perinatal outcomes including congenital anomalies.
By means of the national identification numbers, births in the MBRN were linked to their mothers or fathers, all born between 1945 and 1982. Sibship files were established with the mother or father as the observation unit for parents whose first births occurred in 1967 or later. Among cancer patients we constructed two separate groups and performed two separate analyses: individuals in Group1 were childless at the time of the malignant diagnosis and had at least one post-diagnosis pregnancy, for which obstetric and perinatal outcomes were compared with first births in the general population (Control 1). In these analyses, we compared all first childbirths in cancer patients with all first childbirths in the general population, independent of the number of children born later on. Cases in Group 2 had one birth prior to and at least one after the cancer diagnosis, and we compared obstetric and perinatal outcomes for first- (pre-diagnosis) and second- (post-diagnosis) born siblings with outcomes for first- and second-born siblings in the general population (Control 2) (sibling analysis).
Low birthweight (LBW) was birthweight <2500 g, and delivery before 37 completed weeks of gestation was recorded as preterm delivery. Perinatal death was defined as stillbirth (after 16-week gestation) or early neonatal death occurring within the first 7 days of life. All congenital anomalies were grouped together as one entity. The term IVF did not discriminate the different types of ART. Maternal age, maternal education, time period and, when appropriate, paternal age and interbirth interval, were evaluated as possible confounders for the association between a cancer diagnosis and the different perinatal outcomes in the post-diagnosis births.
Statistics
Standard descriptive methods were applied using the Statistical Package for the Social Sciences for Windows version 12.
Substudy I: The cumulative parenthood probability was assessed by the Kaplan Meier procedure with Log Rank tests evaluating differences, the event being first time childbirth recorded in the MBRN. For first-time parenthood probabilty the observation time started at the mother’s/father’s date of birth. The observation time for post-diagnosis parenthood probability started at the date of the malignant diagnosis. All persons were followed to the date of death or emigration, first childbirth or June 30, 2004, whichever occurred first.
Substudy II: Chi-square and logistic regression analyses were used to compare perinatal outcomes recorded in the interval from 1967 to June 2004 in cancer patients and controls. Logistic regression was used to adjust for mother’s age, educational level and time period, and when appropriate, for father’s age and time interval between the two recorded births. Birthweight and preterm delivery were analysed only in singletons. Maternal (and paternal) age was modelled as a categorical variable and grouped as <20 years, 20–24, 25–29, 30–34, 35+ years. Data on parents’ education were obtained from Statistics Norway, and categorized as low (
10 years), medium (11–13 years) and high (14+ years). Time trends were analysed by grouping year of first birth in 5-year categories from 1967 (last category 1997–2004). The interbirth interval was the number of years between births and was modelled as a continuous variable. The level of significance was set at P < 0.05, and all tests were two-sided. 95% confidence intervals (95% CI) were calculated.
|
Results |
|---|
|
TopAbstractIntroductionMaterial and MethodsResultsDiscussionFundingReferences |
|---|
First-time parenthood probability: (Substudy I)
The study population consisted of 367 531 males and 349 860 females, including 463 male and 284 female cancer patients (Fig. 1; Table I). No difference of age at first childbirth was observed between patients and controls. Testicular cancer, malignant lymphoma and gynaecological cancer were the most frequent malignant diagnoses. Seventy percent of the patients had been treated from 1990 and onwards.
|
Fifty-one male and 64 female cancer patients had at least one childbirth registered in the MBRN prior to their cancer diagnosis (Table II). By 30 June 2004, 142 males and 85 females had their first child after the malignant diagnosis. The male cancer patients had a mean of 1.62 children (both before and after diagnosis) compared with 1.72 among male controls (P = 0.08) (Table II). The comparable figures for female cancer patients were 1.76 children versus 1.92 among controls (P = 0.02) (Table II).
