Surviving childhood and reproductive-age malignancy: effects on fertility and future parenthood

doi:10.1016/S1470-2045(09)70317-1

The Lancet Oncology

Volume 11, Issue 5, May 2010, Pages 490-498

https://doi.org/10.1016/S1470-2045(09)70317-1 Get rights and content

Summary

Annually, more than 50 000 cancer diagnoses are made in the USA in patients under the age of 35 years. Despite this staggering statistic, medical advancements have substantially improved survival rates. Thus, for both male and female patients with cancer, quality-of-life issues, such as fertility preservation and parenthood, have become an essential component of treatment. Unfortunately, many of the treatments to eradicate malignant processes can also compromise reproductive function. In these cases, fertility preservation should be discussed and initiated with early treatment planning, to allow the best chance for future parenthood, when appropriate. The effects of cancer and cancer treatments on fertility and future parenthood, including health risks for patients, their gametes, and offspring are discussed.

Introduction

Early detection programmes combined with effective treatment regimens have allowed men and women with cancer to live substantially longer, making fertility preservation an essential component of therapy. Maintaining fertility and future parenthood are quality-of-life issues now desired by many survivors of cancer; in fact, one of the strongest predictors of emotional satisfaction in survivors is feeling healthy enough to be a good parent.¹ However, patients are often fearful that their history of cancer and previous treatment will not only increase their risk of cancer recurrence, but also have an adverse obstetric or postnatal effect on their child (figure 1). Surveys suggest that only 50% of patients are counselled regarding the option of fertility preservation and the potential risks associated with pregnancy and parenthood after cancer,¹ and even fewer are referred to a reproductive endocrinologist. This review discusses survival statistics and the medical and psychological effects of cancer on fertility treatment and future parenthood, including health risks for afflicted patients, their gametes, and offspring.

It is estimated that 1 372 910 people were diagnosed with cancer in the USA in 2005, with 4% (55 000) younger than 35 years.² Overall, more than 75% of cancer patients under the age of 45 years now survive at least 5 years from the time of their diagnosis,³ with childhood cancers seeing striking improvements in survival; now, roughly one in every 1000 adults is a survivor of childhood cancer.⁴ The most common cancer diagnoses in younger patients include melanoma, non-Hodgkin and Hodgkin's lymphoma, leukaemia, breast, cervical, and testicular cancer. Women of reproductive age are most often afflicted with breast or gynaecological malignancies, with up to 15% of breast and 43% of cervical cancer diagnoses in patients younger than 45 years.⁵ Reproductive-age males are most often diagnosed with testicular cancer and Hodgkin's lymphoma, with around 90% of all testicular tumours arising from age 20–54 years. Lastly, haematological malignancies, such as leukaemias and lymphomas, are most often seen in children and young adults. Corresponding with increased survival of cancer is a high incidence of ovarian and testicular failure.⁶ Therefore, the American Society of Clinical Oncology guidelines now recommend that all patients receive some form of fertility preservation counselling.⁶

Section snippets

Women

Although female reproduction requires a functioning hypothalamic-pituitary-gonadal (H-P-G) axis, ovaries, and uterus, reproductive potential in women is mainly limited by available oocytes. The process of oogenesis begins before birth with a peak in oocyte number (6–7 million) at 20 weeks' gestation, followed by progressive atresia and a quantitative oocyte drop to 1–2 million at birth and 300 000 at puberty.⁷ Oocytes remain arrested as primordial follicles until puberty, a stage postulated to

Reproductive success after cancer and treatments

In patients who have cancer treatment without a prior fertility preservation procedure, reproduction seems to be substantially reduced.21, 22, 23, 24, 25 The Childhood Cancer Survivor Study provided information on the reproductive outcome of survivors of paediatric cancer in the USA, who were diagnosed and treated from 1970–86.21, 22 These data showed that female survivors and the partners of male survivors were substantially less likely to have livebirths compared with their siblings.