|
At the end of the observation time, the male cancer patients’ cumulative first-time parenthood probability was 63% (95% CI: 56–70) versus 64% (95% CI: 63.7–64.3) among controls (P = 0.41). The first-time parenthood probability among female cancer patients was 66% (95% CI: 59–73), compared with 79% (95% CI: 78.8–79.2) among the controls (P = 0.007) (Fig. 2A and B). There was no statistically significant difference between the most frequent cancer types as to 10-year first-time post-diagnosis parenthood probability in patients who were childless at diagnosis [malignant lymphoma (41%) versus testicular cancer (42%) in males (P = 0.47), malignant lymphoma (44%) versus gynaecological cancer (33%) in females (P = 0.30)] (Fig. 2C and D). Patients with localized or regional disease at diagnosis displayed a 44% 10-year post-diagnosis parenthood probability compared with 34% in those with distant metastases (P = 0.047), without differences between overall treatment modalities (data not shown).
|
Perinatal outcome: (Substudy II)
A total of 487 male and 251 female cancer patients, childless at diagnosis, achieved at least one post-diagnosis pregnancy (Group 1, Table III), whereas 130 males and 104 females were identified as having parented one child before and at least one child after the cancer diagnosis (Group 2). Compared with patients from Group 2 those from Group 1 were younger at diagnosis and had less advanced disease. The majority of the first childbirths in Group 1 occurred after 1990,
10 years later than the first births in Group 2 (all P-values <0.05). At their first childbirth patients from Group 1 were also older than those from Group 2 (Table IV). Both in male and female cancer patients the interval between the malignant diagnosis and the first post-diagnosis childbirth was significantly shorter in Group 2 than in Group 1. The intervals between the first and second childbirth to both male and female cancer patients in Group 2 were significantly longer (4.2 and 5.3 years) than what was observed in the general population (2.8 and 3.2 years).
|
|
Successful IVF was used by 39 of the males from Group1 (8%) compared with 0.8% in the Control 1 [adjusted odds ratio (ORadj) 5.3; 95% CI: 3.8–7.5] (Table V). Twenty-seven post-diagnosis first-born infants (5.5%) of male cancer patients had congenital anomalies, compared with 3.2% among first births to males in the general population [odds ratio (OR) 1.8; 95% CI: 1.2–2.6; ORadj 1.5; 95% CI: 1.1–2.3]. Among the male cancer patients, no significant association was found between the children with congenital anomalies and the use of IVF (2/39 versus 25/448, P = 1.0, Fisher’s exact test). The 27 post-cancer infants were fathered by patients with testicular cancer (n = 12); malignant lymphoma (n = 10) and others (n = 5). Anomalies in the musculoskeletal system (limbs, hands and feet) were diagnosed in 21 of the infants (skeletal deformities: 12; hip joint dysplasia: 8: anomaly of m.sterno-cleidomastoideus: 1). In four children, three of them fathered by survivors after testicular cancer, anomalies of the genito-urinary tract were reported. Treatment of the 27 fathers had consisted of surgery only in 4, radiotherapy (±surgery) in 9, chemotherapy (±surgery) in 6 and radiotherapy and chemotherapy (±surgery) in 8. The 27 children were born after a median of 54 months after diagnosis (range: 2–244).
|
No increased risk of congenital anomalies was observed among post-diagnosis infants to female cancer patients. However, perinatal mortality was significantly increased in first births to females who were childless at diagnosis [seven perinatal deaths (2.8% versus 1.4% in the general population) (ORadj 2.3; 95% CI: 1.1–5.0)] (Table V). Further, there was a significantly increased risk of LBW and preterm delivery in these births (Table V): 10% of first-born singleton infants delivered by female cancer patients were LBW compared with 5% in the general population (ORadj 2.1; 95% CI: 1.4–3.2) and 15% were delivered preterm compared with 7% in the general population (Table V).
The sibling analysis (Group 2; Table VI) further revealed that the risk of LBW was 4-fold increased in the post-diagnosis second birth (Table VI, second sibling) to females who had one child before diagnosis, whereas the risk of LBW in their first birth (first sibling; delivered before the cancer diagnosis) did not differ significantly from first-born infants in the general population. Contrary to the well known parity effect in birthweight from first to second births (Beaty et al., 1997), observed in the general population (Fig. 3), a reduction (163 g) in mean birthweight was found for the second relative the first sibling among female cancer patients from Group 2. This reduction in mean birthweight was even more pronounced after adjustment for the time interval between the births (data not shown). Second siblings (post-diagnosis) in Group 2 were also significantly more often than the Control 2 delivered preterm (ORadj: 3.1; 95% CI: 1.8–5.5), whereas this was not so for the first (pre-diagnosis) siblings.
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterial and MethodsResultsDiscussionFundingReferences |
|---|
First-time parenthood probability
Main findings
Male cancer patients’ first-time parenthood probability at the age of 35 was similar in those with adult-onset cancer (63%) and in the general population (64%), but was significantly reduced in female cancer patients (66% versus 79%). The 10-year cumulative post-diagnosis parenthood probabilities in pre-diagnosis childless survivors after testicular cancer or malignant lymphoma approached 45%, with a non-significantly lower probability (33%) in females with gynaecological cancer.
Several explanations can be provided to explain our observations on first-time parenthood probability in 35-year old cancer patients, in particular the surprisingly favourable probability in males. First, it must be kept in mind that about 43% (64/149) of female cancer patients had their first child prior to the cancer diagnosis [26% (51/193) in males]. Second, most of our patients had been treated from 1985–90 and onwards when fertility-saving treatment had been introduced for testicular cancer and malignant lymphoma (Viviani et al., 1985; Fossa et al., 2003; Klimm et al., 2005), the most frequent cancer types in young adulthood in men. These therapeutic strategies have contributed to the relatively high post-diagnosis parenthood probability in male patients with these malignancies, though only few patients use their frozen semen for ART (Blackhall et al., 2002; Magelssen et al., 2005; Kiserud et al., 2007).
Young patients with gynaecological malignancies still represent a major challenge for the oncologist: except for choriocarcinoma, germ cell ovarian cancer and early cases of invasive cancer of the ovaries and cervix with the possibility of fertility-saving procedures (Farthing, 2006; Shepherd et al., 2006), treatment for most cases of gynaecological cancer consists of hystero-oophorectomy (Kaern et al., 1993; Farthing, 2006). Our reduced parenthood probability in female cancer patients must also be viewed on the background of the limited technical possibilities of ART (Blumenfeld et al., 2002; Davis, 2006). Further, the possibility exists that additional young females who were childless at the end of our observation period may become pregnant with longer follow-up, thus reducing the demonstrated difference. On the other hand, the possibility of future motherhood also exists for controls childless at the cut-off date of our study.
Perinatal outcome
Main findings
A significantly increased risk of congenital anomalies in first-born infants fathered after the cancer diagnosis, and an increased perinatal mortality among first births delivered after diagnosis to female cancer patients was observed. Further, infants delivered after diagnosis in females had increased risk of LBW and preterm birth, and the acknowledged parity effect in birthweight from first to second births was lacking in offspring of females who had one child before and one after their cancer diagnosis.
The question about the risk of congenital anomalies is one of the most frequent issues raised by cancer patients who plan post-treatment parenthood. So far, no studies analysing congenital anomalies in offspring to cancer patients (Reichman and Green, 1994; Blatt, 1999; Nagarajan and Robison, 2005) have reported any increased risk of congenital anomalies. Our finding of an increased risk of congenital anomalies in the post-diagnosis first-born offspring of male cancer patients is therefore unexpected, not least as we did not find any association with the use of IVF. The anomalies reported in our study were observed after all types of treatment, and in some patients in infants born 15–20 years after the cancer diagnosis. Due to limited numbers, in depth analyses could not be performed for elucidation of etiological relations. Both the treatment and an inherent genetic instability in the male cancer survivors should be considered as possible etiological factors for these congenital anomalies. We can not exclude the possibility of a diagnostic bias influencing our results, with more thorough examination of offspring to cancer survivors than of offspring to healthy parents. Also, ascertainment of congenital anomalies has improved during the time period of the MBRN, especially after 1998, when notification from neonatal care units was introduced. However, the increased odds remained statistically significant when adjusting for time period, as well as for maternal age, paternal age and education.