Congenital anomalies in offspring

The incidence of congenital anomalies after chemotherapy and radiation has been studied extensively. Patients with cancer often report fear of increased risk of congenital anomalies in their offspring as the primary reason for abstaining from pregnancy after a cancer diagnosis.⁴⁵ This concern is valid because drugs used to treat cancer are designed to interfere with DNA, cell division, and cellular metabolism, processes essential to embryogenesis and fetogenesis. Initial data from survivors of

Cancer recurrence in women related to post-diagnosis pregnancy

Another fear associated with fertility after a cancer diagnosis is the effect that pregnancy will have on cancer recurrence. This is a particular concern for patients with breast cancer since oestrogen, a hormone markedly increased during pregnancy, is a growth factor for these tumours. Much debate has centred on whether women with breast cancer should be advised to abstain from pregnancy after diagnosis. Most studies addressing the prognostic effect of pregnancy after breast-cancer treatment

Conclusion

Despite the desire of many cancer patients to maintain fertility, several factors hinder the initiation of this discussion. In a survey given to oncologists, knowledge of resources, practice behaviours, perceptions of patient characteristics, and quality of discussion were identified as barriers to discussing fertility preservation.⁷⁶ Discussions are further limited for paediatric patients, likely because of the consent process, issues surrounding the experimental nature of procedures, and

Search strategy and selection criteria

References for this review were identified by searches of Medline and PubMed by use of the search terms “fertility”, “pregnancy”, “reproduction”, “cancer”, “recurrence rates”, “chemotherapy”, “radiation therapy”, “congenital anomalies”, “perinatal outcome after cancer treatment”, “obstetrical complications and cancer”, and “emotional side-effects of cancer”. Abstracts and reports from previous meetings were not included. Only papers published in English between January, 1979, and June,

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Cited by (71)