When discussing congenital anomalies, the impact of IVF should be considered. More cancer patients than controls used IVF to achieve parenthood. In contrast to a recent study (Zhu et al., 2006), we could not demonstrate any associations between IVF and adverse outcomes in pregnancy in our admittedly small group of cancer patients. In line with previous observations (Davis, 2006; Farthing, 2006; Shepherd et al., 2006; Signorello et al., 2006), pregnancies in female cancer patients were, however, high-risk pregnancies even without the use of IVF, ending with an increased percentage of preterm childbirths, LBW and, for first-born post-cancer births, perinatal loss. The findings of a decreased birthweight after the mother’s cancer became even more evident when the mean weight of the second sibling, born as the first post-diagnosis child, was compared with the weight of second siblings in the general population. Neither LBW nor preterm delivery were significantly more frequent than in the general population for the pre-diagnosis births (first siblings), providing an indirect control for confounding by unmeasured socio-economic variables that tend to be stable between births. Post-diagnosis pre-term birth and LBW children may in part be due to the altered anatomy after abdomino-pelvic surgery and due to fibrotic changes in the irradiated myometrium (Green et al., 2002).
Strengths and limitations
We consider it advantageous that we were able to analyse the first-time reproduction rate in all consecutive patients referred to a tertiary cancer centre for malignancies which are typical for young adulthood. The direct comparison with the general population is also a strength. Further, by comparing outcomes for first and second siblings born to parents who had a cancer diagnosis between these births, we could indirectly use the pre-diagnosis births as ‘controls’ for unmeasured confounding. Finally, most of our patients have been treated from 1985–1990 and onwards, thus reflecting modern treatment policies.
The study has several limitations. Post-treatment fertility after cancer may be decreased due to the malignant process itself, as suggested for testicular cancer (Skakkebaek et al., 2001), its treatment or, not at least due to psychosocial and economical concerns (Syse et al., 2007). This registry-based study can only address selected demographic and medical variables. To compensate for this limitation, we restricted analyses in special cancer types to previously childless individuals assuming that surviving cancer patients would try to have at least one child after their treatment. Further, we did not have any information on the number and timing of attempts of post-treatment parenthood. Finally, half of our patients and controls were only 35 years or younger in 2004, the cut-off date of our observation time, and some individuals childless at that time may become parents during prolonged follow-up.
In summary, cancer patients aged 35 years have an 60% probability of first-time parenthood. Pregnancies in women with a prior cancer diagnosis should be considered as high-risk pregnancies. There may be increased risk of congenital anomalies in the first post-diagnosis infant fathered by male cancer survivors and increased perinatal mortality in first births to female cancer survivors, but this needs confirmation in larger series.
|
Funding |
|---|
|
TopAbstractIntroductionMaterial and MethodsResultsDiscussionFundingReferences |
|---|
The Lance Armstrong Foundation, The Norwegian Research Council.
|
References |
|---|
|
TopAbstractIntroductionMaterial and MethodsResultsDiscussionFundingReferences |
|---|
Beaty TH, Skjaerven R, Breazeale DR, Liang KY. Analyzing sibship correlations in birth weight using large sibships from Norway. Genet Epidemiol (1997) 14:423–433.[CrossRef][Web of Science][Medline]
Ben Arush MW, Solt I, Lightman A, Linn S, Kuten A. Male gonadal function in survivors of childhood Hodgkin and non-Hodgkin lymphoma. Pediatr Hematol Oncol (2000) 17:239–245.[CrossRef][Web of Science][Medline]
Blackhall FH, Atkinson AD, Maaya MB, Ryder WD, Horne G, Brison DR, Lieberman BA, Radford JA. Semen cryopreservation, utilisation and reproductive outcome in men treated for Hodgkin’s disease. Br J Cancer (2002) 87:381–384.[CrossRef][Web of Science][Medline]
Blatt J. Pregnancy outcome in long-term survivors of childhood cancer. Med Pediatr Oncol (1999) 33:29–33.[CrossRef][Web of Science][Medline]
Blumenfeld Z, Dann E, Avivi I, Epelbaum R, Rowe JM. Fertility after treatment for Hodgkin’s disease. Ann Oncol (2002) 13(Suppl. 1):138–147.
Curwen GB, Winther JF, Tawn EJ, Smart V, Whitehouse CA, Rees GS, Olsen JH, Guldberg P, Rechnitzer C, Schroder H, et al. G(2) chromosomal radiosensitivity in Danish survivors of childhood and adolescent cancer and their offspring. Br J Cancer (2005) 93:1038–1045.[CrossRef][Web of Science][Medline]
Davis M. Fertility considerations for female adolescent and young adult patients following cancer therapy: A guide for counseling patients and their families. Clin J Oncol Nurs (2006) 10:213–219.[CrossRef][Medline]
Farthing A. Conserving fertility in the management of gynaecological cancers. BJOG (2006) 113:129–134.[CrossRef][Web of Science][Medline]
Fossa SD, Kravdal O. Fertility in Norwegian testicular cancer patients. Br J Cancer (2000) 82:737–741.[CrossRef][Web of Science][Medline]
Fossa SD, Dahl AA, Loge JH. Fatigue, anxiety, and depression in long-term survivors of testicular cancer. J Clin Oncol (2003) 21:1249–1254.
Fossa SD, Magelssen H, Melve K, Jacobsen AB, Langmark F, Skjaerven R. Parenthood in survivors after adulthood cancer and perinatal health in their offspring: a preliminary report. J Natl Cancer Inst Monogr (2005) 77–82.
Green DM, Peabody EM, Nan B, Peterson S, Kalapurakal JA, Breslow NE. Pregnancy outcome after treatment for Wilms tumor: a report from the National Wilms Tumor Study Group. J Clin Oncol (2002) 20:2506–2513.
Huddart RA, Norman A, Moynihan C, Horwich A, Parker C, Nicholls E, Dearnaley DP. Fertility, gonadal and sexual function in survivors of testicular cancer. Br J Cancer (2005) 93:200–207.[CrossRef][Web of Science][Medline]
Ishikawa T, Kamidono S, Fujisawa M. Fertility after high-dose chemotherapy for testicular cancer. Urology (2004) 63:137–140.[CrossRef][Web of Science][Medline]
Kaern J, Trope CG, Kristensen GB, Abeler VM, Pettersen EO. DNA ploidy; the most important prognostic factor in patients with borderline tumors of the ovary. Int J Gynecol Cancer (1993) 3:349–358.[CrossRef][Web of Science][Medline]
Kiserud CE, Fossa A, Holte H, Fossa SD. Post-treatment parenthood in Hodgkin’s lymphoma survivors. Br J Cancer (2007) 96:1442–1449.[Web of Science][Medline]
Klimm B, Reineke T, Haverkamp H, Behringer K, Eich HT, Josting A, Pfistner B, Diehl V, Engert A. Role of hematotoxicity and sex in patients with Hodgkin’s lymphoma: an analysis from the German Hodgkin Study Group. J Clin Oncol (2005) 23:8003–8011.
Magelssen H, Haugen TB, von Duhring V, Melve KK, Sandstad B, Fossa SD. Twenty years experience with semen cryopreservation in testicular cancer patients: who needs it? Eur Urol (2005) 48:779–785.[CrossRef][Web of Science][Medline]
Nagarajan R, Robison LL. Pregnancy outcomes in survivors of childhood cancer. J Natl Cancer Inst Monogr (2005) 34:72–76.