Adverse birth outcomes among offspring born to women diagnosed with cancer: a population-based cohort study
2023, American Journal of Obstetrics and Gynecology MFM
With increasing cancer incidence and survival rates, the prevalence of maternal cancer and its effect on adverse birth outcomes are important for prenatal care and oncology management. However, the effects of different types of cancer at different gestational stages have not been widely reported.
This study aimed to describe the epidemiologic characteristics of pregnancy-associated cancers (during and 1 year after pregnancy) and evaluate the association between adverse birth outcomes and maternal cancers.
Of 983,162 cases, a history of maternal cancer, including pregestational cancer, pregnancy-associated cancer, and subsequent cancer, was identified in 16,475 cases using a health information network. The incidence and 95% confidence interval of pregnancy-associated cancer were calculated with the Poisson distribution. The adjusted risk ratio with 95% confidence interval of the association between adverse birth outcomes and maternal cancer were estimated using the multilevel log-binomial model.
A total of 38,295 offspring were born to mothers with a cancer history. Of these, 2583 (6.75%) were exposed to pregnancy-associated cancer, 30,706 (80.18%) had a subsequent cancer diagnosis, and 5006 (13.07%) were exposed to pregestational cancer. The incidence of pregnancy-associated cancer was 2.63 per 1000 pregnancies (95% confidence interval, 2.53‰–2.73‰), with cancer of the thyroid (1.15‰), breast (0.25‰), and female reproductive organs (0.23‰) being the most common cancer types. The increased risks of preterm birth and low birthweight were significantly associated with cancer diagnosed during the second and third trimester of pregnancy, whereas increased risks of birth defects (adjusted risk ratio, 1.48; 95% confidence interval, 1.08–2.04) were associated with cancer diagnosed in the first trimester. Increased risks of preterm birth (adjusted risk ratio, 1.16; 95% confidence interval, 1.02–1.32), low birthweight (adjusted risk ratio, 1.24; 95% confidence interval, 1.07–1.44), and birth defects (adjusted risk ratio, 1.22; 95% confidence interval, 1.10–1.35) were observed in thyroid cancer survivors.
Careful monitoring of fetal growth should be implemented for women diagnosed with cancer in the second and third trimester to ensure timely delivery and balance the benefits of neonatal health and cancer treatment. The higher incidence of thyroid cancer and increased risk of adverse birth outcomes among thyroid cancer survivors suggested that the regular thyroid function monitoring and regulation of thyroid hormone levels are important in maintaining pregnancy and promoting fetal development among thyroid cancer survivors before and during pregnancy.
Evaluation of ovarian reserve before and after chemotherapy
2021, Journal of Gynecology Obstetrics and Human Reproduction
Citation Excerpt :
The younger the patient is, the better she resists to chemotherapy, thanks to a higher initial stock of follicles. In addition, it has been reported that in the pubescent girl, the ovary was more resistant to chemotherapy on the one hand thanks to her young age and on the other hand because most chemotoxics only attack the growing follicles [31]. Another evidence of the importance of age and the initial stock of follicles in the secondary risk of infertility supports the positive correlation found, in fact, the increase of AMH level at the second control after chemotherapy including BEACOPP, despite being considered to be at high risk of gonadotoxicity, in three patients can be explained by their young age (17, 17 and 27 years).
Progress in oncology has improved patient survival. However, cancer chemotherapy can be gonadotoxic and affect their fertility. Recourse to fertility preservation before starting these treatments is therefore necessary in order to allow a better life quality after survival. The aim of this work was to study the impact of chemotherapy on ovarian reserve by AMH measurement.
This is a descriptive and longitudinal study from 2015 to 2018 carried out at Aziza Othmana hospital ART center in Tunis on patient aged less than 41 years who were candidates for fertility preservation. Patients included had AMH measurement prior to cancer treatment. We called them back to follow up the AMH level after chemotherapy. The AMH assay was performed by electrochemilumiescence technique. At the end, only 66 patients met the inclusion criteria.
The most frequent pathologies were Hodgkin's lymphoma and breast cancer. The mean age of patients was 26.7 ± 6.8. The most used chemotherapy protocols were BEACOPP, ABVD or the combination of both in lymphoma and FEC + TXT for breast cancer treatment. A significant difference between AMH before and after chemotherapy was found for BEACOPP and FEC + TXT protocols (p < 10 3). The patient’s age was correlated with the AMH decrease after chemotherapy (r = 0.577, p < 10 3).
Our results showed that the high risk gonadotoxicity protocols were BEACOPP for lymphoma treatment and FEC + TXT for breast cancer treatment. However, studies with a larger sample and more time extended monitoring are necessary for a better gonadotoxicity understanding of the cancer treatments available today.
Fertility in female cancer survivors: a systematic review and meta-analysis
2020, Reproductive BioMedicine Online
Data on the effects of cancer treatments on fertility are conflicting. The aim of the present systematic review and meta-analysis was to determine the chances of childbirth in women survivors of different types of cancer. PubMed, MEDLINE, Embase and Scopus were searched from database inception to 17 July 2019 for published cohort, case-control and cross-sectional studies that investigated the reproductive chances in women survivors of different cancer types. Random-effects models were used to pool childbirth hazard ratios, relative risks, rate ratios and odds ratios, and 95% confidence intervals were estimated; 18 eligible studies were identified. Childbirth chances were significantly reduced in women with a history of bone cancer (HR 0.86, 95% CI 0.77 to 0.97; I² = 0%; P = 0.02 (two studies); RaR 0.76, 95% CI 0.61 to 0.95; I² = 69%; P = 0.01 (two studies); breast cancer (HR 0.74, 95% CI 0.61 to 0.90 (one study); RaR 0.51, 95% CI 0.47 to 0.57; I² = 0%; P < 0.00001 (two studies); brain cancer (HR 0.61, 95% CI 0.51 to 0.72; I² = 14%; P < 0.00001 (three studies); RR 0.62, 95% CI 0.42 to 0.91 (one study); RaR 0.44, 95% CI 0.33 to 0.60; I² = 95%; P < 0.00001 (four studies); OR 0.49, 95% CI 0.40 to 0.60 (one study); and kidney cancer (RR 0.66, 95% CI 0.43 to 0.98 (one study); RaR 0.69, 95% CI 0.61 to 0.78 (one study). Reproductive chances in women survivors of non-Hodgkin's lymphoma, melanoma and thyroid cancer were unaffected. Women with a history of bone, breast, brain or kidney cancer have reduced chances of childbirth. Thyroid cancer, melanoma and non-Hodgkin's lymphoma survivors can be reassured.
Parental Attitudes Toward Fertility Preservation in Female Adolescent Cancer Patients in Lebanon
2019, Journal of Pediatric and Adolescent Gynecology
To measure parental attitudes toward fertility preservation (FP) in female adolescent cancer patients in a Middle Eastern country to understand barriers to decision-making and decisional conflicts.
A questionnaire was distributed to parents of all female adolescents at a tertiary care center from February 2018 to September 2018.
A total of 70 families.
None.
Parental attitudes toward FP.
The educational level of parents was associated with the knowledge about the side effects of treatment (P < .001). FP options were not offered to parents in 60/70 (85.6%) of cases. Oocyte cryopreservation was an acceptable option for 23/70 (32.9%) of interviewed parents who agreed on collecting the oocytes using vaginal ultrasound. The fear of disrupting the hymen was the main reason for disapproval in 20/70 (28.6%) of cases. The religious preference of the family was a significant factor in the acceptance of vaginal ultrasound and vaginal oocyte retrieval. The educational level of parents, the monthly income, and the current employment status were not linearly associated with their acceptance to approve their daughters’ undergoing oocyte cryopreservation through the vaginal route (χ² = 100.651; P < .001).
Parents are not aware of the effect of cancer treatment on future fertility of their daughters. Ethical, social, and religious barriers affect the decision-making for FP. However, a major interest exists among parents for FP, highlighting the importance of development of an oncofertility program, involving a multidisciplinary team to initiate proper counseling and guidance.
Therapeutic exposures and pubertal testicular dysfunction are associated with adulthood milestones and paternity after childhood cancer
2023, Cancer
Disparities in fertility preservation use among adolescent and young adult women with cancer
2023, Journal of Cancer Survivorship