Pritchard-Jones K, Kaatsch P, Steliarova-Foucher E, Stiller CA, Coebergh JW. Cancer in children and adolescents in Europe: developments over 20 years and future challenges. Eur J Cancer (2006) 42:2183–2190.[CrossRef][Web of Science][Medline]
Reichman BS, Green KB. Breast cancer in young women: effect of chemotherapy on ovarian function, fertility, and birth defects. J Natl Cancer Inst Monogr (1994) 125–129.
Rustin GJ, Booth M, Dent J, Salt S, Rustin F, Bagshawe KD. Pregnancy after cytotoxic chemotherapy for gestational trophoblastic tumours. Br Med J (Clin Res Ed) (1984) 288:103–106.[Medline]
Shepherd JH, Spencer C, Herod J, Ind TE. Radical vaginal trachelectomy as a fertility-sparing procedure in women with early-stage cervical cancer-cumulative pregnancy rate in a series of 123 women. BJOG (2006) 113:719–724.[CrossRef][Web of Science][Medline]
Signorello LB, Cohen SS, Bosetti C, Stovall M, Kasper CE, Weathers RE, Whitton JA, Green DM, Donaldson SS, Mertens AC, et al. Female survivors of childhood cancer: preterm birth and low birth weight among their children. J Natl Cancer Inst (2006) 98:1453–1461.
Skakkebaek NE, Rajpert-De ME, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod (2001) 16:972–978.
Skjaerven R, Wilcox AJ, Lie RT, Irgens LM. Selective fertility and the distortion of perinatal mortality. Am J Epidemiol (1988) 128:1352–1363.
Skjaerven R, Wilcox AJ, Lie RT. A population-based study of survival and childbearing among female subjects with birth defects and the risk of recurrence in their children. N Engl J Med (1999) 340:1057–1062.
Stiller CA, Desandes E, Danon SE, Izarzugaza I, Ratiu A, Vassileva-Valerianova Z, Steliarova-Foucher E. Cancer incidence and survival in European adolescents (1978–1997). Report from the Automated Childhood Cancer Information System project. Eur J Cancer (2006) 42:2006–2018.[CrossRef][Web of Science][Medline]
Syse A, Kravdahl O, Tretli S. Parenthood after cancer-a population-based study. Psychooncology (2007) 16:920–927.[CrossRef][Medline]
Viviani S, Santoro A, Ragni G, Bonfante V, Bestetti O, Bonadonna G. Gonadal toxicity after combination chemotherapy for Hodgkin’s disease. Comparative results of MOPP vs ABVD. Eur J Cancer Clin Oncol (1985) 21:601–605.[CrossRef][Web of Science][Medline]
Zhu JL, Basso O, Obel C, Bille C, Olsen J. Infertility, infertility treatment, and congenital malformations: Danish national birth cohort. BMJ (2006) 333:679.
Submitted on June 28, 2007; resubmitted on October 9, 2007; accepted on October 18, 2007.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. J. Chow, A. Kamineni, J. R. Daling, A. Fraser, C. L. Wiggins, G. P. Mineau, M. R. Hamre, R. K. Severson, C. Drews-Botsch, and B. A. Mueller Reproductive Outcomes in Male Childhood Cancer Survivors: A Linked Cancer-Birth Registry Analysis Arch Pediatr Adolesc Med, October 1, 2009; 163(10): 887 - 894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Cvancarova, S. O. Samuelsen, H. Magelssen, and S. D. Fossa Reproduction Rates After Cancer Treatment: Experience From the Norwegian Radium Hospital J. Clin. Oncol., January 20, 2009; 27(3): 334 - 343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R. Schover Rates of Postcancer Parenthood J. Clin. Oncol., January 20, 2009; 27(3): 321 - 322. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||