View all citing articles on Scopus

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ReviewSurviving childhood and reproductive-age malignancy: effects on fertility and future parenthood

Summary

Introduction

Section snippets

Women

Reproductive success after cancer and treatments

Congenital anomalies in offspring

Cancer recurrence in women related to post-diagnosis pregnancy

Conclusion

Search strategy and selection criteria

Placenta

Int J Radiat Oncol Biol Phys

Ann Oncol

Lancet

Blood

Mutat Res

Am J Obstet Gyencol

Gynecol Oncol

Gynecol Oncol

Reprod Biomed Online

Eur J Cancer Clin Oncol

Blood

Am J Hum Genet

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Lancet

Fertil Steril

Lancet

Am J Obstet Gynecol

Clin Oncol

The Breast

Lancet

Patient Educ Couns

Having children after cancer: a pilot survey of survivors' attitudes and experiences

Cancer

SEER Cancer Statistics Review

Gonadal damage and options for fertility preservation in female and male cancer survivors

Asian J Androl

Cancer statistics, 2003

CA Cancer J Clin

American Society of Clinical Oncology recommendations on fertility preservation in cancer patients

J Clin Oncol

Premature ovarian failure

Obstet Gynecol

Risk of menopause during the first year after breast cancer diagnosis

J Clin Oncol

The radiosensitivity of the human oocyte

Hum Reprod

Pregnancy outcomes in childhood cancer survivors: probable effects of abdominal irradiation

Int J Cancer

Radiation damage to the uterus—review of the effects of treatment of childhood cancer

Hum Fertil (Camb)

Testicular dysgenesis syndrome: an increasingly common development disorder with environmental aspects

Hum Reprod

The effects of cancer and cancer treatments on male reproductive function

Nat Clin Pract Urol

Male fertility and strategies for fertility preservation following childhood cancer treatment

Endocr Dev

Review
Surviving childhood and reproductive-age malignancy: effects on fertility and future parenthood